Case 1: Dizziness, nausea, increased urination
A 75-year-old woman is hospitalized for a 1-week history of dizziness, nausea, vomiting, increased urination, and decreased appetite. History is significant for hypertension treated with hydrochlorothiazide. She also takes calcium carbonate for bone health.
On physical examination, blood pressure is 150/85 mm Hg supine and 122/70 mm Hg standing, pulse rate is 78/min supine and 100/min standing, and respiration rate is 18/min. There is no neck vein distention. Cardiac, pulmonary, and abdominal examinations are unremarkable. There is no lower extremity edema.
Laboratory studies show hematocrit 30%, leukocyte count 3000/μL (3.0 × 109/L), platelet count 82,000/μL (82 × 109/L), calcium 12.8 mg/dL (3.2 mmol/L), and creatinine 3.7 mg/dL (327.1 µmol/L). Electrolytes are sodium 132 mEq/L (132 mmol/L), potassium 4.9 mEq/L (4.9 mmol/L), chloride 115 mEq/L (115 mmol/L), and bicarbonate 17 mEq/L (17 mmol/L). Phosphorus is 6.2 mg/dL (2.0 mmol/L) and urine sodium is 15 mEq/L (15 mmol/L). Urinalysis shows specific gravity 1.018, trace protein, few erythrocytes/hpf, occasional leukocytes/hpf, few granular casts, and numerous hyaline casts.
Which of the following is the most likely cause of this patient's hypercalcemia and acute kidney injury?
A. Hydrochlorothiazide therapy
B. Milk alkali syndrome
C. Multiple myeloma
D. Primary hyperparathyroidism
Case 2: Preventing acute kidney injury
A 68-year-old woman is hospitalized for a non–ST-elevation myocardial infarction. History is significant for hypertension, hyperlipidemia, type 2 diabetes mellitus, and stage G3b chronic kidney disease. Medications on admission are furosemide, irbesartan, atorvastatin, basal and prandial insulin, and low-dose aspirin.
Vital signs and the physical examination are normal.
Transthoracic echocardiogram shows anterolateral hypokinesis with an estimated left ventricular ejection fraction of 35% to 40%.
Coronary angiography is scheduled.
In addition to stopping furosemide, which of the following is the most appropriate measure to prevent acute kidney injury?
A. Begin intravenous 0.9% saline
B. Begin oral N-acetylcysteine
C. Discontinue atorvastatin
D. Discontinue irbesartan
Case 3: Hyperkalemia in the surgical ICU
A 79-year-old woman is evaluated for hyperkalemia. She was admitted to the surgical ICU after having an urgent partial colectomy for a ruptured diverticulum with peritonitis. She was treated with intravenous fluids, antibiotics, and vasopressor therapy. Today, postoperative day 1, she is oliguric with urine output <5 mL/h for the past 4 hours. She is now weaned off the vasopressor therapy. History is significant for hypertension and stage G4 chronic kidney disease. Outpatient medications are amlodipine, irbesartan, and furosemide. Current medications are morphine, propofol, cefotaxime, and metronidazole.
On physical examination, the patient is intubated and mechanically ventilated. A urinary catheter is in place. Temperature is 38.9 °C (102.0 °F), blood pressure is 108/70 mm Hg, and pulse rate is 101/min. There is generalized anasarca. The abdomen is distended and quiet.
Laboratory studies show creatinine 3.6 mg/dL (318.2 µmol/L) from a baseline of 2.0 mg/dL (176.8 µmol/L), sodium 142 mEq/L (142 mmol/L), potassium 7.1 mEq/L (7.1 mmol/L), chloride 102 mEq/L (102 mmol/L), total bicarbonate 17 mEq/L (17 mmol/L), and arterial pH 7.25. Urine sediment shows brown granular casts. Electrocardiogram shows peaked T waves with a QRS of 140 ms.
In addition to intravenous calcium, insulin, and dextrose, which of the following is the most appropriate treatment?
A. Continuous renal replacement therapy
C. Intravenous furosemide
D. Sodium bicarbonate
E. Sodium polystyrene sulfonate enema
Case 4: Young patient with bloody diarrhea
An 18-year-old man is evaluated in the emergency department for abdominal cramping and bloody diarrhea of 6 days' duration. Medical history is unremarkable, and he takes no medications.
On physical examination, temperature is 37.0 °C (98.6 °F), blood pressure is 98/60 mm Hg, pulse rate is 100/min, and respiration rate is 16/min. Oxygen saturation is normal breathing ambient air. His abdomen is tender, without guarding or organomegaly. The examination is otherwise unremarkable.
Laboratory studies show undetectable haptoglobin, hemoglobin 6.1 g/dL (61 g/L), leukocyte count 6800/µL (6.8 × 109/L), platelet count 37,000/µL (37 × 109/L), reticulocyte count 9.8% of erythrocytes, and creatinine 3.6 mg/dL (318 µmol/L).
Urinalysis shows 3+ blood, 3+ protein, 0-2 erythrocytes/hpf, 0-2 leukocytes/hpf, and several granular casts. The peripheral blood smear shows schistocytes and scant platelets without clumps. The direct antiglobulin (Coombs) test is negative.
What is the most likely diagnosis?
A. Atypical hemolytic uremic syndrome
B. Hemolytic uremic syndrome
C. Immune hemolytic anemia and thrombocytopenia
D. Rapidly progressive glomerulonephritis
Answers and commentary
Correct answer: C. Multiple myeloma.
This patient's acute kidney injury (AKI) is due to hypercalcemia from multiple myeloma. Classic symptoms of polyuria, polydipsia, and nocturia sometimes occur with elevated serum calcium levels of 11 mg/dL (2.8 mmol/L) or less. Other symptoms such as anorexia, nausea, abdominal pain, constipation, increased serum creatinine levels, and mild mental status changes are more likely to occur with levels >11 mg/dL (2.8 mmol/L). Kidney dysfunction is found in about 30% of patients diagnosed with multiple myeloma, often due to cast nephropathy (also termed myeloma kidney), a condition in which excess monoclonal free light chains precipitate in the distal tubules and incite tubulointerstitial damage. Hypercalcemia and exposure to nephrotoxic agents are other frequent causes of kidney dysfunction. Hypercalcemia can decrease glomerular filtration rate through renal vasoconstriction, the natriuretic effects of high serum calcium levels, and impaired renal concentrating ability. This patient has orthostatic hypotension, a bland urinalysis with hyaline casts, and a low urinary sodium, consistent with a prerenal AKI from hypovolemia. The constellation of hypercalcemia, normal anion gap metabolic acidosis, pancytopenia, and AKI suggests multiple myeloma as the etiology.
Hydrochlorothiazide can cause volume depletion, decreased excretion of calcium and mild hypercalcemia, prerenal AKI, and metabolic alkalosis (due to hypovolemic stimulation of aldosterone release). However, the effect on serum calcium is usually minimal, and the patient has a metabolic acidosis, not metabolic alkalosis as might be seen with thiazide therapy.
Milk alkali syndrome occurs with the ingestion of large amounts of calcium and absorbable alkali (for example, calcium carbonate). It presents as hypercalcemia, metabolic alkalosis, and AKI. This patient has a metabolic acidosis, not a metabolic alkalosis, making this diagnosis unlikely.
Primary hyperparathyroidism is the most common cause of hypercalcemia in otherwise healthy outpatients and is diagnosed with a simultaneously elevated serum calcium level and an inappropriately normal or elevated intact parathyroid hormone level. Serum phosphorus levels are typically low or low-normal in these patients. This patient's phosphorus level is elevated, making the diagnosis of primary hyperparathyroidism unlikely.
- A diagnosis of multiple myeloma is suggested by the constellation of anemia, hypercalcemia, normal anion gap metabolic acidosis, and acute kidney injury.
Correct answer: A. Begin intravenous 0.9% saline.
The administration of 0.9% saline is an appropriate measure to prevent contrast-induced nephropathy (CIN), which is recognized as a distinct subset among patients with contrast-associated nephropathy (CAN). CAN is defined as an increase in serum creatinine levels within 24 to 48 hours of contrast exposure, and is a common cause of reversible acute kidney injury in the hospital. Several large, well-controlled observational studies suggest that a substantial proportion of acute kidney injury that follows administration of intravenous contrast material is not, in fact, directly attributable to the contrast agent. CIN includes that subset of CAN in which the kidney injury can be more definitively linked to the contrast exposure, rather than other potential causes of nephrotoxicity. Adequate intravenous volume expansion with isotonic crystalloids before the procedure and continued for 6 to 24 hours afterward has been shown to decrease the incidence of CIN in patients at risk. Intravenous hydration induces an increase of urine flow rate, reduces the concentration of contrast in the tubule, and increases the excretion of contrast. Because administration of intravenous crystalloid remains the primary strategy for reducing the risk of CIN, patients with compensated heart failure should still be given intravenous volume. Patients with uncompensated heart failure should undergo hemodynamic monitoring with continuation of diuretics. This patient has compensated heart failure noted on examination and should be given fluids.
A recent large randomized trial among patients at high risk for kidney complications compared three different strategies to prevent CIN: intravenous 1.26% sodium bicarbonate or intravenous 0.9% sodium chloride and 5 days of oral acetylcysteine or oral placebo. For fluid administration, this study used a protocol of 1 to 3 mL/kg/h before angiography, 1 to 1.5 mL/kg/h during angiography, and 1 to 3 mL/kg/h 2 to 12 hours after angiography. There was no benefit of intravenous sodium bicarbonate over intravenous sodium chloride or of oral acetylcysteine over placebo for the prevention of death, need for dialysis, or persistent decline in kidney function at 90 days or for the prevention of CIN.
Some but not all studies suggest that statins may reduce the risk of CIN. A 2016 meta-analysis suggested that statins given with N-acetylcysteine plus intravenous saline reduced the risk of CIN compared with N-acetylcysteine plus intravenous saline alone in relatively low-risk patients. Based on these results, there is no need to discontinue atorvastatin in this patient.
Discontinuation of ACE inhibitors or angiotensin receptor blockers such as irbesartan has not been clearly shown to decrease the risk of CIN.
- Intravenous volume expansion with isotonic crystalloids has been shown to decrease the incidence of contrast-induced nephropathy in patients at risk.
Correct answer: B. Hemodialysis.
Intermittent hemodialysis (IHD) is the most efficient way to correct this patient's hyperkalemia in the setting of anuric-oliguric acute kidney injury (AKI). IHD, typically delivered 3 to 6 times a week for 3 to 5 hours per session, allows for rapid correction of electrolyte disturbances and rapid removal of drugs or toxins. This patient has severe hyperkalemia with electrocardiographic changes, which should be corrected urgently to prevent lethal cardiac arrhythmias. Calcium, insulin, and dextrose are only temporizing measures and will not result in potassium removal from the body. Only dialysis will result in potassium removal from the body.
Continuous renal replacement therapy (CRRT) is a type of dialysis that is performed in critically ill patients who are hemodynamically unstable. CRRT provides hemodynamic stability by removing fluid and solutes at a much slower rate than IHD. As a result, CRRT would not be able to clear potassium rapidly but may be considered if the patient cannot tolerate IHD.
Furosemide can induce urinary potassium loss by increasing urine flow and delivery of sodium to the distal nephron for exchange with potassium. However, this patient is nearly anuric with acute tubular necrosis based on urine microscopy and unlikely to respond to furosemide.
Sodium bicarbonate causes a shift of hydrogen ion from the intracellular fluid compartment to the extracellular compartment, causing an opposing net intracellular potassium shift to maintain electroneutrality. The effect of bicarbonate is transient and ineffective in end-stage kidney disease or severe AKI.
Sodium polystyrene sulfonate is a cation exchange resin that removes potassium through the gastrointestinal tract. The onset of action is hours to days, and its effectiveness is disputed. It is contraindicated in patients with recent bowel surgery because of an increased risk for intestinal necrosis.
- In the setting of anuric-oliguric acute kidney injury, intermittent hemodialysis allows for rapid correction of electrolyte disturbances and rapid removal of drugs or toxins.
Correct answer: B. Hemolytic uremic syndrome.
This patient most likely has hemolytic uremic syndrome (HUS). HUS is a diarrhea-associated syndrome of microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury caused by Shiga toxin–producing Escherichia coli, typically with serotypes O157:H7, O104:H4, and, less commonly, Shigella dysenteriae. Shiga toxin binds to endothelial cells, triggering thrombosis and resulting in a thrombotic microangiopathy. It also binds to renal mesangial cells, podocytes, and renal tubular cells, causing direct damage. These actions lead to acute kidney injury. Although it is more commonly seen in children, it can also present in adults. Supportive care is a cornerstone of treatment, and fluid management with volume expansion is critical despite any existing oliguria.
Atypical HUS is a congenital syndrome caused by overwhelming complement activation that is not preceded by a diarrheal illness as typical HUS is. The distinction between thrombotic thrombocytopenic purpura and typical and atypical HUS is difficult but important to make because atypical HUS is effectively treated by infusions of eculizumab, a monoclonal antibody directed against the terminal components of the complement cascade.
The combination of an immune-mediated hemolytic anemia, usually warm antibody, IgG mediated, and immune thrombocytopenic purpura is known as Evans syndrome. Although this patient has evidence of a hemolytic anemia and thrombocytopenia, the direct antiglobulin test is negative, and schistocytes, reflecting microangiopathic hemolysis, were noted on the peripheral blood smear. Spherocytes would be expected in IgG-mediated autoimmune hemolytic anemia.
Patients with rapidly progressive glomerulonephritis (RPGN) typically present with the nephritic syndrome and may sometimes be in advanced kidney failure at the time of presentation. Other symptoms and clinical findings related to an underlying cause may also be present, such as systemic signs of vasculitis (arthritis, epistaxis, hemoptysis) or lung hemorrhage (Goodpasture syndrome). The absence of active urinary sediment and the presence of microangiopathic hemolytic anemia make RPGN an unlikely diagnosis.
- Classic hemolytic uremic syndrome is a diarrhea-associated syndrome of microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury caused by Shiga toxin–producing Escherichia coli and, less commonly, Shigella dysenteriae.