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USMLE Step 3 (Subject) / Nephrology (Lesson)

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• Hyponatremia Serum concentration < 135 mEql/L Hypotonic hyponatremia (↓ serum osmolality)  - Hypovolemic hyponatremia→ Renal causes: diuretics, aldosterone deficiency (Addison's disease)→ Extrarenal causes: pancreatitis, vomiting, diarrhea, burns, bleeding- Euvolemic hyponatremia→ Syndrome of inappropriate ADH secretion (SIADH)→ Psychogenic polydipsia→ Hypothyroidism  - Hypervolemic hyponatremia→ Congestive heart failure→ Liver cirrhosis→ Nephrotic syndrome Isotonic hyponatremia (↔︎ serum osmolality) = Pseudohyponatremia: Elevated concentrations of serum proteins or lipids lead to a dilution of plasma sodium.- Hyperlipidemia- Paraproteinemia (e.g., multiple myeloma) Hypertonic hyponatremia (↑ serum osmolality)- Hyperglycemia  - Use of mannitol- Aldosterone- ADH Clinical features:- Mild symptoms: Anorexia, Nausea, Vomiting, Headache, Muscle cramps- Moderate symptoms: Muscle weakness, Lethargy, Confusion- Severe symptoms: Seizures, Altered consciousness, Coma Diagnostics:1. Serum sodium concentration2. Serum osmolality to assess volume status - Hypotonic hyponatremia (most common): serum osmolality < 280 mOsmol/kg- Hypertonic hyponatremia: serum osmolality > 295 mOsmol/kg- Isotonic hyponatremia: serum osmolality 280–295 mOsmol/kg- ↓ Hematocrit: possibly fluid overload, ↑ Hematocrit: hypovolemia, dehydration3. Urine examination  > 20 mEq/L implies renal sodium loss  < 20 mEq/L implies extrarenal sodium loss  Treatment:- Patients with serum sodium values < 120 mEq/L require intensive care.- Careful correction of sodium levels: maximum correction within 24 hours is 10 mEq/L (rate of correction: 0.5-1 mEq/L per hour). Rapid increase in sodium levels → risk of central pontine myelinolysis- Hypovolemic hyponatremia→ Mild to moderate symptoms: normal saline  → Severe symptoms: hypertonic saline- Euvolemic hyponatremia:→ Mild to moderate symptoms: fluid restriction→ Severe symptoms: hypertonic saline- Hypervolemic hyponatremia:→ Mild to moderate symptoms: fluid restriction ± loop diuretic→ Severe symptoms: isotonic saline
• Hypernatremia Serum concentration > 145 mEql/L Hypovolemic hypernatremia:- Dehydration (e.g., due to poor oral fluid intake, diarrhea)- Diuretics  - Osmotic diuresis (e.g., hyperglycemia, uremia, high-protein tube feeding) Euvolemic hypernatremia:- Diabetes insipidus (central or renal)- Lack of access to water Hypervolemic hypernatremia:- Primary hyperaldosteronism- Cushing's syndrome- Iatrogenic: excessive infusion of NaCl or sodium bicarbonate solutions- Drinking sea water Clinical features:- Mild symptoms: Anorexia, Nausea, Vomiting, Headache, Muscle cramps- Moderate symptoms: Muscle weakness, Lethargy, Confusion- Severe symptoms: Seizures, Altered consciousness, Coma Diagnostics:1. Serum osmolality to assess volume status: ↑ serum osmolality2. Urine osmolality  > 800 mOsmol/kg implies extrarenal water loss  < 800 mOsmol/kg implies renal water loss. The kidneys continue to excrete water despite a water deficit. Treatment:- Correct free water deficit  - Mild hypernatremia in non-hospitalized patients: oral rehydration  - Moderate to severe hypernatremia, or hypernatremia in hospitalized patients: IV route→ Acute hypernatremia (< 48 hours): hypotonic saline (e.g., ½ NS) or 5% dextrose (D5W)  → Subacute or chronic hypernatremia (> 48 hours): 5% dextrose in 0.45% NS (D5½NS)  - Hypovolemic hypernatremia→ Fluid resuscitation→ Once adequately resuscitated: correct free water deficit- Euvolemic hypernatremia: correct free water deficit- Hypervolemic hypernatremia: loop diuretic + 5% dextrose
• Hypokalemia Serum potassium level < 3.5 mEq/L  Etiology:- Renal loss→ Endocrine causes: hyperaldosteronism, hypercortisolism  → Drugs: diuretics, glucocorticoids, licorice (aldosterone-like action)→ Hypomagnesemia  → Type I and II renal tubular acidosis- Gastrointestinal loss: vomiting, diarrhea, laxatives (e.g., in bowel preparation prior to medical procedures)- Alkalosis- Insulin therapy- β2-mediated stimulation of Na+/K+-ATPase Clinical features:- Symptoms usually occur if serum potassium levels are < 3.0 mEq/L or they change rapidly.- Cardiac arrhythmias (e.g., premature atrial and ventricular complexes, ventricular fibrillation)- Muscle weakness, paralysis- ↓ Deep tendon reflexes- Nausea, vomiting, constipation- Fatigue- Polyuria  - In patients treated with digoxin: symptoms of digoxin toxicity   Diagnostics:- Serum potassium levels (always confirm abnormal serum potassium levels with a repeat blood draw)- Urinary potassium level> 20 mEq/L: renal loss< 20 mEq/L: extrarenal loss- Arterial blood gas (ABG): influence of pH on the potassium homeostasis→ Metabolic alkalosis: hypokalemia→ Metabolic acidosis: hyperkalemia- ECG changes:→ Presence of U waves: small waveform following the T wave that is often absent and becomes more pronounced in the context of hypokalemia or bradycardia→ ST depression→ T-wave flattening Treatment:- Treat the underlying cause or adjust an existing treatment; correct possible hypomagnesemia- If diuretic-induced (e.g., loop or thiazide diuretics):→ Discontinue the diuretic or reduce the dose and combine with potassium-sparing diuretic spironolactone, ACE inhibitors, or beta blockers.→ Rehydrate with normal saline in the case of volume depletion and contraction alkalosis.- Repletion→ Intake of high-potassium foods→ Potassium chloride (KCl): oral→ In severe hypokalemia (< 2.5 mEq/L): IV
• Hyperkalemia Serum potassium level > 5 mEq/L Etiology:- Reduced excretion: acute and chronic kidney disease - Endocrine causes: hypocortisolism, hypoaldosteronism  - Drugs: potassium-sparing diuretics, ACE inhibitors, angiotensin receptor blockers, NSAIDs, and trimethoprim-sulfamethoxazole  - GI absorption: increased intake of high-potassium foods (e.g., fresh fruits, dried fruits and legumes, vegetables, nuts, seeds, bran products, milk, and dairy products)- Type IV renal tubular acidosis- Release from cells: myolysis, tumor lysis, hemolysis- Acidosis - Insulin deficiency- Drugs: succinylcholine, digoxin  - Pseudohyperkalemia: due to the release of potassium from red blood cell lysis Clinical features:- Symptoms usually occur if serum potassium levels are > 7.0 mEq/L or they change rapidly.- Cardiac arrhythmias (e.g., atrioventricular block, ventricular fibrillation)- Muscle weakness, paralysis- ↓ Deep tendon reflexes  - Nausea, vomiting, diarrhea Diagnostics:- Always confirm abnormal serum potassium levels with a repeat blood draw- Creatinine, GFR to assess renal function- In normal renal function: aldosterone level to rule out Addison disease- Arterial blood gas (ABG): influence of pH on the potassium homeostasis- ECG changes:→ Tall, peaked T waves→ P-wave flattening, lengthening of the PR interval→ Shortened QT interval→ Lengthening of the QRS interval Treatment:- Potassium level ≤ 6.5 mEq/L and no signs of cardiotoxicity: decrease intake/absorption (slow-acting option)→ Cation-exchange resins (e.g., sodium polystyrene sulfonate): bind potassium in the gut via the exchange of Na+ for K+ → Adverse effect (rare): intestinal necrosis→ Loop diuretics: promote excretion of potassium and lower total body potassium stores→ Intravenous, non potassium containing fluids: normal saline, dextrose 5% in water- Potassium level > 6.5 mEq/L or cardiotoxicity: IV therapy for cardioprotection and to induce elimination/intracellular shift (rapid-acting option)→ Calcium gluconate: should be administered first!  → Insulin and glucose  → Sodium bicarbonate: in acidemic patients  → Beta-2-adrenergic agonists  → Forced diuresis (loop diuretics with normal saline solution)- Renal failure or ineffective initial treatment: Hemodialysis
• Hypocalcemia = total serum calcium concentration < 8.5 mg/dL (< 2.12 mmol/L), or ionized (or free) calcium concentration < 4.65 mg/dL (< 1.16 mmol/L) Etiology:- Low PTH – Hypoparathyroidism: Surgical or autoimmune- High PTH – Secondary Hyperparathyroidism→ Vitamin D deficiency→ Pseudohypoparathyroidism (Albright hereditary osteodystrophy): PTH resistance→ Hyperphosphatemia→ Acute necrotizing pancreatitis- Medications: Loop diuretics, glucocorticoids- Multiple blood transfusions: Citrate in blood products chelates serum calcium- Hypomagnesemia → reduction of PTH secretion or PTH resistance → hypocalcemia- Hyperventilation Clinical features:- Increased neuromuscular excitability → tetany - Paresthesias (typically acral and/or perioral tingling or "pins and needles" sensation)- Muscle spasms, such as carpopedal spasm (possible in any muscle) and cramps- Chvostek's sign = contraction of the facial muscles elicited by tapping the facial nerve in the area of the cheek (approx. 2 cm ventral to the ear lobe)- Trousseau's sign = ipsilateral carpopedal spasm occurring several minutes after inflation of a blood pressure cuff to pressures above the systolic blood pressure- Seizures- Cardiac arrhythmias- Abdominal cramping and diarrhea Diagnostics:1. Evaluate calcium imbalance  - Initial test: serum calcium concentration  - Confirm true hypocalcemia/hypercalcemia: measure ionized calcium or use serum albumin to calculate corrected calcium.  2. Differentiate between low PTH and high PTH: to determine the underlying cause of calcium imbalance 3. Further tests: ECG QT interval prolonged Treatment:- Calcium supplementation→ IV calcium (1-2 g calcium gluconate in 50 mL of 5% dextrose infused over 10-20 mins): indicated in severely symptomatic patients (e.g., tetany, seizures), those with a prolonged QT interval, and asymptomatic patients with an acute decrease in serum corrected calcium to ≤ 7.5 mg/dL (≤ 1.9 mmol/L) → Oral calcium: indicated in patients with mild neuromuscular irritability (e.g., paresthesias), and those with serum corrected calcium > 7.5 mg/dL (> 1.9 mmol/L)→ Vitamin D supplementation: indicated in hypocalcemia caused by hypoparathyroidism or vitamin D deficiency→ For patients taking loop diuretics, medication change to thiazides  → Magnesium supplementation: indicated in hypocalcemia caused by hypomagnesemia
• Hypercalcemia = total serum calcium concentration > 10.5 mg/dL (> 2.62 mmol/L), or ionized (free) calcium concentration > 5.25 mg/dL (> 1.31 mmol/L) Etiology:- PTH-mediated→ Primary hyperparathyroidism: Adenoma (sporadic) or multiple endocrine neoplasia→ Familial hypocalciuric hypercalcemia→ Tertiary hyperparathyroidism- Hypercalcemia of malignancy- Granulomatous disorders (e.g., sarcoidosis)- Medications: Thiazide diuretics, excess vitamin D, calcium supplements- Hyperthyroidism: Thyroid hormones have osteoclastic activity.- Long periods of immobilization- Milk-alkali syndrome: Consumption of calcium carbonate- Paget's disease of the bone: Increased rate of bone remodeling Clinical features:- Nephrolithiasis, nephrocalcinosis (calcium oxalate > calcium phosphate stones)- Bone pain, arthralgias, myalgias, fractures- Abdominal pain, nausea and vomiting, peptic ulcer disease, constipation, pancreatitis- Neuropsychiatric symptoms such as anxiety, depression, fatigue, and cognitive dysfunction→ Somnolence progressing to obtundation and coma (hypercalcemic crisis!)- Diminished muscle excitability→ Cardiac arrhythmias→ Muscle weakness, paresis- Polyuria and dehydration Diagnostics:1. Evaluate calcium imbalance  - Initial test: serum calcium concentration  - Confirm true hypocalcemia/hypercalcemia: measure ionized calcium or use serum albumin to calculate corrected calcium.  2. Differentiate between low PTH and high PTH3. Further tests: ECG shows shortened QT interval  Treatment:- Mild or asymptomatic hypercalcemia: total calcium < 12 mg/dL (< 3 mmol/L) or ionized calcium < 8 mg/dL(< 2 mmol/L)→ Encourage adequate oral hydration→ Reduced dietary intake of calcium→ Avoidance of thiazide diuretics, lithium, high-calcium diet- Moderate hypercalcemia: total calcium between 12-14 mg/dl (3–3.5 mmol/L)→ Asymptomatic: same treatment as for mild hypercalcemia (see above)→ Symptomatic: same treatment as for severe hypercalcemia (see below)- Severe or symptomatic hypercalcemia: total calcium > 14 mg/dL (> 3.5 mmol/L) or ionized calcium > 12 mg/dL (> 3 mmol/L) → IV hydration with isotonic saline  → Loop diuretics (with monitoring of serum potassium!) in patients with renal insufficiency or heart failure to avoid volume overload → Bisphosphonates (e.g., zoledronic acid, pamidronate), in cases of excessive bone resorption (e.g., hypercalcemia of malignancy, immobilization)  → Calcitonin  → Dialysis in severe cases or renal failure: > 18 mg/dL (> 4.5 mmol/L)
• Acute kidney injury Etiology:- Prerenal (∼ 60% of cases)→ Volume depletion: e.g., hemorrhage, vomiting, diarrhea, sweating, burns, diuretics, poor oral intake, acute pancreatitis→ Decreased circulating volume: e.g., hepatorenal syndrome, cirrhosis, nephrotic syndrome, congestive heart failure→ Hypotension: e.g., sepsis, dehydration, cardiogenic shock, anaphylactic shock→ Renal artery stenosis→ Drugs affecting glomerular perfusion: e.g., cyclosporine, tacrolimus, NSAIDs, ACE inhibitors  - Intrinsic (∼ 35% of cases)→ Acute tubular necrosis (causes ∼ 85% of intrinsic AKIs)→ Glomerulonephritis (e.g., rapidly progressive glomerulonephritis)  → Vascular: Hemolytic uremic syndrome (HUS), Thrombotic thrombocytopenic purpura (TTP), Malignant hypertension, Vasculitis→ Tubulointerstitial nephritis: Drug-induced, Infectious, Immunological- Postrenal (∼ 5% of cases)→ Congenital malformations→ Acquired obstructions: benign prostatic hyperplasia (BPH), iatrogenic/catheter-associated tumors, stones, bleeding→ Neurogenic bladder (e.g., multiple sclerosis, spinal cord lesions, or peripheral neuropathy) Phases of AKI:- Kidney injury: Hours to days- Oliguric or anuricphase: Generally < 2 weeks- Polyuric phase: ∼ 3 weeks- Recovery phase: Up to 2 years Clinical features:- Oliguria or anuria- Signs of volume depletion: Orthostatic or frank hypotension and tachycardia, Reduced skin turgor- Signs of fluid overload: Edema, Shortness of breath- Signs of renal obstruction (in postrenal AKI): Distended bladder, Incomplete voiding, Pain over the bladder or flanks- Fatigue, confusion, and lethargy- In severe cases: seizures or coma Stages of AKI by Kidney Disease Improving Global Outcomes (KDIGO, 2012)Stage 1: - Serum creatinine: Increase of 0.3 mg/dL (within 48 h) or 1.5-1.9 times baseline (within 7 days)- Urine output: < 0.5 mL/kg/h for 6-12 hStage 2:- Serum creatinine: 2-2.9 times baseline- Urine output: < 0.5 ml/kg/h for ≥12 hStage 3:- Serum creatinine:  ≥ 3 times baseline or Increase to ≥ 4 mg/dL or Initiation of renal replacement therapy orPatients < 18 years: decrease in eGFR to < 35mL/min/1.73m2- Urine output: < 0.3 mL/kg/h for ≥ 24 h or Anuria for ≥ 1 Treatment:- General measures→ Patient should discontinue nephrotoxic substance use.→ Adjust dosages of medications cleared by the kidney (e.g., amiodarone, digoxin, cyclosporin, tacrolimus, antibiotics, chemotherapeutic agents).→ Monitor and manage changes in pH, water, and electrolyte balance.→ Assess uremic signs and symptoms (e.g., anorexia, nausea, vomiting, metallic taste, altered mental status) daily→ Perform dialysis if necessary.- Prerenal→ Replete volume with normal saline in patients with hypovolemia→ Administer diuretics in patients with hypervolemia who are hemodynamically stable and not anuric- Intrinsic→ Replete volume with normal saline in suspected ATN or contrast-induced renal dysfunction→ Consider corticosteroid or immunosuppressive therapy in RPGN or interstitial nephritis.→ Treat infection.- Postrenal: Remove outflow obstructions with Foley catheter insertion, an indwelling bladder catheter, nephrostomy, or stenting.
• Acute tubular necrosis Causes ∼ 85% of intrinsic AKIs Location:- The straight segment of the proximal tubule and the straight segment of the distal tubule (i.e., the thick ascending limb) are particularly susceptible to ischemic damage.- The convoluted segment of the proximal tubule is particularly susceptible to damage from toxins. Etiology:- Ischemic→ Prolonged hypovolemia/shock→ Thromboembolism→ Thrombotic microangiopathy→ Cholesterol embolism (atheroemboli)- Toxic→ Contrast-induced nephropathy→ Medication: aminoglycosides, cisplatin, amphotericin→ Pigment nephropathy: Myoglobinuria due to rhabdomyolysis (crush syndrome), Hemoglobinuria associated with hemolysis→ Acute uric acid nephropathy   Clinical features: same as for AKI  Diagnostics:- Blood findings: azotemia, hyperkalemia, and metabolic acidosis- Urinary sediment: muddy brown granular casts, epithelial cell casts, free renal tubular epithelial cells (due to denudation of the tubular basement membrane)   Prognosis: After 1-3 weeks, most patients with ATN will experience tubular re-epithelization and full recovery.
• Contrast-induced nephropathy Definition: AKI after IV administration of iodinated contrast medium Risk factors:- Chronic kidney disease (CKD): esp. in patients with diabetes mellitus, multiple myeloma- Congestive heart failure, arterial hypotension- Nephrotoxic drugs: esp. NSAIDs- Anemia- Dehydration  Course:- Creatinine is highest after 3-5 days after injury and usually falls back to the baseline level within 1 week.- The course is typically mild because end-stage renal disease usually only occurs in patients with pre-existing CKD. Prevention:- Always evaluate kidney function before administering a contrast agent.- Use a low dose and low concentration of contrast medium.- The patient should discontinue nephrotoxic substances before administration.- Ensure hydration: isotonic NaCl before and after administration of contrast medium- Acetylcysteine (no clear recommendations)
• Hematuria Physical exam:- Initial hematuria typically suggests a urethral cause.- Terminal hematuria suggests damage to the bladder, prostate, or trigonal area.- Total hematuria suggests damage in the kidneys or ureter.- Microhematuria: hematuria that is not grossly visible  - Macrohematuria: hematuria that is grossly visible (see also red urine)   Urinalysis: > 3 erythrocytes/HPF or > 5 erythrocytes/μL- If normal → evaluate for coagulation disorders, kidney stones, and malignancy - If pyuria → urine culture - If RBC casts and proteinuria → evaluate for glomerular diseases Differential diagnosis:- Nephritic syndrome  - Infection: Cystitis, Urethritis, Prostatitis- If asymptomatic, consider malignancy: Urothelial cancer, Renal cell carcinoma, Prostate cancer, In children, Wilms tumor- Urolithiasis- Coagulation disorder (e.g., hemophilia)- Polycystic kidney disease- Myoglobinuria in professional athletes or crush syndrome  - Medication side effect  - Porphyrias
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• Proteinuria Proteinuria = urinary protein excretion of > 150 mg/day Urinalysis:- Urine dipstick → repeat to rule out transient proteinuria (primarily detects albumin)- Sulfosalicylic acid test: sulfosalicylic acid is added to urine to measure total urine proteins (not specific for albumin)- 24-hour urine collection or urine protein-to-creatinine ratio in a spot urine sample to rule out orthostatic proteinuria- Urine sediment to rule out glomerular disease- Electrophoresis: to rule out tubulointerstitial diseases and multiple myeloma Classification according quantitiy:Microalbuminuria:- Urine albumin excretion of 30-300 mg/day- Diagnosis is made if two out of three tests are positive. Because the amount of protein excreted in urine varies, testing should be repeated three times over the course of 6-8 weeks.- Early symptom of diabetic nephropathy and hypertensive nephropathy- Specific urine dipstick tests, radioimmunoassay, or ELISA required for detection Overt proteinuria (formerly "macroalbuminuria"):- Urine albumin excretion > 300 mg/day- Standard urine dipstick tests can be used for detection.- Nephrotic syndrome: massive proteinuria (> 3.5 g/24 h), hypoalbuminemia, edema, and hyperlipidemia Classification according to origin:Glomerular proteinuria: - Characteristic finding: appearance of large proteins in the urine- Selective glomerular proteinuria→ Loss of negative charge of glomerular basement membrane→ Only small- to medium-sized proteins can be found in the urine (primarily albumin) → Can be found in diseases with mild damage to the glomeruli (e.g., minimal change disease, IgA nephropathy)- Non-selective glomerular proteinuria→ Damage to the glomerular basement membrane→ All types of protein of any size can be found in the urine (albumin, transferrin, and IgG are commonly detected)→ Can be found in diseases with severe damage to the glomeruli and subsequent permeability to all components of the blood (e.g., rapidly progressive glomerulonephritis, lupus nephritis, amyloid nephropathy) Tubular proteinuria:- Damage to the tubules → failure to reabsorb small proteins in the tubules → urinary protein excretion- The detection of beta-2 microglobulin without large proteins is typical.- Can be found in tubulointerstitial nephritis, analgesics nephropathy, acute renal failure Prerenal proteinuria (or overflow proteinuria):- Increased production of low-molecular-weight proteins → The reabsorption capacity of the tubules is exceeded. → Light chains or Bence-Jones protein (see myeloma kidney)→ Hemoglobinuria (in hemolysis)→ Myoglobinuria (in rhabdomyolysis) Postrenal proteinuria:- Proteins that are being produced in the tubules (Tamm-Horsfall protein)- Proteins that reach the urine in the lower urinary tract (e.g., trauma or inflammation)
• Acute tubulointerstitial nephritis Acute tubulointerstitial nephritis is most commonly caused by a hypersensitivity reaction to drugs (allergic interstitial nephritis). Some drugs may also lead to crystal-induced acute kidney injury. Allergic interstitial nephritis:- Etiology: Antibiotics, NSAIDs, diuretics, allopurinol, PPIs, phenytoin- Clinical features:→ Painless hematuria→ Flank pain→ Sterile pyuria→ Peripheral eosinophilia→ Rash  → Fever→ Arthralgias- Diagnostics→ Pyuria, Eosinophiluria→ Histology: diffuse interstitial inflammatory infiltrate (T lymphocytes, monocytes)   Crystal-induced acute kidney injury:- Etiology: E.g, acyclovir, indinavir, ciprofloxacin, methotrexate- Pathophysiology: Drugs with low urine solubility precipitate within the renal tubules → tubular obstruction & toxicity to tubules- Clinical features: Patients are usually asymptomatic, Renal colic- Diagnostics: Crystals on brightfield microscopy Therapy: Discontinue drugs and administer IV fluids Other etiologies:- Infectious: staphylococci, streptococci, Brucella, Legionella, hantaviruses- Systemic diseases: Sjögren's syndrome, systemic lupus erythematosus (SLE), sarcoidosis
• Chronic tubulointerstitial nephritis Analgesic nephropathy- Etiology: NSAIDs and acetaminophen  - Pathophysiology: Inhibition of prostacyclin synthesis → vasoconstriction of the medullary blood vessels → papillary ischemia and papillary necrosis- Clinical features: Painless hematuria, Pyuria, Fatigue, Nausea Myeloma kidney (myeloma cast nephropathy)- Pathophysiology: Excessive amounts of light chains are produced and filtered into the primary urine → precipitation of light chains in renal tubules → tubular obstruction & toxicity to renal tissue- Clinical features: Painless hematuria, Pyuria, Fatigue, Nausea- Treatment: Forced diuresis; If necessary, plasmapheresis/dialysis
• Chronic kidney disease (CKD) Chronic kidney disease is defined as an abnormality of the kidney structure or function for ≥ 3 months. Etiology of CKD in the US:- Diabetic nephropathy: Most common cause, accounts for 44% of cases in the US- Hypertensive nephropathy: 28%- Glomerulonephritis: 8%- Polycystic kidney disease/hereditary: 2%- Urological disease: 0.5%- Other causes: amyloidosis, toxins, chronic inflammation Clinical features:- Patients are often asymptomatic until later stages.- Hypertension- Peripheral edema- Pulmonary edema (usually interstitial pulmonary edema)- Clinical features of uremia  → Fatigue, weakness, loss of appetite, headaches → Uremic fetor→ Pigmented spots→ Pruritus  → Anemia→ Uremic pericarditis: Friction rub on auscultation. Uremic pericarditis does not show typical ECG changes such as diffuse ST-segment elevation.  → Pleuritis→ Asterixis→ Encephalopathy: seizures, somnolence, coma→ Peripheral neuropathy: paresthesias→ Gastrointestinal symptoms: nausea, vomiting→ ↑ Risk of infection: leukocyte dysfunction→ ↑ Bleeding tendency secondary to platelet dysfunction  - Chronic kidney disease-mineral and bone disorder (CKD-MBD): mostly due to secondary hyperparathyroidism → high-turnover renal osteodystrophy or osteitis fibrosa cystica Stage 1: GFR > 90Stage 2: GFR 60-89Stage 3: GFR 30-59Stage 4: GFR 15-29Stage 5: GFR < 15 Treatment:- Salt restriction in patients with edema or hypertension- Nephrotoxic substances avoidance- Strict blood pressure control- Vaccinations: Pneumococcal vaccine every 5 years; Influenza vaccine annually- Anemia of chronic kidney disease: EPO
• Nephrotic syndrome Defining features:- Proteinuria > 3.5 g/day- Edema- Hypoalbuminemia, hyperlipidemia- Hypercoagulability (due to loss of protein C and S and antithrombin III)- Immunodeficiency (due to loss of immunoglobulins/complement protein) Urinalysis findings:- Bland, RBCs, or fatty vacuoles in a maltese cross pattern Diagnostics:- Evaluate for nonrenal causes with ANA, a hepatitis panel, RPR, a fasting glucose or HbA1c, a pregnancy test, and HIV ELISA.- A biopsy may be needed for definitive diagnosis Differential diagnosis:- Minimal change disease- Focal segmental glomerulosclerosis- Membranous nephropathy- Membranoproliferative glomerulonephritis  - Diabetic nephropathy- Amyloidosis- Lupus nephritis
• Nephritic syndrome Defining features:- Proteinuria (usually < 3.5 g/day)- Edema- Oliguria, hematuria, hypertension Urinalysis findings:- Dysmorphic RBCs, RBC casts Diagnostics:- Check complement levels, ANCA, ANA, anti-dsDNA, cryoglobulin, a hepatitis panel, anti-GBM antibodies, anti-streptolysin antibody, and blood cultures- A renal biopsy is the gold standard of diagnosis Differential diagnosis:- Poststreptococcal glomerulonephritis- IgA nephropathy (Berger's disease)- Small vessel vasculitis- Goodpasture syndrome (Anti-GBM antibody disease)- Alport syndrome- Lupus nephritis- Rapidly progressive glomerulonephritis (RPGN)
• Minimal change disease Description: Effacement of glomerular basement membrane podocytes Associations:- Most common cause of nephrotic syndrome in children- Can be associated with tumors (e.g., Hodgkin lymphoma) Findings:- LM: no changes- EM: effacement of the foot processes- Selective glomerular proteinuria  Treatment:- Responds well to corticosteroids- Good prognosis
• Focal segmental glomerulosclerosis Associations:- Most common cause of nephrotic syndrome in black populations- Can be associated with heroin abuse, HIV infection, obesity, and sickle cell disease Findings:- LM: segmental sclerosis  - IM: IgM and C3 inside the sclerotic regions- EM: effacement of the foot processes Treatment:- Usually leads to ESRD if left untreated- Immunosuppressive treatment (but often shows poor response to corticosteroids)
• Membranous nephropathy Associations:- Most common cause of nephrotic syndrome in white populations- Primary: Anti-phospholipase A2 receptor antibodies- Secondary: can be associated with infections (hepatitis B and C), SLE, tumors, gold, and medications Findings:- LM: glomerular capillary loops and basement membrane appear thickened  - IM: subepithelial deposits- EM: subepithelial dense deposits (“spike and dome appearance”) Treatment: Corticosteroids
• Membranoproliferative glomerulonephrititis Membranoproliferative glomerulonephritis can also manifest as nephritic syndrome. Associations:- Immunoglobulin (IG)-mediated membranoproliferative glomerulonephritis: Associated with SLE, hepatitis C, monoclonal gammopathy- Complement-mediated membranoproliferative glomerulonephritis: dense deposit disease and C3 glomerulonephritis Findings:- IG-mediated→ Low serum complement level→ IM: IgG deposits on basement membrane- Complement-mediated→ Low serum C3 levels: patients with dense deposit disease often have IgG antibodies, so-called nephritic factor, against the C3 convertase, leading to persistent complement activation.→ IM: C3 deposits on basement membrane- Both: EM: basement membrane thickening, GBM splitting (“train-track” appearance) Treatment: No single effective treatment
• Poststreptococcal glomerulonephritis Associations:- Occurs weeks after group A β-hemolyticstreptococci infections→ Pharyngitis/tonsillitis (most common): 1-2 weeks→ Skin infections: 3-4 weeks- Usually affects children between the ages of 3-12 years- Can lead to RPGN in some cases Findings:- Positive antistreptococcal antibodies (ASO, ADB)- ↓ Serum C3 complement levels- Tea- or cola-colored urine- LM: glomeruli appear enlarged and hypercellular- IM: granular subepithelial immune complex depositions (IgG, IgM, C3) → “lumpy-bumpy” appearance- EM: dome-shaped, subepithelial deposits (“humps”) Treatment: Usually self-limiting
• IgA nephropathy (Berger's disease) Associations:- Most common idiopathic glomerulonephritis worldwide- Episodic gross hematuria during or directly after upper respiratory tract (URT), gastrointestinal (GI) infections, or strenuous exercise- Occurrence: ♂ > ♀- Peak incidence: 2nd to 3rd decade of life- ∼ 25-30% of the patients progress to end-stage renal disease (ESRD) within 20-25 years Findings:- Asymptomatic microhematuria with intermittent gross hematuria- ↑ Serum IgA- Normal C3 complement levels- LM: mesangial proliferation- IM: mesangial IgA deposits- EM: mesangial immune complex deposits
• Goodpasture syndrome (Anti-GBM antibody disease) Associations:- Two peaks of occurrence: 3rd decade of life (♂ > ♀) and ≥ 60 years of age (♀ > ♂)- Caused by antibodies against type IV collagen- Antibodies can cross-react with basement membrane of pulmonary capillaries and lead to pulmonary hemorrhage and hemoptysis- Can lead to RPGN Findings:- Pulmonary infiltrates on chest x-ray- IM: linear deposition of immunoglobulin (IgG) along the glomerular basement membrane Treatment:- Immunosuppressive therapy- Plasmapheresis
• Alport syndrome Associations:- X-linked (usually affects males)- Mutation in gene for type IV collagen- Often leads to ESRD Findings:- Persistent microhematuria with intermittent gross hematuria- Associated with sensorineural hearing loss and abnormalities of the eye  - EM: splitting and alternating thickening and thinning of the glomerular basement membrane
• Rapidly progressive glomerulonephritis (RPGN) Associations:- Glomerular diseases that progress to ESRD within weeks to months Findings:- Can be caused by a variety of diseases:→ Goodpasture syndrome (anti-GBM disease)→ Poststreptococcal glomerulonephritis→ Systemic lupus erythematosus (SLE)→ Microscopic polyangiitis→ Granulomatosis with polyangiitis (Wegener's)→ LM, IM, EM: crescent formation, monocytes, macrophages Treatment:- Immunosuppressive therapy- Plasmapheresis
• Type I renal tubular acidosis (distal RTA) Pathophysiology: Inability of the intercalated cells of the distal tubule to secrete H+ Etiologies: Hereditary, amphotericin, collagen vascular disease (e.g., scleroderma), cirrhosis, nephrocalcinosis Serum potassium levels: Hypokalemia Urine pH: > 5.5 Urine anion gap ([urine Na+ + urine K+] - [urine Cl-]): Positive Calcium excretion: ↑ Bone involvement: Bone demineralization without overt rickets or osteomalacia Nephrolithiasis: Usually present Treatment: Alkali therapy with sodium bicarbonate or sodium citrate (Shohl's solution)
• Type II renal tubular acidosis (Proximal RTA) Pathophysiology: Inability of the proximal convoluted tubule cells to reabsorb HCO3- Etiologies: Hereditary, carbonic anhydrase inhibitors, Fanconi's syndrome, tenofovir Serum potassium levels: Hypokalemia Urine pH: < 5.5 Urine anion gap: Negative Calcium excretion: Normal Bone involvement: Vitamin D-resistant rickets/osteomalacia Nephrolithiasis: Absent Treatment: Alkali therapy with orally administered potassium citrate
• Type IV renal tubular acidosis (hyperkalemic RTA) Incidence: Common Pathophysiology: Aldosterone deficiency and/or resistance Serum potassium levels: Hyperkalemia Urine pH: < 5.5 Urine anion gap: Positive Calcium excretion: Normal or ↓ Bone involvement: Bone demineralization without overt rickets or osteomalacia Nephrolithiasis: Absent Treatment: - Furosemide- Mineralocorticoid replacement (fludrocortisone)- Low-potassium diet
• Nephrolithiasis –Treatment Approach considerations:- Hemodynamically stable patients with uncomplicated stones ≤ 10 mm → a trial of observation with symptomatic treatment to enable spontaneous passage- Urological intervention required for:→ Patients with stones > 10 mm→ Complicated stones i.e., concomitant high-grade obstruction, urosepsis, impending acute kidney injury, intractable pain vomiting→ Failure to pass the stone spontaneously after 4-6 weeks- For most patients with kidney or ureteral stones ≤ 20 mm, first-line interventional treatments include both ureterorenoscopy and shock wave lithotripsy.- For patient with kidney stones > 20 mm, percutaneous nephrolithotomy is preferred. Medical therapy- Uncomplicated stones ≤ 10 mm: offer observation with symptomatic treatment and, especially in case of distal ureteral stones > 5 mm, medical expulsive therapy→ Hydration  → Analgesia (NSAIDs, IV morphine)→ Medical expulsive therapy: alpha blockers (e.g., tamsulosin) or calcium-channel blockers (e.g., nifedipine)→ Antibiotics: indicated in case of concomitant UTI- Uric acid stones: dissolve with urine alkalinization   Urological intervention:- Ureteral stenting or percutaneous nephrostomy: Surgical decompression in case of severely obstructed or infected pyelon; in those cases, definite stone treatment should be delayed until the infection has resolved.- Extracorporeal shock wave lithotripsy (SWL)  → First-line treatment option for renal stones ≤ 20 mm and ureteral stones→ Lowest complication rate but often repeated SWL is necessary for patients with residual stone burden→ Stones have to be clearly visible on x-ray and/or ultrasound→ Contraindicated in case of untreated UTI, during pregnancy, and in patients with bleeding diathesis; not preferred in morbidly obese patients  - Ureterorenoscopy (URS): First-line treatment option for renal stones ≤ 20 mm and ureteral stones→ Greatest stone-free rate- Percutaneous nephrolithotomy: first-line treatment for renal stones > 20 mm- Laparoscopic or open stone removal (pyelolithotomy or ureterolithotomy): only considered in rare cases where other interventional methods have previously failed or are likely to do so (e.g., because of complex staghorn stones)
• Urethral diverticulum Urethral mucosa herniated into surrounding tissue Clinical features:- Dysuria- Postvoid dribbling- Dyspareunia- Anterior vaginal wall mass Diagnostic testing:- Urinalysis- Urine culture- MRI of the pelvis- Transvaginal ultrasound
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• Living kidney donation Risks:- Perioperative:→ Mortality→ Hemorrhage→ Infection→ Thromboembolic events- Long-term:→ End-stage kidney disease→ Hypertension Absolute contraindications:- Inability to consent (age <18, intellectual disability, untreated psychiatric disease)- Diabetes mellitus- Hypertension with end-organ dysfunction- BMI >35 kg/m2- Malignancy
• Hepatorenal syndrome Deterioration of kidney function in patients with advanced liver disease. The condition is caused by renal vasoconstriction resulting in hypoperfusion of the kidneys. Triggers: loss of volume- Drainage of ascites- Gastrointestinal bleeding- Forced diuresis- Excess use of laxatives (lactulose) Symptoms:- Oliguria up to anuria with progressive kidney failure- Clinically associated with decompensated cirrhosis- Renal water retention leads to edema and hydrops (ascites, pleural, or pericardial effusion) Diagnostics:- Serum creatinine > 1.5 mg/dL- Elevated BUN:creatinine ratio (> 20:1)- Protein excretion < 500 mg/d- Hyponatremia with relative sodium deficiency  - Low sodium excretion in urine (< 10 mmol/L)   Therapy:- General measures: improvement of liver function if possible (e.g., cessation of alcohol use)- Pharmacotherapy: combination of midodrine, octreotide, and albumin  - Surgical/interventional:→ Placement of a transjugular intrahepatic portosystemic shunt (TIPS)  → A liver transplant is the only curative option in advanced liver disease
• Autosomal dominant polycystic kidney disease (ADPKD) Etiology: mutation on chromosome 16 (85% of cases) or 4 (15% of cases) with an alteration of polycystin-1 or 2 (the gene products of PKD1 and PKD 2 respectively) Clinical features:- Chronic renal failure- Flank or abdominal pain  - Recurrent urinary tract infections- Nephrolithiasis- Multiple hepatic cysts (in up to 70% of cases); cysts may also occur in the pancreas, spleen, ovary, and testicles- Signs of arterial hypertension (e.g., morning headaches)- Heart valve defects (particularly mitral valve prolapse)- Left ventricular hypertrophy- Colon diverticula, abdominal or inguinal hernias- Cerebral berry aneurysm (5-20%) Diagnostics:- Positive family history- Physical examination: palpable, bilateral upper abdominal masses that are not tender to touch- Ultrasound→ In adults: enlarged kidneys with multiple cysts bilaterally of varying sizes (anechoic masses)→ In children: evidence of cysts in combination with a positive family history→ Hepatic, pancreatic, splenic cysts may be visible.- Computer tomography (CT)   Treatment:- Prevent or delay progression to end stage renal disease (ESRD)→ Regular sonographic monitoring and laboratory evaluation of renal function→ Avoid nephrotoxic substances- Early treatment of arterial hypertension: ACE-inhibitors or Angiotensin receptor blockers (ARBS)- Monitor and treat liver failure- Genetic counseling- Hemodialysis or peritoneal dialysis for ESRD- Kidney transplantation is the only curative option (see also end stage renal disease).
• Recurrent urinary tract infection Definition- > 2 infections in 6 months- > 3 infections in 1 year Risk factors:- History of cystitis at < 15 years- Spermicide use- New sexual partner- Postmenopausal status Evaluation:- Urinalysis- Urine culture Prevention:- Behavior modification- Postcoital or daily antibiotic prophylaxis 
• Priapism A sustained erection that lasts more than 4 hours, is not caused by sexual excitation, and is not relieved by ejaculation. Low-flow priapism:- More common- Pathophysiology: Inadequate venous outflow from corpus cavernosum as a result of: → Thrombosis and/or compression of the penile, prostatic, and/or pelvic veins→ Prolonged tumescence  → Penile ischemia- Etiology→ Drugs: Treatment of erectile dysfunction: sildenafil, intracavernosal injection of alprostadil; Trazodone; Prazosin→ Hypercoagulable states: Sickle cell disease, Leukostasis reactions associated with leukemia→ Autonomic dysfunction: spinal cord stenosis, autonomic neuropathy, cauda equina syndrome→ Renal pelvic tumors: bladder cancer, prostatic cancerDrug use (especially for erectile dysfunction) is the most common cause of low-flow priapism among adults. Among children, sickle cell disease is the most common cause of low-flow priapism! High-flow priapism- Less common- Pathophysiology: Excessive arterial influx with sufficient venous outflow→ No penile ischemia- Etiology:→ Blunt perineal trauma (e.g., saddle injury) and/or penetrating injury (e.g., local penile injections) → injury to the cavernosal artery → fistula between the cavernosal artery and corpus cavernosum→ Congenital vascular malformations Clinical features:- Low-flow (ischemic) priapism→ Early presentation→ Painful erection (differential diagnosis: Peyronie's disease) → The corpus cavernosum is completely rigid.→ Recurrent priapism (stuttering priapism): a form of ischemic priapism that occurs in men with sickle cell disease  - High-flow (non-ischemic) priapism→ There is up to a 72-hour delay between the initial injury and the onset of priapism.  → Not painful→ The corpus cavernosum is not completely rigid.→ Symptoms of perineal trauma: perineal swelling, hematuria, dysuria Treatment:Low-flow priapism is a urological emergency. Rapid treatment of low-flow priapism within 12 hours is crucial because delayed treatment may result in permanent damage (cavernous body fibrosis with irreversible impotence)!Low-flow priapism:- First-line therapy→ Repeating intracavernosal injections of phenylephrine (alpha receptor agonist) up to an hour  → Aspiration of sludged blood (up to 500 mL) from the corpus cavernosum with/without irrigation with normal saline- Second-line therapy (if detumescence does not occur): decompression of the penis by creating a shunt between the corpus cavernosum and either the glans or the corpus spongiosum (e.g., Winter or Ebbehoj techniques)- Supportive measures→ Oxygen, adequate analgesia (with opiates if necessary), and hydration with IV fluids→ Patients with sickle cell disease who develop priapism require exchange transfusion. High-flow priapism- Usually no treatment is necessary.  - Persistent high-flow priapism can be treated electively with selective arterial embolization.
• Premature ejaculation – Treatment - Psychotherapy/behavioral therapy   - Local: topical anesthetics (e.g., lidocaine-prilocaine spray) can also be used in combination with SSRIs and psychotherapy. - Systemic: SSRIs (e.g., paroxetine) are first-line treatment.
• Premature ejaculation – Treatment - Psychotherapy/behavioral therapy   - Local: topical anesthetics (e.g., lidocaine-prilocaine spray) can also be used in combination with SSRIs and psychotherapy. - Systemic: SSRIs (e.g., paroxetine) are first-line treatment.
• Treatment of LUTS with BPH and erectile dysfunction Tadalafil (phosphodiesterase-5-inhibitor)

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