kidney and electrolyte disorders

Rarely reversible, progressive decline in renal function. • Affects more than 13 million Americans, most of whom are unaware. • Over 70% of cases of stage 5 CKD and end-stage renal disease (ESRD) in the United States are caused by diabetes mellitus or hypertension/vascular disease. • Glomerulonephritis, cystic diseases, chronic tubulointerstitial diseases, and other urologic diseases account for the remainder. • Genetic polymorphisms of the APOL-1 gene have been shown to be associated with an increased risk of the development of CKD in African Americans.

Bland urine sediment with few, if any, cells or casts; may have oval fat bodies. • Proteinuria >3 g/d, serum albumin <3 g/dL, edema. • Hyperlipidemia is typical.

Serum K+ is <3.5 mEq/L (<3.5 mmol/L). • Severe hypokalemia may induce dangerous arrhythmias and rhabdomyolysis. • Transtubular potassium concentration gradient (TTKG) can distinguish renal from nonrenal loss of potassium.

Hyperkalemia is treated with sodium polystyrene sulfonate. • Acid–base disorders can be treated with sodium bicarbonate. • Hypertension is treated with ACEIs or ARBs (if serum potassium and GFR permit) and diuretics. • Heart failure is treated with salt and water restriction, loop diuretics, and ACE inhibitors with close monitoring if serum creatinine >3 mg/dL. • Anemia is treated with iron supplementation (if evidence of iron deficiency) and erythropoietin or darbepoetin. • Coagulopathy may be helped acutely with desmopressin (DDAVP) and chronically by dialysis. • Renal osteodystrophy and osteomalacia are treated with phosphorous-binding agents (calcium carbonate or acetate), vitamin D or vitamin D analogs, and calcitriol.

Cholecystitis • Appendicitis • Diverticulitis • Epididymitis • Pyelonephritis • Prostatitis • Pancreatitis • Lower lobe pneumonia • Abdominal aortic aneurysm • Musculoskeletal pain

• Nausea, vomiting • Malaise • Hypertension • Pericardial friction rub, effusions, and cardiac tamponade • Arrhythmias • Rales and volume overload • Abdominal pain and ileus • Bleeding secondary to platelet dysfunction • Encephalopathy, altered sensorium, asterixis, seizures • Oliguria, defined as urinary output <500 mL/d or <20 mL/h

Primary glomerular diseases (eg, focal and segmental glomerulosclerosis, IgA nephropathy) • Secondary glomerular diseases (eg, diabetic nephropathy, amyloidosis, sickle cell nephropathy, HIV-associated nephropathy) • Tubulointerstitial nephritis (eg, drug hypersensitivity, analgesic nephropathy, chronic pyelonephritis) • Hereditary disease (eg, polycystic kidney disease, Alport syndrome, medullary cystic disease) • Obstructive nephropathies (eg, prostatic disease, nephrolithiasis, congenital) • Vascular diseases (eg, hypertensive nephrosclerosis, renal artery stenosis)

Diet: low sodium, low potassium, low phosphorus, water restriction to maintain fluid balance • Kidney transplantation • Hemodialysis or peritoneal dialysis for end-stage CKD with unresponsive fluid overload, hyperkalemia, metabolic acidosis, or severe uremia (eg, pericarditis, encephalopathy, and coagulopathy) despite treatment measures outlined above, or when GFR is <10 mL/min/1.73 m2

• ATN: ischemia, toxins (eg, NSAIDs, antibiotics, radiographic contrast, rhabdomyolysis, chemotherapy, multiple myeloma, hemolysis, hyperuricemia, cyclosporine) • Acute glomerulonephritis: immune complex (immunoglobulin A nephropathy, endocarditis, systemic lupus erythematosus [SLE], cryoglobulinemia, postinfectious, membranoproliferative); pauci-immune or antineutrophil cytoplasmic antibody positive (granulomatosis with polyangiitis, Churg-Strauss syndrome microscopic polyangiitis); antiglomerular basement membrane or anti-GBM (Goodpasture syndrome, anti-GBM glomerulonephritis) • Vascular: malignant hypertension, atheroembolism, thrombotic thrombocytopenic purpura • Acute interstitial nephritis (AIN): drugs (sulfa, NSAIDs, β-lactams, allopurinol, diuretics, rifampin, phenytoin), infections (Streptococcus, leptospirosis, cytomegalovirus, histoplasmosis, Rocky Mountain spotted fever), immune (SLE, Sjögren syndrome, sarcoidosis, cryoglobulinemia)

Calculation of the anion gap is useful in determining the cause of the metabolic acidosis. • A normochloremic (increased anion gap) metabolic acidosis generally results from addition to the blood of organic acids such as lactate, acetoacetate, β-hydroxybutyrate, and exogenous toxins (eg, ethylene glycol, methanol, or salicylate). • Most common causes of hyperchloremic, normal (non-) anion gap metabolic acidosis are gastrointestinal (GI) HCO3− loss and defects in renal acidification (renal tubular acidoses).

GI loss from infectious diarrhea is the most common cause. • Potassium shift into the cell is transiently stimulated by insulin and glucose and facilitated by β-adrenergic stimulation; α-adrenergic stimulation blocks potassium shift into the cell. • Aldosterone increases potassium secretion in the distal renal tubule. • Magnesium is a cofactor for potassium uptake and is required for maintenance of potassium levels; magnesium depletion should be suspected in persistent or refractory hypokalemia.

Acute kidney injury, dependent edema, and hypertension • Hematuria, dysmorphic red cells, RBC casts, and mild proteinuria

Abnormal GFR persisting for at least 3 months • Plot of the inverse of serum creatinine (1/SCr) versus time if three or more prior measurements are available helps estimate time to ESRD • Anemia, platelet dysfunction, bleeding time prolongation • Metabolic acidosis • Hyperphosphatemia, hypocalcemia, hyperkalemia • Proteinuria, urinary sediment with broad waxy casts

Urinalysis: microscopic or gross hematuria in 90%. • Urinary pH: <5.5 suggests uric acid or cystine stones; ≥7.2 suggests a struvite stone; between 5.5 and 6.8 typically indicates calcium-containing stones. • Serum calcium, parathyroid hormone, uric acid, electrolytes (including bicarbonate), and creatinine and blood urea nitrogen should also be obtained. • Stone analysis of any recovered stones. • Recurrent stones or family history may require 24-hour urine collection for volume, pH, calcium, uric acid, oxalate, phosphate, sodium, and citrate.

Serum Na+ <135 mEq/L (<135 mmol/L). • Hyponatremia usually reflects excess water retention relative to sodium rather than sodium deficiency. • Sodium concentration is not a measure of total body sodium. • Volume status and serum osmolality are essential to determine the cause. • Hypotonic fluids commonly cause hyponatremia in hospitalized patients.

Possible renal biopsy if cause is unclear

Postinfectious GN commonly appears 1 to 3 weeks after pharyngitis or impetigo. • Pauci-immune necrotizing GN is caused by granulomatosis with polyangiitis (formerly Wegener granulomatosis), microscopic polyangiitis, or Churg-Strauss syndrome. • Membranoproliferative GN (MPGN) is an idiopathic renal disease that usually presents with nephritic features ranging from asymptomatic glomerular hematuria and proteinuria to episodes of gross hematuria to the acute nephritic syndrome. • Essential (mixed) cryoglobulinemia is associated with cold-precipitable immunoglobulins (cryoglobulins) precipitating in glomerular capillaries. • Rapidly progressive acute GN requires rapid identification and treatment.

Blood pH, serum HCO3−, and Pco2 are decreased; hyperkalemia may be seen. • Anion gap is increased (normochloremic), normal, or decreased (hyperchloremic). • In lactic acidosis, lactate levels are at least 4 to 5 mEq/L but are commonly 10 to 30 mEq/L. • The diagnosis of alcoholic ketoacidosis is supported by the absence of a diabetic history and no evidence of glucose intolerance after initial therapy. • Urinary anion gap from a random urine sample (urine [Na+ + K+] – Cl−) helps differentiate between renal and GI etiologies of hyperchloremic (normal or nonanion gap) acidosis. The urinary anion gap is negative if the cause is GI HCO3− loss (diarrhea) since renal acidification remains normal and NH4Cl excretion increases. If the cause is distal RTA, the urinary anion gap is positive since the kidney cannot excrete NH4Cl.

Serum creatinine may or may not be elevated depending on severity and chronicity. • Urinalysis shows proteinuria; few cellular elements or casts; oval fat bodies, appearing as “grape clusters” under light microscopy and “Maltese crosses” under polarized light. • Serum albumin <3 g/dL, serum protein <6 g/dL; hyperlipidemia; elevated erythrocyte sedimentation rate. • Elevated hemoglobin A1C in diabetics. • Hyperlipidemia. • Serum complement levels, serum and urine protein electrophoresis, antinuclear antibodies, and serologic tests for hepatitis (as indicated).

Decline in the glomerular filtration rate (GFR) over months to years. • Persistent proteinuria or abnormal renal morphology may be present. • Symptoms and signs of uremia when nearing end-stage disease. • Hypertension in most cases. • Bilateral small or echogenic kidneys on ultrasonogram in advanced disease.

There is no consensus about the optimal rate of sodium correction in symptomatic hyponatremic patients but recent guidelines recommend A relatively small increase of 4 to 6 mEq/L in the serum sodium (perhaps all that is necessary to reverse the neurologic manifestations of symptomatic hyponatremia) Rapid infusion of 100 mL of 3% hypertonic saline over 10 minutes (repeated twice as necessary) for acute hyponatremia (eg, exercise-associated) with severe neurologic manifestations Lower correction rates, as low as 4 to 8 mEq/L per 24 hours, for chronic hyponatremia in patients at high risk for demyelination Treatment with a combination of DDAVP and intravenous dextrose 5% to relower the serum sodium for chronic hyponatremic patients at high risk for demyelination who are corrected too rapidly

Oral potassium is the safest way to treat mild-to-moderate deficiency. • Dietary potassium is almost entirely coupled to phosphate—rather than chloride—and does not correct potassium loss associated with chloride depletion, such as from diuretics or vomiting. • In the setting of abnormal kidney function and mild-to-moderate diuretic dosage, daily oral potassium therapy is generally sufficient to prevent hypokalemia. • Indications for intravenous potassium replacement include severe, life-threatening hypokalemia or an inability to tolerate oral supplementation. • Coexisting magnesium and potassium depletion can result in refractory hypokalemia despite potassium repletion if there is no magnesium repletion.

Corticosteroids and cytotoxic agents as indicated for primary renal lesion. • Loop and thiazide diuretics in combination and often in large doses. • ACE inhibitors and angiotensin receptor blockers (ARBs) (except in the setting of acute kidney injury) Published studies have not found benefit from combined ARB and ACE inhibitor therapy. • Glucose and blood pressure control in diabetic nephropathy. • Antilipidemic agents. • Patients with frequent relapses may require cyclophosphamide or rituximab. • Warfarin for patients with thrombosis for at least 3 to 6 months.

Renal ultrasound

The diagnosis of cryoglobulinemia calls for aggressive treatment of the underlying infection, including α-interferon for hepatitis C–related cryoglobulinemia in some patients, as well as pulse corticosteroids, plasma exchange, and cytotoxic agents. • Treatment of pauci-immune disease is high-dose corticosteroids and cytotoxic agents (cyclophosphamide) followed by long-term azathioprine or mycophenolate mofetil. • Treatment for MPGN is controversial, but there may be some role for corticosteroids, cyclophosphamide, cyclosporine, and mycophenolate mofetil, though adults are less likely to respond than children. Renal transplantation is an option but the disease may recur in the transplanted kidney; plasma exchange has been used with mixed results to treat posttransplant recurrence of MPGN.

Renal biopsy is indicated in adults with new-onset idiopathic nephrotic syndrome.

Severe flank pain, hematuria, nausea, and vomiting • Identification of stone on noncontrast helical CT scan or ultrasonography

Heart failure • Cirrhosis • Venous insufficiency • Protein-losing enteropathy • Malnutrition • Hypothyroidism

• Renal hypercalciuria: thiazide diuretics decrease renal calcium excretion • Hyperoxaluric calcium nephrolithiasis: oral calcium supplements • Hypocitraturic calcium nephrolithiasis: potassium citrate, oral lemonade • Uric acid calculi: potassium citrate alkalinization of the urine (goal pH between >6.2 and <6.5, monitored by the patient with nitrazine pH paper) and, if hyperuricemia is present, treatment with allopurinol • Struvite calculi: stone extraction, consideration of suppressive antibiotics, acetohydroxamic acid (an effective urease inhibitor, but poorly tolerated) • Cystine calculi: alkalinization of the urine, increase fluid intake, penicillamine and tiopronin

Symptoms include severe, colicky, episodic pain in the flank radiating to the abdomen with nausea and vomiting. • Patients are constantly moving in sharp contrast to those with an acute abdomen. • With a stone in the ureter, pain may be referred into the ipsilateral groin. • With a stone at the ureterovesical junction, marked urinary urgency and frequency occur; pain may radiate to the tip of the penis. • After the stone passes into the bladder, there is minimal pain with passage through the urethra. • Stone size does not correlate with the severity of symptoms.