Note: the following material is for personal use only see below for
Download 3.95 Mb.
|
ARF in AIDS patients (one study)Causes: ATN/Sepsis, HUS/TTP (TMA-like) > HIV meds (indinavir) > rhabdomyolysis (from IVDA) > lymphoma > HIVAN (13:1 M:F, avg. 8 months of HIV) > HBV/HCV > SLE-like Tumor Lysis Syndrome esp. important with lymphoproliferative malignancies; usually 1-3 after starting chemo but may occur spontaneously (Burkitt’s, acute B-cell lymphoblastic leukemia) Risk factors: large tumor burden, high LDH, not being on allopurinol
urinary uric acid:urinary creatinine ratio > 1 (normal < 0.60-0.75) supports uric acid nephropathy (higher than in rhabdo where urate is elevated but itself does not cause nephropathy) PO4 usu. elevated but may not be in spontaneous TLS (because tumor cells can incorporate it) ↑ lactic acid, ↑K, ↓Ca Treatment: volume repletion / consider dialysis when uric acid reaches 15-20 / can also give uricase to metabolize uric acid to allantoins (should have already given allopurinol) / phosphate binders can be given / alkalinization of urine not proven to prevent tubular damage from urate crystals (may increase CaPO4 precipitation as well and further decrease Ca levels) Rhabdomyolysis (see other) Atheroembolic Syndrome (see cardiac) cause of renal failure Hepatorenal failure (see liver) Note: almost never see without CNS signs Drug-Induced Nephrotoxicity Prerenal Renal Postrenal Drug-induced acid/base abnormalities 20% of ARF is drug-related Prerenal (due to drug effect) ↑ serum Cr at least 0.5 mg/dL over 24 hours / FeNa < 1%, Uosm > 500, benign sediment Causes: diuretics, NSAIDs, ACE inhibitors, IV contrast, tacrolimus vasoconstriction IL-2 volume depletion from capillary leak cyclosporine vasoconstriction of afferent/efferent arterioles decreases GFR mannitol > 300 g can cause prerenal failure
CRF, DM, volume depletion, and MM predispose to IV contrast toxicity Renal protection protocol: Mucomyst (600 mg bid prior to administration) and IV fluids plus aminophylline 5 mg/kg during contrast administration Aminoglycosides reabsorption by pinocytosis can increase half-life over 100 hours (normal 3 hours) / Treatment is primarily supportive Amphotericin B 1) decreases renal blood flow because of acute renal vasoconstriction in a dose-dependent manner (causes ATN) 2) direct tubular injury in cumulative doses exceeding 2 to 3 g / classic distal RTA, concentrating defects (it punches holes in the membrane), and potassium wasting / usually nonoliguric and reversible on discontinuation
up to 50% get enzymuria, Mg and K wasting (Medstudy says only K, not Mg), and ATN / urine output of at least 100 mL/hr decreases risk
lovastatin, ethanol, codeine, barbiturates, diazepam (elevated CPK, brown casts) Severe hemolysis quinine, quinidine, sulfonamides, hydralazine, triamterene, nitrofurantoin, mephenytoin Acute interstitial nephritis (AIN) penicillins, cephalosporins, rifampin, sulfonamides, thiazide, cimetidine, phenytoin, allopurinol, cytosine arabinoside, furosemide, interferon, NSAIDs, ciprofloxacin Findings: fever, rash, arthralgias, eosinophilia, renal failure (may be absent in 30%) UA shows pyuria, WBC casts, eosinophiluria / nephrotic range/proteinuria with NSAIDs Note: above findings Treatment: steroids may* speed recovery in aggressive AIN NSAID nephritis (esp. fenoprofen and mefenamate) / nephrotic range proteinuria (80%), minimal change disease (10%), membranous nephropathy (rare) / signs of hypersensitivity often absent due to anti-inflammatory action, FeNa often < 1%, *steroids are not beneficial for NSAID nephritis (and some say not for other AIN either) HUS (see other) afferent arteriolar thrombosis Cyclosporine, mitomycin C, cocaine, tacrolimus, conjugated estrogens, quinine, 5-fluorouracil
Causes: gold, penicillamine, captopril, NSAIDs, mercury Findings: edema, moderate to severe proteinuria, hematuria, RBC casts (sometimes) / nephrotic range proteinuria esp. in penicillamine, gold and captopril (rare) / complete resolution may take up to several years (esp. gold)
Acyclovir ( > 500 mg/m2), MTX, sulfonamides (only at super high doses), ethylene glycol, high-dose vitamin C Findings: urine sediment can be benign, or if severe can cause an ATN-like sediment
Phenacetin, NSAIDs, acetaminophen, aspirin, cyclosporine, FK-506, lithium Findings: history of long-term medication use
B-blockers (pindolol, atenolol), migraine meds (ergotamine, dihydroergotamine), methysergide, hydralazine, methyldopa Findings: usually benign urine sediment, ultrasound reveals hydronephrosis
substantial ( < 20% normal) and irreversible reduction in renal function Major causes: DM >> HTN (20%), tubulointerstitial (7%), APKD (5%) Prerenal: severe, long-standing renal artery stenosis and bilateral renal arterial embolism Renal: chronic glomerulonephritis, chronic TIN, Alport’s, SLE, diabetes, amyloidosis, HTN, cystic diseases, neoplasia, and radiation nephritis Postrenal: chronic urinary obstruction Complications: normochromic normocytic anemia, renal osteodystrophy (via PTH), metabolic acidosis, malnutrition, decreased immunity, HTN, dyslipidemia, LVH, neuropathy Electrolyte imbalances (hypocalcemia, hyperkalemia, hyperphosphatemia) Treatment: provide supplemental 1,25-D3, CaCO3 (binds intestinal phosphate and provides Ca) Uremia CNS: lethargy, somnolence, confusion, and neuromuscular irritability (gradual or abrupt) CVS: HTN, CHF, pericarditis (can be abrupt) GI: anorexia, N/V (very common) Bones: pain from secondary hyperparathyroidism Other: fatigue, pruritis, and sleep disturbances Uremic Immunodeficiency T-cell abnormalities (lymphopenia), reduced response to vaccination Other Complications: Hematologic: chronic anemia (from reduction in erythropoietin and mildly reduced red cell half-life) and bleeding CVS: HTN, pericarditis, cardiomyopathy, arrhythmias, and CHF CNS: generalized seizures, confusion, lethargy, emotional lability, myopathy, peripheral neuropathy, and syndromes related to nerve compression (carpal tunnel) GI: ulcers, gastroduodenitis, colitis, angiomas Endocrine: secondary hyperparathyroidism, euthyroid hypothyoxinemia, hyperprolactinemia, bad GnRH axis (amenorrhea, impotence), gynecomastia Immune: lymphocytopenia, anergy, increased anticomplement activity, abnormal monocyte motility Metabolic: renal osteodystrophy (osteitis fibrosa and osteomalacia) and altered drug-metabolism Treatment: Meds ACE inhibitors: cause mild (10 ml/min) decrease in GFR but overwhelmingly proven effective by multiple mechanisms avoid peripheral calcium blockers: used alone may speed progression of renal failure Blood pressure control: MAP of 92 (not too low, too low actually does harm) / MDRD study showed this is only helpful if proteinuria is 0.5 to 1 g/day restrict protein < 0.6 g/kg lean body weight restrict dietary sodium < 4 g/day (unless residual urine obligates greater daily losses) restrict K+, Mg2+, PO43+ and fluid intake to match daily losses pregnancy can accelerate pre-existing renal disease give vitamin D early on to decrease PTH levels (which if unchecked, speed renal damage) correct acidosis (which also contributes to renal damage) correct lipid abnormalities (for usual reasons) correct anemia with erythropoietin (ideal target level still not determined; some evidence suggests overly aggressive correction can worsen heart failure; mechanisms not completely worked out 11/06) Dialysis or transplant for clinical uremia, severe azotemia (GFR < 10 ml/min), intractable hyperkalemia or acidemia, intravascular volume overload Nephritic Glomerulopathies Findings: hematuria and/or RBC casts, variable proteinuria, oliguria, hypertension (fluid retention and disturbed renal homeostasis), azotemia, edema (salt and water retention) Immune complex diseases (some of these overlap with nephrotic section) Primary: IgA nephropathy, Anti-GBM (C3), membranoproliferative I and II (MPGN) (C4), membranous (C3) / mesangioproliferative (MSGN) / fibrillary glomerulonephritis Systemic: SLE, HCV/HBV-related cryoglobulinemia (C4), post-infectious glomerulonephritis: PSGN (C3), infective endocarditis, vasculitides (W, C-S, PAN, mPAN, HSP (IgA),) Acute Poststreptococcal GN (PSGN) follows Strep A infection (pharyngitis or skin) by 10 days (different strains from those causing RF; renal involvement not impacted by antibiotic) Presentation: hematuria, edema, proteinuria, decreased urine output, possible HTN Labs: acute phase with decreased complement (C3 more than C4) / may have (+) ASO titres Pathology: diffuse proliferation / exudative PMN’s / crescents / coarse granular immune deposits by IF/EM (sub-epithelial > sub-endothelial > intramembranous) Course: usually self-limiting / occasionally progress to RPGN or chronic latent stage (more common and less likely to produce chronic renal disease in younger patients) Treatment: B-lactam, diuretics and antihypertensives as needed, rarely steroids IgA Nephropathy or Mesangial Glomerulopathy or (Berger’s Disease) - good prognosis most common GN in the world / 15-30 yrs Presentation: similar to HSP / sore throat followed shortly with nephritic syndrome, hematuria micro (older), macro (younger) / synpharyngitic Pathology: mesangial proliferation / IgA and other deposition by IF / dense deposits in mesangium by EM Labs: elevated IgA (50%) Prognosis: good in 80% cases, more proteinuria is worse Treatment: fish oil, IVIG, CSA Goodpasture’s Syndrome (Anti-GBM) (see other) – poor prognosis Occurs in two forms young men, hemoptysis and hematuria older people (male=female) / RPGN with no lung involvement Labs: C-ANCA (+) in up to 40%, this may improve prognosis / complement usually normal Pathology: linear deposition of C3 and IgG by IF / no dense deposits by EM Treatment: immunosuppressives, plasmapheresis Cryoglobulinemia Type I - usually asymptomatic monoclonal Ig’s (usually IgM) Causes: hematologic cancers (Waldenstrom’s, myeloma, lymphoma) Manifestations: may cause MPGN Type II monoclonal IgM against polyclonal IgG (causes precipitation) / immune-complex vasculitides (50% renal involvement)
autoimmune (collagen), skin (PAN, PCT), essential mixed monoclonal/polyclonal cryoglobulinemia
vascular purpura (almost always involves lower extremities) leg ulcers – up to 8% mono / 30% poly acrocyanosis/necrosis – 15-40% urticaria – complement, mast cell livedo reticularis (1% mono / < 5% poly) Arthritis 60% poly, < 10% mono Renal disease monoclonal endomembranous deposits of precipitate polyclonal proliferative glomerulonephritis immune complex azotemia (late) Hemorrhagic Liver poly (esp. AP) GI 5-20% poly (acute abdominal pain) CNS vasculitis of vasa vasorum – up to 40% symmetric, peripheral neuropathy secondary to associated disease (amyloid, vasculitis) Sjögren’s (80% have cryoglobulinemia) Diagnosis: quantitative cryoglobulins < 2 normal / cryocrit (% cryoIg’s/serum) / SPEP / low serum complement (C4 more than C3) Treatment: avoid cold / bed rest – for ulcers / low-dose corticosteroids / IFN-alpha (60-70% response, 30% sustained) / cytotoxic agents Type III - usually no clinical significance mixed polyclonal (no monoclonal component) Causes: infections, autoimmune (SLE), liver disease (HBV, HCV), renal disease (proliferative GN), essential mixed polyclonal cryoglobulinemia Crescentic Glomerulopathy (RPGN) Immune Complex Deposition Goodpasture’s collagen vascular diseases as a potential evolution of most any other forms of GN Pauci-immune (ANCA) glomerulonephritis Wegener’s (C-ANCA, proteinase 3) microscopic polyangiitis (P-ANCA, MPO) Churg-Strauss (asthma and eosinophilia) Idiopathic RPGN (renal limited vasculitis) 50% of glomeruli involved / over weeks to months / non-specific symptoms Pathology: epithelial proliferation and capillary necrosis / IF and EM depend on etiology Course: rapidly fatal Treatment: massive IV steroids, Cytoxan Nephrotic Glomerulopathies (MCD, FSGS, MGN, MPGN) Nephrotic syndrome (see proteinuria) Minimal Change Disease (lipoid nephrosis, Nil disease) most common cause of nephrotic syndrome in children peak at 2-3 yrs, 10-12 yrs Pathology: effacement of podocytes / usually not hypertensive Cause: usu. idiopathic Drugs: NSAIDS, rifampin, IFN-a, heroin, iron dextran Other: lymphoma, HIV, IgA, diabetes, Fabry’s, sialidosis Treatment: if needed, steroids, cyclosporin, others / ?ACE inhibitors Focal Segmental Glomerulosclerosis (FSGS) 25% of adult nephropathies / common in children, young black men, association with obesity / HTN / most common idiopathic nephrotic GN in blacks Primary: typical > collapsing (blacks) > glomerular tip Secondary causes/associations: HIV, IVDA, obesity, sickle cell, congenital heart disease
(33%) / collapsing variant: more proteinuria, more ARF, viral/URI Sx from days to weeks before nephrosis Labs: low albumin (can be < 2), decreased immunoglobulins, increased lipids, normal compliment Ultrasound: normal to large echogenic kidneys Renal biopsy: shows FSGS / can be confused with hereditary nephritis, IgA nephropathy, Wegener’s / EM can diagnose these other causes Treatment: steroids 60-80 4 wks then 40-60 mg 3d/wk 4 wks then taper / alternate steroid regimens used / late relapse, more steroids / early relapse, cyclosporine or Cytoxan ACE inhibitors (yes, yes and yes) / works by inhibition of TGF-B Prognosis: variable (more proteinuria is worse), often refractory to therapy HIV nephropathy – poor prognosis 20% of hospitalized AIDS patients develop ARF / often collapsing variant with same characteristics / black males with IVDA / more on East coast / no HTN (maybe) Treatment: similar to idiopathic, ACE inhibitors may help, HIV meds ? Note: HIV patients also get RF from idiopathic, HCV, heroin, drugs, prerenal C1Q nephropathy Rare mimic of FSGS occurring mostly in young, black men Membranous Glomerulopathy (MGN) – poor prognosis most common adult idiopathic nephrotic syndrome in whites / 40-60 yrs/ men > women Pathology: thickened BM matrix and vessel walls / more mesangial proliferation with systemic causes / sub-epithelial IgG and C3 granular deposits by IF (Heyman model) / spikes alternate with deposits Secondary causes: HBV, syphilis, SLE, solid tumors (20% of MGN), thyroiditis, malaria, gold, d-penicillamine, PCN, captopril
primary or secondary forms / more in children, teenagers Pathology: increased cellularity and mesangial matrix / mesangial proliferation with duplication of the glomerular basement membrane, splitting of capillary BM (silver stain) / immune deposits and low serum compliment (C3 more than C4)
type II dense deposit disease (alternate pathway of complement) type III Burkholder subtype and Strife and Anders subtype
Findings: cryoglobulinemia, MPGN on biopsy, systemic manifestations (50%), abnormal LFT (70%), low complement (C4 more than C3) (80%), RF (70%) Treatment: plasma exchange, treat the HCV (IFN-a, etc), cytotoxic agents
infection-related (including HBV, HCV, cryoglobulinemia types II or III, endocarditis, schistosomiasis, HIV-associated) autoimmune diseases (such as class IV lupus nephritis), dysproteinemia-associated (including light chain deposition disease, amyloidosis, cryoglobulinemia types I or II, fibrillary, and immunotactoid GN) Membranoproliferative pattern but lack immune deposits diabetic nephropathy, hepatic glomerulopathy, and chronic TMA’s (HUS, TTP, APA), radiation nephritis, sickle cell nephropathy, eclampsia, and transplant glomerulopathy Renal Other hydronephrosis, mechanical, hypertension, renal artery stenosis, acid-base, RTA Download 3.95 Mb. Share with your friends:
|