Pocket Medicine

NEPHROLOGY

GLOMERULAR DISEASE

GLOMERULONEPHRITIS (GN)

Definition (NEJM 1998;339:888; Lancet 2005;365:1797)

•  Pathologically: intraglomerular inflammation (ranging from focal proliferative [<50% of glomeruli] to diffuse proliferative to crescentic) (Lancet 2006;368:404)

•  Clinically: hematuria w/ dysmorphic RBCs or RBC casts, ± subnephrotic proteinuria

often w/ renal failure, HTN, edema

•  Progression: acute GN  days; rapidly progressive GN (RPGN)  wks; chronic GN  mos; can simply have asx hematuria

•  Crescentic GN (pathologic description)  RPGN (clinical description)

Workup (Archives 2001;161:25)

•  Acute GN/RPGN ± lung hemorrhage is an emergency → requires early Dx and Rx

•  ANCA (Lancet 2006;368:404), anti-GBM, complement levels

•  Depending on clinical hx: ANA, ASLO, BCx, cryocrit, hepatitis serologies, skin bx

•  Consider GN mimics

thrombotic microangiopathy: ↓ Hct & Plts, schistocytes on smear, ↑ LDH cholesterol emboli (Lancet 2010;375:1650): purple toes, livedo, ↓ C3/C4, eos, prior cath AIN: rash, new drug exposure, urine WBCs (incl eos) ± WBC casts (and  UCx) myeloma: anemia, hypercalcemia, lytic bone lesions,  SPEP/serum free light chains

•  Renal biopsy with immunofluorescence (IF) ± electron microscopy (EM)

Figure 4-8 Approach to glomerulonephritis

Treatment (Kid Int Sup 2012;2:143)

•  If acute GN/RPGN suspected, give 1 g methylprednisolone IV qd x 3 d ASAP while awaiting bx results, further Rx based on underlying disease (AJKD 1988;11:449)

•  SLE nephritis: steroids + cyclophosphamide (CYC) or MMF (JASN 2009;20:1103)

•  ANCA  or anti-GBM: pulse steroids + CYC (or rituximab) ± plasmapheresis (JASN 2007;18:2180; NEJM 2010;363:221)

•  See “Vasculitis” for further disease specific treatment details

ASYMPTOMATIC GLOMERULAR HEMATURIA

Definition and etiologies

•  Hematuria ± proteinuria of glomerular origin w/o renal insufficiency or systemic disease (nonglomerular hematuria more common; see “Hematuria”)

•  Ddx: any cause of GN (esp. IgA); also consider Alport’s (X-linked, deafness, renal failure), thin basement membrane nephropathy (autosomal dominant, benign; JASN 2006;17:813)

IgA nephropathy (NEJM 2002;347:738; JASN 2005;16:2088)

•  Most common cause of GN; male predominance w/ peak incidence 20–30s

•  Wide range of clinical presentations: asx hematuria (30–40%), gross hematuria ~1–3 d after URI (30–40%), chronic GN (10%), nephrotic syndrome (5%), RPGN (<5%)

•  Though clinical presentation can be highly suggestive, definitive dx only w/ bx

•  Prognosis: 25–30% will reach ESRD w/in 20–25 y of presentation

•  Treatment: ACEI/ARB, ± fish oils (JASN 1999;10:1772); steroids (JASN 2012;23:1108); ± cytotoxic therapy for crescentic GN and nephrotic sx, consider for progressive chronic GN

NEPHROTIC SYNDROME

Definition (NEJM 1998;338:1202)

•  Proteinuria >3.5 g/d, albumin <3.5 mg/dL, edema, ↑ cholesterol

Primary glomerular diseases (grouped by pathology)

•  Focal segmental glomerulosclerosis (40%; NEJM 2011;365:2398;): 1º (? ↑ soluble urokinase receptor; Nat Med 2011:17;952), HIV (collapsing variant), NSAIDs, lymphomas, pamidronate, heroin, congenital, ↑ filtration from prior nephron loss, obesity, vesicoureteral reflux, anabolic steroids, genetic (trypanolytic ApoL1 mutation in AA; Science 2010;329:841)

•  Membranous nephropathy (30%; JASN 2012;23:1617) idiopathic (phospholipase A2 receptor Abs; NEJM 2009;361:11), infxn (esp. HBV, also HCV, syphilis), autoimmune (esp. SLE), carcinomas, drugs (NSAIDs, penicillamine)

•  Minimal change disease (20%, more common in children; NDT 2003;18:vi52) idiopathic, NSAIDs, Hodgkin’s disease, & other lymphoproliferative disorders

•  Membranoproliferative GN (5%, mixed nephrotic/nephritic features; NEJM 2012;366:1119) Immune complex-mediated: infection (esp. HCV ± cryos, IE, HBV, “shunt” nephritis, other chronic infxns), SLE, cryos, Sjögren’s, lymphomas, dysproteinemia, idiopathic Complement-med (rare); abnl C3 convertase activity, dense deposit dis, C3GN

•  Fibrillary-immunotactoid glomerulopathy (1%; Kid Int 2003;63:1450)

•  Mesangial proliferative GN (? atypical forms of MCD/FSGS, 5%) IgM, C1q nephropathy

Systemic diseases

•  Diabetes mellitus: nodular glomerulosclerosis (Kimmelstiel-Wilson lesion); large kidneys hyperfiltration → microalbuminuria → dipstick  → nephrotic range (10–15 y) concomitant proliferative retinopathy seen in 90% of type 1 and 60% of type 2

•  Amyloidosis: AL or light chain amyloid or AA amyloid secondary to inflammation

•  SLE: typically with membranous nephropathy (WHO class V)

•  Cryoglobulinemia: typically with membranoproliferative GN

Workup (Archives 2001;161:25; BMJ 2008;336:1185)

•  Urine sediment: usually benign; ± oval fat bodies (“Maltese crosses”; NEJM 2007;357:806)

•  Measure proteinuria: 24-h urine collection or urine prot/Cr ratio (not accurate in AKI)

•  r/o 2° causes: ↑ HbA1C + retinop. → presumpt. dx of diab. nephrop.; ✓ ANA, anti-dsDNA, C3/C4, SPEP/free light chains, fat pad bx, cryocrit, HBV/HCV, HIV, RPR, PLA2 recept. Ab

•  Renal biopsy

Treatment (Kid Int Sup 2012;2:143; NEJM 2013;368:10)

•  General: protein suppl.; diuretics for edema; treat hyperlipidemia, Na restriction (<2 g/d)

•  ACEI/ARB: decrease proteinuria → slow nonimmunologic progression of renal disease

•  1° glomerular dis: steroids ± cytotoxic therapy; cancer screening if membranous neph.

•  Secondary causes: treat underlying disease

•  Watch for malnutrition (protein loss), thrombosis (in ~25%, esp. renal vein, b/c loss of ATIII & other endogenous anticoags), infxn (esp. encaps. organisms b/c loss of Ig)