Essentials of Nephrology: Acute and Chronic Kidney Disease

Shieva Khayam-Bashi, MD, Associate Clinical Professor, Department of Family and Community Medicine, University of California, San Francisco, School of Medicine, and Medical Director, Ward 4A/SNF, San Francisco General Hospital

Acute Kidney Disease

Educational Objectives

The goal of this program is to improve management of acute and chronic kidney disease. After hearing and assimilat­ing this program, the clinician will be better able to:

1.   List intrinsic renal problems that lead to acute kidney injury.

2.   Identify causes of acute kidney injury, based on urinalysis with microscopy.

3.   Perform appropriate laboratory studies to evaluate kidney function.

4.   Use appropriate methods to accurately screen for proteinuria.

5.   Counsel patients about therapy and lifestyle modification.

Faculty Disclosure

In adherence to ACCME Standards for Commercial Support, Audio-Digest requires all faculty and members of the plan­ning committee to disclose relevant financial relationships within the past 12 months that might create any personal con­flicts of interest. Any identified conflicts were resolved to ensure that this educational activity promotes quality in health care and not a proprietary business or commercial interest. For this program, Dr. Khayam-Bashi and the planning committee reported nothing to disclose.

Acknowledgements

Dr. Khayam-Bashi spoke in San Francisco, CA, at Family Medicine: Board Review Course, presented July 6-9, 2009, by the University of California, San Francisco, School of Medicine. The Audio-Digest Foundation thanks Dr. Khayam-Bashi and the University of California, San Francisco, School of Medicine for their cooperation in the production of this program.

Acute kidney injury: consider whether problem prerenal (problem of flow to kidneys), postrenal (obstructive pro­cess at level of ureter, bladder, or urethra), or intrinsic (“is it the kidneys?”); 66% of time, problem prerenal (10% of time, postrenal; 33% of time, intrinsic)

Case presentation: man 55 yr of age with diabetes, hypertension, and degenerative joint disease (DJD) presents with 3-day history of nausea, vomiting, diarrhea, and low oral intake; becomes oliguric, anuric, confused, and complains of pruritus; medications include benazepril, hydrochlorothiazide, glipizide, and ibuprofen; physical examination  —dehydration; hypotension; tachycardia; tachypnea; hypoxia; confusion; dry mucous membranes; rales on lung ex­amination; no abdominal mass; normal prostate examination; no petechiae or purpura; laboratory studies  —  potassium high (6 mEq/L); sodium low (129 mEq/L); CO₂ low (20 mEq/L); serum urea nitrogen (BUN) high; cre­atinine high; treatment  —normal saline boluses for hypotension; Foley catheter inserted to rule out obstruction (no urine excreted); no acute changes on electrocardiography (ECG); hyperkalemia treated with transcellular shifting-mediated mechanism of insulin and glucose, calcium, and sodium polystyrene to help bind potassium in gut; blood pressure (BP) medications and nonsteroidal anti-inflammatory drugs (NSAIDs) held; urinalysis (UA) showed con­centrated urine, with no red blood cells (RBCs), white blood cells (WBCs), or tubular cell casts (acute tubular ne­crosis [ATN] ruled out); renal ultrasonography (US) negative for hydronephrosis; patient's BP, urine output, mental status, BUN, and creatinine improved; man discharged after few days with diagnosis of acute kidney injury (prere­nal azotemia secondary to acute viral gastroenteritis)

Acute kidney injury: rapid rise in creatinine over £2 wk; if baseline creatinine <2.5 mg/dL, often defined as rise of ³0.5 mg/dL; if baseline creatinine >2.5 mg/dL, defined as increase in creatinine >20%; can be nonoliguric or oligu­ric (oliguria in adults, urine output of <400 mL/day; in children, <0.5 mL/kg per hr); anuria (urine output <100 mL/day) usually associated with poorer prognosis, except in dehydration; mortality rates vary (25%-90%; in-hospi­tal mortality, £50%); higher mortality rates usually seen in patients who require dialysis; complications  —  electrolyte disorders (eg, hyperkalemia, metabolic acidosis); infections; gastrointestinal (GI) bleeding; arrhythmia; myocardial infarction (MI); pulmonary edema

Causes of acute kidney injury: volume depletion  —decreased oral intake; vomiting; diarrhea; diuretic use; anaphy­laxis; sepsis; MI; congestive heart failure (CHF); cirrhosis; signs of obstruction  —  patients often asymptomatic; ab­dominal or flank pain; hematuria; sudden anuria; weight loss or cancer symptoms (pelvic cancers lead to obstruction of ureters, urethra, or bladder); agitation; intrinsic renal problems  —  most commonly due to medica­tions (eg, intravenous [IV] contrast, aminoglycosides, amphotericin, penicillins, cephalosporins, sulfonamides); positive family history of kidney disease; personal renal history; autoimmune disease and vasculitis (eg, lupus, Sjögren’s syndrome); viral diseases (eg, hepatitis B or C, HIV)

Consequences of acute kidney injury: encephalopathy; uremic pericarditis; CHF and fluid overload (eg, pulmonary or peripheral edema, significant hypertension); acute platelet dysfunction; indications for dialysis

Physical examination: volume status; orthostatic vital signs; dry mucous membranes; pericardial rub (pericarditis; emergent hemodialysis indicated); pulmonary edema; bladder distention; petechiae might suggest uremic syn­drome or thrombotic thrombocytopenic purpura (TTP); palpable purpura suggest vasculitis; pelvic and prostate ex­amination

Laboratory studies: complete blood cell count (CBC); platelet count normal in acute kidney failure; chemistry panel (CHEM-7); stat ECG; UA with microscopy; urine culture and renal US helpful; serum sodium and creatinine and urinary sodium and creatinine (to calculate fractional excretion of sodium [FENa]); x-ray of kidneys, ureter, and bladder optional; computed tomography (CT) of abdomen for masses or symptoms suggestive of cancer; ECG in hyperkalemia  —  ventricular tachycardia or ventricular fibrillation can be sudden or gradual; peaked T waves with prolonged PR intervals; with progression, P waves lost and QRS intervals widen with peaked T waves; FENa  —  indicates how well kidneys retain sodium in setting of dehydration; (urinary sodium/plasma sodium) ÷ (urinary creatinine/plasma creatinine) x 100; obtain urinary and plasma values at same time of day; <1% usually suggests prerenal etiology (>1% usually suggests ATN); FENa often elevated by diuretic use, or decreased due to certain in­trinsic renal problems (eg, acute glomerulonephritis, ATN, rhabdomyolysis, contrast nephropathy, sepsis); patients with chronic kidney disease can have chronically elevated FENa; fractional excretion of urea  —  useful in patients with recent use of diuretic; (urinary urea/plasma urea) ÷ (urinary creatinine/plasma creatinine) x 100; <35% usually suggests prerenal etiology (>35% usually suggests ATN); more reliable than FENa; if clinical setting suggests pre­renal etiology, low urinary sodium and low fractional excretion of sodium confirm prerenal etiology; FENa can be low in acute glomerulonephritis or vascular disorder; in intrinsic renal problems, urinary sodium high; UA with microscopy  —  tubular epithelial cell casts usually indicate ATN, and sometimes acute interstitial nephritis; white cell casts without bacteria often indicative of interstitial nephritis (most commonly caused by drugs; ask nephrolo­gist to look for >10% eosinophils), but sometimes seen in chronic glomerulonephritis; red cell casts indicative of glomerulonephritis; hyaline casts nonspecific (often seen in prerenal cases); oval fat bodies indicative of nephrotic syndrome; when urine dipstick positive for blood (eg, 1+, 2+, or 3+) with no RBCs on UA microscopy, consider rhabdomyolysis (reversible cause of acute renal failure; irreversible if missed) and check serum creatine kinase  

Treatment: manage consequences; consider need for emergent hemodialysis; give IV fluids unless patient volume overloaded; inserting Foley catheter helpful for ruling out distal obstruction of urethra (flush catheter with normal saline to clear any obstructive sediment or clot)

Indications for emergent hemodialysis: hyperkalemia; metabolic acidosis; CHF; uremic encephalopathy; pericardi­tis; BUN and creatinine values alone not indication for dialysis; certain drug overdoses; ECG of pericarditis  —  diffuse ST segment elevations with audible rub; PR interval depressions

Treatment before dialysis: hyperkalemia  —  treat with glucose and insulin or IV calcium; sodium polystyrene (Kayexalate); furosemide; check ECG and monitor; CHF  —  treat with O₂ and diuresis; severe acidosis  —  treat with sodium bicarbonate; NSAIDs and anticoagulants contraindicated in patients with uremic pericarditis; avoid  —po­tassium, potassium-sparing diuretics, angiotensin-converting enzyme (ACE) inhibitors, NSAIDs, and IV contrast

Postrenal causes: masses; tumors; stones; anticholinergic drugs (eg, tricyclic antidepressants; diphenhydramine [eg, Benadryl])

Intrinsic renal causes: aortic dissection; 90% of time, due to ATN (often induced by hypotension); most common problems due to nephrotoxic drugs and rhabdomyolysis (treat with hydration and IV bicarbonate); acute intersti­tial nephritis  —  can develop as late as 10 to 30 days after last drug dose; drug history important; only »33% of patients have eosinophils in urine (diagnostic finding); vascular  —less likely; emboli from left heart; aortic ather­oma; postaortic surgery; left heart endocarditis; atrial fibrillation; renal artery stenosis (consider in young people with refractory hypertension) or thrombosis; glomerulonephritis; autoimmune diseases; renal infiltration (rare)

Nephritis: interstitial  —  clinical clues include fever, rash, and eosinophilia in blood; urine sediment; protein in urine; consider viral testing (for, eg, cytomegalovirus [CMV], HIV, hepatitis B virus [HBV]) and autoimmune testing (for, eg, sarcoidosis, Sjögren’s syndrome); consult nephrologist before treating; glomerulonephritis  —clinical clues include preexisting infection (eg, Streptococcus), rash, arthritis; urine sediment; RBC casts; protein in urine; look for infections (eg, HIV, hepatitis B and C); in patients with rash or arthritis, look for cryoglobuline­mia or lupus; consider multiple myeloma in patients >40 yr of age (perform urine and serum protein electropho­resis); consult nephrologist

Vasculitis: clinical clues include fever, constitutional symptoms, rash, respiratory symptoms; RBC casts; autoim­mune testing, testing for HIV, hepatitis B and C

Summary of acute renal failure: adjust doses of all drugs; choose lowest dosing; diuretics for converting oliguric to nonoliguric renal failure no longer used (benefits unclear and may worsen mortality); no benefit of low doses of do­pamine; prevention of contrast nephropathy  —  in patients with risk factors for acute renal failure (eg, advanced age, chronic kidney or liver disease), hold metformin, diuretics, and NSAIDs for 2 days; start IV fluids or advise high oral fluid intake 1 day before; giving sodium bicarbonate 1 hr before and 6 hr after may be beneficial (data conflict­ing); acetylcysteine (eg, Mucomyst; 600 mg bid) 1 day before and on day of study (controversial)

Chronic Kidney Disease (CKD)

Screening for CKD: screen patients with risk factors (eg, diabetes, hypertension, age >60 yr); positive family history, history of recurrent urinary tract infection (UTI) or obstruction, or systemic illness (eg, autoimmune disease, vascu­litis) less common risk factors; reasons for screening  —  to slow disease progression; to prevent or reduce risk for cardiovascular disease; check BP and creatinine; CHEM-7; random urine sample for protein or albumin to creati­nine ratio; UA with microscopy

Estimated glomerular filtration rate (eGFR): normal GFR, 95 to 120 mL/min per 1.73 m²; GFR decreases with age; renal dysfunction can occur despite normal creatinine; eGFR better measure of kidneys’ ability to filter, and helps detect early kidney disease; calculation based on age, sex, and ethnicity (ie, black or white)

Screening for proteinuria: can detect kidney disease even before changes in eGFR occur; proteinuria associated with more rapid decline of kidney function; reducing proteinuria slows progression of CKD; treat with ACE inhib­itor or angiotensin receptor blocker (ARB); urine dipstick detects large amounts (>300 mg) of protein (albumin); measure albumin directly in patients with microalbuminuria; 24-hr urine collection gold standard for protein, but inconvenient and prone to error; measure protein or albumin to creatinine ratio; normal urinary protein to creatinine ratio, <200 mg to 1 g (for albumin, <30 mg to 1 g); microalbuminuria, 30 to 300 mg of albumin to 1 g of creatinine; macroalbuminuria, >300 mg of albumin to 1 g of creatinine; in patients with protein in urine, obtain total protein to creatinine ratio; in patients with risk factors and positive dipstick (protein >30 mg), perform albumin or total pro­tein to creatinine ratio; perform 24-hr urine for patients “in extremes” (eg, extremes of age or weight, high muscle mass) or with malnutrition, muscle diseases, paraplegia, vegetarianism, pregnancy

Diagnosing CKD: presence of kidney damage for ³3 mo (based on abnormal structure on imaging study or abnormal function), or eGFR <60 mL/min per 1.73 m² for ³3 mo; end-stage renal disease  —  eGFR <15 mL/min per 1.73 m² (kidney failure);  need for dialysis or transplantation; stages  —  stage 5 most severe; stage 3, eGFR, 30 to 60 mL/min per 1.73 m²; eGFR underestimates renal function at normal creatinine levels (eg, creatinine of 0.6 mg/dL may cor­relate with stage 1 eGFR value; creatinine of 0.9 mg/dL may correlate with lower eGFR); eGFR values <60 mL/min per 1.73 m² reliable; CKD commonly caused by diabetic kidney disease, vascular problem (eg, hyperten­sion, large vessel disease), and glomerular diseases (eg, tubular interstitial disease, drug toxicities); in patients with risk factors for parenterally transmitted diseases consider eg, HIV, hepatitis B and C, associated kidney diseases; in patients with rash, consider lupus and cryoglobulinemia; laboratory studies  —  recent UA; CHEM-7; urine protein or albumin to creatinine ratio; renal US  —  may show stones, hydronephrosis, or cysts; small hyperechoic kidneys generally indicate CKD; large kidneys may be associated with hydronephrosis (obstructive process), or infiltrating process (eg, sarcoidosis or lymphoma); size disparity between kidneys indicates renal vascular disease (eg, fibro­muscular dysplasia or renal artery thrombosis); slow progression of CKD by controlling BP, glucose, and protein­uria

Complications: hyperkalemia; hyperphosphatemia; hypocalcemia (secondary hyperparathyroidism); hyponatremia; decreased immunoglobulins; dyslipidemia  —  coronary artery disease number 1 cause of mortality in patients with CKD; animal studies suggest dyslipidemia can worsen kidney function; recent meta-analysis of 13 small studies showed lipid reduction might preserve GFR; patients with CKD tend to have high triglycerides and elevated low-density lipoprotein (LDL) to high-density lipoprotein (HDL) ratios; guidelines recommend aggressive targets (eg, LDL <100 mg/dL, triglycerides <200 mg/dL); hypertension  —  ACE inhibitors and ARBs preferentially lower glo­merular pressures and reduce proteinuria; in patients with normal urine protein, target BP, <130/80 mm Hg; in pa­tients with protein in urine, target BP, <125/75 mm Hg; when starting ACE inhibitors in CKD patients, GFR initially decreases, and creatinine increases mildly (£30%; check CHEM-7 1-2 wk after initiating therapy; do not discontinue therapy unless increase does not stabilize; monitor); anemia  —  normochromic; normocytic; hypoprolif­erative; caused by low erythropoietin; reduces quality of life; causes fatigue and can lead to cardiomyopathy from left ventricular hypertrophy; correction of anemia may help improve CKD; recommended hemoglobin (Hb) target, 10 g/dL to 12 g/dL; check ferritin and supplement with iron if indicated; give erythropoietin to predialysis patients if Hb <10 g/dL; renal osteodystrophy  —  common; early CKD patients have hyperphosphatemia and increased para­thyroid hormone (PTH), resulting in increased bone turnover, decreased bone strength, and fractures; check PTH and restrict dietary phosphate intake; treat with calcium acetate and vitamin D; refractory patients may need surgi­cal treatment to remove parathyroid

Nutrition and lifestyle: CKD patients at risk for malnutrition; study showed patients on restricted protein diet did not fare better; refer patients to nutritionist and consult nephrologist; be aggressive about tobacco smoking cessation; social support and screening for depression  

When to refer to nephrologist: underlying cause unclear after work-up; need for biopsy; diagnosis unclear; stage 3 or 4 CKD; rapid progression of CKD or superimposed acute kidney failure; www.kidney.org or www.mdrd.com useful resources

Suggested Reading

Kleinknecht D: Interstitial nephritis, the nephrotic syndrome, and chronic renal failure secondary to nonsteroidal anti-inflammatory drugs. Semin Nephrol 15:228, 1995; Levin A et al: Canadian Society of Nephrology. Guidelines for the management of chronic kid­ney disease. CMAJ 179:1154, 2008; Lines S et al: Acute kidney injury. Clin Med 9:273, 2009; Schwarz A et al: The outcome of acute interstitial nephritis: risk factors for the transition from acute to chronic interstitial nephritis. Clin Nephrol 54:179, 2000; Singh D: Sodium bicarbonate therapy and contrast-induced nephropathy. Am J Kidney Dis 54:390, 2009; Solomon R: Contrast-induced acute kidney injury (CIAKI). Radiol Clin North Am 47:783, 2009; Thakar CV et al: Incidence and outcomes of acute kidney injury in intensive care units: a Veterans Administration study. Crit Care Med 37:2552, 2009; Trivedi H et al: High-dose N-acetylcysteine for the prevention of contrast-induced nephropathy. Am J Med 122:874, 2009; van Heyningen C: Lipid metabolism and causal path­ways for cardiovascular disease in chronic kidney disease. Curr Opin Lipidol 20:440, 2009.