Nephrology Flashcards

Question

PE for RRT

Answer 1

Mode of RRT (PD: sacs and Tenckhoff catheter, HD: tunnelled CVC, AV fistula/graft, Renal transplant Adequacy of RRT - hydration status - Signs of uraemia: confusion, asterixis, scratch mark, tachypnea, pericardial rub Complications of Renal failure - Anemia - Collar scar: parathyroidectomy Complication of immunosuppressants: • Steroids: BP, H’stix marks, proximal myopathy, abdominal striae immunosuppressants • CNI: gum hypertrophy, hirsutism, coarse tremor Underlying cause of renal failure • PCKD: ballotable kidneys • Stigmata of rheumatological diseases

Answer 2

• Malnutrition • Accelerated atherosclerosis • Dialysis-related amyloidosis • Acquired cystic disease ± malignant transformation • Dialysis-related dementia (cerebral aluminium toxicity)

Answer 3

Mechanism • Advantages of peritoneal membrane: thin & semi-permeable, large surface area, highly vascularized • Solutes are removed via o Diffusion: movement across concentration gradient, effective for molecules NOT present in dialysate o Ultrafiltration: movement across osmotic pressure gradient ( by adding dextrose / icodextrin to dialysate) Contraindications • Abdominal adhesions (decrease peritoneal membrane surface area): multiple abdominal surgery, peritonitis, pelvic irritation, diverticulitis • VP shunt placement • Pleuroperitoneal leak • Poor self-care: frequent PD peritonitis Types • Manual: o Continuous ambulatory PD (CAPD): 3 exchanges during day + overnight dwell o Intermittent PD: used post-Tenckhoff insertion, to allow wound healing & CAPD training • Automated (APD) o Nocturnal intermittent PD (NIPD): cycling at night without daytime dwell o Continuous cycling PD (CCPD): cycling at night + daytime dwell Setup and components 1. Catheter Tenckhoff catheter: silicon • Tip of catheter: face downwards inside peritoneal cavity • Dacron cuffs x2: o Inserted ≥2 weeks before PD for local inflammation & fibrosis o Prevent fluid leak and bacterial migration along catheter • Entrance site (catheter enters peritoneum): paramedian incision • Exit site (catheter exits skin) o Face downwards to prevent accumulation of bacteria o Visible by patient o Usually left side: reserve right side for transplant 2. System “Y-set” (fig.): “flush before fill” to reduce risk of peritonitis 3. Osmotic agent • Low MW agents: e.g. dextrose (MC) o Different concentrations available: 1.5%, 2.5%, 4.25% (higher conc. for DM patients) o Problems: metabolic complications, glucose degradation products (GDP) affect peritoneal host defence mechanism • High MW agents: e.g. icodextrin (glucose polymer), amino-acid based solutions o Less absorption: increase duration of ultrafiltration, suitable for uncontrolled DM patients 4. Electrolytes and buffers • Lactate buffer: control metabolic acidosis • No K: patients usually hyperK Other additives to dialysate: • Heparin: prevent obstruction of catheter lumen by fibrin, added if blood-stained dialysis effluent (likely subcutaneous bleed) • Insulin: DM patients, better than OHA in ESRD Prescription Example: “1.5% 2 litre dwell, 3 bags per day” • Volume: 2L (1L if just after Tenchkoff insertion) • Concentration: 1.5% or 2.3% usually • Adequacy: Kt/V ratio ≥ 1.7 (K = dialysate flow rate, t = time, V = body water volume) Complications Monitor exit site condition and dressing daily • Early o Insertion: bleeding (inf. epigastric a.), infection, perforation o Catheter: kinked catheter, thrombosis, omental wrapping (Mx: Tenckhoff revision + omentectomy) o Pleuro-peritoneal fistula • Late o CAPD peritonitis o Exit site infection o Metabolic complications: hyperglycaemia, hyperlipidemia o Dialysis-related amyloidosis: accumulation of large β2-microglobulin o Encapsulating peritoneal sclerosis (intermittent IO, fatal) Blood-stained dialysate • Causes: o Old blood (dark red without clots): residual blood in peritoneum after laparotomy o New blood (bright red with clots): arterial puncture during laparotomy • Management: IP heparin to prevent clot formation Outflow failure • Sites of obstruction o Inside catheter: blood / fibrin clot o Outside catheter, inside patient: faecal loading, kinking of catheter, omental wrap o Outside catheter, outside patient: kinking of catheter, clamped catheter • Management: o Check all knobs and tubing o Assess whether it is inflow or outflow problem - inflow problem, —> spike off, inform renal team - outflow problem: fibrin—>IP heparin, Turbid—>treat CAPD peritonitis, clear but slow effluent —> change to lateral/standing positive, fleet enema, KUB, spike off, surgical removal and insertion of new catheter Pleuro-peritoneal fistula • Suspect when pleural effusion with high glucose level (“sweet hydrothorax”) • Diagnosis: CT peritoneogram (inject dye via Tenckhoff), peritoneal scintigraphy (Tc-99m albumin), IP methylene blue • Management: o Supportive treatment: stop PD and change to HD for 4-8 weeks o Definitive treatment if large hole: VATS-guided pleurodesis (Talc on fistula) CAPD peritonitis • Pathogens: G+ (50%, S aureus), G- (25%), no growth (15%), mixed (workup for intra-abdominal pathology!) • Diagnostic criteria: at least two of o Clinical S/S (abdominal pain, vomiting, diarrhoea, fever) and/or cloudy PD effluent o PD effluent cell count: WBC > 100 and >50% polymorphs o PD effluent culture +ve • Management (important!) o PD effluent Ix: cell count d/c, Gram stain and culture o Analgesia e.g. Panadol ± tramadol o Rapid flush 3 bags of PD fluid with IP heparin 500units/L to prevent catheter block (decrease fibrin clot) o Step up to 4 exchanges per day to improve ultrafiltration o Empirical antibiotics to cover both G+ and G-: IP cefazolin 1g (G+) + ceftazidime 1g (G-) - Dwelling time: at least 6h (loading dose + maintenance dose in last bag every day) - Use IV if features of sepsis - Duration: at least 21 days o Consider PO nystatin to prevent secondary fungal peritonitis o Adjust antibiotics according to C/ST: - G-: give 2 different antibiotics acting in different ways (e.g. IP amikacin + IP ceftazidime) - Fungal: IV amphotericin B, until 2 weeks after catheter removal o Repeat PD effluent Ix at Day 4 & after completion of antibiotics o Refractory peritonitis: - Remove Tenckhoff catheter —> temporary HD - Continue antimicrobials for 2 weeks after catheter removal - Work-up for fungal & mycobacterium causes - Re-insert catheter after completion of treatment CAPD exit site infection (ESI) • Purulent discharge ± erythema of skin around exit site • Management: o Equivocal ESI: chlorhexidine dressing tds + local Tx (e.g. mupirocin cream) tds o Definitive ESI: - Exit site swab for microscopy, Gram stain, C/ST - Oral antibiotics x 14 days: cloxacillin/cephalexin (if suspect G+), levofloxacin (if suspect G-) - Adjust antibiotics: add rifampicin if unresolving S. aureus, - Consider removal of catheter / shaving of external cuff • Prevention: personal hygiene, avoid excessive traction on catheter, screen for MRSA carriage

Answer 4

Usually if C/I to PD (e.g. abdominal adhesions) or failed PD (fibrosis of peritoneal membrane) Mechanism • Counter-current: blood is always meeting a less concentrated dialysate • Solutes are removed via o Diffusion: movement across concentration gradient, for small solutes (e.g. urea) o Ultrafiltration: for larger solutes and water Types of vascular access AV fistula / AV graft: for long-term HD AV fistula - preferred if large vein (>2mm) available - Adv: Better long-term patency, Lower risk of thrombosis & infection - Technicality: Maturation of AV fistula: rule of 6 (evaluated 4-6 weeks after creation, ≥6mm diameter, ≤6mm deep, flow ≥600mL/min) End-to-side anastomosis preferred, usually between cephalic vein & radial artery AV graft - options if small vein - Adv: Shorter time to first cannulation Easier cannulation Less likely 1° failure - Material: Teflon (PTFE) Types: looped / straight Examination of AV fistula • Inspection: o Erythema / swelling (infection) o Distal extremities: ischemia (vascular steal), edema (venous hypertension) o Collapse during elevation of arm • Palpation o Tenderness o Pulse o Thrills (soft thrill is normal) o Direction of flow • Auscultation for bruits Double-lumen (or triple-lumen) central venous catheter: • Types: non-tunnelled (emergency HD), tunnelled (long-term HD but poor candidate or bridging for AV access) • Access sites: jugular, subclavian, femoral • Lumens: red port (proximal), blue port (distal), ± extra port for blood taking • Insertion: USG-guided, Seldinger technique (guidewire), Trendelenburg position (decrease risk of air embolism), fluoroscopy to confirm position Prescription • 2-3 sessions/ week (4-6h each) • Blood flow rate 150-250mL/min • Dialysate flow rate 500mL/min (fixed) • Anticoagulation: UFH or LMWH • Adequacy: Kt/V ratio ≥ 1.2 (K = dialysate flow rate, t = time, V = body water volume) • Avoid blood taking / BP measurement from AV fistula arm • Monitor AV fistula daily Complications • First-use syndrome: anaphylactoid reaction with chills, urticaria, loin pain • Dialysis washout: hypotension, fatigue, chest pain, leg cramp, headache • Dialysis dysequilibrium syndrome: o Cerebral oedema due to rapid reduction of plasma urea and change in extracellular osmolarity o S/S: n/v, confusion, seizure o Diagnosis by exclusion: after ruling out hypoglycaemia, uraemic encephalopathy, haemorrhagic stroke (due to heparin), sepsis o Management: slow down/ stop ultrafiltration, infuse isotonic (hypertonic saline if severe) o Prevention: short (1-2h), slow dialysis for the first session • Vascular access-related: o Related to insertion: pneumothorax, bleeding, arrhythmia, air embolism (Mx: left lateral + 100% O2) o Infection: Any febrile HD patient with a catheter has catheter-related infection until proven otherwise • Pathogens: CoNS, S aureus • Investigations: blood culture through catheter • Management: remove catheter + vancomycin after each HD for 2-3 weeks o Thrombosis: • Catheter: Mx urokinase • Native AV fistula: usually stenosis at AV anastomosis, Mx balloon angioplasty or embolectomy • Teflon AV graft: alert if sudden loss of thrill; similar Mx as thrombosis in native AV fistula o Vascular steal syndrome: upper limb ischemia • Ix: Allen’s test (occlude radial artery and ask patient clench fist) • Dialysis-related amyloidosis: due to accumulation of β2-microglobulin

Answer 5

Types of allograft • Living: (genetically) related or unrelated • Cadaveric: heart-beating (brainstem death) or non-heart-beating (cardiac death) Procedure • Donor nephrectomy: open (cadaveric), laparoscopy (living) • Transplanted kidney placed in iliac fossa (usually right-sided: vessels more superficial) extraperitoneally (∵more rapid return of bowel function, easier to observe haemorrhage / urine leak) • Vessel anastomosis: usually to external iliac artery & vein (∵IIA many branches & risk of pelvic organ ischemia) • Ureteroneocystostomy Criteria for living donor • Donor factor: first-degree relative, married couple > 2y • Disease factor: no significant comorbidities (long-standing HT/DM) • Organ factor: HLA-A, B and DR matched (ABO-incompatible transplant permitted) C/I for living donor: uncontrolled infections, Hx of malignancy (with exceptions) Pre-transplant work-up 1. Donor - HLA typing, ABO typing - Bloods: CBC, RFT (GFR ≥80), LFT, OGTT (to rule out DM kidney), HBV/ HCV/ HIV Urinalysis: proteinuria / hematuria - Imaging: CXR, ECG Renal arteriogram (to confirm vascular supply, notify surgeon if renal accessory artery +ve) 2. Recipient - HLA typing, ABO typing, X-match (antibodies against foreign HLA) - Bloods: HBV/HCV/HIV/TB/CMV, G6PD (Septrin prophylaxis) • Give prophylactic antivirals before immunosuppressants • Match hepatitis status of donors and recipients (usually possible for HBV, +/- for HCV) Nephrectomy Native diseased kidney is usually not removed unless • Huge polycystic kidney • RCC • Resistant infection, e.g. abscess, tuberculoma Post-transplant management Monitoring • Urine output, serum Cr, GFR • Proteinuria at 3, 6, 12mo and every 12mo afterwards • Screen for infections: CMV, polyomavirus (BK, JC virus), bacterial UTI Immunosuppressant therapy • Triple therapy: steroid + CNI (cyclosporin/ tacrolimus) + antimetabolite (azathioprine/ MMF / sirolimus) o Usual regimen: prednisolone + cyclosporin A + MMF • Add antibodies for induction (first 2 weeks) if at high risk of rejection o Polyclonal: anti-thymocyte globulin (ATG), anti-lymphocyte globulin (ALG) - S/E: cytokine release syndrome (fever, chills, hypotension), serum sickness (Type 3 HSR) o Monoclonal: anti-CD3 (OKT3), anti-IL2 / anti-CD25 (basiliximab, daclizumab) • Switch CNI to mTOR inhibitors (e.g. sirolimus, everolimus) if CNI toxicity / new cancer after renal transplant Additional medications • Prophylaxis for infections: cotrimoxazole (PJP) + acyclovir (CMV) for 6 months • Anti-hypertensive: diltiazem is preferred (DDI: can reduce dosage of CyA needed) • Statins Complications • Transplant rejection: immunosuppressants - Hyperacute —> Minutes —> Preformed IgG —> No effective treatment Prevention: cross-match - Acute —> Days - weeks —> T cell mediated rejection (TCMR): anti- foreign HLA T cells Antibody-mediated rejection (ABMR) —> Mx: TCMR: pulse steroid + Ab ABMR: plasma exchange + Ab - Chronic —> Months – years —> Immune + non-immune (e.g. HT, DM, cyclosporin-related toxicity) —> Untreatable once initiated Control BP, lipid, DM Change cyclosporin to MMF or sirolimus • Metabolic: HT, DM, lipid, Cushing's, obesity, IHD o Disease-related o Drug-related, e.g. steroid, CNI, mTORi • Infection: o Types of infection - First month: line/ wound infection, pre-existing infection (e.g. HSV, TB) - 1-6 months: opportunistic infections (CMV, PJP) - After 6 months: chronic viral infection o Management - Mild (e.g. uncomplicated cystitis): PO Augmentin (outpatient), no need stop immunosuppressants - Severe (e.g. graft pyelonephritis): admit and stop MMF ± decrease CNI + increase stress-dose steroids + IV broad- spectrum antimicrobials (e.g. 3rd generation cephalosporin) - Avoid giving macrolides: may increase CyA levels • Bone (persistent hyperPTH): AVN, osteopenia • Malignancy: related to immunosuppression - HCC (HBV), post-transplant lymphoproliferative disease (EBV), Kaposi's sarcoma (HHV8) • Recurrence of original disease: MPGN > IgAN Emergency in renal transplant patients 1. Fever • Infection: opportunistic infections if <6 months post-transplant, usual infections if ≥6 months • Graft rejection: increase serum Cr >20% after excluding other causes 2. AKI • Pre-renal: dehydration, transplant artery stenosis / vein thrombosis • Renal: transplant rejection, calcineurin inhibitor toxicity, recurrence of renal disease, acute tubular necrosis • Post-renal: ureteric anastomotic stenosis, urinary leakage Workup: • Bloods: CBC, LRFT, CaPO4, INR immunosuppressant trough level • Septic work-up • ± CMV pp65 antigen / CMV DNA, • ± urine BK virus / JC virus, decoy cells* • Urine: MSU C/ST, 24h urine protein & Cr • ± Drain urea & Cr (if suspect urine leakage) • Urgent USG graft kidney + Doppler study • ± Stand-by MAG-3 / DTPA scan • Early graft renal biopsy for acute rejection Note: Acute GE, macrolide antibiotics and fluconazole may increase CyA / tacrolimus levels *Decoy cells: pathognomonic for BK nephropathy à Mx: reduce immunosuppressants

Answer 6

Protein - <150mg/day* - Proteinuria: >150mg/day - Nephrotic range proteinuria: >3.5g/day Albumin - <30mg/day - Microalbuminuria: 30- 300mg/day; not detectable by urine dipstick - Macroalbuminuria: >300mg/day Methods to quantify proteinuria 1. Urine dipstick - Easy to use, low cost, Specific but not sensitive to albumin - Cannot detect microalbuminuria / others (e.g. BJ, IgG) 2. 24h urine collection - Gold standard, Best for monitoring proteinuria - common for incomplete collection 3. Spot uPCR - only 1 spot sample - Inaccurate if proteinuria >1g/day Influenced by daily Cr production 4. Spot uACR - Only 1 spot sample Only for screening DM microalbuminuria - Inaccurate if proteinuria >1g/day Influenced by daily Cr production • Unit conversion: spot urine (mg/g) —> 24h urine (mg/day) Algorithm: • Screening for proteinuria: routine urine albustix ≥1+ (non-DM); high-sensitivity urine dipstick +ve / uACR (DM) • Screening test +ve x 2 but asymptomatic: o Early morning uPCR for quantification of proteinuria & exclude orthostatic proteinuria o Urine microscopy for casts / white cells / red cells, blood for RFT (GN) o Urine for C/ST (UTI) Classification of proteinuria 1. Physiological - Orthostatic - Transient (exercise, CHF, fever) 2. Pathological A. Tubulointerstitial (impaired resorption) - <2g/d - Faconi’s syndrome B. Glomerular Primary: - Minimal change GN - Membranous GN - FSGS - Membranoproliferative GN - Post-streptococcal GN - IgA nephropathy Secondary - Systemic disease: SLE, DM, vasculitis - Infectious: HIV, HBV, HCV, bacterial endocarditis - Hereditary: Alport’s - Medications: NSAIDS - Cancer: lymphoma, solid tumour - Others: cryoglobulinemia, hypertensive nephrosclerosis C. Overflow (overproduction of low molecular weight proteins) - multiple myeloma, amyloidosis, Waldenstrom’a macroglobulinemia

Answer 7

Indicated if: Proteinuria > 1g/day or proteinuria > 0.5g/day with microscopic haematuria • Refer nephrology, start ACEI/ARB if not C/I • Urine: microscopy, C/ST, UPCR • Bloods: BP, CBC, CRP/ ESR, clotting, RFT, LFT (decrease albumin), CaPO4, HbA1c • Imaging: CXR (pleural effusion), abdominal USG (ascites, kidney size, obstruction, renal vein thrombosis) • Etiology: o C3/C4, ANA, anti-dsDNA, ANCA, anti-GBM o HBsAg, anti-HCV, ASOT o Immunoglobulin: - Age < 50y: simple Ig pattern for IgA - Age > 50y: SPE + urine for BJ protein/ serum FLC (amyloidosis) o Optional (with clinical suspicion): anti-HIV, VDRL, cryoglobulin o Malignancy screening (e.g. FOBT, colonoscopy, CXR, AFP) if age >50y • Renal biopsy (refer to prev section for indications and C/I) Reduced C3/ C4: • Lupus nephritis • HCV-related MPGN • Post-strep GN • Cryoglobulinemia

Answer 8

Definitions • Gross haematuria: red-coloured urine visible to naked eye • Microscopic haematuria: ≥3 RBC/HPF in 2/3 properly collected urine (freshly voided, clean-catch, mid-stream urine processed by centrifugation) Aetiology 1. -ve dipstick, no RBCs - pseudohematuria by food, medication 2. +ve dipstick, +ve RBCs A. Haematological - Coagulopathy, sickle cell B. Renal - Primary: - Membranoproliferative GN - Post-streptococcal GN - Rapidly=progresion - Interstitial nephritis GN - Papillar necrosis - IgA nephropathy Secondary - Connective tissue disease: Granulomatosis with polyangiitis, Goodpasture’s, SLE, Churg-Strauss, HSP - Infectious: pyelonephritis - Hereditary: Alport’s, PCKD C. Urologic: - Nephrolithiasis, trauma, tumour, prostatitis, urethritis - Dysuria or flank pain common - Isomorphic RMCs, no casts - Blood at beginning (urethritis) or end (prostate, bladder) of stream History taking - highlights • Timing relative to urine stream: beginning (lower urinary tract), throughout (above bladder), terminal (prostate) • Any blood clots = urologic causes (urokinase in glomerular filtrate prevents formation of blood clots) • Gross painless haematuria: malignant until proven otherwise —> urological examination • Associated symptoms: o Concomitant frothy urine (GN) o Urologic: - Dysuria, frequency, urgency (UTI) - Obstructive symptoms, hematospermia (prostate) - Loin pain: colicky (stone), constant (inflammation, infection) o Autoimmune: - Rash: purpuric rash (HSP, vasculitides), malar rash (SLE) - Arthralgia, myalgia (SLE) o Respiratory: - Recent URTI (concurrent = IgA nephropathy; 7-10d ago = post-strep GN) - Epistaxis, rhinorrhoea (GPA) - Pleuritic chest pain, SOB (SLE) - Haemoptysis (pulmonary-renal syndrome) o Systemic: fever, weight loss, TOCC (TB) • Drug history: cyclophosphamide/ifosfamide (haemorrhagic cystitis), RT (radiation cystitis) • Family history: PCKD, hereditary nephritis (e.g. Alport’s, TBMD) Investigations Urine dipstick +Ve —> repeat several days later —> if +ve again —> urine microscopy and culture —>treat UTI if positive -Isomorphic RBC —> urologic disease —> cystoscopy and TU - dysmorphic RBC or RBC casts —> glomerular disease —> if concomitant proteinuria or renal insufficiency —> refer nephrology —> check BP, RFT, uPCR —> if isolated microscopic haematuria —> periodic FU Pearls • All Hb-positive dipstick should be accompanied by urine microscopy to differentiate haematuria vs pigmenturia • Antiplatelet/ anticoagulant use is not a satisfactory explanation for haematuria, except in warfarin OD • Evaluation for o Haemoglobinuria: centrifuged urine for supernatant haem, LDH, bili, haptoglobin o Myoglobinuria: centrifuged urine for supernatant haem, CK • If urological cancer is ruled out, treat as CKD, i.e. monitor RFT & urinalysis yearly

Answer 9

Histological terms of glomerular changes Types of changes • Membranous changes: thickened GBM (2: membranous nephropathy) • Proliferations: o Hyperplasia +/- inflammation in VEC (3: MCD) o Mesangial cells (4: IgA nephropathy) o Parietal epithelial cell (5: crescentic GN) Extent of changes • % of glomeruli affected: diffuse (>50%), focal (<50%) • Affected part of involved glomeruli: global, segmental (only part of glomerulus abnormal) Spectrum of clinical presentations Glomerulopathies can present as more than one syndrome at different times • Asymptomatic haematuria/ proteinuria • Nephrotic syndrome: nephrotic range proteinuria, hypoalbuminaemia, generalised oedema, hypercholesterolaemia • Acute nephritis: haematuria + proteinuria, HT, impaired RFT (oliguria, oedema) • ESRD GN with predominant nephrotic features Definition of nephrotic syndrome • Heavy proteinuria >3.5 g/day (>40mg/h/m2 in children) • Generalized edema • Hypoalbuminemia (<30g/L) • Hyperlipidemia —> Lipiduria Pathophysiology 1. Bland sediment (no cellular element) - Primary Minimal change disease Focal segmental glomerulosclerosis (FSGS) Membranous nephropathy - Seconadry Diabetic nephropathy Amyloidosis 2. Active sediment (RBC/WBC/cast) - Primary Membranoproliferative GN MCD variants (e.g. IgM nephropathy, C1q nephropathy) - Secondary Lupus nephritis Cryoglobulinemia General management • Monitor: I/O, vitals, BW daily (aim 1kg/day loss), urine dipstick • Anti-edema: Low sodium diet + fluid restriction + diuretics o High dose frusemide +/- thiazide/ spironolactone • Anti-proteinuric drugs (ACEI/ARB): for all glomerulopathies - decrease glomerular pressure, decrease rate of GFR decline • Statins: if hyperlipidemia persists after Tx • DVT prophylaxis: compressive stockings ± anticoagulation if high risk • Investigations: refer to above for details o Children: steroid trial (90% MCD); renal biopsy if atypical features or failed response to steroid o Adults: immunological screen, renal biopsy (unless diagnosis obvious e.g. DM nephropathy, PLA2R+) • Management of complications 1. Resistant oedema/ anasarca - Causes: Poor drug/ diet compliance Frusemide malabsorption due to gut wall oedema - Mx: Change to IV frusemide Add thiazide/ potassium-sparing diuretics IV albumin 2. AKI - Hypovolaemia due to over-diuresis ATN Crescentic transformation (RPGN) - Lower dose/ withhold diuretics Rehydration 3. Renal vein thrombosis - Hypercoagulability by compensatory production of clotting factors by liver - Doppler USG, CT angiography If AKI: thrombolysis ± embolectomy If non-AKI: LMWH/UFH —> warfarin for minimum 6-12 months while still nephrotic 4. SBP (only in child) - Loss of Ig - Antibiotics 5. CV disease - Long-term complications - CV risk modifications Clinical course • Steroid dependent: 2 consecutive relapses during tapering of steroids / within 14 days of cessation • Steroid resistant (10%): persistent proteinuria despite full-dose prednisolone x 4 weeks Specific diseases 1. Minimal change disease (MCD) - MC cause in children - Causes: Idiopathic (MC) Haematological neoplasms (e.g. HL, NHL) Drugs: NSAID, COX2 - Presentation: Nephrotic - Lab finding: LM normal EM podocyte effacement IF -ve - Mx 1st line: high dose prenisolone (1mg/kg) x 4-8 weeks 2nd line: cyclophosphamide, cyclosporine Resistant: repeat renal Bx 2. Membranous nephropathy - MC cause in adult - Causes: 1°: a/w anti-PLA2R 2°: - SLE, RA - Infections: HBV/HCV, syphilis - Malignancy: adenoCA (lung, prostate, GIT) - Drugs: captopril, gold, penicillamine - Presentations: Nephrotic Prognosis: 1/3 remit, 1/3 remain nephrotic, 1/3 progress to ESRD - Lab findings: Anti-PLA2R LM: diffuse GBM thickening EM: subepithelial electron-dense deposits (spike and dome) IF: granular staining - IgG/C3 - Mx: Primary: Observation (low risk), immunosuppressant (high risk) - poor RFT: High dose steroid +CyP (+Mesna to prevent haemorrhaging cystitis+ PCP prophylaxis) - Good RFT: rituximab Secondary: treat underlying cause 3. Focal segmental glomerulosclerosis - Causes: 1° 2°: Analgesic nephropathy, heroin, HIV, HBV - Presentations: 1°: nephrotic —> progress to ESRD 2°: non-nephrotic - Lab findings LM: segmental sclerosis EM: podocyte effacement Mx: 1°: steroids (poor response) —> cyclosporine 2°: steroids not helpful, treat underlying cause 4. Membranoproliferative GN - Causes: Viral: HBV, HCV Autoimmune: SLE, RA, scleroderma - Presentations: 70% Nephrotic 30% Nephritic Mixed nephrotic/nephritic - Lab findings: LM: GBM mesangial thickening - Mx: Treat underlying cause Idiopathic MPGN: Steroid +/- Cyclophosphamide (if dRFT) 5. Amyloidosis - Causes: MM, malignancy Inflammatory: TB, RA - Presentations: Nephrotic, POEMS syndrome - Mx: treat underlying cause

Answer 10

Definition of nephritic syndrome / acute glomerulonephritis Acute onset of glomerular inflammation • Glomerular haematuria • Variable proteinuria (usually non-nephrotic) • Variable renal impairment: azotemia (urea, Cr), fluid retention (HT, APO), oliguria 1. IgA nephropathy - S/S: IgAN (variable) • Recurrent synpharyngitic haematuria (gross haematuria within 1-2 days of URTI) • Microscopic hematuria • Nephrotic syndrome • RPGN - Lab findings: Blood: increase IgA (50%) Renal biopsy: MEST criteria (mesangial hypercellularity, endocapillary hypercellularity, segmental glomerulosclerosis, tubular atrophy) - Mx: Tight BP control & proteinuria: diet, ACEI/ARB, monitor Q6-12m Immunosuppressants only if • Proteinuria >1g/day despite ACEI • Crescentic GN (as below) Regimen: steroids ± cyclophosphamide/azathioprine 2. Henoch-Schonlein purpura - S/S: Systemic vasculitis “FA GASP”: Fever, arthralgia, GN, colicky abdominal pain, skin rash, periarticular edema -Mx: Self-limiting, analgesia with NSAIDS GI bleed / intussusception: steroids 3. Post-strep GN - S/S: 7-10 days after strep throat / impetigo Variable: asymptomatic haematuria to full blown nephritic Sx / RPGN - Lab findings: Decrease C3 (normalise by 4 weeks; persist —> consider lupus nephritic / MPGN) - Mx: Ix: ASOT, throat swab Self resolved Penicillin V if active strep throat No need prophylactic Abx 4. Anti-GBM disease (Good-pasture’s syndrome if lung involved) - S/S: RPGN +/- Pulmonary haemorrhage (SOB, cough, haemoptysis) - Lab findings: Anti-GBM +ve CXR DLCO IF: linear - Mx: IV pulse MP x 3 days + oral prednisone +/- cyclophosphamide / IV rituximab +/- plasma exchange Crescentic / Rapidly progressive glomerulonephritis (RPGN) • Clinical syndrome but NOT a specific etiology of GN – can be caused by all types of GN (except MCD) o Haematuria, proteinuria and decrease RFT that leads to ESRD within 2 weeks of onset if untreated • Histology: >50% glomeruli with crescent • Classified based on IF staining pattern (refer to above figure) o Type I (linear IF): anti-GBM o Type II (granular IF): immune complex-mediated o Type III (negative IF): pauci-immune, usually ANCA +ve • Management: usually require IV pulse steroids ± other immunosuppressants (e.g. cyclophosphamide, rituximab) o Plasma exchange for fulminant MPA / GPA or Goodpasture’s syndrome Hereditary nephritis • Alport syndrome: XR mutation in COL4A5 (Type IV collagen), present as asymptomatic hematuria and bilateral SNHL (Ix: pure tone audiogram) • Thin basement membrane disease: heterozygous AD mutation in COL4A3/4

Answer 11

Definition • Inflammatory infiltrates affecting primarily the renal interstitium and tubular cells 1. Acute tubular necrosis - Decline in RFT in mins - Aetiology: Ischaemic: progression of prerenal failure Nephrotoxins: paracetamol, AG, contrast 2. Acute interstitial nephritis (AIN) - Decline in RFT in days - Classical triad: fever + eosinophilia + rash - Aetiology: Drugs: antibiotics (esp. penicillin), NSAID Infection: bacterial pyelonephritis Inflammation: SLE, Sjogren's syndrome 3. Chronic interstitial nephritis (CIN) - Decline in RFT in weeks - Aetiology: Drugs: analgesics (NSAID, paracetamol), cisplatin Urinary tract obstruction: reflux nephropathy Radiation Inflammation: TB, GPA, sarcoidosis

Answer 12

Aetiology • Atherosclerosis • Takayasu's arteritis (common in Asia) • Fibromuscular dysplasia Possible presentations • Secondary/ resistant hypertension with hypokalemia (hyperreninaemia) • Multiple episodes of flash pulmonary oedema • AKI (esp. after ACEI) Investigations • Screening: duplex doppler USG • Confirmatory: angiogram (renal/ CTA/ MRA) Management • Medical: antihypertensive (avoid ACEI), CV risk reduction (aspirin) • Radiological: angioplasty +/- stenting • Surgical: grafting

Answer 13

• Incidence: 1/400 to 1/1000 • Genetics: Autosomal dominant, 100% penetrance, variable expressivity - PKD1 gene (Chr 16): polycystin 1 (85%) -> More severe: more renal cysts, poorer prognosis - PKD2 gene (Chr 4): polycystin 2 (15%) Less severe: later onset of cysts / ESRD • Pathogenesis: Ciliopathy —> Progressive formation of epithelial-lined cysts in kidney • Differential diagnoses: multiple renal cysts, acquired cystic disease (long-term dialysis), TSC, VHL Clinical features Renal S/S • Bilateral ballotable kidneys • Flank pain: cyst complications / stones • Haematuria: cyst haemorrhage • UTI: cyst infections • Frequency / urgency / nocturia: loss of urinary concentrating ability • RCC: NOT more common, but more likely bilateral and more difficult to diagnose Extra-renal cysts • Polycystic liver disease (MC): esp. women with multiple pregnancies • Pancreatic cysts (5%) • Seminal vesicles Cardiac S/S • Mitral valve prolapse (30%) • Aortic regurgitation: aortic root dilation • Young-onset hypertension Vascular S/S • Berry aneurysm: may cause SAH • Aortic dissection Other S/S • Respiratory: bronchiectasis • GI: diverticular diseases, ventral hernia Investigations • Bloods: CBC D/C, LFT, RFT • Urine: dipstick (haematuria, seldom proteinuria), osmolarity (aim <280), PCr • Imaging: o USG if asymptomatic o CT/MRI if palpable kidneys / decrease eGFR: more sensitive than USG, MRI preferred if eGFR < 60 - Allow measure of height-adjusted total kidney volume (htTKV) • ± Genetic testing (if imaging equivocal) • ± Detection of complications o Echocardiogram o MRI angiography for aneurysm screening (indicated if symptomatic, PMHx/FHX of stroke, high-risk OT, high-risk occupations) Diagnostic criteria • Positive family history + imaging-based criteria (age-dependent: frequency of simple renal cyst with age) o Example: Ravine USG criteria for PKD1 - Age 15-29 ≥ 2 renal cysts (totally) - Age 30-59 ≥ 2 renal cysts in each kidney - Age ≥ 60 ≥ 4 renal cysts in each kidney • No family history: no established imaging-based criteria o ≥ 10 cysts, each ≥5mm, in each kidney: support Dx of ADPKD o Genetic testing should be performed Prognostic tools • Mayo’s classification: o Typical (bilateral diffuse cysts) vs Atypical (unilateral / asymmetric / parenchymal artrophy) o Further divide into Class 1A-1E based on age, eGFR, rate of htTKV • Pro-PKD score: estimate median age of ESRD onset Management • Screening in family members ≥20y • Na restriction (<2g/day) • Encourage fluid intake (unless ESRD): suppress ADH —> inhibit cyst growth o Maintain UOsM ≤ 280 • Analgesics for flank pain • BP control by ACEI/ARB o Target: 110/75 (if 18-50yo & eGFR > 60), otherwise 130/80 • Treat CKD: renal diet, treat hyperPO4, low threshold for statins • Treat complications o Cyst infection: lipid-soluble antibiotics (e.g. quinolones, vancomycin) for cyst penetration o Cyst haemorrhage: bed rest, analgesics, segmental arterial embolization if severe • Disease-modifying agent: tolvaptan (V2 receptor antagonist) [TEMPO, REPRISE] o Rationale: vasopression bind to V2R à—> stimulate cAMP —> stimulate cyst growth via fluid secretion & cyst cell proliferation o Indications: Mayo Class 1C-1E + eGFR ≥ 25 o C/I: liver impairment, concurrent use of CYP3A4 inhibitors (e.g. azoles)

Nephrology Flashcards

(37 cards)