Nephrology Essentials

Cheatsheet Content

Diuretics and their Nephron Targets Nephron Segment Diuretic Class Drugs Proximal Convoluted Tubule (PCT) Carbonic Anhydrase Inhibitors Acetazolamide PCT + Descending Limb Osmotic Diuretics Mannitol Thick Ascending Limb (TAL) of Loop of Henle Loop Diuretics Furosemide, Bumetanide, Torsemide, Ethacrynic acid Distal Convoluted Tubule (DCT) Thiazide Diuretics Hydrochlorothiazide (HCTZ), Indapamide, Chlorthalidone, Metolazone Collecting Duct ENaC Blockers (Potassium-sparing) Amiloride, Triamterene Collecting Duct Aldosterone Antagonists (Potassium-sparing) Spironolactone, Eplerenone, Finerenone Collecting Duct Antidiuretic Hormone (ADH) Antagonists Tolvaptan, Conivaptan PCT Sodium-Glucose Co-transporter 2 (SGLT2) Inhibitors Dapagliflozin, Empagliflozin, Canagliflozin Renal Function Tests Glomerular Function Tests Serum Creatinine: Waste product from muscle metabolism, excreted by kidneys. Rises with decreased GFR. Blood Urea Nitrogen (BUN): End product of protein metabolism. BUN/Creatinine ratio: $>20:1 \implies$ Pre-renal azotemia (e.g., dehydration) $ Estimated GFR (eGFR): Calculated using equations (e.g., CKD-EPI, MDRD) based on creatinine, age, sex, race. Preferred for CKD staging. Cystatin C: Alternative filtration marker, less affected by muscle mass. Proteinuria Assessment Albumin-Creatinine Ratio (ACR): On spot urine sample. Detects microalbuminuria (early sign of kidney damage, especially in diabetes). Protein-Creatinine Ratio (PCR): On spot urine sample. Estimates total protein excretion. 24-hour urine protein collection: Gold standard for quantifying proteinuria. Urinalysis (UA) Dipstick: Tests for protein, glucose, ketones, blood, nitrites (bacterial infection), leukocyte esterase (WBCs, infection). Specific Gravity: Measures urine concentration (normal 1.003–1.030). High in dehydration, low in diabetes insipidus or severe kidney damage. Microscopic Examination: RBC casts: Glomerulonephritis (GN). WBC casts: Pyelonephritis, Acute Interstitial Nephritis (AIN). Muddy brown granular casts: Acute Tubular Necrosis (ATN). Fatty casts / Oval fat bodies: Nephrotic syndrome. Crystals: Kidney stones. Tubular Function Tests Fractional Excretion of Sodium (FENa): Differentiates pre-renal from intrinsic AKI. $ $>2\%$ in ATN (tubular damage impairs sodium reabsorption). Fractional Excretion of Urea (FEUrea): Useful when diuretics are used (affect FENa). $ Urine Osmolality: $>500 \text{ mOsm/kg}$ in pre-renal AKI (kidneys concentrating urine). $350–450 \text{ mOsm/kg}$ in ATN (loss of concentrating ability). Electrolytes & Acid-Base Status Hyperkalemia ($\uparrow K^+$) and metabolic acidosis ($\downarrow HCO_3^-$) are common in advanced renal failure. Imaging Renal Ultrasound: Assesses kidney size, cortical thickness, hydronephrosis (obstruction), cysts. CT/MRI: Detailed imaging for stones, masses, vascular abnormalities. Glomerular Filtration Rate (GFR) The rate at which blood is filtered by the glomeruli per unit time. Best overall measure of kidney function. Normal GFR: Men: approx. $130 \text{ mL/min/1.73 m}^2$ Women: approx. $120 \text{ mL/min/1.73 m}^2$ Urine Microscopy Direct microscopic examination of urine sediment. Helps identify casts, cells, crystals, and bacteria, which are crucial for diagnosing various kidney diseases. Renal Biopsy Invasive procedure to obtain a small piece of kidney tissue for microscopic examination. Gold standard for diagnosing most glomerular diseases and certain interstitial diseases. Performed under ultrasound guidance. Hematuria Presence of red blood cells in urine. Macroscopic (gross) hematuria: Visible blood in urine. Microscopic hematuria: Detected by dipstick or microscopy ($>3 \text{ RBCs/HPF}$). Always warrants investigation to rule out serious causes (e.g., malignancy, glomerulonephritis, stones). Proteinuria and Microalbuminuria Proteinuria: Excretion of $>150 \text{ mg}$ of protein per day. Indicative of kidney damage. Microalbuminuria: Albumin excretion of $30-300 \text{ mg}$ per day. Early sign of diabetic nephropathy and other kidney diseases. Acute Kidney Injury (AKI) A sudden, rapid decline in kidney function over hours to days, resulting in accumulation of nitrogenous waste products. Diagnostic Criteria (KDIGO): Increase in serum creatinine by $\ge0.3 \text{ mg/dL}$ within 48 hours, OR Increase in serum creatinine to $\ge1.5$ times baseline within the prior 7 days, OR Urine volume $ Types of AKI 1. Pre-renal AKI ("Perfusion Problem") Caused by decreased renal perfusion, leading to reduced GFR. Causes: Hypovolemia (dehydration, hemorrhage, severe burns), Decreased effective circulating volume (heart failure, cirrhosis, nephrotic syndrome), Renovascular obstruction (renal artery stenosis), Drugs (NSAIDs, ACEIs/ARBs). Clinical Features: Thirst, orthostatic hypotension, tachycardia, dry mucous membranes. Urine is concentrated (high specific gravity, low FENa). 2. Intrinsic Renal AKI ("Kidney Damage") Direct damage to kidney structures (tubules, glomeruli, interstitium, blood vessels). Acute Tubular Necrosis (ATN): Most common cause of intrinsic AKI. Causes: Ischemia (prolonged pre-renal AKI), Nephrotoxins (aminoglycosides, contrast dyes, rhabdomyolysis, ethylene glycol). Clinical Course: Oliguric phase (10-14 days), Diuretic phase, Recovery. Urinalysis: Muddy brown granular casts. Urine is dilute (high FENa, low urine osmolality). Acute Interstitial Nephritis (AIN): Causes: Drugs (penicillins, NSAIDs, PPIs), Infections, Autoimmune diseases. Clinical Features: Fever, rash, eosinophilia (classic triad). Urinalysis: WBC casts, eosinophiluria. Acute Glomerulonephritis (GN): Inflammation of glomeruli. Causes: Post-infectious (post-streptococcal), Autoimmune (SLE, vasculitis, Goodpasture's). Urinalysis: RBC casts, dysmorphic RBCs, proteinuria. Acute Vascular Syndromes: Thrombotic microangiopathy, renal artery/vein thrombosis. 3. Post-renal AKI ("Obstruction Problem") Caused by obstruction of urine outflow anywhere from the renal pelvis to the urethra. Causes: Benign Prostatic Hyperplasia (BPH), kidney stones, tumors (bladder, prostate, cervical), neurogenic bladder, retroperitoneal fibrosis. Clinical Features: Anuria or fluctuating urine output, suprapubic pain, distended bladder. Diagnosis: Renal ultrasound to detect hydronephrosis. Uremic Symptoms (Seen in ANY AKI) Non-specific: Anorexia, nausea, vomiting, fatigue, pruritus. Neurological: Confusion, altered mental status, asterixis, seizures (late). Cardiovascular: Pericarditis (uremic pericarditis), fluid overload (pulmonary edema, peripheral edema). Key Features to Differentiate AKI Types Parameter Pre-renal Intrinsic (ATN) Post-renal FENa $ $>2\%$ Variable (early $ 2\%$) Urine Osmolality $>500 \text{ mOsm/kg}$ $350-450 \text{ mOsm/kg}$ Variable Urine Sediment Hyaline casts Muddy brown granular casts Normal or crystals/RBCs (if stones) BUN/Cr Ratio $>20:1$ $10:1$ to $15:1$ Variable Nephrotic Syndrome (NS) A clinical syndrome characterized by massive proteinuria, hypoalbuminemia, generalized edema, and hyperlipidemia. Results from increased glomerular permeability to proteins. Key diagnostic criteria: Proteinuria $>3.5 \text{ g/day}$ (or PCR $>3-3.5 \text{ mg/mg}$). Hypoalbuminemia ($ Edema. Hyperlipidemia. Etiology Primary Glomerular Diseases Disease Key Pathologic Finding Clinical Notes Minimal Change Disease (MCD) Effacement of podocyte foot processes on EM Most common cause in children; abrupt onset edema; usually steroid-responsive. Focal Segmental Glomerulosclerosis (FSGS) Segmental scarring of glomeruli Common in adults; often steroid-resistant; can be primary, secondary (HIV, obesity), or genetic. Membranous Nephropathy (MN) Subepithelial immune deposits (spikes on silver stain) Most common primary cause in adults; associated with anti-PLA2R antibodies; high risk of renal vein thrombosis. Membranoproliferative Glomerulonephritis (MPGN) Mesangial and endothelial proliferation, GBM thickening ("tram-track") Mixed nephrotic/nephritic features; often associated with hepatitis C or complement dysregulation. Secondary Causes Diabetic Nephropathy: Most common cause of NS worldwide. Microalbuminuria progresses to proteinuria. Systemic Lupus Erythematosus (SLE): Lupus nephritis (Class V membranous LN). Amyloidosis: AL (light chain) or AA (serum amyloid A protein) deposition in glomeruli. Infections: Hepatitis B/C, HIV, Syphilis, Malaria. Drugs: NSAIDs, gold, penicillamine. Malignancy: Lymphoma (MCD), solid tumors (MN). Clinical Features Edema: Pitting, generalized, starting periorbital, then dependent (legs, sacrum), leading to anasarca. Due to low oncotic pressure and renal sodium/water retention. Frothy urine: Due to heavy proteinuria. Hyperlipidemia: Elevated cholesterol and triglycerides, leading to lipiduria (oval fat bodies, fatty casts with "Maltese cross" appearance). Increased susceptibility to infection: Due to loss of immunoglobulins and complement factors in urine. Hypercoagulability: Due to urinary loss of anticoagulant proteins (e.g., Antithrombin III) and increased procoagulant factors. High risk of DVT, PE, and renal vein thrombosis. Acute Kidney Injury: Can occur due to severe hypovolemia, ATN, or renal vein thrombosis. Management General/Supportive: Salt and fluid restriction: To manage edema. Diuretics: Loop diuretics (often combined with albumin infusion for severe edema). ACE inhibitors/ARBs: To reduce proteinuria and control blood pressure. Statins: To manage hyperlipidemia. Anticoagulation: Considered in patients with very low albumin ($ Infection prevention: Vaccinations (pneumococcal, influenza), prompt treatment of infections. Disease-Specific Treatment: Based on kidney biopsy findings (e.g., corticosteroids for MCD, immunosuppressants like cyclophosphamide, MMF, calcineurin inhibitors, or rituximab for others). Acute Glomerulonephritis (AGN) / Nephritic Syndrome A clinical syndrome characterized by acute onset of hematuria, proteinuria (non-nephrotic range), hypertension, and often impaired renal function (AKI). Results from inflammation of the glomeruli. Key features: Hematuria (often macroscopic), RBC casts, hypertension, oliguria, edema (especially periorbital). Pathophysiology Immune-mediated damage to glomerular capillaries. Inflammation leads to capillary wall damage, allowing RBCs and protein to leak into urine. Reduced glomerular filtration results in fluid retention, leading to edema and hypertension. Etiology Post-infectious Glomerulonephritis (PIGN): Post-streptococcal GN (PSGN): Most common cause. Occurs 1-3 weeks after streptococcal pharyngitis or skin infection. Low C3. Other infections: Bacterial endocarditis, viral infections (Hepatitis B/C, HIV). Rapidly Progressive Glomerulonephritis (RPGN): Severe, rapidly progressive form leading to ESRD within weeks to months. Characterized by crescents on biopsy. Type I (Anti-GBM disease / Goodpasture syndrome): Antibodies against glomerular basement membrane (GBM). Can cause lung hemorrhage (hemoptysis). Type II (Immune complex mediated): SLE, IgA nephropathy, Post-infectious GN. Type III (Pauci-immune / ANCA-associated vasculitis): No or few immune deposits. Associated with ANCA antibodies (Wegener's granulomatosis, microscopic polyangiitis). IgA Nephropathy (Berger's disease): Most common primary GN worldwide. Recurrent gross hematuria following upper respiratory tract infections. Lupus Nephritis (LN): Various classes can present as nephritic syndrome (Class III, IV). Clinical Features Hematuria: Often macroscopic, cola-colored or smoky urine. Microscopic hematuria with dysmorphic RBCs and RBC casts. Edema: Often periorbital, especially in children, due to fluid retention. Hypertension: Due to fluid overload and activation of RAAS. Oliguria: Reduced urine output, reflecting decreased GFR. Flank pain: Due to kidney swelling. Systemic symptoms: Fever, malaise, anorexia (especially in post-infectious GN). Diagnosis Urinalysis: Hematuria (dysmorphic RBCs), RBC casts, proteinuria (usually $ Blood tests: Elevated creatinine/BUN, low C3/C4 (in immune complex diseases), elevated ASO titer (PSGN), ANCA, anti-GBM antibodies, ANA, anti-dsDNA (SLE). Kidney Biopsy: Essential for definitive diagnosis and classification, especially in RPGN. Management Supportive: Blood pressure control: Antihypertensives (ACEIs/ARBs if GFR allows). Fluid and salt restriction: To manage edema and hypertension. Diuretics: Loop diuretics for fluid overload. Dialysis: If severe AKI, fluid overload, or hyperkalemia. Disease-specific: PSGN: Supportive, antibiotics for ongoing infection (not to prevent GN). RPGN: High-dose corticosteroids, cyclophosphamide, rituximab, plasmapheresis (especially in anti-GBM disease). Lupus Nephritis: Immunosuppressants (corticosteroids, MMF, cyclophosphamide). IgA Nephropathy: ACEIs/ARBs, possibly steroids in high-risk patients. Chronic Kidney Disease (CKD) Defined as abnormalities of kidney structure or function, present for $>3$ months, with implications for health. Diagnostic criteria include GFR $ Stages of CKD (KDIGO Classification) Stage GFR ($\text{mL/min/1.73 m}^2$) Description G1 $\ge90$ Normal or high GFR with kidney damage G2 $60-89$ Mildly decreased GFR with kidney damage G3a $45-59$ Mildly to moderately decreased GFR G3b $30-44$ Moderately to severely decreased GFR G4 $15-29$ Severely decreased GFR G5 $ Kidney failure (End-Stage Renal Disease - ESRD) Albuminuria categories (A1: $ 300 \text{ mg/g}$) further stratify risk. Etiology Diabetes Mellitus: Most common cause. Hypertension: Second most common cause. Glomerular diseases: IgA nephropathy, FSGS, lupus nephritis. Polycystic Kidney Disease (PKD): Genetic. Obstructive uropathy: BPH, stones, tumors. Tubulointerstitial diseases: Chronic pyelonephritis, analgesic nephropathy. Clinical Features (Uremic Syndrome) Often asymptomatic in early stages. Symptoms appear as GFR declines. Cardiovascular: Hypertension, heart failure, pericarditis, accelerated atherosclerosis. Hematologic: Anemia (normocytic, normochromic due to decreased EPO), bleeding diathesis (platelet dysfunction). Mineral and Bone Disorders (CKD-MBD): Hypocalcemia, hyperphosphatemia, secondary hyperparathyroidism, renal osteodystrophy. Neurological: Fatigue, lethargy, impaired concentration, peripheral neuropathy, restless legs syndrome, uremic encephalopathy (asterixis, seizures). Gastrointestinal: Anorexia, nausea, vomiting, metallic taste, uremic fetor. Endocrine: Insulin resistance, erectile dysfunction, menstrual irregularities. Dermatologic: Pruritus, pallor, hyperpigmentation, uremic frost (rare). Metabolic: Metabolic acidosis, hyperkalemia. Management Slow Progression: Blood Pressure Control: Target $ Glycemic Control: HbA1c target $ Dietary Protein Restriction: $0.8 \text{ g/kg/day}$ (in later stages). Avoid Nephrotoxins: NSAIDs, contrast agents. Manage Complications: Anemia: Iron supplementation, Erythropoiesis-Stimulating Agents (ESAs). CKD-MBD: Phosphate binders, vitamin D analogs, calcimimetics, parathyroidectomy (for severe secondary hyperparathyroidism). Metabolic Acidosis: Oral sodium bicarbonate. Hyperkalemia: Dietary restriction, potassium binders, diuretics. Fluid Overload: Diuretics, salt restriction. Renal Replacement Therapy (RRT): When GFR falls to $ Hemodialysis, peritoneal dialysis, kidney transplantation. Urinary Tract Infection (UTI) Bacterial infection of any part of the urinary tract. Can be lower UTI (cystitis, urethritis) or upper UTI (pyelonephritis). Etiology Most common: Escherichia coli ($80-90\%$). Other common bacteria: Klebsiella pneumoniae , Proteus mirabilis , Staphylococcus saprophyticus (in young women), Enterococcus faecalis . Risk Factors Female sex (shorter urethra, proximity to anus). Sexual activity. Pregnancy. Urinary tract obstruction (BPH, stones, strictures). Diabetes mellitus. Catheterization. Immunosuppression. Vesicoureteral reflux (VUR). Clinical Features Cystitis (Lower UTI): Dysuria (painful urination), frequency, urgency, suprapubic pain, hematuria, cloudy/foul-smelling urine. Fever usually absent. Pyelonephritis (Upper UTI): Fever, chills, loin/flank pain (costovertebral angle tenderness), nausea, vomiting, malaise. May have cystitis symptoms. Asymptomatic Bacteriuria: Presence of bacteria in urine without symptoms. Generally not treated except in pregnancy or before urologic procedures. Diagnosis Urinalysis: Dipstick: Positive for nitrites (suggests Gram-negative bacteria), leukocyte esterase (suggests WBCs). Microscopy: Pyuria ($>10 \text{ WBCs/HPF}$), bacteriuria. WBC casts in pyelonephritis. Urine Culture: Gold standard. Confirms diagnosis and provides antibiotic sensitivity. Significant bacteriuria: $\ge10^5 \text{ CFU/mL}$ (midstream clean catch) or $\ge10^2 \text{ CFU/mL}$ (catheterized). Management Uncomplicated Cystitis: First-line: Nitrofurantoin, Trimethoprim-Sulfamethoxazole (TMP-SMX), Fosfomycin. Short courses (3-5 days). Pyelonephritis / Complicated UTI: Requires broader spectrum antibiotics, often initially IV for severe cases. Fluoroquinolones (ciprofloxacin, levofloxacin), ceftriaxone, aminoglycosides, piperacillin-tazobactam. Duration 7-14 days. UTI in Pregnancy: Always treat, even if asymptomatic. Safe antibiotics: Amoxicillin-clavulanate, cephalexin, nitrofurantoin (avoid near term). Avoid fluoroquinolones, tetracyclines, TMP-SMX in 1st trimester. Recurrent UTIs: Lifestyle modifications (hydration, post-coital voiding). Low-dose prophylactic antibiotics (e.g., TMP-SMX, nitrofurantoin) or post-coital prophylaxis. Vaginal estrogen for postmenopausal women. Hemodialysis (HD) An extracorporeal (outside the body) method of renal replacement therapy that filters blood to remove waste products and excess fluid. Principle Blood is drawn from the patient, pumped through a dialyzer (artificial kidney), and returned to the patient. Dialyzer: Contains a semipermeable membrane that separates blood from dialysate. Diffusion: Solutes (urea, creatinine, potassium) move from blood (higher concentration) to dialysate (lower concentration). Ultrafiltration: Water and small solutes are removed from blood by hydrostatic pressure gradient across the membrane. Vascular Access Arteriovenous (AV) Fistula: Surgical connection between an artery and a vein (e.g., radial artery to cephalic vein). Most durable, lowest complication rate. Requires maturation time. AV Graft: Synthetic tube connecting an artery and a vein. Used if patient's veins are unsuitable for fistula. Central Venous Catheter: Temporary access for acute dialysis or while fistula/graft matures. Higher risk of infection and thrombosis. Indications for Dialysis (AEIOU Mnemonic) A cidosis (severe, refractory metabolic acidosis) E lectrolytes (severe, refractory hyperkalemia) I ntoxication (dialyzable toxins/drugs) O verload (severe fluid overload, e.g., pulmonary edema, unresponsive to diuretics) U remia (uremic pericarditis, encephalopathy, neuropathy, severe nausea/vomiting) Also indicated for ESRD (CKD G5) when symptoms develop. Complications Intradialytic Hypotension: Most common complication. Due to rapid fluid removal. Muscle Cramps: Common during or after dialysis. Dialysis Disequilibrium Syndrome: Neurological symptoms (headache, nausea, confusion, seizures) due to rapid solute removal from blood, causing osmotic shift into brain. Infections: Catheter-related bloodstream infections. Access Complications: Thrombosis, stenosis, infection, aneurysm (fistula/graft). Cardiovascular events: Arrhythmias, myocardial ischemia. Peritoneal Dialysis (PD) A method of renal replacement therapy that uses the patient's peritoneal membrane as a natural semipermeable filter. Principle A catheter (Tenckhoff catheter) is surgically placed into the peritoneal cavity. Dialysate fluid (containing dextrose) is instilled into the peritoneal cavity. Diffusion: Waste products (urea, creatinine) and excess electrolytes move from the blood in peritoneal capillaries to the dialysate. Ultrafiltration: Glucose in the dialysate creates an osmotic gradient, drawing excess water from the blood into the dialysate. After a "dwell time," the dialysate is drained and replaced with fresh fluid. Types of PD Continuous Ambulatory Peritoneal Dialysis (CAPD): Manual exchanges performed by the patient (usually 3-5 times a day). No machine required. Automated Peritoneal Dialysis (APD): A cycler machine performs multiple exchanges overnight while the patient sleeps. Advantages of PD Greater patient independence and flexibility. More continuous clearance of solutes and fluid, leading to better hemodynamic stability. No need for vascular access. Better preservation of residual kidney function. Disadvantages & Complications Peritonitis: Most common and serious complication. Infection of the peritoneal cavity. Presents with cloudy dialysate, abdominal pain, fever. Often caused by skin flora ( Staphylococcus epidermidis, S. aureus ). Catheter-related infections: Exit-site infection, tunnel infection. Mechanical complications: Catheter malfunction, leaks, hernias. Metabolic complications: Hyperglycemia (from dialysate glucose absorption), weight gain. Inadequate dialysis: Due to peritoneal membrane failure over time. Renal Transplantation Surgical implantation of a healthy kidney from a deceased or living donor into a recipient with ESRD. Considered the optimal treatment for most patients with ESRD, offering improved quality of life and survival compared to dialysis. Donor Types Living Donor: Genetically related (sibling, parent) or unrelated (spouse, friend). Better outcomes, shorter wait times. Deceased Donor: From brain-dead donors. Organs allocated based on factors like blood type, tissue match (HLA), and waiting time. Recipient Evaluation Thorough medical and psychosocial evaluation to ensure fitness for surgery and adherence to immunosuppression. Contraindications: Active malignancy, active infection, severe irreversible extra-renal disease (e.g., severe heart failure, lung disease), substance abuse, non-adherence. Surgical Procedure The donor kidney is usually placed in the iliac fossa. Renal artery and vein are anastomosed to the recipient's iliac vessels. Ureter is implanted into the bladder. The native kidneys are usually left in place. Immunosuppression Lifelong therapy to prevent graft rejection. Typically a multi-drug regimen: Induction therapy: High-dose immunosuppression at the time of transplant (e.g., basiliximab, antithymocyte globulin). Maintenance therapy: Usually a combination of: Calcineurin inhibitors (tacrolimus, cyclosporine). Antiproliferative agents (mycophenolate mofetil, azathioprine). Corticosteroids (prednisone). Complications Graft Rejection: Hyperacute: Within minutes/hours. Pre-formed antibodies. Rare with modern cross-matching. Acute: Days to months post-transplant. T-cell or antibody-mediated. Treatable with increased immunosuppression. Chronic: Gradual decline in graft function over years. Multifactorial. Infections: Increased risk due to immunosuppression (CMV, EBV, fungal, bacterial). Malignancy: Increased risk of skin cancers, post-transplant lymphoproliferative disorder (PTLD). Cardiovascular disease: Remains a major cause of death. Drug Toxicity: Nephrotoxicity (calcineurin inhibitors), diabetes, hypertension, hyperlipidemia. Surgical Complications: Vascular thrombosis, ureteral obstruction/leak. Renal Tubular Acidosis (RTA) A group of disorders characterized by a normal anion-gap (hyperchloremic) metabolic acidosis due to a defect in renal acid excretion or bicarbonate reabsorption, despite relatively normal GFR. Types of RTA 1. Type 1 (Distal) RTA Defect: Impaired hydrogen ion ($H^+$) secretion in the distal nephron (collecting duct). Features: Inability to acidify urine: Urine pH consistently $>5.5$ despite systemic acidosis. Hypokalemia (due to increased distal K+ secretion). Nephrocalcinosis and kidney stones (due to increased urine calcium and decreased citrate). Bone demineralization (osteomalacia/rickets). Causes: Autoimmune diseases (Sjögren's, SLE), drugs (amphotericin B, lithium), genetic. Treatment: Oral bicarbonate (sodium bicarbonate or sodium citrate) to correct acidosis and prevent complications. 2. Type 2 (Proximal) RTA Defect: Impaired bicarbonate ($HCO_3^-$) reabsorption in the proximal tubule. Features: Initial bicarbonate wasting, but urine can be acidified ($ Hypokalemia (due to increased distal K+ secretion in response to volume depletion). Often part of Fanconi syndrome (generalized proximal tubular dysfunction with glycosuria, aminoaciduria, phosphaturia, uricosuria). Causes: Genetic disorders (cystinosis, Wilson's disease), drugs (acetazolamide, ifosfamide), multiple myeloma. Treatment: Large doses of oral bicarbonate (as much is lost in urine), potassium supplementation. 3. Type 4 (Hyperkalemic) RTA Defect: Hypoaldosteronism or aldosterone resistance, leading to impaired potassium excretion and impaired ammoniogenesis in the collecting duct. Features: Hyperkalemia (hallmark). Mild metabolic acidosis (due to impaired NH4+ excretion). Normal urine pH (can acidify urine). Causes: Diabetic nephropathy (hyporeninemic hypoaldosteronism), adrenal insufficiency, drugs (ACEIs/ARBs, potassium-sparing diuretics, TMP-SMX). Treatment: Treat underlying cause. Fludrocortisone (mineralocorticoid) for aldosterone deficiency. Loop diuretics, dietary potassium restriction, potassium binders for hyperkalemia. Summary Table for RTA Types Type Defect Serum K$^+$ Urine pH Causes 1 (Distal) Distal H$^+$ secretion Low $>5.5$ Autoimmune, Amphotericin B 2 (Proximal) Proximal HCO$_3^-$ reabsorption Low Variable (can be $ Fanconi syndrome, Myeloma 4 (Hyperkalemic) Aldosterone deficiency/resistance High $ Diabetes, ACEIs/ARBs Polycystic Kidney Disease (PKD) A genetic disorder characterized by the growth of numerous cysts in the kidneys, which eventually destroy normal kidney tissue and lead to kidney failure. Types Autosomal Dominant Polycystic Kidney Disease (ADPKD): Most common hereditary kidney disease. Onset in adulthood (typically 30s-40s). Mutations in PKD1 (more severe, earlier onset) or PKD2 (milder, later onset) genes, encoding polycystin-1 and polycystin-2. Cysts develop in both kidneys, gradually enlarging and replacing functional renal parenchyma. Associated with extrarenal manifestations. Autosomal Recessive Polycystic Kidney Disease (ARPKD): Rare, severe form, usually presenting in infancy or childhood. Mutation in the PKHD1 gene, encoding fibrocystin. Associated with congenital hepatic fibrosis and portal hypertension. Clinical Features (ADPKD) Renal Manifestations: Loin pain: Due to cyst enlargement, hemorrhage, infection, or stones. Hematuria: Macroscopic, often due to cyst rupture. Hypertension: Common and often early. Recurrent UTIs/Cyst infections: Difficult to treat. Nephrolithiasis: Kidney stones. Progressive CKD: Leading to ESRD in about 50% of patients by age 60. Palpable, enlarged kidneys. Extrarenal Manifestations: Cerebral Aneurysms (Berry Aneurysms): Increased risk of subarachnoid hemorrhage. Screening recommended for high-risk individuals. Hepatic Cysts: Very common, usually asymptomatic. Cardiac Valvular Defects: Mitral valve prolapse, aortic regurgitation. Diverticulosis: Colon. Abdominal wall hernias. Pancreatic cysts. Diagnosis Renal Ultrasound: Initial diagnostic tool. Number and size of cysts depend on age and genetic mutation. CT/MRI: More sensitive for smaller cysts, monitoring cyst growth, or evaluating complications. Genetic Testing: Confirms diagnosis, especially in atypical cases or for family planning. Management (ADPKD) Blood Pressure Control: Aggressive control (ACEIs/ARBs) to slow disease progression. Pain Management: Analgesics. Avoid NSAIDs if kidney function is impaired. Cyst Infection Treatment: Fluoroquinolones (ciprofloxacin) or TMP-SMX as they penetrate cysts well. Tolvaptan: A vasopressin V2 receptor antagonist, approved to slow cyst growth and preserve kidney function in rapidly progressing ADPKD. Lifestyle: Hydration, caffeine restriction. Screening: For cerebral aneurysms in high-risk patients (family history of aneurysm or rupture). ESRD Management: Dialysis or kidney transplantation. Lupus Nephritis (LN) Kidney inflammation caused by Systemic Lupus Erythematosus (SLE), an autoimmune disease. Results from deposition of immune complexes (DNA-anti-DNA) in the glomeruli. Pathophysiology Formation of autoantibodies (e.g., anti-dsDNA, anti-Smith) and immune complexes. Immune complexes deposit in various parts of the glomerulus (mesangium, subendothelial, subepithelial). Activation of complement and inflammatory cells leads to glomerular damage, proteinuria, hematuria, and reduced GFR. Classification (ISN/RPS 2003/2018) - Based on Kidney Biopsy Class Description Clinical Presentation Prognosis & Treatment I Minimal Mesangial LN Asymptomatic, mild hematuria/proteinuria Good prognosis, no specific treatment II Mesangial Proliferative LN Hematuria, proteinuria (non-nephrotic) Good prognosis, mild immunosuppression (steroids) III Focal LN ($ Hematuria, proteinuria, nephritic/nephrotic syndrome, HTN, AKI Variable, requires aggressive immunosuppression IV Diffuse LN ($>50\%$ glomeruli affected) Severe nephritic/nephrotic syndrome, HTN, AKI. Most severe form. Poor if untreated, aggressive immunosuppression (high-dose steroids + cyclophosphamide/MMF) V Membranous LN Nephrotic syndrome (prominent proteinuria) Variable, increased risk of thrombosis. Treat with steroids + MMF/calcineurin inhibitors. VI Advanced Sclerosing LN Progressive CKD/ESRD Irreversible damage, no role for immunosuppression. RRT. Clinical Features Can range from asymptomatic proteinuria to rapid kidney failure. Proteinuria, hematuria, RBC casts. Hypertension. Edema. Signs of SLE (rash, arthritis, serositis, cytopenias, etc.). Serology: Positive ANA, anti-dsDNA, low complement levels (C3, C4). Diagnosis High suspicion in SLE patients with renal abnormalities. Kidney Biopsy: Essential for diagnosis, classification, and guiding treatment. Management General: BP control (ACEIs/ARBs), proteinuria reduction, lipid management, infection prophylaxis. Immunosuppression (for Class III, IV, V): Induction therapy: High-dose corticosteroids (IV methylprednisolone) combined with cyclophosphamide or mycophenolate mofetil (MMF). Maintenance therapy: Lower dose corticosteroids with MMF or azathioprine. Newer agents: Belimumab, Voclosporin. Monitoring: Regular assessment of renal function, proteinuria, serological markers (anti-dsDNA, complement levels). IgA Nephropathy (Berger's Disease) The most common primary glomerulonephritis worldwide. Characterized by IgA immune complex deposition in the mesangium of the glomeruli. Pathogenesis Abnormal IgA1 (galactose-deficient IgA1) is produced. Autoantibodies (IgG/IgA) recognize these abnormal IgA1 molecules, forming immune complexes. These immune complexes deposit in the glomerular mesangium. Mesangial cell proliferation and inflammation lead to glomerular damage. Clinical Features Recurrent Macroscopic Hematuria: Classically occurs shortly after (within hours to days) an upper respiratory tract infection or GI infection ("synpharyngitic hematuria"). Microscopic Hematuria: Persistent, often with mild proteinuria. Proteinuria: Can range from mild to nephrotic range. Higher proteinuria indicates worse prognosis. Hypertension: Common. Some patients may present with AKI or slowly progressive CKD. Diagnosis Kidney Biopsy: Definitive diagnosis. Immunofluorescence shows dominant IgA deposition in the mesangium. Light microscopy shows mesangial proliferation. Serum IgA levels may be elevated but are not diagnostic. Management Supportive Care (for all patients): BP Control: Target $ Proteinuria Reduction: ACEIs/ARBs. SGLT2 inhibitors are emerging as beneficial. Immunosuppression (for high-risk patients with progressive disease, e.g., proteinuria $>1 \text{ g/day}$ despite optimized supportive care): Corticosteroids (oral prednisone). Mycophenolate mofetil (MMF) or cyclophosphamide in severe cases (e.g., RPGN presentation). Targeted-release budesonide for gut-associated IgA production. Fish Oil: May be considered for proteinuria reduction. Tonsillectomy: May be considered for patients with recurrent tonsillitis and IgA nephropathy. Alport Syndrome A genetic disorder affecting the type IV collagen in the glomerular basement membrane (GBM), cochlea, and eye. Characterized by progressive kidney disease, sensorineural hearing loss, and ocular abnormalities. Genetics and Inheritance X-linked Alport Syndrome (XLAS): Most common ($80-85\%$). Mutation in COL4A5 gene. Males are typically more severely affected, progressing to ESRD in early adulthood. Females are carriers but can develop variable renal disease (hematuria, proteinuria, sometimes ESRD). Autosomal Recessive Alport Syndrome (ARAS): Mutations in COL4A3 or COL4A4 genes. Both sexes equally affected, usually severe. Autosomal Dominant Alport Syndrome (ADAS): Less common, mutations in COL4A3 or COL4A4 . Milder phenotype, later onset of ESRD. Clinical Features Renal: Persistent Microscopic Hematuria: Often present from childhood. May have episodes of macroscopic hematuria. Proteinuria: Progresses over time, eventually leading to nephrotic range proteinuria. Progressive CKD: Leads to ESRD. Males with XLAS typically reach ESRD by age 20-30. Kidney biopsy: Thinning of GBM, then progressive thickening and splitting ("basket-weave" appearance on electron microscopy). Auditory: Sensorineural Hearing Loss: Bilateral, high-frequency hearing loss, typically developing in late childhood or adolescence. More severe in males with XLAS. Ocular: Anterior Lenticonus: Conical protrusion of the anterior lens capsule, specific to Alport syndrome. Dot-and-fleck retinopathy: Pigmentary changes in the retina. Recurrent corneal erosions. Diagnosis Clinical suspicion based on family history, hematuria, hearing loss, and ocular findings. Genetic Testing: Confirms the diagnosis by identifying mutations in COL4A3, COL4A4, or COL4A5. Kidney Biopsy: Electron microscopy shows characteristic GBM changes (thinning, then splitting/lamellation). Immunostaining for type IV collagen chains can be helpful. Management Renoprotection: ACE Inhibitors/ARBs: Started early (even in childhood) to delay progression of proteinuria and CKD. SGLT2 Inhibitors: Emerging as beneficial. Hearing Aids: For sensorineural hearing loss. Ophthalmologic Care: For ocular abnormalities. ESRD Management: Dialysis or kidney transplantation. Recurrence of Alport syndrome in the transplanted kidney is rare, but anti-GBM disease can occur in some recipients.