A 55-year-old man comes to the office due to a week of nausea and generalized weakness. He also has had muscle cramps for the past 3 days. The patient has a history of type 2 diabetes mellitus diagnosed 2 years ago, hypertension diagnosed 10 years ago, and hyperlipidemia. The patient has been on a stable medication regimen of metformin, lisinopril, and rosuvastatin for 2 years. He does not use tobacco, alcohol, or illicit drugs. Temperature is 37 C (98.6 F), blood pressure is 160/98 mm Hg, pulse is 84/min, and respirations are 18/min. The mucous membranes are moist. Bilateral basal crackles are present. The abdomen is soft and nontender. Bilateral 2+ lower extremity edema is present. Laboratory results are as follows:
| Serum chemistry | |
| Potassium | 7.4 mEq/L |
| Bicarbonate | 14 mEq/L |
| Blood urea nitrogen | 82 mg/dL |
| Creatinine | 8 mg/dL (3 months ago: 1.1 mg/dL) |
| Calcium | 10.9 mg/dL |
| Glucose | 100 mg/dL |
| Urinalysis | |
| Protein | +1 |
| White blood cells | 1-2/hpf |
| Red blood cells | 1-2/hpf |
| Casts | none |
Urine sodium is 70 mEq/L. Renal ultrasound shows normal-sized kidneys with no evidence of hydronephrosis. Which of the following is the most likely cause of this patient's current condition?
Acute kidney injury | ||
Prerenal | Acute tubular necrosis | |
BUN/creatinine ratio | Typically >20 | Typically normal (~10-15) |
Urine sodium | <20 mEq/L | >40 mEq/L |
Fractional excretion of sodium | <1% | >2% |
Urine osmolality | >500 mOsm/kg | ~300 mOsm/kg |
Urine specific gravity | >1.020 | <1.020 |
Microscopy | Bland | Muddy brown casts |
This patient presents with several features of significant acute kidney injury (AKI), including a rapid rise in creatinine, hyperkalemia, metabolic acidosis (eg, bicarbonate <18 mEq/L), volume overload (eg, crackles, edema), and systemic manifestations of uremia (eg, weakness, nausea). AKI is often categorized as follows:
Prerenal: characterized by low urine sodium (eg, <20 mEq/L) and elevated blood urea nitrogen (BUN)/creatinine ratio (eg, >20) due to passive urea reabsorption.
Postrenal: classically causing hydronephrosis on ultrasound.
Intrinsic: characterized by high urine sodium (typically >40 mEq/L) and fractional excretion of sodium (>2%) due to tubular damage limiting reabsorptive capacity; in contrast to prerenal injury, BUN/creatinine ratio tends to be normal (~10-15:1).
This patient's ultrasound findings and chemistry results (eg, high urine sodium, BUN/creatinine ratio ~10:1) make postrenal and prerenal injury unlikely and suggest that his AKI reflects intrinsic injury. Although confirmation of the underlying cause of intrinsic renal injury would require further evaluation, the presence of hypercalcemia provides an important diagnostic clue.
Most cases of renal failure result in hypocalcemia due to reduced renal phosphorus excretion; because phosphorous combines with calcium to form calcium phosphate salts, serum calcium levels usually decline. Patients who have acute renal failure and hypercalcemia often have an underlying malignancy that is driving calcium release. This is most often seen in the setting of multiple myeloma (MM), which classically presents with anemia, bone pain, hypercalcemia, and acute renal failure. MM-induced hypercalcemia is due to osteoclast activating factors and can cause AKI due to clogging of the renal tubules with calcium deposits or immunoglobulin light chains. Glassy light chain casts are often present, but the urinalysis may be bland if cast formation has not yet occurred. Urine dipstick typically demonstrates mild proteinuria (only detects albumin); however, a quantitative 24-hour protein assay will show elevated protein excretion (Bence-Jones proteinuria).
(Choices A and D) Decreased cardiac output and intravascular volume depletion cause prerenal AKI (eg, BUN/creatinine ratio >20, urine sodium <20 mEq/L). Hypercalcemia-induced diuresis is unlikely in this case due to the presence of moist mucous membrane, which would be uncommon in the setting of significant volume depletion.
(Choices B and C) Drug-induced interstitial nephritis is associated with rash, fever, and white blood cells/white blood cell casts on urinalysis, whereas glomerulonephritis is characterized by hematuria with red blood cell casts. None of these conditions are associated with hypercalcemia.
(Choice E) Progression of diabetic nephropathy typically occurs over a period of years; this significant increase is highly unlikely to occur over 3 months. Although mild proteinuria is common, ultrasound typically demonstrates shrunken, atrophic kidneys, and hypocalcemia (not hypercalcemia) is common.
Educational objective:
Damage to the renal tubules causes intrinsic renal failure with limited resorptive capacity. This results in high urine sodium (>40 mEq/L) and a normal blood urea nitrogen/creatinine ratio (~10-15:1). Renal injury usually results in hypocalcemia; the presence of hypercalcemia suggests an underlying malignancy, particularly multiple myeloma.