Dr Anthony Zambelli - The South African Veterinary Association
Kidneys, protein and pressure - a veterinary Bermuda triangle?Dr Anthony ZambelliChronic Kidney Disease, or CKD, is the modern definition that encompasses chronic renal failure (CRF), chronic renal insufficiency (CRI) and “Interstitial Nephritis” that has progressed to the point of no return. Many patients present to the private veterinarian in an advanced state of CKD, which is a huge shame, because early intervention brings about longer survival times. However, the diagnosis of renal disease is complex, as no one test is totally effective. In fact, because of the massive reserve capacity of the kidneys, early diagnosis is incredibly hard. A diagnosis of CKD is often made by combining the results of several different modalities:1260475205105BiopsyImagingClinical & historical findingsBlood pressureUrine evaluationBlood tests00BiopsyImagingClinical & historical findingsBlood pressureUrine evaluationBlood testsThe relationships and importance of different tests varies between patients as well. We’ll get into the importance of each modality in a bit, but the most critical factors that will determine the success or failure of your clinic and staff in the EARLY diagnosis and SUCCESSFUL management of CKD are:Creating client awareness at every visit;Starting senior pet monitoring schemes and publicising them;Acting on early disease by recognising and communicating its importance;Creating awareness means you need to have a real heart-to-heart discussion with all members of your team – from reception to nurses, and all vets. Everyone must be shown the evidence that early diagnosis means better outcomes – and if you are not trying to achieve better health outcomes for your patients, then what exactly are you there for? Better outcomes (longer survival once diagnosed + better quality of life during this period) comes from earlier diagnosis.Early diagnosis comes from frequent and appropriate testing of at-risk patients;Appropriate testing means identifying the:at-risk population; andthe available, meaningful and affordable tests;Knowing the results of these investigations;Acting on these results; andMonitoring the response to any intervention using the same tests and modifying or maintain your actions accordinglyEarlier diagnosis = Better OutcomesInstinctively, this makes sense, but what evidence is there for this?Firstly, let’s discuss the importance of age. Increased age is a risk factor for the development of CKD in cats.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5EaUJhcnRvbGE8L0F1dGhvcj48WWVhcj4xOTg3PC9ZZWFy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ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5EaUJhcnRvbGE8L0F1dGhvcj48WWVhcj4xOTg3PC9ZZWFy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ADDIN EN.CITE.DATA 1, 2Identifying at-risk patientsThe mortality rate due to CKD is greater in cats over 9 years old, than in younger animals. Therefore, testing for CKD or the conditions that lead to CKD, such as hyperthyroidism or hypertension, should begin no later than 9 years old (we use 7 years in my hospital). In one study, 30.5% of aged, apparently healthy cats became azotaemic within 12 months of being observed in the study. Only blood creatinine and proteinuria at presentation were predictive of cats being at risk of developing azotaemia within this period. ADDIN EN.CITE <EndNote><Cite><Author>Jepson</Author><Year>2009</Year><RecNum>12755</RecNum><DisplayText><style face="superscript">3</style></DisplayText><record><rec-number>12755</rec-number><foreign-keys><key app="EN" db-id="es0pxpxx2asa54exz21vvddgs9f2zxa5wsff" timestamp="1392118875">12755</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Jepson, R. E.</author><author>Brodbelt, D.</author><author>Vallance, C.</author><author>Syme, H. M.</author><author>Elliott, J.</author></authors></contributors><auth-address>Department of Veterinary Basic Science, Royal Veterinary College, Royal College Street, Camden, London, USA. rjepson@rvc.ac.uk</auth-address><titles><title>Evaluation of predictors of the development of azotemia in cats</title><secondary-title>J Vet Intern Med</secondary-title><alt-title>Journal of veterinary internal medicine / American College of Veterinary Internal Medicine</alt-title></titles><periodical><full-title>Journal of Veterinary Internal Medicine</full-title><abbr-1>J. Vet. Intern. Med.</abbr-1><abbr-2>J Vet Intern Med</abbr-2></periodical><pages>806-13</pages><volume>23</volume><number>4</number><keywords><keyword>Animals</keyword><keyword>Azotemia/blood/pathology/urine/*veterinary</keyword><keyword>Blood Pressure</keyword><keyword>Cat Diseases/blood/*pathology/urine</keyword><keyword>Cats</keyword><keyword>Female</keyword><keyword>Logistic Models</keyword><keyword>Longitudinal Studies</keyword><keyword>Male</keyword><keyword>Multivariate Analysis</keyword><keyword>Prospective Studies</keyword><keyword>Risk Factors</keyword></keywords><dates><year>2009</year><pub-dates><date>Jul-Aug</date></pub-dates></dates><isbn>0891-6640 (Print)
0891-6640 (Linking)</isbn><accession-num>19566846</accession-num><urls><related-urls><url> Aging itself is not the cause of azotaemia, which may, in fact, represent a form of compensatory response.Hypertension is also considered to be a potential risk factor for the development of CKD in cats, although the evidence is equivocal, and HT is also not “caused” by aging. ADDIN EN.CITE <EndNote><Cite><Author>Lawler</Author><Year>2006</Year><RecNum>12754</RecNum><DisplayText><style face="superscript">2</style></DisplayText><record><rec-number>12754</rec-number><foreign-keys><key app="EN" db-id="es0pxpxx2asa54exz21vvddgs9f2zxa5wsff" timestamp="1392118531">12754</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Lawler, D. F.</author><author>Evans, R. H.</author><author>Chase, K.</author><author>Ellersieck, M.</author><author>Li, Q.</author><author>Larson, B. T.</author><author>Satyaraj, E.</author><author>Heininger, K.</author></authors></contributors><auth-address>Nestle Research Center St. Louis, Nestle Purina PetCare Company, 2 Research South, St. Louis, MO 63164, USA. dennis.lawler@rdmo.</auth-address><titles><title>The aging feline kidney: a model mortality antagonist?</title><secondary-title>J Feline Med Surg</secondary-title><alt-title>Journal of feline medicine and surgery</alt-title></titles><periodical><full-title>J Feline Med Surg</full-title><abbr-1>Journal of feline medicine and surgery</abbr-1></periodical><alt-periodical><full-title>J Feline Med Surg</full-title><abbr-1>Journal of feline medicine and surgery</abbr-1></alt-periodical><pages>363-71</pages><volume>8</volume><number>6</number><keywords><keyword>Age Distribution</keyword><keyword>*Aging</keyword><keyword>Animals</keyword><keyword>Autopsy</keyword><keyword>Cat Diseases/*mortality/*pathology</keyword><keyword>Cats</keyword><keyword>Cause of Death</keyword><keyword>Kidney Diseases/mortality/*veterinary</keyword><keyword>Retrospective Studies</keyword></keywords><dates><year>2006</year><pub-dates><date>Dec</date></pub-dates></dates><isbn>1098-612X (Print)
1098-612X (Linking)</isbn><accession-num>17092751</accession-num><urls><related-urls><url> Nonetheless, hypertension can aggravate existing CKD and HCM and complicate their management. Consider also the indirect effects of HT for example, retinal detachment. The sudden onset blindness caused by retinal detachment can cause inappetance in a cat with stable CKD, precipitating dehydration and full blown renal crisis. These are but two examples, so my question to you is: what are you doing about it, and what are you looking for?There is enormous debate about the frequency of vaccination of adult pets. I have my own opinions, but these are based on the fact that, in KwaZulu-Natal (where I practice in South Africa), only 3.9% of pets are vaccinated against rabies, whilst 94% of all South African rabies incidents occur in this province. So let’s just accept that I have a good argument for annual vaccination, life long. In the decidedly first-world, vets may be switching to core/non-core vaccination strategies. The big challenge for practitioners is then to convince clients for the need to continue ANNUAL HEALTH CHECKS. I find my clients understand the importance better when I use the human example of annual mammograms/pap smears/PSA tests/Cholesterol/blood pressure etc etc. A 7-year-old cat is pretty much equivalent to a 40-year-old human and her body functions change accordingly.Thus, ANY cat of 7+ years, and particularly cats of 11+ (when hyperthyroidism begins to increase in incidence) is an AT RISK patient.My suggestion is to put together a reduced-cost, standard practice protocol for SENIOR HEALTH CHECKS. If you have an in-practice blood machine, this will help. If not, seriously consider it. A simple, robust machine like the IDEXX VetTest 8008 shouldn’t set you back much and will pay itself off – not least in convenience (rapid results). A good, high definition oscillometric blood pressure machine like the machine from S+B Medvet is an excellent investment as well. Of course, you need a microscope and centrifuge (which IDEXX give you with the VetTest).A suggested senior profile is: ADDIN EN.CITE <EndNote><Cite><Author>Paepe</Author><Year>2013</Year><RecNum>11894</RecNum><DisplayText><style face="superscript">4</style></DisplayText><record><rec-number>11894</rec-number><foreign-keys><key app="EN" db-id="es0pxpxx2asa54exz21vvddgs9f2zxa5wsff" timestamp="1378504659">11894</key><key app="ENWeb" db-id="">0</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Paepe, D.</author><author>daminet, S.</author></authors></contributors><titles><title>Feline CKD. Diagnosis, staging and screening - what is recommended?</title><secondary-title>Journal of Feline Medicine & Surgery</secondary-title></titles><periodical><full-title>Journal of Feline Medicine & Surgery</full-title></periodical><pages>15-27</pages><volume>15</volume><number>S1</number><dates><year>2013</year></dates><urls></urls><electronic-resource-num>10.1177/1098612X13495235</electronic-resource-num></record></Cite></EndNote>4(The clinical evaluation – if at the time of vaccination, consider not charging extra for the consultation as you should be doing a thorough physical examination anyway);The most important questions to ask are those that determine if the patient is inappetant (reduced appetite, “picky” eater, PU, PD, weight loss, lethargy, halitosis and vomiting). Train your staff to ACCURATELY measure every patient’s weight at EVERY VISIT. In a cat, a loss of 150g can be quite substantial – you need to know!Urine – collect by cystocentesis, and do the following:SgDipstick testSediment (because we always do sediment on any urine obtained but this is probably not necessary in cases with a normal USG and negative dipstick)Sternheimer stain +Diff-quick stainIf there is proteinuria on the dipstick, measure the Urine Protein:Creatinine ratio on your vet-test; this may be an additional charge but is well worth it. For example, a 2+ proteinuria and 1.015 sg could be significant – how significant? Well, measure it, don’t guestimate! Also, do BP (see (4), below)Blood – as a minimum, do a “preanaesthetic profile” + Albumin, Calcium and Phosphate.SDMA is a useful test (discussed later)Phosphate is very frequently forgottenElectrolytes if you can as wellHaematology is also important if you canTotal T4 to check for hyperthyroidism Blood pressure (I do this after the examination, but before the blood tests, so that the patient is accustomed to me but not yet stressed out by clippers and needles!)Get 5 measurements which must all agree to within 15mmHg of the mean (The HDO monitor calculates this for you on the screen). Give the patient 5 - 10 minutes to acclimate.Apart from a blanket prescription of any cat >7 yo being at risk, are there any others at risk? Well, patients with polycystic kidney disease, for one; those with a history of previous long-term NSAID therapy might be (although this is controversial as one group suggests meloxicam can prolong survival in cats with CKD!)PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Hb3dhbjwvQXV0aG9yPjxZZWFyPjIwMTE8L1llYXI+PFJl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ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Hb3dhbjwvQXV0aG9yPjxZZWFyPjIwMTE8L1llYXI+PFJl
Y051bT4xMTgyMjwvUmVjTnVtPjxEaXNwbGF5VGV4dD48c3R5bGUgZmFjZT0ic3VwZXJzY3JpcHQi
PjUsIDY8L3N0eWxlPjwvRGlzcGxheVRleHQ+PHJlY29yZD48cmVjLW51bWJlcj4xMTgyMjwvcmVj
LW51bWJlcj48Zm9yZWlnbi1rZXlzPjxrZXkgYXBwPSJFTiIgZGItaWQ9ImVzMHB4cHh4MmFzYTU0
ZXh6MjF2dmRkZ3M5ZjJ6eGE1d3NmZiIgdGltZXN0YW1wPSIxNDY0NzAyMjk2Ij4xMTgyMjwva2V5
PjwvZm9yZWlnbi1rZXlzPjxyZWYtdHlwZSBuYW1lPSJKb3VybmFsIEFydGljbGUiPjE3PC9yZWYt
dHlwZT48Y29udHJpYnV0b3JzPjxhdXRob3JzPjxhdXRob3I+R293YW4sIFIuIEEuPC9hdXRob3I+
PGF1dGhvcj5CYXJhbCwgUi4gTS48L2F1dGhvcj48YXV0aG9yPkxpbmdhcmQsIEEuIEUuPC9hdXRo
b3I+PGF1dGhvcj5DYXR0LCBNLiBKLjwvYXV0aG9yPjxhdXRob3I+U3RhbnNlbiwgVy48L2F1dGhv
cj48YXV0aG9yPkpvaG5zdG9uLCBMLjwvYXV0aG9yPjxhdXRob3I+TWFsaWssIFIuPC9hdXRob3I+
PC9hdXRob3JzPjwvY29udHJpYnV0b3JzPjxhdXRoLWFkZHJlc3M+MVRoZSBDYXQgQ2xpbmljLCAx
IE1pbGxlciBTdHJlZXQsIFByYWhyYW4sIE1lbGJvdXJuZSwgQXVzdHJhbGlhLiBpbmZvQGNhdGRv
Y3Rvci5jb20uYXU8L2F1dGgtYWRkcmVzcz48dGl0bGVzPjx0aXRsZT5BIHJldHJvc3BlY3RpdmUg
YW5hbHlzaXMgb2YgdGhlIGVmZmVjdHMgb2YgbWVsb3hpY2FtIG9uIHRoZSBsb25nZXZpdHkgb2Yg
YWdlZCBjYXRzIHdpdGggYW5kIHdpdGhvdXQgb3ZlcnQgY2hyb25pYyBraWRuZXkgZGlzZWFzZTwv
dGl0bGU+PHNlY29uZGFyeS10aXRsZT5KIEZlbGluZSBNZWQgU3VyZzwvc2Vjb25kYXJ5LXRpdGxl
PjxhbHQtdGl0bGU+Sm91cm5hbCBvZiBmZWxpbmUgbWVkaWNpbmUgYW5kIHN1cmdlcnk8L2FsdC10
aXRsZT48L3RpdGxlcz48cGVyaW9kaWNhbD48ZnVsbC10aXRsZT5KIEZlbGluZSBNZWQgU3VyZzwv
ZnVsbC10aXRsZT48YWJici0xPkpvdXJuYWwgb2YgZmVsaW5lIG1lZGljaW5lIGFuZCBzdXJnZXJ5
PC9hYmJyLTE+PC9wZXJpb2RpY2FsPjxhbHQtcGVyaW9kaWNhbD48ZnVsbC10aXRsZT5KIEZlbGlu
ZSBNZWQgU3VyZzwvZnVsbC10aXRsZT48YWJici0xPkpvdXJuYWwgb2YgZmVsaW5lIG1lZGljaW5l
IGFuZCBzdXJnZXJ5PC9hYmJyLTE+PC9hbHQtcGVyaW9kaWNhbD48cGFnZXM+ODc2LTgxPC9wYWdl
cz48dm9sdW1lPjE0PC92b2x1bWU+PG51bWJlcj4xMjwvbnVtYmVyPjxlZGl0aW9uPjIwMTIvMDcv
MjQ8L2VkaXRpb24+PGtleXdvcmRzPjxrZXl3b3JkPkFuaW1hbHM8L2tleXdvcmQ+PGtleXdvcmQ+
QW50aS1JbmZsYW1tYXRvcnkgQWdlbnRzLCBOb24tU3Rlcm9pZGFsLyphZG1pbmlzdHJhdGlvbiAm
YW1wOyBkb3NhZ2UvYWR2ZXJzZSBlZmZlY3RzPC9rZXl3b3JkPjxrZXl3b3JkPkF1c3RyYWxpYS9l
cGlkZW1pb2xvZ3k8L2tleXdvcmQ+PGtleXdvcmQ+Q2F0IERpc2Vhc2VzLypkcnVnIHRoZXJhcHkv
KmVwaWRlbWlvbG9neTwva2V5d29yZD48a2V5d29yZD5DYXRzPC9rZXl3b3JkPjxrZXl3b3JkPktp
ZG5leSBGdW5jdGlvbiBUZXN0czwva2V5d29yZD48a2V5d29yZD4qTG9uZ2V2aXR5PC9rZXl3b3Jk
PjxrZXl3b3JkPk9zdGVvYXJ0aHJpdGlzL2RydWcgdGhlcmFweS8qdmV0ZXJpbmFyeTwva2V5d29y
ZD48a2V5d29yZD5SZW5hbCBJbnN1ZmZpY2llbmN5LCBDaHJvbmljL2NoZW1pY2FsbHkgaW5kdWNl
ZC9lcGlkZW1pb2xvZ3kvdmV0ZXJpbmFyeTwva2V5d29yZD48a2V5d29yZD5SZXRyb3NwZWN0aXZl
IFN0dWRpZXM8L2tleXdvcmQ+PGtleXdvcmQ+UmlzayBGYWN0b3JzPC9rZXl3b3JkPjxrZXl3b3Jk
PlRoaWF6aW5lcy8qYWRtaW5pc3RyYXRpb24gJmFtcDsgZG9zYWdlL2FkdmVyc2UgZWZmZWN0czwv
a2V5d29yZD48a2V5d29yZD5UaGlhem9sZXMvKmFkbWluaXN0cmF0aW9uICZhbXA7IGRvc2FnZS9h
ZHZlcnNlIGVmZmVjdHM8L2tleXdvcmQ+PC9rZXl3b3Jkcz48ZGF0ZXM+PHllYXI+MjAxMTwveWVh
cj48cHViLWRhdGVzPjxkYXRlPkRlYzwvZGF0ZT48L3B1Yi1kYXRlcz48L2RhdGVzPjxpc2JuPjEw
OTgtNjEyeDwvaXNibj48YWNjZXNzaW9uLW51bT4yMjgyMTMzMTwvYWNjZXNzaW9uLW51bT48dXJs
cz48L3VybHM+PGVsZWN0cm9uaWMtcmVzb3VyY2UtbnVtPjEwLjExNzcvMTA5ODYxMngxMjQ1NDQx
ODwvZWxlY3Ryb25pYy1yZXNvdXJjZS1udW0+PHJlbW90ZS1kYXRhYmFzZS1wcm92aWRlcj5OTE08
L3JlbW90ZS1kYXRhYmFzZS1wcm92aWRlcj48bGFuZ3VhZ2U+ZW5nPC9sYW5ndWFnZT48L3JlY29y
ZD48L0NpdGU+PENpdGU+PEF1dGhvcj5Hb3dhbjwvQXV0aG9yPjxZZWFyPjIwMTE8L1llYXI+PFJl
Y051bT4xMTgyMzwvUmVjTnVtPjxyZWNvcmQ+PHJlYy1udW1iZXI+MTE4MjM8L3JlYy1udW1iZXI+
PGZvcmVpZ24ta2V5cz48a2V5IGFwcD0iRU4iIGRiLWlkPSJlczBweHB4eDJhc2E1NGV4ejIxdnZk
ZGdzOWYyenhhNXdzZmYiIHRpbWVzdGFtcD0iMTQ2NDcwMjI5NiI+MTE4MjM8L2tleT48L2ZvcmVp
Z24ta2V5cz48cmVmLXR5cGUgbmFtZT0iSm91cm5hbCBBcnRpY2xlIj4xNzwvcmVmLXR5cGU+PGNv
bnRyaWJ1dG9ycz48YXV0aG9ycz48YXV0aG9yPkdvd2FuLCBSLiBBLjwvYXV0aG9yPjxhdXRob3I+
TGluZ2FyZCwgQS4gRS48L2F1dGhvcj48YXV0aG9yPkpvaG5zdG9uLCBMLjwvYXV0aG9yPjxhdXRo
b3I+U3RhbnNlbiwgVy48L2F1dGhvcj48YXV0aG9yPkJyb3duLCBTLiBBLjwvYXV0aG9yPjxhdXRo
b3I+TWFsaWssIFIuPC9hdXRob3I+PC9hdXRob3JzPjwvY29udHJpYnV0b3JzPjxhdXRoLWFkZHJl
c3M+VGhlIENhdCBDbGluaWMsIFByYWhyYW4sIE1lbGJvdXJuZSwgQXVzdHJhbGlhLiByZ293YW43
NUBnbWFpbC5jb208L2F1dGgtYWRkcmVzcz48dGl0bGVzPjx0aXRsZT5SZXRyb3NwZWN0aXZlIGNh
c2UtY29udHJvbCBzdHVkeSBvZiB0aGUgZWZmZWN0cyBvZiBsb25nLXRlcm0gZG9zaW5nIHdpdGgg
bWVsb3hpY2FtIG9uIHJlbmFsIGZ1bmN0aW9uIGluIGFnZWQgY2F0cyB3aXRoIGRlZ2VuZXJhdGl2
ZSBqb2ludCBkaXNlYXNlPC90aXRsZT48c2Vjb25kYXJ5LXRpdGxlPkogRmVsaW5lIE1lZCBTdXJn
PC9zZWNvbmRhcnktdGl0bGU+PGFsdC10aXRsZT5Kb3VybmFsIG9mIGZlbGluZSBtZWRpY2luZSBh
bmQgc3VyZ2VyeTwvYWx0LXRpdGxlPjwvdGl0bGVzPjxwZXJpb2RpY2FsPjxmdWxsLXRpdGxlPkog
RmVsaW5lIE1lZCBTdXJnPC9mdWxsLXRpdGxlPjxhYmJyLTE+Sm91cm5hbCBvZiBmZWxpbmUgbWVk
aWNpbmUgYW5kIHN1cmdlcnk8L2FiYnItMT48L3BlcmlvZGljYWw+PGFsdC1wZXJpb2RpY2FsPjxm
dWxsLXRpdGxlPkogRmVsaW5lIE1lZCBTdXJnPC9mdWxsLXRpdGxlPjxhYmJyLTE+Sm91cm5hbCBv
ZiBmZWxpbmUgbWVkaWNpbmUgYW5kIHN1cmdlcnk8L2FiYnItMT48L2FsdC1wZXJpb2RpY2FsPjxw
YWdlcz43NTItNjE8L3BhZ2VzPjx2b2x1bWU+MTM8L3ZvbHVtZT48bnVtYmVyPjEwPC9udW1iZXI+
PGVkaXRpb24+MjAxMS8wOS8xMzwvZWRpdGlvbj48a2V5d29yZHM+PGtleXdvcmQ+QW5pbWFsczwv
a2V5d29yZD48a2V5d29yZD5BbnRpLUluZmxhbW1hdG9yeSBBZ2VudHMsIE5vbi1TdGVyb2lkYWwv
KmFkbWluaXN0cmF0aW9uICZhbXA7IGRvc2FnZS9hZHZlcnNlIGVmZmVjdHM8L2tleXdvcmQ+PGtl
eXdvcmQ+Q2FzZS1Db250cm9sIFN0dWRpZXM8L2tleXdvcmQ+PGtleXdvcmQ+Q2F0IERpc2Vhc2Vz
LypkcnVnIHRoZXJhcHkvKmVwaWRlbWlvbG9neS9wYXRob2xvZ3k8L2tleXdvcmQ+PGtleXdvcmQ+
Q2F0czwva2V5d29yZD48a2V5d29yZD5GZW1hbGU8L2tleXdvcmQ+PGtleXdvcmQ+S2lkbmV5IEZ1
bmN0aW9uIFRlc3RzPC9rZXl3b3JkPjxrZXl3b3JkPk1hbGU8L2tleXdvcmQ+PGtleXdvcmQ+TmV3
IFNvdXRoIFdhbGVzL2VwaWRlbWlvbG9neTwva2V5d29yZD48a2V5d29yZD5Pc3Rlb2FydGhyaXRp
cy9kcnVnIHRoZXJhcHkvKnZldGVyaW5hcnk8L2tleXdvcmQ+PGtleXdvcmQ+UmVuYWwgSW5zdWZm
aWNpZW5jeSwgQ2hyb25pYy9jaGVtaWNhbGx5IGluZHVjZWQvZXBpZGVtaW9sb2d5Lyp2ZXRlcmlu
YXJ5PC9rZXl3b3JkPjxrZXl3b3JkPlJldHJvc3BlY3RpdmUgU3R1ZGllczwva2V5d29yZD48a2V5
d29yZD5UaGlhemluZXMvKmFkbWluaXN0cmF0aW9uICZhbXA7IGRvc2FnZS9hZHZlcnNlIGVmZmVj
dHM8L2tleXdvcmQ+PGtleXdvcmQ+VGhpYXpvbGVzLyphZG1pbmlzdHJhdGlvbiAmYW1wOyBkb3Nh
Z2UvYWR2ZXJzZSBlZmZlY3RzPC9rZXl3b3JkPjwva2V5d29yZHM+PGRhdGVzPjx5ZWFyPjIwMTE8
L3llYXI+PHB1Yi1kYXRlcz48ZGF0ZT5PY3Q8L2RhdGU+PC9wdWItZGF0ZXM+PC9kYXRlcz48aXNi
bj4xMDk4LTYxMng8L2lzYm4+PGFjY2Vzc2lvbi1udW0+MjE5MDY5ODQ8L2FjY2Vzc2lvbi1udW0+
PHVybHM+PC91cmxzPjxlbGVjdHJvbmljLXJlc291cmNlLW51bT4xMC4xMDE2L2ouamZtcy4yMDEx
LjA2LjAwODwvZWxlY3Ryb25pYy1yZXNvdXJjZS1udW0+PHJlbW90ZS1kYXRhYmFzZS1wcm92aWRl
cj5OTE08L3JlbW90ZS1kYXRhYmFzZS1wcm92aWRlcj48bGFuZ3VhZ2U+ZW5nPC9sYW5ndWFnZT48
L3JlY29yZD48L0NpdGU+PC9FbmROb3RlPn==
ADDIN EN.CITE.DATA 5, 6The value of the different tools available to the general practitionerIt is generally accepted that the first “thing to go” is the ability to concentrate. Beware! This is not true of all cats! Occasionally we see cats that are already azotaemic, but have a urine SG >1.035. ADDIN EN.CITE <EndNote><Cite><Author>Paepe</Author><Year>2013</Year><RecNum>11894</RecNum><DisplayText><style face="superscript">4</style></DisplayText><record><rec-number>11894</rec-number><foreign-keys><key app="EN" db-id="es0pxpxx2asa54exz21vvddgs9f2zxa5wsff" timestamp="1378504659">11894</key><key app="ENWeb" db-id="">0</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Paepe, D.</author><author>daminet, S.</author></authors></contributors><titles><title>Feline CKD. Diagnosis, staging and screening - what is recommended?</title><secondary-title>Journal of Feline Medicine & Surgery</secondary-title></titles><periodical><full-title>Journal of Feline Medicine & Surgery</full-title></periodical><pages>15-27</pages><volume>15</volume><number>S1</number><dates><year>2013</year></dates><urls></urls><electronic-resource-num>10.1177/1098612X13495235</electronic-resource-num></record></Cite></EndNote>4 Generally, however, this is uncommon and you can rely on a REPEATABLE USG in the 1.012-1.025 range to indicate early renal disease, when conjoined to other appropriate historical and clinical findings such as:Polydipsia (>45 ml/kg/day, certainly >60 ml/kg/day)Remember to take into account that a cat eating wet food (80% moisture) and one eating kibbles (8% moisture) have the same fluid requirements overall, so you must calculate their fluid intake from their food intake, and, if necessary, have the client do a 5-day “measured water intake” trial with records.PolyuriaPossibly decreased appetitePossibly weight loss or poor condition (DDx Diabetes mellitus and hyperthyroidism, as well as inflammatory bowel disease, infiltrative bowel disease, cholangiohepatitis, FIP, etc)In addition, recent evidence suggests that elevation in SDMA (>14, or >15 for juveniles) is an earlier indicator of declining renal tubular function than a fall in USG, and earlier intervention makes more of an impact than waiting until USG falls ADDIN EN.CITE <EndNote><Cite><Author>Peterson</Author><Year>2018</Year><RecNum>14430</RecNum><DisplayText><style face="superscript">7</style></DisplayText><record><rec-number>14430</rec-number><foreign-keys><key app="EN" db-id="es0pxpxx2asa54exz21vvddgs9f2zxa5wsff" timestamp="1521733690">14430</key><key app="ENWeb" db-id="">0</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Peterson, M. E.</author><author>Varela, F. V.</author><author>Rishniw, M.</author><author>Polzin, D. J.</author></authors></contributors><auth-address>Animal Endocrine Clinic , New York, NY.
College of Veterinary Medicine , Cornell University, Ithaca, NY.
Veterinary Information Network , Davis, CA.
University of Minnesota College of Veterinary Medicine , St. Paul, MN.</auth-address><titles><title>Evaluation of Serum Symmetric Dimethylarginine Concentration as a Marker for Masked Chronic Kidney Disease in Cats With Hyperthyroidism</title><secondary-title>J Vet Intern Med</secondary-title></titles><periodical><full-title>Journal of Veterinary Internal Medicine</full-title><abbr-1>J. Vet. Intern. Med.</abbr-1><abbr-2>J Vet Intern Med</abbr-2></periodical><pages>295-304</pages><volume>32</volume><number>1</number><keywords><keyword>Creatinine</keyword><keyword>Feline</keyword><keyword>Thyroid gland</keyword><keyword>Thyroid-stimulating hormone</keyword><keyword>Thyroxine</keyword><keyword>Urine specific gravity</keyword></keywords><dates><year>2018</year><pub-dates><date>Jan</date></pub-dates></dates><isbn>1939-1676 (Electronic)
0891-6640 (Linking)</isbn><accession-num>29377360</accession-num><urls><related-urls><url> is NOT a clinical or historical finding but a clin path finding – you have to be looking for it (i.e. measuring it), in order to find it. There’s no magical “clinical sign” for proteinuria. And herein lies the challenge – how many of us do a proper urinalysis? Another complication in cats is that albumin is NOT the principal protein in cat urine – a pre-pheromone protein called CAUXIN that is turned into “felinine”, is the primary cat urinary protein.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5NaXlhemFraTwvQXV0aG9yPjxZZWFyPjIwMDY8L1llYXI+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ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5NaXlhemFraTwvQXV0aG9yPjxZZWFyPjIwMDY8L1llYXI+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ADDIN EN.CITE.DATA 8-10 This may not be clinically significant, but we don’t know enough about this “fly in the ointment”.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5MaTwvQXV0aG9yPjxZZWFyPjIwMTE8L1llYXI+PFJlY051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ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5MaTwvQXV0aG9yPjxZZWFyPjIwMTE8L1llYXI+PFJlY051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ADDIN EN.CITE.DATA 10 One article suggests cat urine should be passed through a special “filter” which enhances the utility of dipsticks but I haven’t found this is widespread.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5NaXlhemFraTwvQXV0aG9yPjxZZWFyPjIwMTE8L1llYXI+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==
ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5NaXlhemFraTwvQXV0aG9yPjxZZWFyPjIwMTE8L1llYXI+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==
ADDIN EN.CITE.DATA 9, 11Firstly, you need to collect a urine sample from every elderly cat (>7 years old), on an annual basis – even biannually on geriatrics (>15 years old). Then, do the following:Urine sg on a refractometer, NOT the dipstickDipstick for glucose, ketones, blood, protein and bilirubin/urobilinogen (other strips not helpful in cats)If there are abnormalities in the above, or a clinical suspicion:Sternheimer stain for crystals, casts, gross cellular evaluationDiff-Quick stain for bacteriaUrine protein:creatinine ratioWhen evaluating a urine sediment, take note of the presence of bacteria and casts. Most casts are due to the production of Tamm-Horsfall proteins in the renal tubules. ADDIN EN.CITE <EndNote><Cite><Author>Tamm</Author><Year>1952</Year><RecNum>9185</RecNum><DisplayText><style face="superscript">12</style></DisplayText><record><rec-number>9185</rec-number><foreign-keys><key app="EN" db-id="es0pxpxx2asa54exz21vvddgs9f2zxa5wsff" timestamp="1373873285">9185</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Tamm, I.</author><author>Horsfall, F.L.</author></authors></contributors><titles><title>A MUCOPROTEIN DERIVED FROM HUMAN URINE WHICH REACTS WITH INFLUENZA, MUMPS, AND NEWCASTLE DISEASE VIRUSES</title><secondary-title>Journal of Experimental Medicine</secondary-title></titles><periodical><full-title>Journal of Experimental Medicine</full-title><abbr-1>J. Exp. Med.</abbr-1><abbr-2>J Exp Med</abbr-2></periodical><pages>71-97</pages><volume>95</volume><number>1</number><dates><year>1952</year></dates><urls></urls></record></Cite></EndNote>12 They represent a “cytological brush biopsy” of the renal tubules and can be very helpful in understanding pathology.I would argue that older cats should have a quantified (i.e. machine-measured) urine protein:creatinine ratio performed as well, if there is a low USG and a 2+ or greater proteinuria. If in doubt, MEASURE. If >0.2:1 (cats; dogs >0.4:1), it is significant and warrants attention. The urine protein:creatinine ratio (UPC) is associated with the development of azotaemia, but ageing in cats with CKD is not a risk factor for increasing proteinuria. ADDIN EN.CITE <EndNote><Cite><Author>Reynolds</Author><Year>2013</Year><RecNum>11897</RecNum><DisplayText><style face="superscript">13</style></DisplayText><record><rec-number>11897</rec-number><foreign-keys><key app="EN" db-id="es0pxpxx2asa54exz21vvddgs9f2zxa5wsff" timestamp="1378504673">11897</key><key app="ENWeb" db-id="">0</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Reynolds, B. S.</author><author>Lefebvre, H. P.</author></authors></contributors><auth-address>Clinical Research Unit, National Veterinary School of Toulouse, 23 chemin des Capelles, 31076 Toulouse cedex 03, France.</auth-address><titles><title>Feline CKD: Pathophysiology and risk factors -- what do we know?</title><secondary-title>J Feline Med Surg</secondary-title><alt-title>Journal of feline medicine and surgery</alt-title></titles><periodical><full-title>J Feline Med Surg</full-title><abbr-1>Journal of feline medicine and surgery</abbr-1></periodical><alt-periodical><full-title>J Feline Med Surg</full-title><abbr-1>Journal of feline medicine and surgery</abbr-1></alt-periodical><pages>3-14</pages><volume>15 Suppl 1</volume><dates><year>2013</year><pub-dates><date>Sep</date></pub-dates></dates><isbn>1532-2750 (Electronic)
1098-612X (Linking)</isbn><accession-num>23999182</accession-num><urls><related-urls><url> This means that if you can arrest proteinuria, you DELAY the onset of CKD or even (perhaps) mitigate it completely. Isn’t that worthwhile?At this point, we can turn to blood tests. Urea and/or creatinine elevations – azotaemia – are not particularly sensitive or specific for renal disease so should be interpreted with some caution - SDMA is better. The use of “urea strips” is to be discouraged wherever possible as they are inaccurate, time-dependent, and temperature-dependent. They are best left to field conditions i.e. for cattle vets. In-hospital, an appropriate baseline evaluation, if you don’t want to do a complete profile, and you are wanting to rule renal disease IN or OUT, is to ALWAYS ask for phosphate, calcium and potassium as well. Sometimes, an elevation in phosphate or decline in potassium is the first sign of problems, LONG before azotaemia. It can certainly be prognostic AND gives you SPECIFIC TREATMENT TARGETS. Always look for a target that you can treat – measure – evaluate – change/maintain your course of action. Urea can be elevated by gastric ulceration or blood ingestion (eg bleeding gums). Cats rarely develop macroscopic GI ulceration but can develop microscopic gastritis from uraemia ADDIN EN.CITE <EndNote><Cite><Author>Tolbert</Author><Year>2017</Year><RecNum>13558</RecNum><DisplayText><style face="superscript">14</style></DisplayText><record><rec-number>13558</rec-number><foreign-keys><key app="EN" db-id="es0pxpxx2asa54exz21vvddgs9f2zxa5wsff" timestamp="1507552851">13558</key><key app="ENWeb" db-id="">0</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Tolbert, M. K.</author><author>Olin, S.</author><author>MacLane, S.</author><author>Gould, E.</author><author>Steiner, J. M.</author><author>Vaden, S.</author><author>Price, J.</author></authors></contributors><auth-address>University of Tennessee College of Veterinary Medicine, Knoxville.
Appalachian Animal Hospital, Piney Flats, TN.
Gastrointestinal Laboratory, Texas A&M University, College Station, TX.
North Carolina State University College of Veterinary Medicine, Raleigh, NC.</auth-address><titles><title>Evaluation of Gastric pH and Serum Gastrin Concentrations in Cats with Chronic Kidney Disease</title><secondary-title>J Vet Intern Med</secondary-title></titles><periodical><full-title>Journal of Veterinary Internal Medicine</full-title><abbr-1>J. Vet. Intern. Med.</abbr-1><abbr-2>J Vet Intern Med</abbr-2></periodical><pages>1414-1419</pages><volume>31</volume><number>5</number><keywords><keyword>Acid suppression</keyword><keyword>Famotidine</keyword><keyword>Feline</keyword><keyword>Omeprazole</keyword><keyword>Renal</keyword></keywords><dates><year>2017</year><pub-dates><date>Sep</date></pub-dates></dates><isbn>1939-1676 (Electronic)
0891-6640 (Linking)</isbn><accession-num>28833548</accession-num><urls><related-urls><url>. It can also be increased by inflammation in some instances – again, dental disease is a common culprit. Creatinine can be DECREASED by low muscle mass and diabetes mellitus– so if a patient has sarcopaenia (and thus low creatinine generation) superimposed on renal disease, ALL you may see is a slightly raised urea. A creatinine of 11.9 (ref range 3.3-9.8) is SIGNIFICANT and if you cannot explain it away, you should investigate it. SDMA is NOT similarly affected by low muscle mass, but is affected by DM ADDIN EN.CITE <EndNote><Cite><Author>Langhorn</Author><Year>2018</Year><RecNum>14404</RecNum><DisplayText><style face="superscript">15</style></DisplayText><record><rec-number>14404</rec-number><foreign-keys><key app="EN" db-id="es0pxpxx2asa54exz21vvddgs9f2zxa5wsff" timestamp="1521733558">14404</key><key app="ENWeb" db-id="">0</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Langhorn, R.</author><author>Kieler, I. N.</author><author>Koch, J.</author><author>Christiansen, L. B.</author><author>Jessen, L. R.</author></authors></contributors><auth-address>Department of Veterinary Clinical Sciences, University of Copenhagen, Copenhagen, Denmark.
Department of Veterinary and Animal Sciences, University of Copenhagen, Copenhagen, Denmark.</auth-address><titles><title>Symmetric Dimethylarginine in Cats with Hypertrophic Cardiomyopathy and Diabetes Mellitus</title><secondary-title>J Vet Intern Med</secondary-title></titles><periodical><full-title>Journal of Veterinary Internal Medicine</full-title><abbr-1>J. Vet. Intern. Med.</abbr-1><abbr-2>J Vet Intern Med</abbr-2></periodical><pages>57-63</pages><volume>32</volume><number>1</number><keywords><keyword>Biomarker</keyword><keyword>Cardiology</keyword><keyword>Companion animals</keyword><keyword>Endocrinology</keyword></keywords><dates><year>2018</year><pub-dates><date>Jan</date></pub-dates></dates><isbn>1939-1676 (Electronic)
0891-6640 (Linking)</isbn><accession-num>29230874</accession-num><urls><related-urls><url> SEQ Figure \* ARABIC 1. From de Brito (2013) - the classic model of the development of renal hyperparathyroidismFigure SEQ Figure \* ARABIC 1. From de Brito (2013) - the classic model of the development of renal hyperparathyroidismRaised phosphate is rare but always significant. A Ca x P product of >6-7 (in mmol/L; >60-70 in mg/gL) is a negative prognostic indicator and means that you must diurese the patient immediately and aggressively, as well as scavenge phosphate from the diet, to prevent nephrocalcinosis and Ca-P complex deposition in other organs with proton pumps (renal tubules, gastric mucosa). In early renal disease, as the renal tubular epithelium (RTE) begin to fail, there is less excretion of phosphate. This stimulates the release of phosphatonin, or FGF-23 (fibroblast growth factor-23) from the bone, which increases phosphate excretion and lowers blood P (i.e. it is “phosphaturic”).PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5kZSBCcml0byBHYWx2YW88L0F1dGhvcj48WWVhcj4yMDEz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==
ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5kZSBCcml0byBHYWx2YW88L0F1dGhvcj48WWVhcj4yMDEz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==
ADDIN EN.CITE.DATA 16-20The IRIS advises on “target” phosphate levels – this is a very useful concept and again, gives you a therapeutic target. If you aren’t measuring phosphate, you can’t aim at a target, so phosphate binders become a bit meaningless. The targets take into account that the “permitted” maximum phosphate may be higher with increasing IRIS stage:IRIS Stage / Creatinine (feline)Target plasma phosphorus (mmol/L)1 / <140μmol/LNot applicable2 / 140 – 249 μmol/L0.81 – 1.453 / 250 – 439 μmol/L0.81 – 1.614 / >440 μmol/L0.81 – 1.94Calcium balance is under-appreciated as an important component of renal function and failure. Unfortunately, calcium physiology is complex and hard to learn (and remember!). Simply put, PTH is largely responsible for the minute-to-minute control of serum iCa concentration, whereas calcitriol maintains day-to-day control of serum iCa concentration; note that TCa is NOT as useful as iCa, but is more accessible to most veterinarians. ADDIN EN.CITE <EndNote><Cite><Author>de Brito Galvao</Author><Year>2013</Year><RecNum>8626</RecNum><DisplayText><style face="superscript">16</style></DisplayText><record><rec-number>8626</rec-number><foreign-keys><key app="EN" db-id="es0pxpxx2asa54exz21vvddgs9f2zxa5wsff" timestamp="1366718042">8626</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>de Brito Galvao, J. F.</author><author>Nagode, L. A.</author><author>Schenck, P. A.</author><author>Chew, D. J.</author></authors></contributors><auth-address>VCA Arboretum View Animal Hospital, Downers Grove, IL, 60515.</auth-address><titles><title>Calcitriol, calcidiol, parathyroid hormone, and fibroblast growth factor-23 interactions in chronic kidney disease</title><secondary-title>J Vet Emerg Crit Care (San Antonio)</secondary-title><alt-title>Journal of veterinary emergency and critical care</alt-title></titles><periodical><full-title>J Vet Emerg Crit Care (San Antonio)</full-title></periodical><alt-periodical><full-title>Journal of Veterinary Emergency and Critical Care</full-title><abbr-1>J Vet Emerg Crit Care</abbr-1></alt-periodical><pages>134-62</pages><volume>23</volume><number>2</number><dates><year>2013</year><pub-dates><date>Mar</date></pub-dates></dates><isbn>1476-4431 (Electronic)
1476-4431 (Linking)</isbn><accession-num>23566108</accession-num><urls><related-urls><url> Ca complexes with phosphate hence knowing both can help you get a feel for the ebb and flow of renal disease. When blood calcium concentration falls, PTH secretion is stimulated and exerts direct effects on bone and kidney and indirect effects on the intestine through calcitriol. PTH increases synthesis of calcitriol by activating renal 1-α-hydroxylation of calcidiol derived from the circulation. Calcitriol, in turn, increases calcium absorption from the intestine. Calcitriol participates with PTH to stimulate osteoclastic bone resorption [quoted from de Brito ADDIN EN.CITE <EndNote><Cite><Author>de Brito Galvao</Author><Year>2013</Year><RecNum>8626</RecNum><DisplayText><style face="superscript">16</style></DisplayText><record><rec-number>8626</rec-number><foreign-keys><key app="EN" db-id="es0pxpxx2asa54exz21vvddgs9f2zxa5wsff" timestamp="1366718042">8626</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>de Brito Galvao, J. F.</author><author>Nagode, L. A.</author><author>Schenck, P. A.</author><author>Chew, D. J.</author></authors></contributors><auth-address>VCA Arboretum View Animal Hospital, Downers Grove, IL, 60515.</auth-address><titles><title>Calcitriol, calcidiol, parathyroid hormone, and fibroblast growth factor-23 interactions in chronic kidney disease</title><secondary-title>J Vet Emerg Crit Care (San Antonio)</secondary-title><alt-title>Journal of veterinary emergency and critical care</alt-title></titles><periodical><full-title>J Vet Emerg Crit Care (San Antonio)</full-title></periodical><alt-periodical><full-title>Journal of Veterinary Emergency and Critical Care</full-title><abbr-1>J Vet Emerg Crit Care</abbr-1></alt-periodical><pages>134-62</pages><volume>23</volume><number>2</number><dates><year>2013</year><pub-dates><date>Mar</date></pub-dates></dates><isbn>1476-4431 (Electronic)
1476-4431 (Linking)</isbn><accession-num>23566108</accession-num><urls><related-urls><url>]. The same group also conclusively made a case for the beneficial effects of calcitriol therapy in retarding the progression of RHPTH, which in turn retards the progression of CKD. There is benefit in managing CKD with both activated Vitamin D and RAAS inhibitors such as telmisartan (Semintra).A recently-releeased test, SDMA (S-methyl diarginine), is an even more sensitive test for early renal insufficiency and has become the mainstay of our renal surveillance. There are a few references that show influences of cardiovascular (endothelial) disease and SDMA elevationsPEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Cb3N3b29kPC9BdXRob3I+PFllYXI+MjAwOTwvWWVhcj48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ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Cb3N3b29kPC9BdXRob3I+PFllYXI+MjAwOTwvWWVhcj48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ADDIN EN.CITE.DATA 21 however most sources agree that SDMA is very sensitive for early declines in tubular functionPEVuZE5vdGU+PENpdGU+PEF1dGhvcj5IYWxsPC9BdXRob3I+PFllYXI+MjAxNjwvWWVhcj48UmVj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ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5IYWxsPC9BdXRob3I+PFllYXI+MjAxNjwvWWVhcj48UmVj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ADDIN EN.CITE.DATA 22-25. Using SDMA you can detect early kidney disease 9 months earlier (cats) to 14 months earlier (dogs) than with urea/creatinine.I hope I have made a reasonably good argument for testing; in the next section I will explain how to USE these test results to manage a patient.What does one do with this information? It is crucial that you place patients into an IRIS STAGE using this data. Pictorially demonstrate where the patient fits into the stage and explain to the client that the lower the stage, the longer the survival time. The stage determines the treatment and monitoring. Using staging you can explain the progression of treatment as the disease advances (which it invariably will, of course).Blood pressure evaluationsPEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Qb3VjaGVsb248L0F1dGhvcj48WWVhcj4yMDE1PC9ZZWFy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ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Qb3VjaGVsb248L0F1dGhvcj48WWVhcj4yMDE1PC9ZZWFy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ADDIN EN.CITE.DATA 25, 26Cats with CKD are often hypertensive due to changes in their neurohormonal and fluid homeostatic mechanisms. The kidneys are essential in controlling Na, H2O and in doing so influencing cardiac output (CO) and BP as well as total vascular volume. In a similar fashion, BP is essential for the maintenance of renal perfusion, reducing proteinuria and surviving hypovolaemia. Sustained hypertension causes damage to a variety of organs – the “End Target Organs/ETO”. As well as being responsible for maintaining normotension, the kidneys are ETO. Consequences of sustained hypertension (on the kidneys at least) include proteinuria, microalbuminuria and progressive decreases in function. Most of these consequences can be diagnosed with the basic tests described beforehand but the cause – hypertension – requires measurement. So how do you know when to do it?Firstly, it’s a good idea to use BP measurements as part of regular evaluation of apparently normal senior or geriatric cats. Always take 5 measurements, which should be averaged and all should be within 20mmHg of each other. NEVER put a patient on antihypertensives or diagnose an apparently healthy cat without ETO TOD (target organ damage) without a repeated measure in 3-4 days. Another important fact to take into account is that although hypertension is RARE in young patients, in-patient reference intervals improve the accuracy and meaningfulness of later screening tests, and also serve as a good acclimator (both for the patient and the client); consider doing free BP measurements at each checkup, from 1 year of age, and recording for that patient ADDIN EN.CITE <EndNote><Cite><Author>Walton</Author><Year>2012</Year><RecNum>439</RecNum><DisplayText><style face="superscript">27</style></DisplayText><record><rec-number>439</rec-number><foreign-keys><key app="EN" db-id="es0pxpxx2asa54exz21vvddgs9f2zxa5wsff" timestamp="1343479294">439</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Walton, R. M.</author></authors></contributors><auth-address>Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. waltonr@vet.upenn.edu</auth-address><titles><title>Subject-based reference values: biological variation, individuality, and reference change values</title><secondary-title>Vet Clin Pathol</secondary-title></titles><periodical><full-title>Vet Clin Pathol</full-title><abbr-1>Veterinary clinical pathology / American Society for Veterinary Clinical Pathology</abbr-1></periodical><pages>175-81</pages><volume>41</volume><number>2</number><keywords><keyword>Animals</keyword><keyword>Dog Diseases/blood/diagnosis/pathology</keyword><keyword>Dogs</keyword><keyword>Reference Values</keyword><keyword>Species Specificity</keyword><keyword>Veterinary Medicine/*methods</keyword></keywords><dates><year>2012</year><pub-dates><date>Jun</date></pub-dates></dates><isbn>1939-165X (Electronic)
0275-6382 (Linking)</isbn><accession-num>22390475</accession-num><urls><related-urls><url> there IS TOD, then repeat the measurement within a few days, even hours, to ensure that a valuable opportunity to treat isn’t missed. Once a retina detaches or a stroke occurs, it’s too late to turn back the clock. Always consider the important differential diagnoses for systemic HT: renal disease (acute or chronic, proteinuric or nonproteinuric); diabetes mellitus; hyperthyroidism; hyperaldosteronism (Conn’s Syndrome); and phaeochromocytoma (very rare in the cat). A blood glucose, urine glucose, TT4, and K+ measurement are good basics that you might have already done and would only miss the last DDx.So how common is HT? 20 – 65% of cats with CKD have it. Basically, there’s a 1 in 2 to 3 chance that every CKD patient has HT. If you’re not measuring it, and not managing it, you’re undermanaging your patient.Imaging – Radiographs and Ultrasound (mainly)Most if not all general practices have X-ray machines. Before the age of ultrasound, radiographs played an important part in the diagnosis of renal disease. Radiography only gives some information, and comes at a cost. Ultrasound gives distinctly different information, and has its own cost. You need to balance the risks associated with radiography, with the expected information. If you are looking for morphology, ultrasound may be better; or even US+tru-cut biopsy; but if you are looking for functional information, excretory urography can be better although contrast agents can be nephrotoxic. In some instances, eg if you are looking for liths, radiography is better than ultrasound if you are not an experienced ultrasonographer. In every instance, the test needs to be tailored to answer a specific question that needs answering. Most cats with CKD do not have renolithiasis, so you might need to identify at-risk factors (eg young age; oxalate crystals on UA; Himalayan breed or Bulldog, Schnauzer or Yorkie) to justify radiography as a test in a newly-diagnosed CKD patient; most patients just don’t need it and it doesn’t add information that you can add on. It’s the same for US; most patients with CKD do not reveal any more information that the basic minimum database reveals. However, whenever you have suspicions that something is not right – for example, asymmetrical kidneys on palpation; peculiar signalment; rapid progressive disease; renal pain; and so forth – then imaging can be helpful in the further evaluation or “EXTENDED DATABASE” (EDB) of a renal patient.BiopsyAs stated before, UA is a form of “brush” cytology of the urinary tract (just as a blood smear is a “delayed” bone marrow aspirate). But in some instances, biopsy is worthwhile. If a patient is in CKD, the techniques for biopsy are probably specialist-level. A General Practitioner needs, however, to have a very clear idea as to WHEN and WHY to refer for a biopsy. For example, any proteinuria in an Abyssinian cat is significant, and should be evaluated by a specialist, as transcorticomedullary biopsy could be required to diagnose amyloidosis – this is a very tricky procedure! On the other hand, biopsying the kidneys of a Persian with US-obvious cysts is NOT generally indicated – nor is cystocentesis (a form of biopsy if you are liberal with definitions).Biopsy should only be done when the results fundamentally change the prognosis and treatment of CKD eg suspected renal lymphoma or carcinoma; excessive proteinuria not ascribable to another cause; or to rule hereditary forms in or out (eg Alports-like syndrome).ConclusionNo single test, including some not mentioned here such as fractional excretion tests, iohexol clearance tests or scintigraphy, is the be all and end all of renal function testing. The key ingredients are suspicion and surveillance; being rigourous with the fundamentals (examination & history; urine; bloods; blood pressure); and ACTING according to not only these results, but also those from ongoing monitoring. The next talk will focus on this ACTION.CKD TREATMENT & MANAGEMENT – What do you need to know?When managing CKD, your starting point is understanding HOW BAD IS THE SITUATION? You don’t bring a flamethrower to a knife-fight! Well, the IRIS STAGING SCHEME tells you not only WHAT YOU NEED TO KNOW, but also guides you as to WHAT YOU NEED TO DO. In other words, it tells you if this is a fistfight or an all-guns blazing fight to the finish. Only do what you absolutely have to, but don’t ever UNDERtreat a patient or you will find yourself paddling furiously to get out of trouble – and it will be too late, in all likelihood.To collect the information for the IRIS staging, understand that this stage is an educational guideline, and also a tool – it is not the be all and end all. With time, it will probably flex and adapt as we learn new things about CKD. For example, the “substages” that incorporate phosphate are a more recent development.Use the IRIS stage to explain to clients where their pet is, and how you are keeping their pet out of the next stage. They need to carry out your instructions, so it is vital you include them as part of your treatment team. Don’t just hand out tablets – ask if they can give them, and if their cat will accept them! In this respect, medications and tools that owners can successfully administer are essential. Cats are difficult sometimes, just because they can be! Once daily medication has a definite advantage over q12h medication. If your client can reliably give the medication, more of your patients will do well. If more do well, your reputation will improve. Use the wrong medication or the right medication the wrong way – your results will be poor. For example, I am constantly surprised at how many of my colleagues use enalapril q24h. Firstly, enalapril would not be my drug of choice, being renally excreted itself, and known to precipitate CRF. Secondly, it’s a q12h drug. Thirdly, many people give enalapril to cats without knowing their BP (it can reduce it – but if the cat is normotensive to start with, this is not ideal) or if they are proteinuric (and this is all it does – reduce proteinuria!). Amazing! It’s analogous to giving an antibiotic to a patient without having ANY evidence for an infection…. And then being surprised when the patient doesn’t recover!!A very useful tool for remembering what tools you have available to manage CKD was published by Joe Bartges ADDIN EN.CITE <EndNote><Cite><RecNum>107</RecNum><DisplayText><style face="superscript">28</style></DisplayText><record><rec-number>107</rec-number><foreign-keys><key app="EN" db-id="es0pxpxx2asa54exz21vvddgs9f2zxa5wsff" timestamp="1343479024">107</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Bartges, J. W.</author></authors></contributors><auth-address>Department of Small Animal Clinical Sciences, College of Veterinary Medicine, The University of Tennessee, 2407 River Drive, Knoxville, TN 37996-4544, USA. jbartges@utk.edu</auth-address><titles><title>Chronic kidney disease in dogs and cats</title><secondary-title>Vet Clin North Am Small Anim Pract</secondary-title></titles><periodical><full-title>Veterinary Clinics of North America. Small Animal Practice</full-title><abbr-1>Vet. Clin. North Am. Small Anim. Pract.</abbr-1><abbr-2>Vet Clin North Am Small Anim Pract</abbr-2></periodical><pages>669-92, vi</pages><volume>42</volume><number>4</number><keywords><keyword>Acid-Base Imbalance/prevention & control/veterinary</keyword><keyword>Animals</keyword><keyword>Cat Diseases/*therapy</keyword><keyword>Cats</keyword><keyword>Disease Progression</keyword><keyword>Dog Diseases/*therapy</keyword><keyword>Dogs</keyword><keyword>Kidney Failure, Chronic/therapy/*veterinary</keyword><keyword>Nutritional Support/*veterinary</keyword><keyword>Prevalence</keyword><keyword>Water-Electrolyte Imbalance/prevention & control/veterinary</keyword></keywords><dates><year>2012</year><pub-dates><date>Jul</date></pub-dates></dates><isbn>1878-1306 (Electronic)
0195-5616 (Linking)</isbn><accession-num>22720808</accession-num><urls><related-urls><url> (Acid-base status) AND ProteinuriaHHydrationRRetention of wastesOOther insults must be avoidedNNeuroendocrine dysfunction – hyperparathyroidism, hypoproliferative anaemia, hypertensionSSerial monitoring – it is progressive and irreversible(see chart, overleaf)The next step is to consider some of the “substages” of your primary IRIS stage. First up is proteinuria:<0.2 = non-proteinuric (NP substage)0.2 – 0.4 = borderline proteinuric; seek another cause and retest in 4 weeks, then biannually (BP)>0.4 = proteinuric; seek a cause and manage (monitor efficacy of your intervention) (PR)It should be mentioned that when you act or investigate is also affected by the CONTEXT. If you do UPC in an otherwise healthy animal, or find proteinuria in a nonazotaemic patient, the criteria at which you investigate is >1.0 (investigate) and >2.0 (intervene).Also note that proteinuria in hypertensive patients SHOULD DECLINE with treatment!I treat from 0.2 or more, but only once I have confirmed it on a 2nd or 3rd reading, and excluded other causes. I wouldn’t wait until 0.4, data suggests that may already be too highIRIS SYSTEMStageCreatinine μmol/LCommentNotesIntervention1<140Non-azotaemicDoes not exclude other renal abnormalities such as: (1) inadequate concentrating ability; (2) renal proteinuria; (3) abnormal renal palpation or imaging; (4) abnormal biopsy resultsRenal dietACEI/ARB if proteinuric2140-249Mild renal azotaemiaClinical signs often absent however stage 2 often falls within the reference ranges for some labs so further investigation is advised for patients at the upper limits of the reference range*Add sevelamer or lanthanum phosphate binder to achieve target P level3250-439Moderate renal azotaemiaMany systemic signs are presentK supplements if hypokalaemicEPO if anaemicAmlodipine if hypertensive(Vit C, E and β-carotene for antioxidative effects)4>440Severe renal azotaemiaMany extrarenal signs AntiemeticsGastroprotectantsAppetite stimulants and/or feeding assistance eg tubeCalcitriol?AlkalinisationEFAs (in diets)ACEI or ARB even if non-proteinuric?* in other words, get out of the habit of calling the reference range “normal” – it’s not.Secondly, we consider the patient’s phosphate:Phosphate is NOT a “substage” in the truest sense of the word but as mentioned earlier, there are phosphate targets for each stage.Lastly, consider the patient’s BP:SBPDBPSubstageRisk<150<95AP0Minimal risk (N)150-15995-99AP1Low risk (L)160-179100-119AP2Moderate risk (M)180+120+AP3High risk (H)You can use these guidelines as TARGETS. For example, I will tell my client what the pet’s BP is – I even give them a printout and encourage them to keep copies and notes (eg “no treatment”/ 1/8th tablet once daily” etc) – I help them understand WHAT WE ARE AIMING FOR. This involves them in the process.So let’s talk about treatments. There are different grades of evidence for each of these, which I will mention briefly. Your approach to formulating a treatment plan goes as follows (adapted from Polzin, 2013) ADDIN EN.CITE <EndNote><Cite><Author>Polzin</Author><Year>2013</Year><RecNum>8667</RecNum><DisplayText><style face="superscript">29</style></DisplayText><record><rec-number>8667</rec-number><foreign-keys><key app="EN" db-id="es0pxpxx2asa54exz21vvddgs9f2zxa5wsff" timestamp="1366718297">8667</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Polzin, D. J.</author></authors></contributors><auth-address>Department of Veterinary Clinical Sciences, College of Veterinary Medicine, University of Minnesota, St. Paul, MN.</auth-address><titles><title>Evidence-based step-wise approach to managing chronic kidney disease in dogs and cats</title><secondary-title>J Vet Emerg Crit Care (San Antonio)</secondary-title><alt-title>Journal of veterinary emergency and critical care</alt-title></titles><periodical><full-title>J Vet Emerg Crit Care (San Antonio)</full-title></periodical><alt-periodical><full-title>Journal of Veterinary Emergency and Critical Care</full-title><abbr-1>J Vet Emerg Crit Care</abbr-1></alt-periodical><pages>205-15</pages><volume>23</volume><number>2</number><dates><year>2013</year><pub-dates><date>Mar</date></pub-dates></dates><isbn>1476-4431 (Electronic)
1476-4431 (Linking)</isbn><accession-num>23470210</accession-num><urls><related-urls><url> that patient HAS renal disease (renal function tests, UA, UPC +/- urine culture; imaging possibly);Confirm that it is CHRONIC KD (from the history, examination and possibly imaging studies);Establish the IRIS stage (2 fasting SDMA/creatinine values in a well-hydrated patient, 2-3 UPC and 5 averaged BP values; phosphate);Develop a treatment planDetermine what options are appropriate (discuss with client, clinical appraisal, stage)Prioritise based on owner, pet and medical factorsReview and discuss with an owner to ensure that what you suggest, can and will be carried out and achieves the goals both you and the client understand you can and both WANT to achieveSchedule your review assessments NOWTrain and book your staff to regularly check up on patients to monitor compliance with your plan and assess the owner’s understanding on an ongoing basis. Ask about any issues or difficulties Assess patient response to therapy to decide whether to change dosages, treatment or monitoring frequencies, and so forth.Dietary Therapy (Strong Evidence)To quote David Polzin: “feeding a kidney diet (diets … manufactured specifically for managing dogs or cats with CKD) is the therapeutic intervention most likely to enhance long-term survival and quality of life for patients with IRIS CKD Stages 3 and 4. As a consequence, feeding a kidney diet to …. cats with IRIS CKD Stages 2–4 should be considered the current standard of care”. ADDIN EN.CITE <EndNote><Cite><Author>Polzin</Author><Year>2013</Year><RecNum>8667</RecNum><DisplayText><style face="superscript">29</style></DisplayText><record><rec-number>8667</rec-number><foreign-keys><key app="EN" db-id="es0pxpxx2asa54exz21vvddgs9f2zxa5wsff" timestamp="1366718297">8667</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Polzin, D. J.</author></authors></contributors><auth-address>Department of Veterinary Clinical Sciences, College of Veterinary Medicine, University of Minnesota, St. Paul, MN.</auth-address><titles><title>Evidence-based step-wise approach to managing chronic kidney disease in dogs and cats</title><secondary-title>J Vet Emerg Crit Care (San Antonio)</secondary-title><alt-title>Journal of veterinary emergency and critical care</alt-title></titles><periodical><full-title>J Vet Emerg Crit Care (San Antonio)</full-title></periodical><alt-periodical><full-title>Journal of Veterinary Emergency and Critical Care</full-title><abbr-1>J Vet Emerg Crit Care</abbr-1></alt-periodical><pages>205-15</pages><volume>23</volume><number>2</number><dates><year>2013</year><pub-dates><date>Mar</date></pub-dates></dates><isbn>1476-4431 (Electronic)
1476-4431 (Linking)</isbn><accession-num>23470210</accession-num><urls><related-urls><url> Dietary therapy is the CORNERSTONE of therapy. ADDIN EN.CITE <EndNote><Cite><Author>Geddes</Author><Year>2013</Year><RecNum>12606</RecNum><DisplayText><style face="superscript">30</style></DisplayText><record><rec-number>12606</rec-number><foreign-keys><key app="EN" db-id="es0pxpxx2asa54exz21vvddgs9f2zxa5wsff" timestamp="1384844335">12606</key><key app="ENWeb" db-id="">0</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Geddes, R. F.</author><author>Elliott, J.</author><author>Syme, H. M.</author></authors></contributors><titles><title>The Effect of Feeding a Renal Diet on Plasma Fibroblast Growth Factor 23 Concentrations in Cats with Stable Azotemic Chronic Kidney Disease</title><secondary-title>Journal of Veterinary Internal Medicine</secondary-title></titles><periodical><full-title>Journal of Veterinary Internal Medicine</full-title><abbr-1>J. Vet. Intern. Med.</abbr-1><abbr-2>J Vet Intern Med</abbr-2></periodical><pages>1354-1361</pages><volume>27</volume><dates><year>2013</year></dates><urls></urls></record></Cite></EndNote>30 But the cat must eat it. If you are looking for an appetite stimulant, do NOT use oral diazepam! Rather use cyproheptidine (1 – 2mg q12h) or mirtazapine (2.5mg q24-48h). Discourage clients from home-prepared diets; they have been found to be inferior to commercial diets. ADDIN EN.CITE <EndNote><Cite><RecNum>1553</RecNum><DisplayText><style face="superscript">31</style></DisplayText><record><rec-number>1553</rec-number><foreign-keys><key app="EN" db-id="es0pxpxx2asa54exz21vvddgs9f2zxa5wsff" timestamp="1357131703">1553</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors></contributors><titles><title><Larsen-Home Diets Chronic Kidney Disease.pdf></title></titles><dates></dates><urls></urls></record></Cite></EndNote>31Fluid therapy Cats with CKD are exquisitely sensitive to the effects of dehydration. In fact, some clients precipitate “acute-on-chronic” crises by using water restriction to limit the “annoying” polyuria – this is bad news! Dehydration leads to lethargy, depression, inappetance, constipation and worsening uraemia.The best route for water is orally, either via moister foods, drinking water or even a feeding tube. I have, on occasion, used subcutaneous administration of fluids. Evidence for its effects is weak, but there are patients who benefit from intermittent (every 1-3 days) SC administration of 50 – 150 ml of water. Be careful of overzealous administration of fluids, never use calcium- or dextrose-supplemented fluids and be aware that the sodium content can aggravate or work against oral antihypertensives or may worsen renal function. The patients that respond, do respond well and you can continue; those that don’t respond well, rarely do well with a higher dose. In some instances, acute-on-chronic crises occur. For these, and after discussion with clients about exactly what we are trying to achieve, we will admit the patient for 2 – 6 days. Patients are cautiously diuresed while paying attention to lowering phosphate; stimulating appetite; avoiding fluid overload and hypertension; and we dose bloods every 48 hours. After the first 48 hrs I try to get at least a 33% reduction in urea, creatinine and phosphate. If the patient does not improve clinically and biochemically, it is doubtful whether further fluids will change the status and euthanasia should be considered. If the patient is clinically better but bloods aren’t improved, consider increasing fluids and retesting after 24-48 hours further. If the patient has responded well, consider another 1 – 2 days of fluids, then retest, and drop to maintenance. Wait 24 hours, reevaluate and retest. If it slips back, that’s bad news; if it restabilises, then consider home care with SC fluids for a week or two and go from there.Phosphate bindersAs mentioned in the previous talk, the goal is to restrict phosphate to BELOW the standard upper reference range limits, to prevent phosphate RETENTION, which leads to hyperphosphataemia. These ranges are based on expert opinion, not lots of science, but are a good start – use them. The first step in phosphate restriction involves DIET. Products such as Hill’s k/d or Royal Canin Renal are well-established and well-described. After starting such a diet, recheck a FASTING phosphate level a month later. If you cannot get the phosphate under control within 2-3 months, additional phosphate scavenging is necessary. In the past, aluminium-based antacids were the main phosphate binders, but I have had much better success with sevelamer (anecdotal evidence I know; but a study is underway). By combining a diet with a PB, you reduce your dependence on these drugs. By combining an Al-containing PB with a sevelamer or lanthanum-based PB (very $$$), you can reduce the risk of aluminium neurotoxicity. Whatever you do, take into account that these are SLOW-ACTING and you should RECHECK and dose according to the response obtained, every 4 – 6 weeks; changes probably wont occur sooner than that.Potassium supplementsMild hypokalaemia is often subclinical, but nonetheless, significant and should be managed aggressively. K-gluconate containing gels are the best way to manage this, and can alter K+ within a week, although clinical improvement occurs within a few days in my experience. Hypokalaemia is relatively common in IRIS 2-3 (20 – 30% of patients) but as renal function declined, RAAS activation is more pronounced, anorexia plays a bigger role and hypokalaemia is quite rare in Stage 4. Any cat with persistent K <3.5 mmol/L should be treated, however (weak evidence).AlkalinisersChronic metabolic acidosis becomes more common as IRIS stage advances (from 10% stage 2-3 to 50% in Stage 4) and affects protein nutrition and causes metabolic abnormalities. A low serum HCO3- or low pH is an absolute indication for therapy; potassium citrate gel or liquid is probably best, as it also helps you manage hypokalaemia. Aim to give 40 – 60mg q8-12h and retest within a week.HaematopoieticsSome patients develop anaemia due to loss of renal mass and EPO production. In the past we used erythropoietin (Eprex) but I found this difficult to titrate if using the prefilled syringes and it tends to produce neutralising antibiodies in many patients, within a few months. These days, I get the 10μg/0.4ml Aranesp (darbopoietin) syringes/pens and give that once every 2 weeks, to a target Ht of 25-30, then drop to every 3-6 weeks and keep monitoring the Ht/PCV! Some patients also benefit from weekly injections of Vit B12 (eg Catosal) and even a single injection of iron dextran. The latter must go IM and these patients are sometimes sarcopaenic so it can hurt! Any patient with a HT <25 should be considered for darbopoietin therapy. Aranesp is expensive and its monitoring is a cost to be considered when advising clients. Evidence level is weak.Anabolic steroidsThese are of anecdotal benefit but may benefit patients by stimulating appetite and as (weak) bone marrow stimulants. Generally 25 – 50 mg of laurabolin once monthly is adequate.GastroprotectantsUraemic gastritis is probably more as a result of micro-bleeds than big ulcers, but can cause inappetance and discomfort. In instances where appetite stimulants and appropriate dietary therapy are not working, or where the urea elevation is >> creatinine, or there is a thrombocytosis or thrombocytopaenia or anaemia, consider antacids. I use Nexiam paediatric sachets (esomeprazole), with a 10mg/15ml sachet lasts up to 7 days refrigerated, and is palatable. Give 0.5 – 1 mg/kg once daily PO. Cimetidine and ranitidine are NOT particularly effective and cimetidine (a) affects the metabolism of other drugs (b) requires q6-8h dosing (c) is renally excreted. Smaller sachets are also available. Do not crush pantoprazole or omeprazole to make a syrup. Omeprazole in particular is enteric-coated for a reason. There is no consistent evidence that cats develop gastritis or require PPI for CKI - reduce pill burden.AntiemeticsThere is no doubt that many patients with uraemia are nauseous. PTH, hyperphosphataemia, hypocalcaemia, hypokalaemia and other uraemic toxins, as well as gastritis, can all contribute to this – ensure you have addressed these causes before just giving antiemetics. In this day and age, maropitant (Cerenia) is definitely the way to go. Be wary of metoclopramide, as cats are more susceptible to its effects (extrapyramidal dyskinesia). Never exceed 0.5 mg/kg q12h in this species. I am not convinced odansetron works any better than the other drugs, but it may help certain individuals.AntihypertensivesSystemic HT (SBP >150 mmHg) should be managed, monitored and therapy adjusted accordingly. The #1 drug of choice is amlodipine. ADDIN EN.CITE <EndNote><Cite><Author>Jepson</Author><Year>2013</Year><RecNum>12701</RecNum><DisplayText><style face="superscript">32</style></DisplayText><record><rec-number>12701</rec-number><foreign-keys><key app="EN" db-id="es0pxpxx2asa54exz21vvddgs9f2zxa5wsff" timestamp="1389076823">12701</key><key app="ENWeb" db-id="">0</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Jepson, R. E.</author><author>Syme, H. M.</author><author>Elliott, J.</author></authors></contributors><titles><title>Plasma Renin Activity and Aldosterone Concentrations in Hypertensive Cats with and without Azotemia and in Response to Treatment with Amlodipine Besylate</title><secondary-title>Journal of veterinary internal medicine</secondary-title></titles><periodical><full-title>Journal of Veterinary Internal Medicine</full-title><abbr-1>J. Vet. Intern. Med.</abbr-1><abbr-2>J Vet Intern Med</abbr-2></periodical><pages>144-153</pages><volume>28</volume><number>1</number><dates><year>2013</year></dates><urls></urls></record></Cite></EndNote>32 ALWAYS TAPER UP. Start with 1/8th (or for very small cats, even 1/16th, by dissolving powder in syrup simplex) of a tablet q24h. Recheck BP in 5 – 7 days and adjust dosage up slowly. In rare instances, a second-tier drug, usually an ACEI (ACE inhibitor) or ARB (ACE receptor blocker) or a β-blocker such as atenolol may be required; in Europe, you should be using Semintra as your second-tier drug, as there are case reports describing its efficacy in selected cases; ACEI are, at best, poor antihypertensives. Be careful in the case of patients already on calcium channel blockers such as diltiazem, or when adding a β-blocker – you can cause profound hypotension. Gently gently and slowly increase. Always recheck 5 – 7 days after any dosage change.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5IZW5pazwvQXV0aG9yPjxZZWFyPjIwMDg8L1llYXI+PFJl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 EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5IZW5pazwvQXV0aG9yPjxZZWFyPjIwMDg8L1llYXI+PFJl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 EN.CITE.DATA 32, 33AntiproteinuricsAntiproteinurics fulfil an important, if incompletely understood role in CKD. Not all CKD patients are azotaemic, but could be proteinuric; heavy and/or sustained proteinuria overloads the cubulin-megalin protein scavenging system in the renal tubules, leading ultimately to tubular cell dysfunction, apoptosis and ultimately loss of concentrating ability and then azotaemia. Proteinuria can result from glomerular disease, systemic disease or hypertension combined with either of the two prior situations. Prevention of proteinuria is believed to improve survival time. ADDIN EN.CITE <EndNote><Cite><Author>Syme</Author><Year>2006</Year><RecNum>11341</RecNum><DisplayText><style face="superscript">34</style></DisplayText><record><rec-number>11341</rec-number><foreign-keys><key app="EN" db-id="es0pxpxx2asa54exz21vvddgs9f2zxa5wsff" timestamp="1375701834">11341</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Syme, H. M.</author><author>Markwell, P. J.</author><author>Pfeiffer, D.</author><author>Elliott, J.</author></authors></contributors><titles><title>Survival of Cats with Naturally Occurring Chronic Renal Failure Is Related to Severity of Proteinuria</title><secondary-title>Journal of Veterinary Internal Medicine</secondary-title></titles><periodical><full-title>Journal of Veterinary Internal Medicine</full-title><abbr-1>J. Vet. Intern. Med.</abbr-1><abbr-2>J Vet Intern Med</abbr-2></periodical><pages>528-535</pages><volume>20</volume><dates><year>2006</year></dates><urls></urls><electronic-resource-num>0891-6640/06/2003-0009</electronic-resource-num></record></Cite></EndNote>34 Although a direct causal link between proteinuria and the development of renal failure has not been proven, we are getting closer all the time and the process makes sense. We know proteinuria is correlated to the development of uraemia at a later date. ADDIN EN.CITE <EndNote><Cite><Author>Jepson</Author><Year>2009</Year><RecNum>12755</RecNum><DisplayText><style face="superscript">3</style></DisplayText><record><rec-number>12755</rec-number><foreign-keys><key app="EN" db-id="es0pxpxx2asa54exz21vvddgs9f2zxa5wsff" timestamp="1392118875">12755</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Jepson, R. E.</author><author>Brodbelt, D.</author><author>Vallance, C.</author><author>Syme, H. M.</author><author>Elliott, J.</author></authors></contributors><auth-address>Department of Veterinary Basic Science, Royal Veterinary College, Royal College Street, Camden, London, USA. rjepson@rvc.ac.uk</auth-address><titles><title>Evaluation of predictors of the development of azotemia in cats</title><secondary-title>J Vet Intern Med</secondary-title><alt-title>Journal of veterinary internal medicine / American College of Veterinary Internal Medicine</alt-title></titles><periodical><full-title>Journal of Veterinary Internal Medicine</full-title><abbr-1>J. Vet. Intern. Med.</abbr-1><abbr-2>J Vet Intern Med</abbr-2></periodical><pages>806-13</pages><volume>23</volume><number>4</number><keywords><keyword>Animals</keyword><keyword>Azotemia/blood/pathology/urine/*veterinary</keyword><keyword>Blood Pressure</keyword><keyword>Cat Diseases/blood/*pathology/urine</keyword><keyword>Cats</keyword><keyword>Female</keyword><keyword>Logistic Models</keyword><keyword>Longitudinal Studies</keyword><keyword>Male</keyword><keyword>Multivariate Analysis</keyword><keyword>Prospective Studies</keyword><keyword>Risk Factors</keyword></keywords><dates><year>2009</year><pub-dates><date>Jul-Aug</date></pub-dates></dates><isbn>0891-6640 (Print)
0891-6640 (Linking)</isbn><accession-num>19566846</accession-num><urls><related-urls><url> There is little benefit in treatment of non-proteinuric CKD patients, except as an adjunct to amlodipine in hypertensive CKD. ADDIN EN.CITE <EndNote><Cite><Author>Taylor</Author><Year>2013</Year><RecNum>11900</RecNum><DisplayText><style face="superscript">35</style></DisplayText><record><rec-number>11900</rec-number><foreign-keys><key app="EN" db-id="es0pxpxx2asa54exz21vvddgs9f2zxa5wsff" timestamp="1378504684">11900</key><key app="ENWeb" db-id="">0</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Taylor, S.</author><author>Sparkes, A. H.</author></authors></contributors><auth-address>International Society of Feline Medicine, High Street, Tisbury, Wiltshire SP3 6LD, UK.</auth-address><titles><title>Feline CKD: New horizons - where do we go from here?</title><secondary-title>J Feline Med Surg</secondary-title><alt-title>Journal of feline medicine and surgery</alt-title></titles><periodical><full-title>J Feline Med Surg</full-title><abbr-1>Journal of feline medicine and surgery</abbr-1></periodical><alt-periodical><full-title>J Feline Med Surg</full-title><abbr-1>Journal of feline medicine and surgery</abbr-1></alt-periodical><pages>45-52</pages><volume>15 Suppl 1</volume><dates><year>2013</year><pub-dates><date>Sep</date></pub-dates></dates><isbn>1532-2750 (Electronic)
1098-612X (Linking)</isbn><accession-num>23999185</accession-num><urls><related-urls><url> ARBs may overcome some of the weaknesses of ACEI, and the cough side effect so important in humans (but not reported in veterinary patients). They selectively bind the AT1 but not AT2 receptors, thereby apparently preventing the phenomenon of “ACE escape” or “angiotensin breakthrough”, where aldosterone and Ang II levels rise to pretreatment levels, thereby blunting the benefits. ADDIN EN.CITE <EndNote><Cite><Author>Taylor</Author><Year>2013</Year><RecNum>11900</RecNum><DisplayText><style face="superscript">35</style></DisplayText><record><rec-number>11900</rec-number><foreign-keys><key app="EN" db-id="es0pxpxx2asa54exz21vvddgs9f2zxa5wsff" timestamp="1378504684">11900</key><key app="ENWeb" db-id="">0</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Taylor, S.</author><author>Sparkes, A. H.</author></authors></contributors><auth-address>International Society of Feline Medicine, High Street, Tisbury, Wiltshire SP3 6LD, UK.</auth-address><titles><title>Feline CKD: New horizons - where do we go from here?</title><secondary-title>J Feline Med Surg</secondary-title><alt-title>Journal of feline medicine and surgery</alt-title></titles><periodical><full-title>J Feline Med Surg</full-title><abbr-1>Journal of feline medicine and surgery</abbr-1></periodical><alt-periodical><full-title>J Feline Med Surg</full-title><abbr-1>Journal of feline medicine and surgery</abbr-1></alt-periodical><pages>45-52</pages><volume>15 Suppl 1</volume><dates><year>2013</year><pub-dates><date>Sep</date></pub-dates></dates><isbn>1532-2750 (Electronic)
1098-612X (Linking)</isbn><accession-num>23999185</accession-num><urls><related-urls><url> therapyWith mild CKD, endogenous calcitriol levels decline, but this decline can be blunted by the use of phosphate-restricted diets. As disease progresses, calcitriol declines further and should be supplemented exogenously. For many years, small studies created uncertainty about the true value of calcitriol therapy. More recent advances in the understanding of the (very complex) calcium metabolism including the role of Vit D reclamation by the tubular epithelium and the role of PTH, FGF-23 and so forth, have clarified the role. Calcitriol therapy can be made complex by the size of the capsules and difficulties with measurement of iCa, PTH etc in private practice. The evidence of the use of calcitriol in Stage 3 and 4 CKD in dogs and humans is strong; but there is insufficient evidence (at this time) for or against its use in cats.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Qb2x6aW48L0F1dGhvcj48WWVhcj4yMDEzPC9ZZWFyPjxS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ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Qb2x6aW48L0F1dGhvcj48WWVhcj4yMDEzPC9ZZWFyPjxS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ADDIN EN.CITE.DATA 17, 29ConclusionsCKD is a complex degenerative-metabolic disease; it may have inflammatory undertones and its course is unpredictable. There is no “one” simple form of CKD; some forms are purely proteinuric, others are azotaemic; some are both. Hypertension lurks behind many cases of CKD, and being older cats, many have comorbidities which complicate treatment choices eg anaesthesia. Instituting proper in-clinic surveillance; understanding the value of different tests in the diagnosis and treatment monitoring; educating clients; and not under-managing CKD cases will improve the survival time of your patients.SELECTED REFERENCES ADDIN EN.REFLIST 1.DiBartola SP, Rutgers HC, Zack PM and Tarr MJ. Clinicopathologic findings associated with chronic renal disease in cats: 74 cases (1973-1984). J Am Vet Med Assoc. 1987; 190: 1196-202.2.Lawler DF, Evans RH, Chase K, et al. The aging feline kidney: a model mortality antagonist? Journal of feline medicine and surgery. 2006; 8: 363-71.3.Jepson RE, Brodbelt D, Vallance C, Syme HM and Elliott J. Evaluation of predictors of the development of azotemia in cats. J Vet Intern Med. 2009; 23: 806-13.4.Paepe D and daminet S. Feline CKD. Diagnosis, staging and screening - what is recommended? Journal of Feline Medicine & Surgery. 2013; 15: 15-27.5.Gowan RA, Baral RM, Lingard AE, et al. A retrospective analysis of the effects of meloxicam on the longevity of aged cats with and without overt chronic kidney disease. Journal of feline medicine and surgery. 2011; 14: 876-81.6.Gowan RA, Lingard AE, Johnston L, Stansen W, Brown SA and Malik R. Retrospective case-control study of the effects of long-term dosing with meloxicam on renal function in aged cats with degenerative joint disease. Journal of feline medicine and surgery. 2011; 13: 752-61.7.Peterson ME, Varela FV, Rishniw M and Polzin DJ. Evaluation of Serum Symmetric Dimethylarginine Concentration as a Marker for Masked Chronic Kidney Disease in Cats With Hyperthyroidism. J Vet Intern Med. 2018; 32: 295-304.8.Miyazaki M, Yamashita T, Suzuki Y, et al. A major urinary protein of the domestic cat regulates the production of felinine, a putative pheromone precursor. Chem Biol. 2006; 13: 1071-9.9.Jepson RE, Syme HM, Markwell P, Miyazaki M, Yamashita T and Elliott J. Measurement of urinary cauxin in geriatric cats with variable plasma creatinine concentrations and proteinuria and evaluation of urine cauxin-to-creatinine concentration ratio as a predictor of developing azotemia. Am J Vet Res. 2010; 71: 982-7.10.Li G, Janecka JE and Murphy WJ. Accelerated evolution of CES7, a gene encoding a novel major urinary protein in the cat family. Mol Biol Evol. 2011; 28: 911-20.11.Miyazaki M, Fujiwara K, Suzuta Y, et al. Screening for proteinuria in cats using a conventional dipstick test after removal of cauxin from urine with a Lens culinaris agglutinin lectin tip. Vet J. 2011; 189: 312-7.12.Tamm I and Horsfall FL. A MUCOPROTEIN DERIVED FROM HUMAN URINE WHICH REACTS WITH INFLUENZA, MUMPS, AND NEWCASTLE DISEASE VIRUSES. J Exp Med. 1952; 95: 71-97.13.Reynolds BS and Lefebvre HP. Feline CKD: Pathophysiology and risk factors -- what do we know? Journal of feline medicine and surgery. 2013; 15 Suppl 1: 3-14.14.Tolbert MK, Olin S, MacLane S, et al. Evaluation of Gastric pH and Serum Gastrin Concentrations in Cats with Chronic Kidney Disease. J Vet Intern Med. 2017; 31: 1414-9.15.Langhorn R, Kieler IN, Koch J, Christiansen LB and Jessen LR. Symmetric Dimethylarginine in Cats with Hypertrophic Cardiomyopathy and Diabetes Mellitus. J Vet Intern Med. 2018; 32: 57-63.16.de Brito Galvao JF, Nagode LA, Schenck PA and Chew DJ. Calcitriol, calcidiol, parathyroid hormone, and fibroblast growth factor-23 interactions in chronic kidney disease. J Vet Emerg Crit Care (San Antonio). 2013; 23: 134-62.17.Geddes RF, Finch NC, Syme HM and Elliott J. The role of phosphorus in the pathophysiology of chronic kidney disease. J Vet Emerg Crit Care (San Antonio). 2013; 23: 122-33.18.Finch NC, Syme HM and Elliott J. Parathyroid hormone concentration in geriatric cats with various degrees of renal function. J Am Vet Med Assoc. 2012; 241: 1326-35.19.Geddes RF, Finch NC, Elliott J and Syme HM. Fibroblast Growth Factor 23 in Feline Chronic Kidney Disease. J Vet Intern Med. 2013; 27: 234-41.20.<finch nc 2013.pdf>.21.Boswood A. Biomarkers in cardiovascular disease: beyond natriuretic peptides. Journal of veterinary cardiology : the official journal of the European Society of Veterinary Cardiology. 2009; 11 Suppl 1: S23-32.22.Hall JA, Yerramilli M, Obare E, Yerramilli M, Almes K and Jewell DE. Serum Concentrations of Symmetric Dimethylarginine and Creatinine in Dogs with Naturally Occurring Chronic Kidney Disease. J Vet Intern Med. 2016.23.Hall JA, Yerramilli M, Obare E, Yerramilli M, Melendez LD and Jewell DE. Relationship between lean body mass and serum renal biomarkers in healthy dogs. J Vet Intern Med. 2015; 29: 808-14.24.Nabity MB, Lees GE, Boggess MM, et al. Symmetric Dimethylarginine Assay Validation, Stability, and Evaluation as a Marker for the Early Detection of Chronic Kidney Disease in Dogs. J Vet Intern Med. 2015; 29: 1036-44.25.Pouchelon JL, Atkins CE, Bussadori C, et al. Cardiovascular-renal axis disorders in the domestic dog and cat: a veterinary consensus statement. J Small Anim Pract. 2015; 56: 537-52.26.Brown SA, Arkins C, Bagley R, et al. Guidelines for the Identification, Evaluation, and Management of Systemic Hypertension in Dogs and Cats. J Vet Intern Med. 2007; 21: 542-58.27.Walton RM. Subject-based reference values: biological variation, individuality, and reference change values. Veterinary clinical pathology / American Society for Veterinary Clinical Pathology. 2012; 41: 175-81.28.Bartges JW. Chronic kidney disease in dogs and cats. Vet Clin North Am Small Anim Pract. 2012; 42: 669-92, vi.29.Polzin DJ. Evidence-based step-wise approach to managing chronic kidney disease in dogs and cats. J Vet Emerg Crit Care (San Antonio). 2013; 23: 205-15.30.Geddes RF, Elliott J and Syme HM. The Effect of Feeding a Renal Diet on Plasma Fibroblast Growth Factor 23 Concentrations in Cats with Stable Azotemic Chronic Kidney Disease. J Vet Intern Med. 2013; 27: 1354-61.31.<Larsen-Home Diets Chronic Kidney Disease.pdf>.32.Jepson RE, Syme HM and Elliott J. Plasma Renin Activity and Aldosterone Concentrations in Hypertensive Cats with and without Azotemia and in Response to Treatment with Amlodipine Besylate. J Vet Intern Med. 2013; 28: 144-53.33.Henik RA, Stepien RL, Wenholz LJ and Dolson MK. Efficacy of atenolol as a single antihypertensive agent in hyperthyroid cats. Journal of feline medicine and surgery. 2008; 10: 577-82.34.Syme HM, Markwell PJ, Pfeiffer D and Elliott J. Survival of Cats with Naturally Occurring Chronic Renal Failure Is Related to Severity of Proteinuria. J Vet Intern Med. 2006; 20: 528-35.35.Taylor S and Sparkes AH. Feline CKD: New horizons - where do we go from here? Journal of feline medicine and surgery. 2013; 15 Suppl 1: 45-52. ................
................
In order to avoid copyright disputes, this page is only a partial summary.
To fulfill the demand for quickly locating and searching documents.
It is intelligent file search solution for home and business.
Related searches
- south african education system pdf
- south african education
- south african education system problems
- history of south african education
- south african government vacancies
- south african education department
- south african words and meanings
- south african government jobs 2020
- south african education problems
- south african government job circular
- dr anthony fisher
- south african name generator