Acute kidney injury - 1 File Download



ErythropoietinA hematopoietic growth factor ++ production of erythrocytes.It is secreted by the kidney in response to cellular hypoxia. The main uses treat the anaemia associated W CKD and Cytotoxic therapy.↑↑Exercise tolerance. It does not improve renal function.S/EAccelerated hypertension encephalopathy and seizures (blood pressure ↑↑ in 25% of patients)Bone achesflu-like symptomsSkin rashes, UrticariaPure red cell aplasia. (due toAbs against erythropoietin)Tthe risk is greatly reduced with darbepoetin↑↑ Polycythemia vera "PCV" ↑↑risk of thrombosis (Fistula)iIon deficiency 2nd to increased erythropoiesisFail to respond to erythropoietin therapy:Iron deficiencyInadequate doseConcurrent infection/inflammationHyperparathyroid bone diseaseAluminium toxicityAcute interstitial nephritisAccounts for 25% of drug-induced acute kidney injury. CausesDrugs (75%): the most common cause, particularly antibioticsPenicillin, Co-trimoxazole, RifampicinNSAIDsallopurinolfurosemidesystemic disease SLE, sarcoidosis, and Sj?gren's syndromeinfection Hanta virus , staphylococcihistology (Definitive diagnosis by biopsy): marked interstitial oedema and interstitial infiltrate in the C.T between renal tubulesFeatures (Fever + Rash + Eosenophilia)fever, Rash, arthralgiaeosinophiliamild renal impairmentHTNInvestigationssterile pyuriawhite cell castsManagement Stopping the offending agent, with severe cases requiring steroids and potentially dialysisTubulointerstitial nephritis with uveitisusually occurs in young females fever, weight loss and painful, red eyes. Urinalysis is positive for leukocytes and protein.Acute kidney injury?inpatient mortality of AKI in the ≥ 25-30%. CausesPrerenalOne of the major causes of AKI is ischaemia, or lack of blood flowing to the kidneys.?hypovolaemia secondary to diarrhoea/vomitingRenal artery stenosisIntrinsic Intrinsic damage to glomeruli, renal tubules or interstitium of the kidneys due to toxins (drugs, contrast etc) or immune-mediated glomuleronephritis.Glomerulonephritis Nephritic Syndrome (hematurea)Acute tubular necrosis (ATN) Acute interstitial nephritis (AIN), respectively inflammatory process (↑↑ WBCs in urine)RhabdomyolysisRumour lysis syndromeAcute tubular necrosis vs. prerenal uraemiaPre-renal uraemia ('azotemia')Acute tubular necrosisUrine sodium< 20 mmol/L ↓> 40 mmol/L ↑Urine osmolality> 500 mOsm/kg ↑< 350 mOsm/kg ↓Fractional sodium excretion*< 1% ↓> 1% ↑Response to fluid challengeGoodPoorSerum urea:creatinine ratioRaised ↑NormalFractional urea excretion< 35% ↓>35% ↑↑Urine:plasma osmolality> 1.5< 1.1Urine:plasma urea> 10:1< 8:1Specific gravity> 1020< 1010UrineNormal/ 'bland' sedimentBrown granular castsPrerenal uraemia - kidneys hold on to sodium to preserve volume Urine Na The most useful test DD (prerenal uraemia or acute tubular necrosis)fractional sodium excretion = (urine Na/plasma Na) / (urine creatinine/plasma creatinine) x 100fractional urea excretion = (urine urea /blood urea ) / (urine creatinine/plasma creatinine) x 100Postrenal'backing-up' and affecting the normal renal function. ( unilateral ureteric stone or bilateral hydroneprosis (caused by benign prostatic hyperplasia.kidney stone in ureter or bladderbenign prostatic hyperplasiaexternal compression of the ureterRisk factors for AKI include:chronic kidney disease if eGFR < 60 Other organ failure/chronic disease heart failure, liver disease, diabetes mellitusHistory of acute kidney injuryDrugs with nephrotoxic potential NSAIDs,?aminoglycosides,?[ACE I]?[ARBs] and?diuretics) within a weekIodinated contrast agents within a week≥ 65 yearsEmergency surgery, risk of sepsis or hypovolaemiaIntraperitoneal surgeryOliguria (urine output < 0.5 ml/kg/hour)neurological or cognitive impairment or disability, which may mean limited access to fluids because of reliance on a carerPrevention patients who are at risk of AKI requiring contrast (IV fluids ↓ risk). Certain drugs (ACE inhibitors and ARBs may also be temporarily stopped.What happens when kidneys stop working?Fluid balance and maintaining homeostasis. Key ways AKI may be detected are:↓↓ urine output. (oliguria < 0.5 ml/kg/hour)Fluid overload pulmonary and peripheral oedema↑↑ kidney normal excretes/maintains a careful balance (potassium, urea and Creatinine arrhythmias, uremia (pericarditis or encephalopathyAKIN or KDIGO definitions↑↑ serum creatinine ≥ 26 micromol/litre within 2 days≥ 50% ↑↑ serum creatinine within 1 Week↓↓ urine output < 0.5 ml/kg/hour?for > 6 hours in adults Urinanalysis all patients with suspected AKI should have urinanalysisImaging renal ultrasound?within 24 hours of assessment.Managementlargely supportive careful fluid balancereview a patient's medication list?Safe to continue stopped (May worsen renal function)May stopped ↑↑risk of toxicity (Not usually worsen AKI itself)??Paracetamol??Warfarin???Statins??Aspirin (dose of 75mg od)??Clopidogrel??Beta-blockers??NSAIDs?(Naproxen)??Aminoglycosides??ACEI ↓↓ GFR by VD efferent arteriole ↓↓Glomerular filtration pressure??ARBs??Diuretics??Metformin No damage to the kidneys but renally cleared, might cause a lactic acidosis??Lithium??DigoxinTreatments not recommend?routinely loop diuretics and low-dose dopamine (in an attempt to increase renal perfusion). (only if overload)Hyperkalaemia prompt treatment to avoid life-threatening arrhythmias. Stabilisation of cardiac membraneshift from extracellular to intracellularRemoval of potassium from the body??Intravenous calcium gluconate??Combined insulin/dextrose infusion??Nebulised salbutamol??Calcium resonium (orally or enema)??Loop diuretics??DialysisRenal replacement therapy (haemodialysis) not responding to medical treatment of complications (hyperkalaemia, acidosis or uraemia.Refer to a nephrologist if any of the following apply:1. Renal tranplant2. ITU patient with unknown cause of AKI3. Vasculitis/ glomerulonephritis/ tubulointerstitial nephritis/ myeloma4. AKI with no known cause5. Inadequate response to treatment6. Complications of AKI7. Stage 3 AKI (see guideline for details)8. CKD stage 4 or 59. Qualify for renal replacement hyperkalaemia metabolic acidosiscomplications of uraemiafluid overload (pulmonary oedema)Papillary necrosisCausesChronic analgesia useSickle cell diseaseTBAcute pyelonephritisD.MFeaturesfever, loin pain, haematuriaIVU - papillary necrosis with renal scarring - 'cup & spill' Chronic kidney diseaseCommon causes Diabetic nephropathyChronic glomerulonephritisChronic pyelonephritisHypertension (IHD the most common cause of death 50% of the mortality in patients receiving dialysis)Adult polycystic kidney diseaseeGFR and classificationSerum creatinine may not provide an accurate estimate of renal function due to differences in muscle. The most commonly used formula for "eGFR" is the Modification of Diet in Renal Disease (MDRD) equation, using following variables (CAGE)serum creatinineagegenderethnicityFactors which may affect the result (Invalidate using MDRD)pregnancymuscle mass ( Amputees, body-builders often have an inappropriately low eGFR.)Eating red meat 12 hours prior to the sample being takenCKD stageGFR range1 (30)> 90 ml/min,+ some sign of kidney damage on other tests (if all the kidney tests "blood & U/S") are normal, there is no CKD)2 (30)60-90 ml/min + some sign of kidney damage (if kidney tests* are normal, there is no CKD)3a (15)45-59 ml/min, a moderate reduction in kidney function3b (15)30-44 ml/min, a moderate reduction in kidney function4 (15)15-29 ml/min, a severe reduction in kidney function5< 15 ml/min, established kidney failure - dialysis or a kidney transplant may be neededHypertensionThe majority of patients with (CKD) > 2 drugs to treat hypertension. ACE inhibitors1st line and are particularly in proteinuric renal disease (diabetic nephropathy). ↓↓eGFR of up to 25% or ↑↑creatinine of up to 30% is acceptable careful monitoring and exclusion of other causes (NSAIDs). ↑↑↑greater than this may indicate underlying renovascular disease.?Furosemide useful as a anti-hypertensive with CKD (particularly GFR < 45 ml/min). Added benefit of lowering serum potassium.↑↑doses are usually required. If the patient at risk of dehydration (Gastroenteritis) consideration to temporarily stopping the drugAnemia Patients with (CKD) anaemia due to a variety of factors CKD Anemia in CKD development of LVH – (3 fold ↑↑mortality in renal patients)Causes of anaemia in renal failure↓↓ Erythropoietin levelsthe most significant factorNormochromic normocytic anaemia (apparent GFR < 35 ml/min, Other causes at GFR > 60 ml/min).↑↑ uremiaToxic effects on bone marrow ↓↓ erythropoiesis Anorexia/nausea ↓↓ absorption of iron↓↓ RBCs survival (especially in haemodialysis)blood loss due to capillary fragility and poor platelet functionStress ulceration leading to chronic blood lossFeatures Very common cause for Tachycardia, Fatigue, pallor and an aortic flow murmur (does not radiate)ManagementTarget Hb (10 - 12 g/dl)Optimisation of iron status? prior to the administration of erythropoiesis-stimulating agents (ESA). Many patients, especially those on haemodialysis, will require IV ironESAs (Erythropoietin and Darbepoetin) 'who are likely to benefit in quality of life and physical function.Bone diseaseBasic problems in chronic kidney disease↓↓ vitamin D (1-alpha hydroxylation normally occurs in the kidneys)↑↑ phosphate ↓↓ Excretion ↓↓ calcium due to lack of vitamin D, high phosphate2ry hyperparathyroidism due to low calcium, high phosphate and low vitamin DSeveral clinical manifestations may result:Osteitis fibrosa cystic aka hyperparathyroid bone disease (Brown Tumor)Adynamic↓↓cellular activity (both osteoblasts and osteoclasts) in bonemay be due to over treatment with vitamin DOsteomalacia due to low vitamin D, & ?high phosphate 'drags' calcium from the bonesOsteosclerosisOsteoporosisManagement The aim is to ↓↓phosphate and PTH levels.↓↓dietary intake of phosphate is the first-line managementPhosphate bindersvitamin D Alfacalcidol, CalcitriolParathyroidectomy may be needed in some casesPhosphate bindersAluminum-based binders are less commonly used nowCalcium-based binders (Ca Carbonate)problems include?hypercalcemia and vascular calcificationSevelamerNon-calcium based binder that is now ↑↑ usedbinds to dietary phosphate and prevents its absorptionOther beneficial effects ↓↓ uric acid and improving the lipid profiles of patients with chronic kidney diseaseCalciphylaxis (CKD+ Painful skin lesions)Rare complication of end-stage renal failure (Unclear mechanism) deposition of Ca++ in arterioles microvascular occlusion of the tissue. It most commonly affects the skin and?presents with painful necrotic skin lesions.?The risk ↑↑ (Ca++ , P+ & PTH). Warfarin causing/exacerbating calciphylaxis in high risk patients (mechanism is not known).?Treatment ↓↓ (Ca++ & P + levels) controlling hyperparathyroidism avoiding contributing drugs such as warfarin and calcium containing compounds.ProteinuriaProteinuria is an important marker of CKD, especially for diabetic nephropathy.Albumin:creatinine ratio (ACR) in preference to the protein:creatinine ratio (PCR) for proteinuria (greater sensitivity).Quantification and monitoring of Proteinuria PCR can be used as an alternative, although ACR is recommended in diabetics. Urine reagent strips are not recommended unless they express the result as an ACRWomen have higher ACRApproximate equivalent valuesACR (mg/mmol)PCR (mg/mmol)Urinary protein excretion (g/24 h)30500.5701001Collecting an ACR sample'spot' sample first-pass morning specimen (avoids 24 hour collection) detect or quantify proteinuriaIf initial ACR (3 - 70 mg/mmol) confirmed by a subsequent early morning sample. If initial ACR ≥ 70 N.Confirmed ACR ≥ 3 mg/mmol Orepeat Clinically important proteinuria'Referral to a nephrologist:Urinary Albumin : Creatinine ratio (ACR)≥ 70 mg/mmol?(unless caused by diabetes and already appropriately treated)Urinary ACR ≥ 30 mg/mmol + persistent haematuria (2 out of 3 dipstick tests ≥ 1+ blood) after exclusion UTIACR (3 - 29 )mg/mmol + Persistent haematuria + Other risk factors (↓↓ eGFR, or CVS) Frequency of monitoring eGFR (number of times per year by eGFR and ACR categories) for people with or at risk of CKDeGFR (mL/min/1.73 m2)ACR (mg/mmol)A1 (< 3) Normal to mildly ↑↑A2 (3-30) Moderately ↑↑A3 (> 30) Severely ↑↑G1 ≥ 90 Normal and high≤ 11≥ 1G2 60-89 Mild ↓↓ related to normal range young adult≤11≥ 1G3a 45-59 Mild to moderate ↓↓112G3b 30-44 Moderate to severe ↓↓≤ 22>= 2G4 15-29 Severe reduction223G5 <15 Kidney failure4>=4>=4Nephritic syndrome (haematuria, HTN)Nephrotic syndrome (proteinuria, oedema)Mixed nephritic/nephrotic presentationRapidly progressive glomerulonephritis "Aka crescentic glomerulonephritis"rapid onset, often as AKIcauses Goodpasture'sWegener's granulomatosisANCA positive vasculitisIgA nephropathy – MesangioproliferativeGN. aka Berger's Typically young adult WHaematuria following URTIMinimal change diseaseA child with nephrotic syndrome (80%)CausesLymphoma "Hodgkin's"NSAIDsGood response to steroidsMembranous glomerulonephritisProteinuria / nephrotic syndrome / CKDCauseInfectionsRheumatoid drugsMalignancy (colorectal)1/3 resolve, 1/3 respond to cytotoxics, 1/3 CKD.Focal segmental glomerulosclerosisIdiopathic or 2ry (HIV, heroin)proteinuria / nephrotic syndrome CKDDiffuse proliferative glomerulonephritisNephritic syndrome / AKICauses Commonest form of renal disease in SLEPost-streptococcal glomerulonephritis "child"Membranoproliferative glomerulonephritis "Mesangiocapillary"Type 1CryoglobulinaemiaHepatitis CType 2Partial lipodystrophy GlomerulonephritideGlomerulonephritis and low complementpost-streptococcal glomerulonephritisSLEMesangiocapillary glomerulonephritisSubacute bacterial EndocarditisNephrotic syndromeTriad of:1. Proteinuria (> 3g/24hr) causing2. Hypoalbuminaemia (< 30g/L) and↓↓ (Antithrombin-III + Proteins C and S) and ↑↑ fibrinogen thrombosis. ↓↓ thyroxine-binding globulin?lowers the total, but not free, thyroxine levels.3. OedemaCausesPrimary glomerulonephritisSystemic diseaseDrugsOthers80% of casesMinimal change glomerulonephritis(80% in children, 30% in adults), LymphomaMembranous glomerulonephritisMalignancies (lung, colon and gastric cancer) Nephrotic S as a paraneoplasticComplication. Association with HLA-DR3.?Focal segmental glomerulosclerosisMembranoproliferative glomerulonephritisNephrotic & Nephritic(about 20%)diabetes mellitusSLEamyloidosisgold"Na aurothiomalate"penicillaminecongenitalNeoplasiacarcinoma, lymphoma, leukaemia, myelomainfection:bacterial endocarditis,hepatitis B,malariaComplicationsimmunoglobulin loss ↑↑ risk of infection loss of antithrombin III and plasminogen ↑↑ risk of thromboembolism renal vein thrombosis,resulting in a sudden deterioration in renal function, loin pain and haematuria.Membranous glomerulonephritis commonest glomerulonephropathy linked to renal vein thrombosis.also at risk of deep vein thromboses and pulmonary embolisms.?hyperlipidaemiahypocalcaemia (vitamin D and binding protein lost in urine)acute renal failureRapidly progressive glomerulonephritisDescribe a rapid loss of renal function associated with the formation of epithelial crescents in the majority of glomeruli.CausesGoodpasture's syndromeWegener's granulomatosisOthersSLE, Microscopic polyarteritisFeaturesNephritic syndrome Haematuria with Red cell casts, Proteinuria, Hypertension, OliguriaFeatures specific to underlying cause Goodpasture's Hemoptysis Wegener's "Granulomatosis with Polyangiitis" Vasculitic Rash or Upper respiratory signs, Sinusitis, crusting around nostrils blocked or a runny nose, Hearing loss. Goodpasture's syndromeA rare condition pulmonary haemorrhage + rapidly progressive glomerulonephritis. Anti-glomerular IgG basement membrane (anti-GBM) ↑↑men (2:1) and a bimodal age (20-30 and 60-70) with HLA DR2. Featurespulmonary haemorrhagefollowed by rapidly progressive glomerulonephritisFactors ↑↑the likelihood of pulmonary haemorrhageSmokingLower respiratory tract infectionPulmonary oedemainhalation of hydrocarbonsyoung malesInvestigationsRenal biopsy: linear IgG deposits along the basement membrane↑↑ Transfer Factor secondary to pulmonary haemorrhagesNormal ESRManagementplasma exchange (plasmapheresis)steroidscyclophosphamideIgA nephropathyIgA nephropathy "Berger's disease" is the commonest cause of glomerulonephritis worldwide.Classically presents as?Macroscopic haematuria in young people following URTI?Associated conditionsAlcoholic cirrhosisCoeliac disease/Dermatitis herpetiformisHenoch-Schonlein purpuraPathophysiologyCaused by mesangial deposition of IgA immune complexes ("histology" Mesangial hypercellularity, +Ve immunofluorescence for IgA & C3Pathological overlap with Henoch-Schonlein purpura (HSP)?Presentationsyoung male, recurrent episodes of macroscopic haematuriatypically associated with a recent respiratory tract infectionNephrotic range Proteinuria RareRenal failure is unusual and seen in a minority of patientsManagementSteroids/immunosuppressants not be shown to be usefulPrognosis25% end stge renal failureMarkers of good prognosis frank haematuriaMarkers of poor prognosis: male gender, proteinuria (especially > 2 g/day), smoking, hypertension, hyperlipidaemia, ACE genotype DDDD. IgA nephropathy and post-streptococcal glomerulonephritispost-streptococcal glomerulonephritis ("Antigen + Antibody complex" deposition) ↓↓complement levelsmain symptom in post-streptococcal glomerulonephritis proteinuria (although haematuria can occur)Typically an interval between (URTI & onset of renal problems) in post-streptococcal glomerulonephritisHenoch-Schonlein purpuraIgA mediated small vessel vasculitis Some overlap with?IgA nephropathy?(Berger's disease). HSP is usually seen in children following an infection. FeaturesPalpable purpuric rash?(with localized oedema) over buttocks and extensor surfaces of arms and legsAbdominal painpolyarthritisfeatures of IgA nephropathy (Nephritic haematuria, renal failure)Investigation Renal Biobsy Mesangial hypercellularityTreatmentanalgesia for arthralgiatreatment of nephropathy is generally supportive. There is inconsistent evidence for the use of steroids and immunosuppressantsPrognosisusually excellent, HSP is a self-limiting condition (especially in children without renal involvement)around 1/3rd of patients have a relapsePost-streptococcal glomerulonephritisTypically occurs?7-14 days? a group A beta-haemolytic?Strept. (Strep. Pyogenes). ?immune complex (IgG, IgM and C3) deposition in the glomeruli. Young children are most commonly affected. Featuresgeneral: headache, malaisehaematuriaproteinuriahypertension↓↓ C3↑↑ ASO titreRenal biopsy featuresacute, diffuse proliferative glomerulonephritisEndothelial proliferation with neutrophilsE/M Subepithelial 'humps' (lumpy immune complex depositsimmunofluorescence:?granular or 'starry sky' appearance Carries a good prognosiMinimal change diseaseAlways presents as nephrotic syndrome (75% of cases in children/ 25% in adults).The majority of cases are idiopathic, but in around 10-20% a cause is found:Drugs NSAIDs, rifampicinHodgkin's lymphoma, Thymomainfectious mononucleosisPathophysiologyT-cell and cytokine-mediated damage to the glomerular basement membrane → polyanion lossthe resultant ↓↓electrostatic charge → ↑↑ glomerular permeability to serum albuminFeaturesNephrotic syndromenormotension - hypertension is rare↑↑ selective proteinuriaonly intermediate-sized proteins (albumin and transferrin leak) through the glomerulusRenal BiopsyL/M Normal glomeruli.E/M Fusion of podocytes and effacement of foot processesManagementmajority of cases (80%) are steroid-responsiveCyclophosphamide is the next step for steroid-resistant casesPrognosis is overall good, although relapse is common. Roughly:1/3 one episode1/3 infrequent relapses1/3 frequent relapses which stop before adulthoodFocal segmental glomerulosclerosisA cause of nephrotic syndrome and CKD. It generally presents in young adults (1/3 Nephrotic) Causeshigh recurrence rate in renal transplants.Idiopathic2ry to other renal pathology IgA nephropathy, reflux nephropathyHIVheroinAlport's syndromesickle-cellInvestigationsRenal biopsyL/M Focal and segmental sclerosis and hyalinosis on light microscopyE/M Effacement of foot processes on (Might be fusion ofpeudocyte less common than minimal change)ManagementSteroids +/- immunosuppressantsPrognosisUntreated FSGS has a < 10% chance of spontaneous remissionMembranous glomerulonephritisThe commonest type of glomerulonephritis in adults (3rd commonest cause (ESRF). nephrotic syndrome or proteinuria.Renal biopsy:E/M Thickened basement membrane with subepithelial dense deposits 'spike and dome' appearanceCausesidiopathic: due to?anti-phospholipase A2 antibodiesinfections: hepatitis B, malaria, syphilismalignancy: lung cancer, lymphoma, leukaemiadrugs: gold, penicillamine, NSAIDsautoimmune diseases: SLE (class V disease), thyroiditis, rheumatoidManagementall patients ACEI or ARBs↓↓ proteinuria and improve prognosisimmunosuppressionOnly with severe or progressive disease require immunosuppressionCorticosteroids alone not effective. A combination (Corticosteroid + another agent "cyclophosphamide" chlorambucil?) often usedAnticoagulation for high-risk patientsPrognosis - rule of thirdsone-third: spontaneous remissionone-third: remain proteinuricone-third: develop ESRFGood prognostic features female sex, young age at presentation and asymptomatic proteinuria (modest degree at the time of presentation.Membranoproliferative glomerulonephritis"Mesangiocapillary glomerulonephritis" Mixed (nephrotic & nephritic syndrome Haematuria or Proteinuria) Poor PrognosisType 1Type 2 - 'dense deposit disease'Type 390% of casesCauseCryoglobulinaemia, Hepatitis CRenal biopsyE/M Subendothelial & mesangium immune deposits of electron-dense material 'Tram-Track' appearanceCausesPartial lipodystrophy?(loss of subcutaneous tissue of face) Factor H deficiencyCaused by persistent (+ +) alternative complement pathway↓↓ C3C3b nephritic factor is (70%) Ab to alternative-pathway C3 convertase (C3bBb)stabilizes C3 convertaseRenal biopsyE/M: intramembranous immune complex W 'dense deposits'Hepatitis B and CManagementSteroids may be effectiveSLE: renal complicationsLupus nephritis is a severe manifestation of (SLE) End-stage renal disease (Pericarditis, Haematuria, Proteinuria and Edema ) SLE patients should be monitored (urinalysis at regular rule out proteinuria.WHO classificationclass I: normal kidneyclass II: mesangial glomerulonephritisclass III: focal (and segmental) proliferative glomerulonephritisclass IV: diffuse proliferative glomerulonephritisclass V: diffuse membranous glomerulonephritisclass VI: sclerosing glomerulonephritisClass IV (diffuse proliferative glomerulonephritis) is the most common and severe form. (Mixed Niphritic & Nephrotic)Renal biopsy characteristically shows the following findings:glomeruli shows endothelial and mesangial proliferation, 'wire-loop' appearanceif severe capillary wall may be thickened secondary to immune complex depositionE/M sub endothelial immune complex depositsImmunofluorescence granular appearance ManagementTreat hypertensionCorticosteroids if clinical evidence of diseaseImmunosuppressants Azathioprine Accepted 2nd line in pregnancy after prednisilone)Cyclophosphamide (not used in pregnancy premature delivery and low birth weight,?Renal transplant: HLA typing and graft failureThe human leucocyte antigen (HLA) system is the name given to the major histocompatibility complex (MHC) in humans coded for on chromosome 6.Class 1 antigens A, B and C. Class 2 antigens DP,DQ and DR HLA matching for a renal transplant the relative importance of the HLA antigens (DR?> B > A)Graft survivalcadaveric transplants 1 year = 90%, 10 years = 60% living-donor transplants 1 year = 95%, 10 years = 70% Post-op problemsATN of graftvascular thrombosisurine leakageUTIHyperacute rejection (minutes to hours)due to pre-existing antibodies against ABO or HLA antigens (IgG)an example of a type II hypersensitivity reactionleads to widespread thrombosis of graft vessels → ischaemia and necrosis of the transplanted organno treatment is possible and the graft must be removedAcute graft failure (< 6 months)usually due to mismatched HLA. Cell-mediated (cytotoxic T cells)other causes include Cytomegalo Virus (Ganciclovir is the treatment of choice)may be reversible with steroids and immunosuppressantsCauses of chronic graft failure (> 6 months)both antibody and cell mediated mechanisms cause fibrosis to the transplanted kidney (chronic allograft nephropathy)recurrence of original renal disease (Minimal Change MCGN > IgA > Focal Segmented FSGS)ImmunosuppressionExample regimeInitial ciclosporin/ tacrolimus + Monoclonal antibodyMaintenance ciclosporin/ tacrolimus + MMF or SirolimusAdd steroids if > 1 "Episode of steroid responsive acute rejection" CiclosporinTacrolimusMycophenolate mofetil (MMF)Sirolimus (rapamycin)Monoclonal antibodies(- -) calcineurin (a phosphotase involved in T cell activation)↓↓ acute rejection > ciclosporin↓↓ hypertension and hyperlipidaemiaS/E ↑↑ IGT and D.M outstretched hands Tremors(x x) purine synthesis by (- -)of Inosine-5′-monophosphate dehydrogenase "IMPDH"(- -) proliferation B and T cellsS/E GI and marrow suppressionblocking the IL-2 receptorblocks T cell proliferation S/E hyperlipidaemiaselective (- -) IL-2 receptordaclizumabbasilximabMonitoringPatients on long-term immunosuppression for organ transplantation require regular monitoring for complications such as:Cardiovascular disease tacrolimus and ciclosporin hypertension and hyperglycaemia. Tacrolimus can also cause hyperlipidaemia. Renal failure - due to Nephrotoxic effects of tacrolimus and ciclosporingraft rejectionrecurrence of original disease in transplanted kidneyMalignancy – Education about minimising sun exposure to reduce the risk of squamous cell carcinomas and basal cell carcinomasHaemolytic uraemic syndromeSeen in young children and produces a triad of:acute kidney injurymicroangiopathic haemolytic anaemiathrombocytopeniaMost cases are secondary 'typical HUS':"Typical" Shiga toxin-producing E. coli (STEC) 0157:H7?('Verotoxigenic', 'Enterohaemorrhagic'). "commonest in children (90%)"pneumococcal infection (Strept. Pneumonia)Campylobacter,?Yersinia?and?Entamoeba.?HIVrare: SLE, drugs, cancerPrimary HUS ('atypical') Coxsackie,?Streptococcus pneumonia?and?influenza causes complement dysregulation.Poorer prognosis (50% progress to renal failure)Investigationsfull blood count: anaemia, thrombocytopaenia, fragmented blood filmHaptoglobin (binds to frgmanted RBCS Hb)U&E: acute kidney injuryStool cultureManagementtreatment is supportive e.g. Fluids, blood transfusion and dialysis if requiredNo role for antibiotics, despite the preceding diarrhoeal illness?in many patientsPlasma exchange reserved for severe cases of HUS not associated with diarrhoeaEculizumab (a C5 inhibitor monoclonal antibody) greater efficiency than plasma exchange alone in the treatment of adult atypical HUSDiabetic nephropathy: stagesClassified as occurring in five stages*:Stage 1Hyperfiltration: ↑↑GFRmay be reversibleStage 2 (silent or latent phase)Most patients do not develop microalbuminuria for 10 yearsGFR remains ↑↑Stage 3 (Incipient nephropathy)Microalbuminuria (albumin excretion of 30 - 300 mg/day, dipstick -Ve)Stage 4 (overt nephropathy)Persistent proteinuria (albumin excretion > 300 mg/day, dipstick +Ve)HTN is present in most patientsHistology diffuse glomerulosclerosis and focal glomerulosclerosis (Kimmelstiel-Wilson nodules)Stage 5End-stage renal disease, GFR < 10ml/minrenal replacement therapy neededThe timeline given here is for type 1 diabetics. Patients with type 2 diabetes mellitus (T2DM) progress through similar stages but in a different timescale - some T2DM patients may progress quickly to the later stagesNephrotoxicity due to contrast mediadefined as a 25% ↑↑creatinine occurring within 3 days of the IV administration of contrast (large concentrations of iodine)occurs 2 -5 days after administration Renal function typically resolves to normal levels after 7 to 10 days. Risk factors includeknown renal impairment (Diabetic nephropathy)> 70 yearsDehydrationCardiac failureNephrotoxic drugs such as NSAIDsPreventionIV 0.9% sodium chloride?at a rate of 1 mL/kg/hour/ 12 hours pre- and post- procedure. (Might use isotonic sodium bicarbonate)N-acetylcysteine has been given in the past but recent evidence suggests it is not effective*Diabetes insipidusCondition characterised by deficiency of ADH (Cranial DI) OR Insensitivity to ADH (Nephrogenic DI).Most hereditary forms diagnosed in childhood. But acquired forms (lithium,..) commoner in adults and slower symptoms.PhysiologyVasopressin (ADH) release from posterior pituitary gland↑↑ insertion of aquaporin 2 channels in distal convoluted tubules and collecting AQP-2 channels ↑↑ water reabsorption ↓↓ plasma osmolality and ↓↓the volume of urine produced i.e. antidiuretic.?↑↑ plasma osmolality which stimulates Alcohol inhibits this mechanism and subsequently leads to polyuria and dehydration. Causes of cranial DIidiopathicpost head injurypituitary surgeryCraniopharyngiomasHistiocytosis XDIDMOAD is the association (DI, D.M, Optic Atrophy and Deafness (also known as "Wolfram's Syndrome")HaemochromatosisCauses of nephrogenic DIGeneticAffects vasopression (ADH) receptor (↑↑common)X- Recessive AVPR2 (arginine vasopressin receptor 2) gene on the X chromosome misfolded protein trapped within the cell.As a result the collecting ducts do not absorb water inappropriately high urine output.?AR Mutation in the gene that encodes the aquaporin 2 channel (less common)Electrolytes ↑↑Ca++, ↓↓ K+Drugs Demeclocycline(tetracycline derivative),?LithiumTubulo-interstitial disease Obstruction, Sickle-cell, PyelonephritisFeaturespolyuriapolydipsiaInvestigation↑↑plasma osmolality, ↓↓ urine osmolalitya urine osmolality of >700 mOsm/kg excludes diabetes insipiduswater deprivation testManagementNephrogenic DI Thiazides, low salt/protein dietCentral DI can be treated with DesmopressinFanconi syndromeA generalised reabsorptive disorder of renal tubular transport in the "Proximal convoluted tubule"?resulting in:Type 2 (proximal) renal tubular acidosisPolyuria (Water)Aminoaciduria (Protein)Glycosuria (Glucose)Phosphaturia (P+)Osteomalacia (Ca++)CausesCystinosis (most common cause in children)Sjogren's syndromeMultiple MyelomaNephrotic syndromeWilson's diseasePolycystic Kidney Disease ADPKDThe commonest inherited kidney disease AD mutation in PKD1 gene encodes polycystin-1(large cell-surface glycoprotein of unknown function1 in 1,000 Caucasians. ADPKD (polycystin – 1)ADPKD (polycystin – 2)85% of cases15% of casesChromosome 16Chromosome 4Renal failure earlierThe screening investigation for relatives abdominal?U\S 99% sensitivity (risk patients > 20 ys diagnostic criteria (+Ve family history)< 30 ys 2 cysts (unilateral or bilateral) 30-59 ys 2cysts (in both kidneys) > 60 ys 4 cysts (in both kidneys) FeaturesHTNrecurrent UTIsabdominal painrenal stoneshaematuriachronic kidney diseaseExtra-renal manifestationsliver cysts?(70% - the commonest extra-renal manifestation) "Hepatomegaly"CNS Berry aneurysms (8%): rupture can cause subarachnoid haemorrhageCVS ?MV prolapse, MV/TV incompetence, Aortic root dilation, Aortic dissectioncysts in other organs: pancreas, spleen; Very rarely: thyroid, oesophagus, ovaryDiverticulosisManagementTolvaptan?(Vasopressin receptor 2 antagonist present in principal cells in the collecting ducts ↓↓ water absorption (↓↓aquaporin 2) and ↑↑ aquaresis without Na+ loss. ADPKD in adults to slow cyst development and renal insufficiency only CKD stage 2 or 3 at the start of treatmentEvidence of rapidly progressing disease andCompany provides it with the discount agreed in the patient access scheme.Autosomal recessive polycystic kidney disease (ARPKD)Much less common defect in gene on chromosome 6 (encodes fibrocystin protein important for normal renal tubule development.Diagnosis may be prenatal U/S OR early infancy abdominal masses and renal failure. Newborns features consistent with Potter's syndrome 2ry to oligohydramnios. End-stage renal failure develops in childhood. Liver involvement portal and interlobular fibrosis.Renal biopsy multiple cylindrical lesions at right angles to the cortical surface.Alport's syndromeX-linked dominant(85%)/AR(15%)?pattern defect in gene codes type IV collagen? abnormal glomerular-basement membrane (GBM). ↑↑severe in males, females rarely developing renal failure. Alport's patient with a failing?renal transplant presence of?anti-GBM antibodies (Goodpasture's syndrome?like picture.Features?(usually presents in childhood) Microscopic haematuriaprogressive renal failureBilateral sensorineural deafnessLenticonus protrusion of the lens surface into the anterior chamberRetinitis PigmentosaRenal biopsy ?splitting of lamina densa seen on electron microscopyDiagnosismolecular genetic testingrenal biopsyElectron microscopy longitudinal splitting of the lamina densa of the glomerular basement membrane, 'basket-weave' appearanceCystinuriaAR formation of recurrent renal stones (defect in the membrane transport of Cystine, Ornithine, Lysine, Arginine) (mnemonic = COLA)Chromosome 2 SLC3A1 gene, Chromosome 19 SLC7A9 , FeaturesRecurrent renal stonesyellow and crystalline, appearing semi-opaque on x-rayDiagnosis Cyanide-Nitroprusside testManagementHydrationD-penicillamineUrinary alkalinizationAmyloidosisExtracellular deposition of an insoluble fibrillar protein "amyloid" derived from many different precursor proteinsin addition to the fibrillar component amyloid contains a non-fibrillary protein (amyloid-P component) derived from "acute phase protein amyloid P"other non-fibrillary components apolipoprotein E and heparan sulphate proteoglycansthe accumulation of amyloid fibrils tissue/organ dysfunctionClassificationsystemic or localizedfurther characterised by precursor protein (AL in myeloma - A for Amyloid, L for immunoglobulin Light chain fragments)DiagnosisCongo red staining Amyloid Apple-green birefringenceserum amyloid precursor (SAP) scanbiopsy of rectal tissue.TypesAL amyloidosisAA amyloidBeta-2 microglobulin amyloidosisThe commonest form of amyloidosisL Ig?Light chain fragmentCausesMyeloma, Waldenstrom's, MGUSFeatures?Nephrotic syndrome Cardiac and neurological involvement,Macroglossia, Periorbital eccymosesA Precursor Serum Amyloid A protein.Causes (chronic infection/inflammation)TB, BronchiectasisRheumatoid arthritisFeatures Renal involvement most common Precursor protein Beta-2 microglobulin (Part of major histocompatibility complex)associated with patients on renal dialysisRenal vascular diseaseMost common cause bilateral renal artery stenosis Atherosclerosis (> 95% of patients). Risk factors smoking and hypertension that cause atheroma elsewhere in the body. It may present hypertension, chronic renal failure(↓↓ renal function) or 'flash' pulmonary oedema specially after ACEI In younger patients however fibromuscular dysplasia (FMD) needs to be considered. (more common in young women and characteristically has a 'string of beads' appearance on angiography. Patients respond well to balloon angioplastyInvestigationMR angiography is now the investigation of choiceCT angiographyconventional renal angiography is less commonly performed used nowadays, but may still have a role when planning surgeryFibromuscular DysplasiaProliferation of cells in the walls of the arteries causing the vessels to bulge or narrow 'String of beads' Renal artery stenosis 2ry to atherosclerosis for 90% of renal vascular disease, Fibromuscular dysplasia (commonest cause of the remaining 10%).Epidemiology 90% of femaleFeaturesYoung female + Hypertension +AKI after ACEI + Asymmetric kidneys + Normal urine dip?HypertensionChronic kidney disease or more acute renal failure e.g.?secondary to ACE-inhibitor initiation'FLash' pulmonary oedema (Fluid retension)Investigation U/S renal tracts asymmetric kidneysRetroperitoneal fibrosisLower back/flank pain is the commonest presenting feature. Fever and lower limb oedema is also seen in some patients.AssociationsRiedel's ThyroiditisPrevious RadiotherapySarcoidosisInflammatory abdominal Aortic AneurysmDrugs MethysergideRhabdomyolysisTypically feature in the exam as a patient had a fall or prolonged epileptic seizure and is found to have an acute kidney injury on admission. Featuresshould always be considered in?lactic acidosis, hyperkalaemia and features of acute tubular necrosisAKI with disproportionately raised creatinine↑↑↑ CK.Myoglobinuria↓↓ Ca++ (myoglobin binds calcium)↑↑ P+ (released from myocytes)↑↑ K+ ?(due to destruction of myocytes and release of K+ may develop before renal failure)Metabolic acidosisCausesseizurecollapse/coma (e.g. elderly patients collapses at home, found 8 hours later)crush injuryMcArdle's syndrome?Malignant neuroleptic syndrome Rheumatological diseases (Dermatomyositis)EcstasyDrugs Statins?(especially if co-prescribed with?clarithromycin)ManagementIV fluids?to maintain good urine outputurinary alkalinization is sometimes usedAnion gap (sodium + potassium) - (bicarbonate + chloride) = Normal anion gap is 8-14 mmol/LIt is useful in metabolic acidosisNormal anion gap OR↑↑Cl metabolic acidosis Loss of HCO3 Acidosis ↑↑Cl to normalize the anion gap↑↑ Anion gap metabolic acidosisGIT HCO3 loss ?diarrhoea, ureterosigmoidostomy, fistulaRenal tubular acidosis "Type 1"Drugs AcetazolamideAmmonium chloride injection (↑↑Cl)Addison's disease (↓↓K)Lactate shock, hypoxiaKetones DKA, alcoholUrate renal failureacid poisoning salicylates, methanol(Alcohol)5-oxoproline chronic paracetamol useMetabolic acidosis secondary to high lactate two types:lactic acidosis type A: sepsis, shock, hypoxia, burnslactic acidosis type B: metforminFluid therapy Requirements for maintenance fluids:25-30 ml/kg/day of water?andapproximately?1 mmol/kg/day of potassium, sodium and chloride andapproximately?50-100 g/day of glucose?to limit starvation ketosisEx: 80kg patient, for a 24 hour period, this would translate to: (2 L water & 80mmol potassiumFor the first 24 hours routine maintenance alone 25-30 ml/kg/day NaCl 0.18% in 4% glucose with 27 mmol/l potassium on day 1 Patient post-op and "having significant losses from drains more fluid 0.9% saline if large volumes are used there is an increased risk of hyperchloraemic metabolic acidosisHartmann's contains potassium and therefore should not be used in patients with hyperkalaemiaNa+Cl-K+HCO3-GlucosePlasma135-14598-1053.5-522-28-0.9% saline154154---5% glucose----50g0.18% saline with 4% glucose3030--40gHartmann's solution131111529-SpironolactoneAldosterone antagonist?which acts in the?Cortical collecting duct.IndicationsAscites: patients with cirrhosis develop a secondary hyperaldosteronism. Relatively large doses such as 100 or 200mg are often usedHypertension: used in some patients as a NICE 'step 4' treatmentHeart failure (see RALES study below)Nephrotic syndromeConn's syndromeAdverse effectsHyperkalaemiaGynaecomastiainterfere with binding of testosterone to androgen receptors ↑↑ metabolic clearance of testosterone, ↑↑metabolism of androgens to estradiol.↓↓ Common with?eplerenone (used in troublesome gynaecomastia on spironolactoneRALESNYHA III + IV, patients already taking ACE inhibitorlow dose spironolactone reduces all cause mortalityHyperkalaemia: managementCauses Precipitating factors (Acute renal failure) and drugs stopped (ACE inhibitors). Management may be categorised by the aims of treatmentStabilisation of the cardiac membrane IV Ca ++ gluconate does NOT ↓↓ potassium levelsShort-term shift in potassium from extracellular to intracellular fluid compartmentcombined insulin/dextrose infusionnebulised salbutamolRemoval of potassium from the bodycalcium resonium (orally or enema)enemas are more effective than oral as potassium is secreted by the rectumloop diureticsDialysishaemofiltration/haemodialysis should be considered for patients with AKI with persistent hyperkalaemiEpididymo-orchitisInfection Epididymis +/- Testes pain and swelling (Most commonly local spread from genital tract (Chlamydia trachomatis?and?N. gonorrhoeae) or bladder.The most important DD. testicular torsion. This needs to be excluded urgently to prevent ischaemia of the testicle.FeaturesUnilateral testicular pain and swellingUrethral discharge may be present, but urethritis is often asymptomaticTesticular torsion patients < 20 years, severe pain and an acute onsetManagementUnknown organism Ceftriaxone 500mg IM single dose, + Doxycycline 100mg by mouth 2*1/ 10-14 daysFurther investigations following treatment to exclude any underlying structural abnormalitiesHIV: renal involvementRenal involvement in HIV consequence of treatment or the virus itself. Protease inhibitors?"Indinavir" can precipitate intratubular crystal obstruction.HIV-associated nephropathy (HIVAN) 10% of end-stage renal failure cases.Antiretroviral therapy has been shown to alter the course of the disease. There are five key features of HIVAN:Massive proteinuria ?nephrotic syndromenormal or large kidneysfocal segmental glomerulosclerosis with "focal or global capillary collapse on renal biopsy"↑↑ urea and creatinineNormotensionBenign prostatic hyperplasiaRisk factorsAge 50% of 50-y (Evidence of BPH) and 30% (symptoms). 80% of 80-y (Evidence of BPH)Ethnicity black > white > AsianFeatureslower urinary tract symptoms (LUTS), which may be categorised into:voiding symptoms (obstructive) weak or intermittent urinary flow, straining, hesitancy, terminal dribbling and incomplete emptyingstorage symptoms (irritative) urgency, frequency, urgency incontinence and nocturiapost-micturition: dribblingcomplications: urinary tract infection, retention, obstructive uropathyManagement optionswatchful waitingMedication alpha-1 antagonists, 5 alpha-reductase inhibitors. "The use of combination therapy supported"Surgery transurethral resection of prostate (TURP)Alpha-1 antagonists5 alpha-reductase inhibitorsEx: Tamsulosin/ Alfuzosin/ Doxazocin↓↓ smooth muscle tone (Prostate and Bladder)1st-lineimprove symptoms (70% )S/E Dizziness, Postural hypotension Dry mouth, DepressionEx: FinasteridaBlock conversion of(testosterone Dihydrotestosterone (DHT)) "which inducee BPH"Unlike alpha-1 antagonists causes ↓↓ prostate volume and slow disease This takes time and symptoms may not improve for 6 months. ↓↓ PSA concentrations by up to 50% (false –Ve)S/E Erectile dysfunction, ↓↓ libido, ejaculation problems, GynaecomastiaPSA testingA serine protease enzyme produced by normal and malignant prostate epithelial cells. It has become an important tumour marker but controversy screening significant ↓↓ death prostate cancer 20% in men aged 55 - 69 years but ↑↑(risk of over-diagnosis and over-treatment)So, allow men to make an informed choice.Age-adjusted upper limits for PSA were recommended by the PCRMP:AgePSA level (ng/ml)50-59 years3.060-69 years4.0> 70 years5.050-69 years PSA >= 3.0 ng/ml OR there is an abnormal DREPSA levels may also be raised by*benign prostatic hyperplasia (BPH)prostatitis and UTI (postpone the PSA ≥ 1 month after treatment)Ejaculation (ideally not in 48 hours)vigorous exercise (ideally not in 48 hours)urinary retentioninstrumentation of the urinary tractdigital rectal examination of debateFinasteride is the only factor likely to decrease the level of serum PSA.Poor specificity and sensitivity33% W PSA of 4-10 ng/ml prostate cancer. rises to 60% PSA of 10-20 ng/ml this of men20% with prostate cancer normal PSAAge-adjusted upper limits and monitoring change in PSA level with time (PSA velocity or PSA doubling time)Prostate cancer Localised prostate cancer (T1/T2)Localised advanced (T3/T4)Metastatic prostate cancer – (hormonal therapyDepends on life expectancy and patient choice. Conservative:? Radical prostatectomyradiotherapy: External beam and brachytherapyHormonal therapy: see belowRadical prostatectomy:?erectile dysfunction "common"Radiotherapy external beam and brachytherapy. ↑↑bladder, colon, and rectal cancer Synthetic?GnRH agonist -Ve feedback to the anterior pituitary Goserelin (Zoladex)Cover 3 daysinitially with anti-androgen to prevent tumour flare↑↑testosteroneAnti-androgenCyproterone acetate prevents DHT binding from intracytoplasmic protein complexesOrchidectomyAbiraterone acetateA selective androgen synthesis (- -) blocking Cytochrome P450 17alpha-hydroxylase. ↓↓ Androgen production (testes and adrenal glands and prostatic tumour tissue).administered orally + prednisolone. significant survival benefit It is indicated for treating metastatic castration "Orchidectomy "resistant (hormone-relapsed) prostate cancer in adult asymptomatic men mildlysymptomatic after failure of androgen deprivation therapy in whom chemotherapy is not yet clinically indicated.Metastatic castration resistant prostate cancer in men whose disease has progressed on or after a docetaxel-based chemotherapy regimen.Testicular cancerThe most common malignancy in men (20-30 y). 95% of cases of testicular cancer are germ-cell tumours divided into:SeminomasNon-Seminomas: (Embryonal/ Yolk sac/ Teratoma/ Choriocarcinoma)Non-germ cell tumours Leydig cell Tumours/ Sarcomas.The peak incidence for teratomas (25 y) and seminomas (35 y). Risk factors include:?Infertility?(increases risk by a factor of 3)CryptorchidismFamily historyKlinefelter's syndromeMumps orchitisFeaturesa painless lump is the most common presenting symptompain may also be present in a minority of menother possible features include?hydrocele, gynaecomastiaAFP is elevated in around 60% of germ cell tumoursLDH is elevated in around 40% of germ cell tumoursSeminomas: hCG may be elevated in around 20%Diagnosisultrasound?is first-lineManagementtreatment depends on whether the tumour is a seminoma or a non-seminomaOrchidectomyChemotherapy and radiotherapy may be given depending on staging and tumour typePrognosis is generally excellent5 year survival for seminomas is around 95% if Stage I5 year survival for teratomas is around 85% if Stage ILower urinary tract symptoms in menVery common and are present in the majority of men > 50 years most commonly 2ry to BPH .Classify the symptoms into 3 broad groups.VoidingStoragePost-micturitionHesitancyPoor or intermittent streamStrainingIncomplete emptyingTerminal dribblingUrgency (overactive bladder)FrequencyNocturiaUrinary incontinencePost-micturition dribblingSensation of incomplete emptyingWork- UpUrinalysis exclude infection & haematuriaDigital rectal examination: size and consistency of prostatea PSA test may be indicated, but the patient should be properly counselled firsturinary frequency-volume chart DD. (urinary frequency, polyuria, nocturia, and nocturnal polyuria.International Prostate Symptom Score (IPSS) assess the impact on the patient's life mild, moderate or severeManagementPredominately voiding symptomsPredominately overactive bladder (Stroge)NocturiaConservative pelvic floor muscle trainingbladder training,prudent fluid intake and containment products'Moderate' or 'severe' alpha-blockerEnlarged Prostate + "high risk progression" 5-alpha reductase inhibitor.Enlarged prostate + 'moderate' or 'severe' symptoms both (alpha-blocker + 5-alpha reductase inhibitorMixed (voiding & storage not responding to an alpha blocker Antimuscarinic (anticholinergic) drug may be addedconservative moderating fluid intakeBladder retraining Persist symptoms "Antimuscarinics" Oxybutynin (immediate release)Tolterodine (immediate release)Darifenacin (once daily preparation)Mirabegron if first-line drugs failModerating fluid intake at nightFurosemide 40mg in late afternoon Desmopressin Renal stonesRisk factorsDehydrationHypercalciuria, Hyperparathyroidism, HypercalcaemiaCystinuriahigh dietary oxalateRenal tubular acidosisMedullary sponge kidney, polycystic kidney diseaseBeryllium or Cadmium exposureRisk factors for urate stonesGoutIleostomy Loss of bicarbonate and fluid Acidic urine (precipitation of uric acid)Drug causesDrugs that (+ +) calcium stones: loop diuretics, Steroids, Acetazolamide, TheophyllineThiazides can prevent calcium stones (increase distal tubular calcium resorption). TypeFrequencyRadiograph appearanceCalcium oxalate40%OpaqueMixed (Ca++ oxalate/phosphate) stones25%OpaqueTriple phosphate stones*10%Opaque "stag-horn calculi"Calcium phosphate10%OpaqueCystine stones1%Semi-opaque, 'ground-glass' appearance, Cystinurea genetic defect ↓↓ reabsorption of dibasic amino acids ( includes cysteine.Urate stones5-10%Radio-lucent requiring U/S or CT KUB (without contrast)Xanthine stones<1%Radio-lucentGenetic defects altering xanthine oxidase inability to convert xanthine to uric acidoxalate stonesprimarily associated with short bowel syndromeStag - Horn calculi involve the renal pelvis and extend into at least 2 calyces.Alkaline Urine Composed of Struvite (Ammonium + Magnesium + Phosphate, triple phosphate). Large stone (PD to infection)Risk Factors Ureaplasma urealyticum and Proteus infections (Split Urea) Initial management of renal colicMedicationNSAID analgesia of choice for renal colicMight ↑↑ risk of CVS events (diclofenac, ibuprofen) Admission parenteral analgesic for rapid relief of severe pain'α-blockers may be for patients amenable to conservative management, (greatest benefit amongst larger stones)Initial investigationsurine dipstick and cultureRenal functionFBC / CRP: look for associated infectioncalcium/urate: look for underlying causesClotting if percutaneous intervention planned and blood cultures if pyrexial or other signs of sepsisImagingNon-contrast CT KUB all patients, within 14 hours of admissionImmediate CT KUB FeverA solitary kidney Uncertain diagnosis exclude other diagnoses (ruptured abdominal aortic aneurysm)CT KUB ureteric stones (97% Sensitivity 95% specificity) U/S still has a role but CT now and greater accurary no longer recommend first-line. The sensitivity 45% and specificity 90%Management of renal stones< 5 mm pass spontaneously(within 4 weeks) of symptom onset. Lithotripsy and nephrolithotomy may be for severe cases. More intensive and urgent treatment ureteric obstructionUreteric obstruction due to stones + infection surgical emergency (decompressed).Options include nephrostomy tube placement, insertion of ureteric catheters and ureteric stent placement.Renal developmental abnormality (horseshoe kidney) Previous renal transplant. Non-emergency extra corporeal shock wave lithotripsy, percutaneous nephrolithotomy, ureteroscopy, open surgery Shockwave lithotripsyA shock wave is generated external to the patient internally cavitation bubbles and mechanical stress lead to stone fragmentation. S/E solid organ injury, Ureteric obstruction (fragmentation of larger stones), Uncomfortable (analgesia) UreteroscopyA ureteroscope is passed retrograde renal pelvis. Indication Lithotripsy is contraindicated (pregnant females) Complex stone disease. In most cases a stent is left in situ for 4 weeks after the procedure.Percutaneous nephrolithotomyAccess is gained to the renal collecting system intra corporeal lithotripsy or stone fragmentation is performed and stone fragments removed.Therapeutic selectionDiseaseOptionStone < 2cm in aggregateLithotripsyStone < 2cm in pregnant femalesUreteroscopyComplex renal calculi and Staghorn calculiPercutaneous nephrolithotomyUreteric calculi < 5mmManage expectantlyPrevention of renal stonesCalcium stones may be due to hypercalciuria, which is found in up to 5-10% of the general population.?↑↑ fluid intakelow animal protein, low salt diet (a low calcium diet has not been shown to be superior to a normocalcaemic diet)Thiazides diuretics?(increase distal tubular calcium resorption)Oxalate stonesCholestyramine reduces urinary oxalate secretionpyridoxine reduces urinary oxalate secretionUrate Stone treatment ?HydrationUrinary alkalinization oral bicarbonateallopurinol if raised uric acid levels. Uricosuric medications should be avoided, especially in renal impairment, as it can precipitate the formation of new calculi.Xanthogranulomatous pyelonephritisA rare chronic granulomatous disease resulting in a non-functioning kidney. Chronic/subacute infection by organisms such as?Proteus mirabilis?"anaerobic, rod-shaped" renal stones including staghorn calculi. Foamy (lipid laden) macrophages are typically seen.Reflux nephropathyVesico-Uretic Reflux causes "Chronic Pyelonephritis" commonest cause due to scarring usually occurs in first 5 yearsstrong genetic dispositionRenal scar may produce increased quantities of renin causing HypertensionDiagnosismicturating cystographyHaematuriaMicroscopic or +Ve dipstick non-visible haematuria 2.5% of the population.whilst macroscopic visible haematuria. Transient/ spurious non-visible haematuriapersistent non-visible haematuria TrueFalse causes - red/orange urine UTIMenstruationvigorous exercise normally settles after 3 daysSexual intercourseCancer (bladder, renal, prostate)StonesBenign Prostatic HyperplasiaProstatitisUrethritis ?ChlamydiaRenal Causes IgA nephropathy, thin basement membrane diseaseNot present on dipstickFoods beetroot, rhubarbDrugs Rifampicin, DoxorubicinManagementDoes not support screening for haematuria.The incidence of non-visible haematuria is similar in patients taking aspirin/warfarin to the general population.Testingurine dipstick is the test of choice for detecting haematuriapersistent non-visible haematuria present in 2 out of 3 samples tested 2-3 weeks apartRenal function, albumin:creatinine (ACR) or protein:creatinine ratio (PCR) and blood pressure should also be checkedurine microscopy may be used but time to analysis significantly affects the number of red blood cells detectedReferral Rules Most haematuria protocols patients (< 40 years) to nephrology initially older patients urology for a cystoscopy.Urgent referral (2 weeks)Non-urgent referralAged >= 45 years +unexplained visible haematuria without UTI ORPersistant/ recurrent visible haematuria after successful treatment of UTIAged >= 60 years + unexplained nonvisible haematuria + (dysuria or a ↑↑blood TLC)Aged >= 60 years + recurrent/ persistent unexplained UTI< 40 years with normal renal function, no proteinuria and normotensive do not need to be referred and may be managed in primary careThin basement membrane diseaseAn inherited disorder of type IV collagen thinning of the basement membrane (5% of the population and 30% patients "family history haematuria".It is generally a benign disorder and biopsy is rarely indicated.Diagnosis History of persistent haematuria,Normal kidney functionFamily history of haematuria without kidney failure. PolyuriaCauses of polyuria by how common they were. Common (>1 in 10)Diuretics, caffeine &?alcoholD.MlithiumHeart failure Infrequent (1 in 100)↑↑ Ca++hyperthyroidismRare (1 in 1000)Chronic renal failure1ry polydipsia↓↓ K+Very rare (<1 in 10 000)Diabetes Insipidus. Bladder cancerTransitional cell carcinomaSquamous cell carcinomaSmokingAniline dyes (2-naphthylamine and benzidine)printing and textile industry Rubber manufactureCyclophosphamideSchistosomiasisSmokingRenal cell cancer"Hypernephroma" 85% 1ry renal neoplasms It arises from?proximal renal tubular epithelium. The most common histological subtype is?clear cell?(75 to 85 % tumours). Associations*↑↑ common in middle-aged menSmokingvon Hippel-Lindau syndrometuberous sclerosisFeaturesClassical triad:?haematuria, loin pain, abdominal masspyrexia of unknown originleft Varicocele?(due to occlusion of left testicular vein)Endocrine effectserythropoietin (polycythaemia),?parathyroid hormone (hypercalcaemia)renninACTH25% Metastases at presentation ?pulmonary cannonball metastases with mediastinal lymphadenopathy.Paraneoplastic hepatic dysfunction syndrome. "Stauffer syndrome"2ry to ↑↑ levels of IL-6Typically presents as?"Non-metastatic liver dysfunction " Cholestasis & Hepatosplenomegaly, but no jaundiceConstitutional symptoms?+ ↑↑ Ca++,., amyloidosis ↑↑ (ALP, ?γ-glutamyl transferase (GGT), Platelet)Managementfor confined disease a partial or total?nephrectomy?depending on the tumour sizeAlpha-interferon and IL-2 ↓↓ tumour size and treat patients with metatasesreceptor tyrosine kinase inhibitors (sorafenib, sunitinib) superior efficacy compared to interferon-alphaHaemodialysis Access Arteriovenous fistulas Direct connections between arteries and veins generally formed surgically to allow access for haemodialysis.The?preferred access for haemodialysis? lower rates of complications.The time taken for an A-V fistula to develop is 6 to 8 weeks.The shunted blood flow ↑↑growth factors and hypertrophy of the venous wall 6 to 8 Ws untill full maturation The fistula can withstand a dialysis flow rate of 500ml/min.Potential complications include:InfectionThrombosis detected by the absence of a bruitStenosis may present with acute limb painSteal syndromePeritoneal dialysisA form of renal replacement therapy used as a stop-gap to haemodialysis or for younger patients who do not want to have to visit hospital 3/ a week.The majority of patients do Continuous Ambulatory Peritoneal Dialysis (CAPD), which involves four 2-litre exchanges/plicationsPeritonitis:?coagulase -Ve staphylococci (Staph. Epidermidis)?is the most common cause.?Staphylococcus aureus?Streptococcus?and?Enterococcus.is another common causeSclerosing peritonitisPlasma exchangeIndications for plasma exchange (also known as plasmapheresis)Guillain-Barre syndromemyasthenia gravisGoodpasture's syndromeANCA +Ve vasculitis if rapidly progressive renal failure or pulmonary haemorrhageTTP/HUSCryoglobulinaemiaHyperviscosity syndrome (2ry to myeloma)Complications of plasma exchangeHypocalcaemia: due to the presence of citrate used as an anticoagulant for the extracorporeal systemMetabolic alkalosisRemoval of systemic medicationsCoagulation factor depletionImmunoglobulin depletionDD. Renal biopsyUnder electron microscopy, minimal change disease results in diffuse loss of visceral epithelial cells' foot processes, vacuolation and growth of microvilli on the visceral epithelial cells. Under light microscopy, very minimal changes are noted.IgA nephropathy is characterised by deposits of immunoglobulin A in a granular pattern in the mesangium seen on immunofluorescence.?In membranous glomerunephritis, the basement membrane is observed to be diffusely thickened. Using Jones' stain, the basement membrane appears to have a 'spiked' or 'holey' appearance.Systemic lupus erythematous can lead to membranous glomerulonephritis which is due to immune complex deposition along the glomerular basement membrane. This appears as a granular appearance on immunofluorescence testing.Alport syndrome (mutation in type IV collagen) would result in a 'basket weave' appearance on electron microscopyFocal segmental glomerulosclerosis would show segmental sclerosis and hyalinosis on light microscopy and effacement of foot process on electron microscopy (similar to minimal change disease).Goodpasture syndrome would result in crescentic glomerulonephritis. Glomeruli appear like a crescent moon on light microscopy and immunofluorescence.Acute post-streptococcal glomerulonephritis would show enlarged and hypercellular glomeruli with 'starry sky' (granular) appearance on light microscopy and immunofluorescence, respectively. There are subepithelial immune complex humps on electron microscopy ................
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