Acute Kidney Injury (AKI)
Definition
AKI is defined by the KDIGO criteria as an increase in serum creatinine by ≥0.3 mg/dL within 48 hours, or ≥1.5× baseline within 7 days, or urine output <0.5 mL/kg/hr for ≥6 hours.
Classification
| Category | Causes | BUN:Cr Ratio | FENa | Urinalysis |
|---|---|---|---|---|
| Prerenal | Dehydration, hemorrhage, heart failure, sepsis, NSAIDs (reduce GFR), ACE inhibitors (bilateral RAS) | >20:1 | <1% | Normal (concentrated urine, SG >1.020, hyaline casts) |
| Intrinsic (renal) | ATN (ischemia, nephrotoxins: aminoglycosides, contrast, myoglobin), AIN (drug hypersensitivity, infection), GN | <20:1 | >2% | Muddy brown granular casts (ATN), WBC casts (AIN/pyelonephritis), RBC casts (GN) |
| Postrenal | BPH, prostate cancer, bilateral ureteral obstruction, bladder outlet obstruction, retroperitoneal fibrosis | >20:1 initially | Variable | Unremarkable unless infection; hydronephrosis on ultrasound |
🧠 Cast Mnemonic — Urinary CastsHyaline = normal/prerenal · Granular/muddy brown = ATN · RBC casts = Glomerulonephritis · WBC casts = pyelonephritis/AIN · Waxy/broad = advanced CKD · Fatty (oval fat bodies) = nephrotic syndrome
🏥 ManagementIdentify and treat cause. Stop nephrotoxic agents (NSAIDs, aminoglycosides, contrast when possible). Volume resuscitation for prerenal. Monitor electrolytes (hyperkalemia, acidosis). Indications for emergent dialysis: AEIOU — Acidosis (pH <7.1), Electrolytes (K+ >6.5 refractory), Intoxication, fluid Overload refractory, Uremic symptoms (pericarditis, encephalopathy).
Chronic Kidney Disease (CKD)
Definition & Staging
CKD is defined as kidney damage or GFR <60 mL/min/1.73m² for ≥3 months. Most common causes: Diabetic nephropathy (#1), Hypertensive nephrosclerosis (#2), Glomerulonephritis.
| Stage | GFR (mL/min/1.73m²) | Description |
|---|---|---|
| G1 | ≥90 | Normal or high GFR with kidney damage markers |
| G2 | 60–89 | Mildly decreased |
| G3a | 45–59 | Mildly to moderately decreased |
| G3b | 30–44 | Moderately to severely decreased |
| G4 | 15–29 | Severely decreased (prepare for RRT) |
| G5 | <15 | Kidney failure (ESRD) |
Complications of CKD
| Complication | Mechanism | Management |
|---|---|---|
| Anemia | Decreased EPO production by peritubular cells | ESAs (epoetin alfa, darbepoetin); iron supplementation; target Hgb 10–11.5 g/dL |
| Renal osteodystrophy | Decreased 1-alpha hydroxylase → decreased active vitamin D → secondary hyperparathyroidism → bone resorption | Phosphate restriction, phosphate binders, calcitriol, cinacalcet (for secondary/tertiary HPT) |
| Metabolic acidosis | Decreased ammoniagenesis → inability to excrete H+ | Sodium bicarbonate supplementation |
| Hyperkalemia | Decreased distal K+ secretion; reduced aldosterone responsiveness | Dietary K+ restriction; patiromer (K+ binder); loop diuretics; dialysis |
| HTN | Sodium/water retention; increased RAAS activation; decreased PGE2 | ACE-I/ARB (first-line, also reduce proteinuria), loop diuretics |
| Cardiovascular disease | Non-traditional risk factors: uremia, oxidative stress, inflammation, calcium-phosphate product | Risk factor modification, statin therapy |
🎯 Boards PearlRefer to nephrology when GFR <30 (Stage G4). Start RRT planning when GFR <20. Absolute indications for dialysis: uremic pericarditis, encephalopathy, bleeding diathesis, electrolyte/acid-base crises. ACE-I/ARB are renoprotective in diabetic nephropathy — reduce intraglomerular pressure, reduce proteinuria. Do NOT use in bilateral renal artery stenosis or pregnancy.
Nephrotic Syndrome
Definition & Hallmarks
Heavy proteinuria (>3.5 g/day) + hypoalbuminemia + edema + hyperlipidemia + lipiduria. Results from damage to the glomerular filtration barrier (podocyte/GBM injury) leading to loss of large proteins (albumin, immunoglobulins, antithrombin III, transferrin).
| Cause | Age | Mechanism | Treatment |
|---|---|---|---|
| Minimal Change Disease (MCD) | Children (#1); adults | T-cell dysfunction → podocyte injury; effacement of foot processes on EM | Prednisone (corticosteroid-responsive in 90% children) |
| Focal Segmental Glomerulosclerosis (FSGS) | Adults (Black patients) | Podocyte injury; associated with HIV, heroin, obesity, sickle cell | Corticosteroids, cyclosporine; poor prognosis |
| Membranous Nephropathy | Adults (>40) | Sub-epithelial immune complex deposits (IgG anti-PLA2R Ab); associated with HBV, SLE, malignancy, NSAIDs | ACE-I, immunosuppression; 1/3 spontaneous remission |
| Diabetic Nephropathy | Diabetics | Glomerular hypertrophy → Kimmelstiel-Wilson nodules; nonenzymatic glycosylation | RAAS blockade, glycemic control, SGLT-2 inhibitors |
| Amyloidosis | Older adults | AL (plasma cell dyscrasia) or AA (chronic inflammation) amyloid deposits in glomeruli | Treat underlying cause; bortezomib for AL |
🏥 ComplicationsThromboembolism: loss of antithrombin III → hypercoagulable state; renal vein thrombosis (membranous nephropathy); PE risk. Infection: loss of IgG and complement → increased risk of encapsulated organisms (pneumococcus). Hyperlipidemia: decreased oncotic pressure → hepatic overproduction of VLDL/LDL. Treat with RAAS blockade, diuretics, statins, and sodium restriction.
Nephritic Syndrome
Definition & Hallmarks
Hematuria (RBC casts), hypertension, proteinuria (subnephrotic, <3.5 g/day), oliguria, azotemia. Results from glomerular inflammation and immune complex deposition causing endothelial/mesangial injury and disruption of the filtration membrane.
| Disease | Age | Mechanism | Key Finding |
|---|---|---|---|
| Post-streptococcal GN | Children (2–3 wks post strep pharyngitis or impetigo) | Immune complex deposition (sub-epithelial humps); low complement (C3) | Cola-colored urine, periorbital edema, low C3, anti-DNase B elevated |
| IgA Nephropathy (Berger's) | Young adults | IgA1 O-glycosylation defect → mesangial IgA deposits | Gross hematuria with URI (concurrent or 1–2 days after); normal complement; IgA deposits on biopsy |
| Membranoproliferative GN | Children-young adults | Type 1: immune complexes; Type 2 (dense deposit disease): C3 nephritic factor | Tram-track appearance (mesangial interposition); low C3 |
| Rapidly Progressive GN (RPGN) | Adults | Crescent formation from proliferating parietal cells; three types: anti-GBM, immune complex, pauci-immune (ANCA+) | Days-to-weeks course; crescent formation on biopsy; ANCA-associated (Wegener's, microscopic polyangiitis) |
| Lupus Nephritis | Young women | SLE immune complex deposition; WHO/ISN class I–VI | Low C3/C4, ANA, anti-dsDNA; "wire loop" lesions (class IV) |
🎯 Boards PearlNephritic vs. Nephrotic: "inflamed" vs. "leaky." RBC casts = nephritic (inflamed glomerulus). Fatty casts/oval fat bodies = nephrotic (leaky glomerulus). IgA nephropathy is most common GN worldwide. ANCA-associated RPGN: treat with high-dose steroids + cyclophosphamide or rituximab. Anti-GBM disease (Goodpasture's): linear IgG deposits on GBM; also affects lungs (hemoptysis). Treatment: plasmapheresis + immunosuppression.
Glomerulopathy Quick Reference
| Disease | Syndrome | EM/IF Pattern | Complement |
|---|---|---|---|
| Minimal Change Disease | Nephrotic | EM: foot process effacement; IF: negative | Normal |
| FSGS | Nephrotic | LM: segmental sclerosis; IF: IgM, C3 deposits | Normal |
| Membranous Nephropathy | Nephrotic | EM: sub-epithelial deposits; IF: granular IgG, C3; LM: spike and dome | Normal |
| Post-strep GN | Nephritic | EM: sub-epithelial humps; IF: granular IgG, C3 | Low C3 |
| IgA Nephropathy | Nephritic | IF: mesangial IgA deposits | Normal |
| Anti-GBM (Goodpasture's) | RPGN | IF: linear IgG along GBM | Normal |
| ANCA-associated RPGN | RPGN | IF: pauci-immune (no deposits) | Normal |
| Lupus Nephritis (Class IV) | Both | IF: "full house" (IgG, IgA, IgM, C3, C1q) | Low C3, C4 |