70 Glomerulopathies SPECIFIC ENTITIES (CONT’D) SPECIFIC ENTITIES (CONT’D) before until h after contrast exposure; (3) IV N acetylcysteine 150 mg/kg in 500 mL 0.9% NS given 30 before contrast exposure, followed by 50 mg/kg in 500 mL 0.9% NS IV given over h after (alternatively, N acetylcysteine 600 mg PO BID on day of and day after contrast exposure) Acute Renal Failure: Post-renal DIFFERENTIAL DIAGNOSIS INVESTIGATIONS (CONT’D) URETHRA stricture, stenosis PROSTATE BPH, prostatitis, cancer BLADDER cancer, stones, clots, neurogenic URETERS (bilateral involvement) INTRALUMINAL cancer, stones, clots, papillary necrosis EXTRALUMINAL cancer, retroperitoneal fibrosis, pregnancy SPECIAL INVESTIGATIONS BASIC LABS CBCD, lytes, Cr/urea, urinalysis U/S abd/pelvis IMAGING - POST RESIDUAL VOLUME obstruction CT ABD/KUB/IVP >200 mL suggests if suspect stones or tumors DIURESIS RENOGRAPHY OR UROGRAPHY DIAGNOSTIC ISSUES RENAL U/S hydronephrosis suggests post renal causes However, retroperitoneal fibrosis and acute post renal obstruction may not show hydronephrosis MANAGEMENT TREAT UNDERLYING CAUSE Foley catheter For BPH (tamsulosin 0.4 mg PO daily or TURP) RENAL REPLACEMENT dialysis (peritoneal, hemo dialysis) Glomerulopathies PATHOPHYSIOLOGY OF GLOMERULOPATHIES AUTOIMMUNE PHENOMENON antibodies binding to structural components of glomeruli (more glomerular basement membrane and podocytes involvement in nephrotic syndrome, more mesangium and endothe lium involvement in nephritic syndrome), circulating antigen antibody complexes, and/or cell mediated PATHOPHYSIOLOGY OF GLOMERULOPATHIES (CONT’D) immunity ! further immune activation and damage to glomeruli PATHOLOGY TERMS focal=50% of glomeruli, segmental=segment of glomerulus, global=entire glomerulus CLINICAL FEATURES CLINICAL MANIFESTATIONS OF GLOMERULAR DISEASES Clinical manifestation Examples Asymptomatic proteinuria FSGS, mesangial proliferative GN, diabetic nephropathy Nephrotic syndrome MCD, FSGS, MGN, MPGN, amyloidosis, light chain deposition disease, diabetic nephropathy Asymptomatic hematuria Thin basement membrane disease, IgA nephropathy, Alport’s syndrome Recurrent gross hematuria Thin basement membrane disease, IgA nephropathy, Alport’s syndrome Acute nephritis Post infectious GN, IgA nephropathy, lupus nephritis, MPGN Rapidly progressive glomerular See text nephritis (RPGN) Pulmonary renal syndrome Antiglomerular basement membrane antibody disease, immune complex vasculitis, pauci immune (ANCA) vasculitis Chronic renal failure Sclerosed glomerular disease 71 Glomerulopathies CLINICAL FEATURES (CONT’D) DISTINGUISHING FEATURES BETWEEN NEPHROTIC AND NEPHRITIC SYNDROMES Nephrotic Nephritic Onset Slower Faster Edema ++++ ++ Blood pressure N/# " Volume/JVP N/# " Proteinuria >3 g/day May be 3 g/day without other symptoms and signs) NEPHROTIC SYNDROME DIFFERENTIAL DIAGNOSIS minimal change dis ease, membranous GN, focal segmental glomerulo sclerosis, membranoproliferative GN, diabetes, amy loidosis, IgA nephropathy, HIV, drug associated (NSAIDs, gold, pamidronate) CLINICAL FEATURES proteinuria (>3 g/day), edema, hypoalbuminemia, hyperlipidemia, lipiduria, hypercoagulopathy INVESTIGATIONS CBCD, lytes, urea, Cr, 24 h urine for protein and Cr, spot urine protein/Cr ratio, renal biopsy (simplification/effacement of visceral podocyte foot processes, classically non inflammatory) POOR PROGNOSTIC FACTORS male, age >50, " creatinine, proteinuria >10 g/day, proteinuria >6 months, hypertension TREATMENTS Na restriction, blood pressure control, ACE inhibitor, treatment of dyslipidemia, steroid, cyclophosphamide, anticoagulate if high risk COMPLICATIONS ARF/hypovolemia, malnutrition, hyperlipidemia, infections (especially encapsulated bacteria), arterial/venous thrombosis (30 40%), renal vein thrombosis, edema NEPHRITIC SYNDROME DIFFERENTIAL DIAGNOSIS membranoprolifera tive GN (type 2), rapidly progressive/crescentic GN (aGBM, immune, pauci immune), IgA nephropathy CLINICAL FEATURES hematuria, proteinuria, hypertension INVESTIGATIONS CBCD, lytes, urea, Cr, ANA, anti dsDNA, ENA, p anca, c anca, anti GBM, C3, C4 (com plements low except for IgA nephropathy), CK, uric acid, ASO titer, HBV serology, HCV serology, cryoglo NEPHRITIC SYNDROME (CONT’D) bulin, quantitative Ig, serum protein electrophoresis, renal biopsy TREATMENTS steroid, cyclophosphamide, myco phenolate mofetil SPECIFIC ENTITIES MINIMAL CHANGE DISEASE (MCD) PATHOPHYSIOLOGY T cell abnormality ! " glo merular permeability CAUSES primary, secondary (NSAIDs, Li, interferon, NHL, Hodgkin’s, leukemia, HIV, mononucleosis) CLINICAL FEATURES pure nephrotic (minimal hematuria, no RBC casts, creatinine not elevated) PATHOLOGY light microscopy (normal), immuno fluorescence (no immune complexes), electron microscopy (effacement of podocyte foot processes) TREATMENTS steroid, cyclophosphamide, cyclosporin PROGNOSIS 90% steroid responsive, 10% steroid resistant, end stage renal disease rare MEMBRANOUS GN (MGN) CAUSES primary, secondary (gold, penicillamine, captopril, solid tumors including breast, colon, and lung, Hodgkin’s, SLE, rheumatoid arthritis, autoim mune thyroiditis, syphilis, HBV, HCV, chronic trans plant rejection) CLINICAL FEATURES pure nephrotic (minimal hematuria, no RBC casts) PATHOLOGY light microscopy (basement mem brane thickening, spikes), immunofluorescence (immune complexes IgG, and complements in sub epithelial space), electron microscopy (same as immunofluorescence) TREATMENTS steroid, cyclophosphamide, cyclo sporin 72 SPECIFIC ENTITIES (CONT’D) 40% remission, 30% stable, 30% end stage renal disease over 10 20 years FOCAL SEGMENTAL GLOMERULOSCLEROSIS (FSGS) (more severe form of MCD) CAUSES primary, secondary (Li, heroin, lympho mas, HIV May also be associated with sickle cell disease, hypertension, and obesity) CLINICAL FEATURES pure nephrotic (minimal hematuria, no RBC casts) PATHOLOGY light microscopy (segmental areas of sclerosis), immunofluorescence (no immune com plexes), electron microscopy (effacement of podo cyte foot processes) TREATMENTS steroid, cyclophosphamide, cyclo sporin PROGNOSIS large percentage with end stage renal disease over 15 20 years MEMBRANOPROLIFERATIVE GN (MPGN) PATHOPHYSIOLOGY type = immune complex deposition disease Type = activation of comple ment system via C3 nephritic factor (IgG against C3 convertase), with decreased C3 and normal C4 CAUSES primary, secondary type (HCV, HBV, endocarditis, abscess, infected shunts, CLL, lym phomas, SLE, cryoglobulinemia), secondary type (partial lipodystrophy, sickle cell, complement deficiency) CLINICAL FEATURES 50% nephrotic (usually type 1), 20% asymptomatic proteinuria/hematuria, 30% acute nephritic (usually type 2) PATHOLOGY light microscopy (basement mem brane thickening, mesangial cell hypercellularity), immunofluorescence (complements along capil lary walls), electron microscopy (type shows dis crete deposits in mesangium, type shows depos its as continuous ribbon in glomerular basement membrane) TREATMENTS steroid, cyclophosphamide, cyclo sporin PROGNOSIS 40 75% end stage renal disease over 10 15 years RAPIDLY PROGRESSIVE GN (RPGN) ANTI GLOMERULAR BASEMENT MEMBRANE ANTIBODY DISEASE PATHOPHYSIOLOGY antibody against a3 chain of type IV collagen CAUSES Goodpasture’s syndrome, anti GBM anti body nephritis CLINICAL FEATURES nephritic (hematuria, protei nuria, ARF) Goodpasture syndrome also has lung PROGNOSIS Glomerulopathies SPECIFIC ENTITIES (CONT’D) involvement whereas anti GBM antibody nephritis affects kidney alone PATHOLOGY immunofluorescence (linear staining) TREATMENTS plasmapheresis with IV pulse ster oids followed by PO steroids with PO cyclopho sphamide for year RAPIDLY PROGRESSIVE GN (RPGN) IMMUNE COMPLEX PATHOPHYSIOLOGY deposition of circulating immune complex in glomeruli, usually in suben dothelial location CAUSES SLE, HBV, HCV, endocarditis, post strep GN, post infectious GN, IgA nephropathy, cryoglo bulinemia, shunt nephritis CLINICAL FEATURES nephritic (hematuria, protei nuria, ARF) PATHOLOGY immunofluorescence (granular staining) TREATMENTS IV pulse steroids followed by PO ster oids with IV monthly cyclophosphamide for year RAPIDLY PROGRESSIVE GN (RPGN) PAUCI IMMUNE COMPLEX CAUSES Wegener’s (c anca), microscopic polyan giitis (p anca), Churg Strauss CLINICAL FEATURES nephritic (hematuria, protei nuria, ARF) May have lung involvement PATHOLOGY immunofluorescence (no staining) TREATMENTS IV pulse steroids followed by PO steroids with PO cyclophosphamide for year IGA NEPHROPATHY PATHOPHYSIOLOGY abnormal regulation of produc tion or structure of IgA in response to environmental antigens ! illness triggers production of IgA and/or IgA immune complex ! deposit in mesangium CAUSES primary, secondary (HSP, celiac disease, dermatitis herpetiformis, cirrhosis, HIV, malignan cies, seronegative spondyloarthropathies) CLINICAL FEATURES 50% recurrent macroscopic hematuria with URTI, 30 40% persistent microhe maturia and proteinuria, 10% rapidly progressive renal failure, 3 months of abnormal renal function, suggests irrever sible component CLASSIFICATION OF CHRONIC KIDNEY DISEASE STAGE I (GFR 90 100 mL/min/1.73 m , protei nuria) observe, consider ACE inhibitor STAGE II (GFR 60 90 mL/min/1.73 m ) consider ACE inhibitor, nephrology referral STAGE III (GFR 30 60 mL/min/1.73 m ) nephrol ogy referral STAGE IV (GFR 15 30 mL/min/1.73 m ) consider renal replacement therapy (dialysis or transplantation) STAGE V (GFR 3 months of elevated creatinine suggests CKD), 74 DIAGNOSTIC ISSUES (CONT’D) anemia, small kidneys from renal U/S (except dia betes, amyloidosis, acromegaly, renal vein thrombo sis, HIV nephropathy), renal osteodystrophy are all consistent with CKD Renal biopsy is also helpful MANAGEMENT SLOW PROGRESSION 0.8 g/kg/day ACE INHIBITION blood pressure and proteinuria control (ramipril 1.25 10 mg PO daily) LIMIT PROTEIN INTAKE LIPID CONTROL AVOID NEPHROTOXINS SMOKING CESSATION Proteinuria TREATMENT ISSUES (CONT’D) ACE INHIBITORS IN RENAL FAILURE ACE inhibi tion leads to vasodilation of efferent arterioles ! # intraglomerular pressure ! # long term remodeling/ stress ! slow progression of chronic kidney disease Other positive effects of ACE inhibition include # blood pressure, # proteinuria, and # mediators of glomerular tubule hypertrophy and fibrosis Should start in all patients with chronic kidney disease Ỉ hypertension Ỉ proteinuria If 5.5 mmol/L) low potassium diet, hydrochlorothiazide 12.5 mg PO daily, kayex alate 30 g PO daily QID, decrease ACE inhibitor METABOLIC ACIDOSIS consider NaHCO3 if low pH or HCO3 ANEMIA (Hb