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Nephrology 2 ace

Question 1 of 40

A 47-year-old man with subarachnoid hemorrhage and hyponatremia is confused post-surgery; what condition does he likely have?

A. Cerebral salt wasting B. Syndrome of inappropriate antidiuretic hormone secretion C. Adrenal insufficiency D. Central diabetes insipidus E. Psychogenic polydipsia

A. Cerebral salt wasting
B. Syndrome of inappropriate antidiuretic hormone secretion
C. Adrenal insufficiency
D. Central diabetes insipidus
E. Psychogenic polydipsia

A 47-year-old male presents with a thunderclap headache. Head imaging reveals a subarachnoid hemorrhage. Neurosurgery team is consulted and the patient undergoes surgical clipping. The next day, he is very confused and disoriented and is hallucinating. Vital signs show his blood pressure to be 126/80mmHg while sitting and upon standing, his blood pressure drops to 92/60mmHg. His pulse is high at 106/min upon standing. Labs show the following:

Na+ 128 mmol/L (135-145)
K+ 4.8 mmol/L (3.5-5.0)
Cl- 96 mmol/L (98-106)
HCO3- 24 mmol/L (24-30)
Serum osmolarity 250 mOsm/kg (275–295)
Urine osmolarity 780 mOsm/kg H2O (38–1400)
Urine sodium 45 mmol/L

Which of the following conditions does this patient likely have?

A. Cerebral salt wasting B. Syndrome of inappropriate antidiuretic hormone secretion C. Adrenal insufficiency D. Central diabetes insipidus E. Psychogenic polydipsia

A. Cerebral salt wasting
B. Syndrome of inappropriate antidiuretic hormone secretion
C. Adrenal insufficiency
D. Central diabetes insipidus
E. Psychogenic polydipsia

Clarification:

The correct answer is A. Cerebral salt wasting (CSW) is characterized by hyponatremia and extracellular fluid depletion due to inappropriate sodium wasting in the urine in the setting of acute disease in the central nervous system (CNS), usually subarachnoid hemorrhage. CSW is a much less common cause of hyponatremia in patients with cerebral injury than the syndrome of inappropriate ADH secretion (SIADH). The pathophysiology of CSW is related to impaired sodium reabsorption, possibly due to the release of brain natriuretic peptide and/or diminished central sympathetic activity. Regardless of the mechanism, sodium wasting can lead sequentially to volume depletion, increased ADH release, hyponatremia due to the associated water retention, and possibly increased neurologic injury.

Why Other Choices Are Incorrect:

B. Syndrome of inappropriate antidiuretic hormone secretion: Also, CSW is often confused with SIADH. Both conditions will exhibit low serum osmolarity, high urine osmolarity, high urine sodium, and low serum sodium. However, patients with SIADH have normal fluid volume status (euvolemia) and in CSW, patients have low volume status (hypovolemia).
C. Adrenal insufficiency: He does not have any predisposing conditions that can lead to adrenal insufficiency like long-term corticosteroid use or sepsis. Also, patients with primary adrenal insufficiency typically have some elevation in potassium. This patient’s potassium is normal.
D. Central diabetes insipidus: Patients with central diabetes insipidus have high serum osmolarity and low urine osmolarity. This patient has the opposite labs.
E. Psychogenic polydipsia: Psychogenic polydipsia presents with low serum osmolarity and low urine osmolarity. This patient’s urine osmolarity is high.

Medical Conclusion:

Cerebral salt wasting (CSW) is characterized by hyponatremia and extracellular fluid depletion due to inappropriate sodium wasting in the urine in the setting of acute disease in the central nervous system (CNS), usually subarachnoid hemorrhage. CSW mimics all of the laboratory findings in the SIADH. The only clue to the presence of CSW rather than SIADH is clinical evidence of extracellular volume depletion, such as hypotension and decreased skin turgor, and/or increased hematocrit, in a patient with a urine sodium concentration above 40 mmol/L.

A 58-year-old woman with flank pain and a passed ureteral stone has hypercalcemia; what’s the next step?

A. Serum uric acid level B. Cystoscopy C. 24-hour urinary calcium measurement D. No further studies unless recurrence E. Repeat serum chemistry and PTH level

E. Repeat serum chemistry and PTH level
A. Serum uric acid level
B. Cystoscopy
C. 24-hour urinary calcium measurement
D. No further studies unless recurrence

A 58-year-old woman comes to the emergency department with left-sided flank pain and dark urine. Vital signs are normal, and physical examination is notable only for left upper abdominal tenderness. Complete blood count is normal. Additional laboratory results are as follows:

Serum chemistry
Sodium 136 mmol/L (135-145)
Potassium 4.2 mmol/L (3.5-5.0)
Chloride 100 mmol/L (98-106)
Bicarbonate 26 mmol/L (24-30)
Blood urea nitrogen 5 mmol/L (2.5-8.0)
Creatinine 71 µmol/L (70-120)
Calcium 2.67 mmol/L (2.18-2.58)
Glucose 6.8 mmol/L (3.3-5.8)
Urinalysis
Specific gravity 1.013
pH 6.2
Protein +1
Blood gross
Leukocyte esterase negative
Bacteria none
White blood cells 1-2/hpf
Red blood cells many/hpf

A noncontrast abdominal CT scan reveals a dense, 4-mm stone in the distal left ureter without hydronephrosis. The patient is treated with intravenous hydration and analgesics, which relieve her symptoms. The stone is passed without further intervention and sent for analysis. Which of the following is the best next step in evaluation of this patient’s condition?

A. Serum uric acid level B. Cystoscopy C. 24-hour urinary calcium measurement D. No further diagnostic studies indicated unless nephrolithiasis recurs E. Repeat serum chemistry and serum parathyroid hormone level

E. Repeat serum chemistry and serum parathyroid hormone level
A. Serum uric acid level
B. Cystoscopy
C. 24-hour urinary calcium measurement
D. No further diagnostic studies indicated unless nephrolithiasis recurs

Clarification:

This patient with nephrolithiasis has hypercalcemia, raising suspicion for symptomatic hyperparathyroidism leading to calcium stone formation. In patients with renal calculi, even high normal serum calcium levels should prompt evaluation for hyperparathyroidism. The diagnosis can be generally confirmed by persistent hypercalcemia with an elevated parathyroid hormone level.

Why Other Choices Are Incorrect:

A. Serum uric acid level: Uric acid stones are relatively uncommon (5%-10% of stones), primarily occur in patients with persistently acidic urine (pH < 5.5), and have a low radiodensity. This patient’s urine pH of 6.2, hypercalcemia, and presence of a dense stone on CT scan make calcium-based stones more likely.
B. Cystoscopy: Cystoscopy is commonly performed to rule out malignancy in patients with hematuria. However, this patient is at low risk for bladder cancer (i.e., female, age <65, nonsmoker) and has a compelling explanation for her hematuria (i.e., nephrolithiasis).
C. 24-hour urinary calcium measurement: 24-hour urine collections can be used to evaluate for supersaturation of common stone metabolites (e.g., calcium, oxalate, uric acid) but are not always required to diagnose hyperparathyroidism. A collection could be considered if parathyroid hormone level is normal or minimally elevated.
D. No further diagnostic studies unless nephrolithiasis recurs: Deferring further diagnostic studies until recurrence of nephrolithiasis may be appropriate for patients without risk factors or abnormalities on initial workup. However, given this patient’s hypercalcemia, hyperparathyroidism must be ruled out.

Medical Conclusion:

The correct answer is E, as repeating serum chemistry and measuring parathyroid hormone level is the best next step to evaluate for hyperparathyroidism in this patient with nephrolithiasis and hypercalcemia.

A 71-year-old man with lung cancer and hyponatremia has mild concentration difficulty; what is the best management?

A. Administer intravenous normal (0.9%) saline B. Initiate fluid restriction C. Initiate hemodialysis D. Administer hypertonic (3%) saline E. Administer hydrochlorothiazide

B. Initiate fluid restriction
A. Administer intravenous normal (0.9%) saline
C. Initiate hemodialysis
D. Administer hypertonic (3%) saline
E. Administer hydrochlorothiazide

A 71-year-old man with a history of lung cancer undergoes follow-up labs after a recent cycle of chemotherapy. He has had mild difficulty with concentration over the past week but is otherwise able to complete all of his daily tasks. He denies any nausea, vomiting, or positional lightheadedness. He has no other significant past medical history. He takes no medications chronically.
His blood pressure is 135/88 mmHg, pulse is 76/min, respiratory rate is 18/min, and temperature is 37.6 C (99.8 F). On examination, he is alert and oriented. Cardiac examination reveals regular rate and rhythm, no murmurs, and jugular venous pressure not elevated. Lung and abdominal examination is normal. There is no lower extremity edema. Skin turgor is normal. Neurologic examination reveals 5/5 strength in all extremities, no focal deficits and normal gait. Laboratory tests reveal the following:

Leukocyte count 8.3× 109/L (3.5–10.5)
Hemoglobin 102 g/L (125–170)
Glucose 5.8 mmol/L (3.3-5.8)
Na+ 121 mmol/L (135-145)
K+ 4.3 mmol/L (3.5-5.0)
Blood urea nitrogen 2.5 mmol/L (2.5-8.0)
Creatinine 35.37 µmol/L (70-120)
TSH 2.0 mU/L (0.4-5.0)
Serum osmolality 250 mOsm/kg (280-300)
Urine Na 45 mmol/L
Urine osmolality 450 mOsm/kg

What would be the most appropriate management of this patient?

A. Administer intravenous normal (0.9%) saline B. Initiate fluid restriction C. Initiate hemodialysis D. Administer hypertonic (3%) saline E. Administer hydrochlorothiazide

B. Initiate fluid restriction
A. Administer intravenous normal (0.9%) saline
C. Initiate hemodialysis
D. Administer hypertonic (3%) saline
E. Administer hydrochlorothiazide

Clarification:

The correct answer is B. The syndrome of inappropriate antidiuretic hormone secretion (SIADH) is defined by the hyponatremia and hypo-osmolality resulting from inappropriate, continued secretion or action of the antidiuretic hormone arginine vasopressin (AVP) despite normal or increased plasma volume, which results in impaired water excretion.
Hyponatremia (ie, serum Na+< 135 mmol/L) with concomitant hypo-osmolality (serum osmolality < 280 mOsm/kg) and high urine osmolality is the hallmark of SIADH. In patients with SIADH, the urinary osmolality is usually submaximally dilute (ie, >100 mOsm/kg) and urinary Na+ is greater than 20 mmol/L.
The patient is euvolemic and has lung cancer, low serum osmolality, and high urine osmolality all suggestive of syndrome inappropriate antidiuretic hormone (SIADH) as the cause. He has very mild symptoms and can be managed with fluid restriction and increased salt intake.

Why Other Choices Are Incorrect:

A. Administer intravenous normal (0.9%) saline: Administering IV normal (0.9%) saline is not the appropriate answer as sodium will be excreted but water will be retained; thus, worsening hyponatremia.
C. Initiate hemodialysis: Initiating hemodialysis is not appropriate as the patient has minimal symptoms, has not failed other therapies, and because it is invasive.
D. Administer hypertonic (3%) saline: Administering hypertonic (3%) saline is not necessary as the patient has minimal symptoms; if the patient had more severe symptoms such as confusion, lethargy, nausea, or vomiting this would be appropriate.
E. Administer hydrochlorothiazide: Administering hydrochlorothiazide is not correct as this medication itself is a cause of hyponatremia; loop diuretics such as furosemide can be used to correct sodium levels in SIADH.

Medical Conclusion:

The patient is euvolemic and has lung cancer, low serum osmolality, and high urine osmolality all suggestive of syndrome inappropriate antidiuretic hormone (SIADH). He has very mild symptoms and can be managed with fluid restriction and increased salt intake.

A 34-year-old man with recurrent calcium oxalate stones has high-normal urinary calcium; what’s the next step?

A. Decrease calcium intake B. Decrease coffee intake C. Decrease oxalate intake D. Start allopurinol E. Start chlorthalidone

E. Start chlorthalidone
A. Decrease calcium intake
B. Decrease coffee intake
C. Decrease oxalate intake
D. Start allopurinol

A 34-year-old man is evaluated during a follow-up visit after passing his third calcium oxalate kidney stone in 4 years despite maintaining a high urine volume. He has no other medical problems. His only medication is potassium citrate, which was initiated after passing the most recent stone. He drinks 4 cups of coffee daily and typically eats meals at fast-food restaurants. Physical examination findings, including vital signs, are normal. Laboratory studies:

24-Hour urine studies
Volume 2600 mL
pH 6.5
Calcium 7.3 mmol (2.5–7.5)
Citrate 9 mmol (0.6–6.0)
Oxalate 0.35 mmol (0.44)
Uric acid 4.0 mmol (1.48–4.43)

The patient is counselled to start a low sodium diet. Which of the following is the most appropriate additional management?

A. Decrease calcium intake B. Decrease coffee intake C. Decrease oxalate intake D. Start allopurinol E. Start chlorthalidone

E. Start chlorthalidone
A. Decrease calcium intake
B. Decrease coffee intake
C. Decrease oxalate intake
D. Start allopurinol

A 46-year-old man with sudden leg edema and proteinuria after a cold; what’s the likely renal biopsy diagnosis?

A. Allergic interstitial nephritis B. IgA nephropathy C. Membranoproliferative glomerulonephritis D. Postinfectious glomerulonephritis E. Minimal change disease

E. Minimal change disease
A. Allergic interstitial nephritis
B. IgA nephropathy
C. Membranoproliferative glomerulonephritis
D. Postinfectious glomerulonephritis

A 46-year-old man with no medical history seeks evaluation for leg edema that started 2 days ago. He had a mild cold a week ago and was taking over-the-counter cold remedies. The patient’s temperature is 36.7 C (98.1 F), blood pressure is 120/70 mm Hg, and pulse is 78/min. He has 3+ pitting edema to the midthigh bilaterally. The remainder of the physical examination is unremarkable. Laboratory results are as follows:

Blood chemistry
Albumin 19 g/L (35-50)
Total cholesterol 11 mmol/L (<5.2)

Urinalysis
Specific gravity 1.015
pH 5.5
Protein 4+
Blood Negative
Glucose Negative
White blood cells 1-2/hpf
Red blood cells 1-2/hpf
Casts None
Crystals None

Which of the following diagnoses is most likely to be made with renal biopsy?

A. Allergic interstitial nephritis B. IgA nephropathy C. Membranoproliferative glomerulonephritis D. Postinfectious glomerulonephritis E. Minimal change disease

E. Minimal change disease
A. Allergic interstitial nephritis
B. IgA nephropathy
C. Membranoproliferative glomerulonephritis
D. Postinfectious glomerulonephritis

Clarification:

The correct answer is E. This normotensive patient has explosive-onset nephrotic syndrome (edema, 4+ proteinuria, low albumin, elevated cholesterol) occurring shortly after an upper respiratory infection and lack of red cells or casts on urinalysis. These findings are typical of minimal change disease (MCD), or nil (nothing in light microscopy) disease, especially in the absence of pre-existing medical illness. Renal function is preserved in most patients. However, some patients with MCD may present with acute kidney injury and hypertension.
MCD accounts for 70%-90% of childhood and 10%-15% of adult nondiabetic nephrotic syndromes, but the cause remains unknown in the majority of cases. The most common cause of idiopathic nephrotic syndrome in adults is focal segmental glomerulosclerosis (FSGS), which is clinically indistinguishable from MCD. A renal biopsy is therefore required in adults with nephrotic syndrome, particularly if it is idiopathic.

Why Other Choices Are Incorrect:

A. Allergic interstitial nephritis: Patients with allergic interstitial nephritis usually do not have proteinuria or nephrotic syndrome. The triad of fever, rash, and eosinophilia due to drug reaction (e.g., nonsteroidal inflammatory drugs, penicillins or other antibiotics) is classic though not commonly seen.
B. IgA nephropathy: Almost all patients with IgA nephropathy have hematuria (microscopic or macroscopic), which sometimes follows an upper respiratory tract infection (synpharyngitic hematuria).
C. Membranoproliferative glomerulonephritis: Membranoproliferative glomerulonephritis (MPGN) causes moderate to severe glomerulonephritis. Patients may have nephrotic-range proteinuria but also have hematuria and red blood cell casts on urinalysis. Declining renal function is seen in most patients with MPGN.
D. Postinfectious glomerulonephritis: Postinfectious glomerulonephritis often presents with edema, hematuria, leukocyturia, and hypertension weeks after respiratory tract or skin infection in adults. This patient’s urine sediment shows no significant leukocytes or erythrocytes.

Medical Conclusion:

Sudden-onset nephrotic syndrome with heavy proteinuria and profound hypoalbuminemia in adults is usually due to focal segmental glomerulosclerosis or minimal change disease (MCD). MCD may follow an upper respiratory infection but the cause remains unknown in most cases. A renal biopsy is usually required in adults with nondiabetic nephrotic syndrome to confirm diagnosis and guide therapy.

A 76-year-old smoker with kidney issues needs angiography; what should be done besides saline and low-dose contrast?

A. Discontinue ibuprofen B. Furosemide during and after C. IV dopamine during D. Low-dose lisinopril before E. Mannitol before and during

A. Discontinue ibuprofen
B. Furosemide during and after
C. IV dopamine during
D. Low-dose lisinopril before
E. Mannitol before and during

A 76-year-old smoker with intermittent claudication is evaluated prior to angiography. She has a history of hypertension, type 2 diabetes mellitus, severe degenerative arthritis of the knees, and hyperlipidemia. Current medications include atorvastatin, ibuprofen, glipizide, and amlodipine. Her creatinine level is 176 µmol/L (50-90) and urinalysis shows 20 proteinuria. In addition to using the smallest dose of a third-generation contrast agent and pre-hydration with normal saline, the patient should have which of the following?

A. Discontinuation of ibuprofen B. Furosemide during and after the procedure C. Intravenous dopamine during the procedure D. Low-dose lisinopril before the procedure E. Mannitol before and during the procedure

A. Discontinuation of ibuprofen
B. Furosemide during and after the procedure
C. Intravenous dopamine during the procedure
D. Low-dose lisinopril before the procedure
E. Mannitol before and during the procedure

A 77-year-old man with diabetes and heavy proteinuria has edema; what’s the likely cause?

A. Chronic urate nephropathy B. Long-standing hypertension C. Post-streptococcal glomerulonephritis D. Diabetes mellitus E. Renal artery stenosis

D. Diabetes mellitus
A. Chronic urate nephropathy
B. Long-standing hypertension
C. Post-streptococcal glomerulonephritis
E. Renal artery stenosis

A 77-year-old man comes in with lower-extremity and facial swelling for the last several weeks. He has a history of hypertension, type 2 diabetes, hyperlipidemia, and gout. He underwent coronary artery bypass surgery 7 years ago and carotid artery stenting 2 years ago. Further evaluation shows heavy proteinuria (4.2 g/day) with no blood, white blood cells, or casts in the urine. Which of the following is most likely responsible for his current presentation?

A. Chronic urate nephropathy B. Long-standing hypertension C. Post-streptococcal glomerulonephritis D. Diabetes mellitus E. Renal artery stenosis

D. Diabetes mellitus
A. Chronic urate nephropathy
B. Long-standing hypertension
C. Post-streptococcal glomerulonephritis
E. Renal artery stenosis

Clarification:

The correct answer is D. This patient has nephrotic-range proteinuria (>3.5 g/day) and edema. He has a number of chronic medical conditions that may affect the kidney, including hypertension, diabetes mellitus, and gout, but only diabetes causes nephrotic syndrome associated with a bland urine sediment.
Moderately increased albuminuria (30-300 mg/day) is seen in the early stages of diabetic nephropathy and gradually progresses to severely increased albuminuria (>300 mg/day) and eventually nephrotic-range proteinuria. The progression of disease may be delayed with the early use of ACE inhibitors/angiotensin receptor blockers, good glycemic control, and control of blood pressure and serum lipids.

Why Other Choices Are Incorrect:

A. Chronic urate nephropathy: Chronic urate nephropathy causes renal impairment with only mild proteinuria. Edema from nephrotic syndrome is not present. A biopsy is often required for diagnosis.
B. Long-standing hypertension: Hypertensive nephrosclerosis also presents with progressive renal impairment, but the associated proteinuria is mild, usually <1 g/day; edema is not usually present.
C. Post-streptococcal glomerulonephritis: Post-streptococcal glomerulonephritis is usually seen after beta-hemolytic streptococcal infection. It may present with nephrotic-range proteinuria and hypertension similar to diabetic nephropathy. However, the urine sediment is usually active with red cell casts. Gross hematuria may also be present.
E. Renal artery stenosis: Renal artery stenosis usually presents with resistant hypertension, bland urine sediment, and mild proteinuria. Other associated features may include acute renal failure after starting ACE inhibitors/angiotensin receptor blockers, recurrent flash pulmonary edema, or a small/atrophic kidney.

Medical Conclusion:

Diabetic nephropathy results in loss of serum protein in the glomerulus. Moderate albuminuria occurs in the early stages and progresses to severe albuminuria. Overt nephrotic syndrome with edema eventually develops due to heavy proteinuria (>3.5 g/day). The urine sediment usually contains no cells or casts even in advanced disease.

A 40-year-old man with seizures has dark red urine; what’s most likely on urine microscopy?

A. White blood cells B. Few red blood cells C. Broad, waxy casts D. Red blood cell casts E. Calcium phosphate crystals

B. Few red blood cells
A. White blood cells
C. Broad, waxy casts
D. Red blood cell casts
E. Calcium phosphate crystals

A 40-year-old man was brought to the emergency department due to a series of generalized tonic-clonic seizures, which occurred after he stopped taking his antiepileptic medications. Upon arriving at the emergency department, he experienced another episode of generalized seizures, which required intravenous lorazepam and fosphenytoin. As part of his medical examination, a Foley catheter was inserted, and it drained 100 mL of dark red urine. The results of the bedside dipstick urinalysis showed that blood was present in the urine. Which of the following is most likely to be detected by urine microscopy?

A. White blood cells B. Few red blood cells C. Broad, waxy casts D. Red blood cell casts E. Calcium phosphate crystals

B. Few red blood cells
A. White blood cells
C. Broad, waxy casts
D. Red blood cell casts
E. Calcium phosphate crystals

A 26-year-old woman with muscle weakness and metabolic acidosis; what’s the likely cause?

A. Salicylate toxicity B. Surreptitious furosemide use C. Surreptitious laxative use D. Topiramate

C. Surreptitious laxative use
A. Salicylate toxicity
B. Surreptitious furosemide use
D. Topiramate

A 26-year-old woman is evaluated for a 1-week history of muscle weakness. Medical history is significant for chronic migraine headaches. Medications are topiramate, sumatriptan, naproxen, and aspirin. On physical examination, vital signs are normal. BMI is 19 Kg/m2. The remainder of the examination is unremarkable. Laboratory studies:

Blood
Sodium 142 mmol/L (135-145)
Potassium 3.1 mmol/L (3.5-5.0)
Chloride 120 mmol/L (98-106)
Bicarbonate 15 mmol/L (24-30)

Urine
Urine sodium 18 mmol/L
Urine potassium 8.0 mmol/L
Urine chloride 32 mmol/L

Which of the following is the most likely cause of this patient’s metabolic acidosis?

A. Salicylate toxicity B. Surreptitious furosemide use C. Surreptitious laxative use D. Topiramate

C. Surreptitious laxative use
A. Salicylate toxicity
B. Surreptitious furosemide use
D. Topiramate

Clarification:

The correct answer is C. Laxative abuse is the most likely cause of this patient’s normal anion gap metabolic acidosis. Normal anion gap metabolic acidosis can be caused by gastrointestinal bicarbonate loss, renal loss of bicarbonate, or the inability of the kidney to excrete acid. The normal physiologic response to systemic acidosis is an increase in urine acid excretion. Therefore, an initial diagnostic step in normal anion gap metabolic acidosis is to determine whether the kidney is appropriately excreting acid.
Increased acid excretion by the kidney is reflected as a marked increase in urine ammonium. However, urine ammonium measurement is difficult to obtain. Because ammonium carries a positive charge, chloride is excreted as the corresponding anion. Therefore, the amount of excreted chloride increases as urine ammonium levels increase. The urine anion gap can be used as an indicator of the ability of the kidney to excrete acid. The urine anion gap is calculated as follows:
Urine Anion Gap = (Urine Sodium + Urine Potassium) – Urine Chloride

Why Other Choices Are Incorrect:

A. Salicylate toxicity: Salicylate toxicity would be associated with an anion gap, which is not present in this patient.
B. Surreptitious furosemide use: Surreptitious furosemide use would be expected to result in metabolic alkalosis, not metabolic acidosis. Renal causes of normal anion gap metabolic acidosis are due to specific defects in bicarbonate reclamation (type 2 renal tubular acidosis [RTA]) or in hydrogen ion secretion (type 1 RTA).
D. Topiramate: Topiramate can cause both type 1 and type 2 RTA. The urine anion gap due to type 1 RTA is positive, which is not the case in this patient.

Medical Conclusion:

Normal anion gap metabolic acidosis can be caused by gastrointestinal bicarbonate loss, renal loss of bicarbonate, or the inability of the kidney to excrete acid. A negative urine anion gap suggests appropriate kidney excretion of acid and therefore gastrointestinal bicarbonate loss as the cause of normal anion gap metabolic acidosis.

A 36-year-old man on acyclovir for HSV encephalitis has AKI; what’s the most likely cause?

A. Acute glomerulonephritis B. Acute interstitial nephritis C. Intratubular obstruction D. Acute tubular necrosis

C. Intratubular obstruction
A. Acute glomerulonephritis
B. Acute interstitial nephritis
D. Acute tubular necrosis

A 36-year-old man is evaluated for acute kidney injury 48 hours after being hospitalized for herpes simplex virus encephalitis. Diagnosis was confirmed with polymerase chain reaction testing of the cerebrospinal fluid. He is being treated with intravenous high-dose acyclovir. Empiric therapy with ceftriaxone plus vancomycin was initiated and then discontinued after the results of the cerebrospinal fluid analysis became available. Medical history is significant for chronic kidney disease due to hereditary nephritis and hypertension. Outpatient medications are lisinopril and hydrochlorothiazide, both held since admission. On physical examination, vital signs are normal. The patient has some difficulty with attention and orientation to time but is otherwise neurologically intact. The remainder of the examination is normal. Current laboratory studies:

Creatinine Current 203.3 μmol/L (70-120)
Baseline 159.1 μmol/L
Electrolytes
Sodium 137 mmol/L (135-145)
Potassium 5.6 mmol/L (3.5-5.0)
Chloride 102 mmol/L (98-106)
Bicarbonate 26 mmol/L (24-30)
Urinalysis
Specific gravity 1.010
pH 7.5
Blood 1+
Protein 2+
Leukocytes 1+
Microscopic examination
Leukocytes 1-3/hpf
Erythrocytes 3-5/hpf
Crystals fine-needle

Kidney ultrasound shows an 11-cm right kidney and an 11.8-cm left kidney with normal cortical appearance and without hydronephrosis. Which of the following is the most likely cause of this patient’s acute kidney injury?

A. Acute glomerulonephritis B. Acute interstitial nephritis C. Intratubular obstruction D. Acute tubular necrosis

C. Intratubular obstruction
A. Acute glomerulonephritis
B. Acute interstitial nephritis
D. Acute tubular necrosis

A 48-year-old woman with shortness of breath, edema, and hematuria; what’s the likely cause of her edema?

A. Hyperthyroidism B. Hypoalbuminemia C. Renal hypoperfusion D. Right ventricular failure E. Primary glomerular damage

E. Primary glomerular damage
A. Hyperthyroidism
B. Hypoalbuminemia
C. Renal hypoperfusion
D. Right ventricular failure

A 48-year-old woman comes to the emergency department with shortness of breath over the past 2 weeks. She has been waking up at night breathless for the past few days. She also reports fatigue, lethargy, and weight gain. The patient finds it difficult to open her eyes in the morning due to facial edema. She has no other medical problems and takes no medications. Her blood pressure is 200/120 mm Hg and pulse is 100/min. Physical examination shows generalized edema with distended jugular veins while sitting upright. Lung auscultation shows bibasilar crackles. Urinalysis shows 2+ protein, no nitrite, trace leukocyte esterase, >50 red blood cells, red blood cell casts, and occasional neutrophils. Which of the following is the most likely cause of this patient’s edema?

A. Hyperthyroidism B. Hypoalbuminemia C. Renal hypoperfusion D. Right ventricular failure E. Primary glomerular damage

E. Primary glomerular damage
A. Hyperthyroidism
B. Hypoalbuminemia
C. Renal hypoperfusion
D. Right ventricular failure

Clarification:

The correct answer is E. This patient’s presentation – anasarca, pulmonary and facial edema, hypertension, and abnormal urinalysis with proteinuria and microscopic hematuria – suggests acute nephritic syndrome with fluid overload. Acute nephritic syndrome is due to primary glomerular damage in disorders such as poststreptococcal glomerulonephritis, IgA nephropathy, lupus nephritis, membranoproliferative glomerulonephritis, and rapidly progressive glomerulonephritis.
Glomerular injury leads to decreased glomerular filtration rate with eventual development of significant volume overload (e.g., pulmonary edema, distended neck veins, anasarca). Abnormal urinary sediment (red blood cells, red blood cell casts) and variable degrees of proteinuria are present on urinalysis. Serum creatinine can also be elevated. The increased volume also leads to hypertension. Significant proteinuria (>3+) eventually leads to hypoalbuminemia, which further contributes to the edema. Decreased glomerular filtration rate is also the cause of edema in patients with end-stage renal disease.

Why Other Choices Are Incorrect:

A. Hyperthyroidism: Pretibial myxedema is a localized nonpitting thickening and induration of the skin over the lower legs, pretibial area, or dorsum of the feet in patients with Graves’ disease. However, anasarca and abnormal urinalysis are usually not seen in patients with hyperthyroidism.
B. Hypoalbuminemia: Hypoalbuminemia may be due to excessive albumin loss (e.g., nephrotic syndrome, protein-losing enteropathy) or decreased albumin synthesis (e.g., cirrhosis, severe malnutrition). It can cause significant peripheral edema but usually does not cause pulmonary edema. Alveolar capillaries have a higher permeability to albumin at baseline (reducing the oncotic pressure difference) and greater lymphatic flow than skeletal muscle, protecting the lungs from edema.
C. Renal hypoperfusion: Renal hypoperfusion can occur in heart failure (decreased cardiac output), leading to increased renal sodium and water retention with edema. However, the urinalysis in patients with heart failure does not show red blood cells or casts, as seen in this patient.
D. Right ventricular failure: Right ventricular failure (RVF) is usually due to underlying left heart failure or severe pulmonary disease. It usually manifests with elevated jugular venous pressure and peripheral edema. Patients with severe RVF can also develop hepatosplenomegaly, ascites, and anasarca. However, abnormal urinalysis with hematuria would not be expected in patients with right heart failure.

Medical Conclusion:

Nephritic glomerulonephritis is characterized by urinary sediment containing red blood cells, occasional white blood cells, and red cell or mixed cellular casts. Edema in these patients is due primarily to decreased glomerular filtration rate and retention of sodium and water by the kidneys due to glomerular damage.

A 57-year-old woman with new type 2 diabetes; what’s the most sensitive test for nephropathy screening?

A. Creatinine clearance B. Dipstick testing of urine for protein C. Renal ultrasound D. Oral glucose tolerance test E. Random urine for microalbumin/creatinine ratio

E. Random urine for microalbumin/creatinine ratio
A. Creatinine clearance
B. Dipstick testing of urine for protein
C. Renal ultrasound
D. Oral glucose tolerance test

A 57-year-old woman presents with polyuria and polydipsia. She has smoked 1 pack of cigarettes daily for the past 25 years. She denies having any past medical problems. Her mother and one maternal uncle are diabetic. Her temperature is 37° C (98.6° F), pulse is 85/min, blood pressure is 150/90 mm Hg, and respirations are 15/min. Her body mass index (BMI) is 30. Examination of all the systems is unremarkable. Chemistry panel shows:

Na+ 141 mmol/L (135-145)
K+ 4.1 mmol/L (3.5-5.0)
HCO-3 26 mmol/L (24-30)
Blood glucose 9 mmol/L (3.3-5.8)
Urea nitrogen (BUN) 4 mmol/L (2.5-8.0)
Creatinine 79 µmol/L (50-90)

The patient is diagnosed with type 2 diabetes mellitus. She is advised to exercise and dietary modification. She is referred to an ophthalmologist and appropriately screened for diabetic retinopathy. What is the most sensitive test to screen for nephropathy in this patient?

A. Creatinine clearance B. Dipstick testing of urine for protein C. Renal ultrasound D. Oral glucose tolerance test E. Random urine for microalbumin/creatinine ratio

E. Random urine for microalbumin/creatinine ratio
A. Creatinine clearance
B. Dipstick testing of urine for protein
C. Renal ultrasound
D. Oral glucose tolerance test

Clarification:

The correct answer is E. The development of nephropathy is preceded by the development of excessive protein excretion, the initial stages of which is termed microalbuminuria. Patients with microalbuminuria typically have a urine albumin excretion value between 30-300 mg/24 hr. (Albumin creatinine ratio or ACR 2.0-20 mg/mmol). Spot urine collection and timed urine collection for the measurement of urine microalbumin to creatinine ratio are generally accepted as good screening methods for microalbuminuria. Although 24-hour urine collection is slightly more accurate in screening for microalbuminuria, its inconvenience to patients makes it less preferred by physicians.

Why Other Choices Are Incorrect:

A. Creatinine clearance: During the initial phases of diabetic nephropathy, there is glomerular hyperfiltration and an increase in creatinine clearance. Creatinine clearance then declines with the progression of diabetic nephropathy; however, it can still be relatively normal with proteinuria (micro and macroalbuminuria) due to high initial values. Low creatinine clearance occurs when the renal damage is fairly advanced. Due to these reasons, creatinine clearance is not used as a screening tool for diabetic nephropathy.
B. Dipstick testing of urine for protein: Routine dipstick testing is not recommended during the initial stages of nephropathy. Dipsticks can only detect excessive urinary protein excretion when the level is > 300 mg/24 hr (macroalbuminuria).
C. Renal ultrasound: Ultrasound is not useful as a screening tool for diabetic nephropathy. The kidney size is relatively preserved until advanced renal failure occurs. Ultrasound should be considered if non-diabetic renal damage (e.g., obstructive uropathy) is suspected clinically.
D. Oral glucose tolerance test: Oral glucose tolerance testing has no role in screening patients for diabetic nephropathy.

Medical Conclusion:

Spot urine collection and timed urine collection for the measurement of urine microalbumin to creatinine ratio are generally accepted as good screening methods for microalbuminuria. Although 24-hour urine collection is slightly more accurate in screening for microalbuminuria, its inconvenience to patients makes it less preferred by physicians.

A 28-year-old man with hypertension and hypokalemia on thiazide; what’s the best next step?

A. Add triamterene to the thiazide B. CT angiography of the abdomen C. Dexamethasone suppression test D. Intravenous potassium supplementation E. Measure plasma renin activity and aldosterone concentration

E. Measure plasma renin activity and aldosterone concentration
A. Add triamterene to the thiazide
B. CT angiography of the abdomen
C. Dexamethasone suppression test
D. Intravenous potassium supplementation

A 28-year-old man comes to the physician for follow-up of newly diagnosed hypertension. His blood pressure is 155/97 mm Hg and pulse is 78/min. Physical examination and basic laboratory studies are unremarkable. The patient is instructed to follow a low-salt diet and started on low-dose (12.5 mg daily) hydrochlorothiazide. Two weeks later, the patient comes to the emergency department complaining of fatigue. His blood pressure is 150/93 mm Hg and pulse is 82/min. He has a thin, athletic build.
Mucous membranes are moist. Cardiovascular and abdominal examination is normal with no abdominal bruits heard. Neurologic examination shows no overt weakness. ECG is normal. Laboratory results are as follows:

Potassium 2.5 mmol/L (3.5-5.0)
Glucose 4.3 mmol/L (3.3-5.8)
Serum creatinine 88 µmol/L (70-120)

Which of the following is the best next step in the management of this patient?

Clarification:

The correct answer is E. This patient has an onset of hypertension at a young age and symptomatic hypokalemia induced by a low-dose thiazide diuretic; he exhibits features suggestive of primary hyperaldosteronism. Patients with mild primary hyperaldosteronism may not have spontaneous hypokalemia but are prone to developing diuretic-induced hypokalemia. Other findings may include metabolic alkalosis and mild hypernatremia (143-147 mmol/L). The best screening test for primary hyperaldosteronism is early-morning plasma aldosterone concentration (PAC) to plasma renin activity (PRA) ratio. Elevated aldosterone (>15 ng/dL or ≥416 pmol/L) with a PAC/PRA ratio >20 (>555 in SI units) suggests primary hyperaldosteronism.

Why Other Choices Are Incorrect:

A. Add triamterene to the thiazide: Addition of a potassium-sparing diuretic to a thiazide may be considered in patients with mild hypokalemia who are otherwise tolerating therapy. However, aldosterone receptor antagonists (e.g., spironolactone or eplerenone) would be preferred for patients with hyperaldosteronism.
B. CT angiography of the abdomen: Abdominal CT angiography screens for renovascular hypertension due to renal artery stenosis or fibromuscular dysplasia. Such conditions cause secondary hyperaldosteronism, and these patients will have a PAC/PRA ratio <10 (<277 in SI units). However, a CT angiogram is not required in this patient at this time.
C. Dexamethasone suppression test: A dexamethasone suppression test can diagnose Cushing syndrome, a condition characterized by central obesity, purple striae, proximal muscle wasting, glucose intolerance, and hypertension. This patient’s normal glucose and lack of Cushingoid features make this unlikely.
D. Intravenous potassium supplementation: Patients who have significant hypokalemia may require large quantities of potassium to replenish total body stores. However, intravenous potassium can cause pain and phlebitis, and should be used only in patients who cannot take the oral form or as an adjuvant to the oral form in severely symptomatic patients. This patient is hemodynamically stable in sinus rhythm; oral potassium supplementation will likely be adequate once thiazide is discontinued.

Medical Conclusion:

Patients with mild primary hyperaldosteronism may have normal serum potassium at baseline but can develop significant hypokalemia if treated with diuretics.

A 53-year-old man with edema, proteinuria, and low calcium; what’s the likely cause of hypocalcemia?

A. Decreased active vitamin D levels B. Decreased levels of parathyroid hormone C. Impaired parathyroid hormone sensitivity D. Decreased serum albumin E. Increased calcitonin levels

D. Decreased serum albumin
A. Decreased active vitamin D levels
B. Decreased levels of parathyroid hormone
C. Impaired parathyroid hormone sensitivity
E. Increased calcitonin levels

A 53-year-old man with no significant past medical history is evaluated for facial and lower-extremity edema. His temperature is 37.1 C (99 F), blood pressure is 130/70 mm Hg, pulse is 78/min, and respirations are 14/min. Examination shows bilateral 1+ pitting ankle edema. Auscultation shows clear lungs, normal heart sounds, and no murmurs. Laboratory results are as follows:

Total serum calcium 1.8 mmol/L (2.18-2.58)
Albumin 22 g/L (35-50)
Phosphorus 1.12 mmol/L (0.8-1.5)
Magnesium 0.9 mmol/L (0.75-0.95)
Creatinine 70 µmol/L (70-120)

Twenty-four-hour urine collection shows proteinuria of 4.6 g/day. Which of the following is the most likely cause of this patient’s low serum calcium level?

A. Decreased active vitamin D levels B. Decreased levels of parathyroid hormone C. Impaired parathyroid hormone sensitivity D. Decreased serum albumin E. Increased calcitonin levels

D. Decreased serum albumin
A. Decreased active vitamin D levels
B. Decreased levels of parathyroid hormone
C. Impaired parathyroid hormone sensitivity
E. Increased calcitonin levels

Clarification:

The correct answer is D. Approximately 40%-45% of total blood calcium is bound to albumin and other plasma proteins, with the remainder (40%-55%) transported in the blood as ionized calcium or complexed with phosphate and other anions (5%-15%). As a result, patients with hypoalbuminemia may have a significant deficit in total blood calcium, but the ionized plasma calcium (physiologically active form) is hormonally regulated and may remain stable.
Assessing the clinical significance of hypocalcemia detected in a common serum metabolic panel, therefore, requires correcting the serum albumin concentration. The serum calcium concentration increases by 0.2 mmol/L for every 10 g/L decreases in serum albumin, as expressed in the following formula:
Corrected Ca2+ (mmol/L) = measured Ca2+ + 0.02 (40 g/L – albumin)
This patient’s corrected calcium is 2.16 mmol/L ([1.8mmol/L] + 0.02 (40g/L- 22]). The hypocalcemia is most likely due to hypoalbuminemia (from nephrotic-range proteinuria) and is not clinically significant. Note that direct measurement of ionized calcium is performed in many clinical laboratories but requires special handling and may not be readily available.

Why Other Choices Are Incorrect:

A. Decreased active vitamin D levels: Vitamin D is formed in the skin or absorbed from the intestine. It is then hydroxylated in the liver (25-hydroxylation) to produce 25 (OH) D, which is physiologically inert. The second step (1-alpha-hydroxylation) occurs in the kidney to form 1, 25 (OH)2 D, which is the physiologically active form of vitamin D. 1, 25 (OH)2 D stimulates calcium and phosphorus absorption from the small intestine. Patients with chronic renal failure are unable to form 1, 25 (OH)2 D, leading to decreased intestinal absorption of calcium and subsequent hypocalcemia. However, this patient’s normal creatinine makes this unlikely.
B. Decreased levels of parathyroid hormone: Hypoparathyroidism can cause hypocalcemia and is most commonly due to surgery (parathyroidectomy, thyroid, or radical head/neck surgery for cancer) or autoimmune destruction of the parathyroid gland. These patients would have hypocalcemia associated with decreased parathyroid hormone (PTH) levels and elevated serum phosphorus. This patient’s normal serum phosphorus makes hypoparathyroidism unlikely.
C. Impaired parathyroid hormone sensitivity: Pseudohypoparathyroidism is a rare disorder characterized by PTH resistance in target organs (e.g., kidney, bone). These patients have hypocalcemia, elevated phosphorus, and high PTH levels.
E. Increased calcitonin levels: Increased production of calcitonin, as seen in medullary carcinoma of the thyroid, might be expected to cause hypocalcemia. However, calcium levels usually remain normal due to calcitonin resistance.

Medical Conclusion:

Patients with hypoalbuminemia can have decreased total plasma calcium. However, the ionized serum calcium (physiologically active form) is hormonally regulated and remains stable.

A 57-year-old man with flank pain and hemolysis after primaquine; what’s the likely diagnosis?

A. Rhabdomyolysis B. Heme pigment nephropathy C. Prerenal acute kidney injury D. Acute interstitial nephritis

B. Heme pigment nephropathy
A. Rhabdomyolysis
C. Prerenal acute kidney injury
D. Acute interstitial nephritis

A 57-year-old man is evaluated in the emergency department for increasing abdominal and bilateral flank pain. The pain began yesterday, 2 days after he took primaquine prescribed as antimalarial prophylaxis for planned travel. On physical examination, temperature is 38.1 °C (100.6 °F), blood pressure is 102/55 mm Hg, pulse rate is 110/min, and respiration rate is 22/min. Cardiac examination reveals tachycardia without extra sounds. There is no edema. The remainder of the examination is unremarkable.
Laboratory studies:

Hemoglobin 79 g/L (125–170)
Haptoglobin 0.1 g/L (0.3-2.0)
Reticulocyte percentage 8% (0.5–1.5)
Total bilirubin 99.2 μmol/L (3–17)
Blood urea nitrogen 11.4 mmol/L (2.5‐8.0)
Creatinine 168 μmol/L (70‐120)
Lactate dehydrogenase 1250 U/L (110-215)

Urinalysis
Specific gravity 1.010
pH 5.0
Heme 3+
Albumin 1+
Erythrocytes no
Leukocytes no
Leukocyte esterase negative
Casts numerous pigmented granular

Examination of peripheral blood smear shows bite cells. Which of the following is the most likely diagnosis?

A. Rhabdomyolysis B. Heme pigment nephropathy C. Prerenal acute kidney injury D. Acute interstitial nephritis

B. Heme pigment nephropathy
A. Rhabdomyolysis
C. Prerenal acute kidney injury
D. Acute interstitial nephritis

Clarification:

The correct answer is B. This patient likely has underlying glucose-6-phosphate dehydrogenase (G6PD) deficiency and acute hemolytic anemia due to primaquine exposure. Primaquine can precipitate hemolytic anemia in such patients, as can other antimalarial agents, rasburicase, sulfonamides (e.g., sulfamethoxazole), some nonsulfa antibiotics (e.g., isoniazid), dapsone, and nitrofurantoin.
Myoglobin and hemoglobin are heme pigment-containing proteins that can cause acute kidney injury (AKI). Heme pigment nephropathy occurs when large amounts of heme pigment are released into the circulation due to massive intravascular hemolysis. Pigment nephropathy can cause acute tubular necrosis as the result of volume depletion, renal vasoconstriction, direct heme protein-mediated cytotoxicity, and intraluminal cast formation.
Laboratory findings include anemia, increased serum lactate dehydrogenase, decreased haptoglobin, and increased serum creatinine. The urine dipstick is positive for blood in the absence of erythrocytes. Other urinary findings include pigmented granular casts and hemoglobinuria. Both myoglobinuria and hemoglobinuria can cause tea-coloured urine and urine dipstick positive for blood; however, hemoglobin produces a reddish-brown colour in centrifuged serum and myoglobin does not discolour the serum. The treatment is expansion of the intravascular volume with 0.9% saline.

Why Other Choices Are Incorrect:

A. Rhabdomyolysis: When exposed to oxidative stress, patients with G6PD deficiency can develop acute hemolytic anemia. Rhabdomyolysis is not part of the clinical syndrome. However, the clinical course of rhabdomyolysis is similar to that of pigment nephropathy due to hemolysis. Laboratory findings of rhabdomyolysis-induced AKI include hyperkalemia, hyperphosphatemia, hyperuricemia, hypocalcemia, metabolic acidosis, elevated serum creatinine, and elevated muscle enzymes such as serum creatine kinase (typically >5000 U/L), lactate dehydrogenase, and aspartate and alanine aminotransferases.
C. Prerenal acute kidney injury: In this patient, the presence of a urine dipstick positive for blood in the absence of erythrocytes and numerous pigmented granular casts supports the diagnosis of heme pigment nephropathy rather than prerenal AKI, which is associated with a benign urinalysis.
D. Acute interstitial nephritis: Although primaquine is a newly initiated medication, the short time course and absence of pyuria are not consistent with drug-induced acute interstitial nephritis.

Medical Conclusion:

Myoglobin and hemoglobin are heme pigment-containing proteins that can cause acute kidney injury. Heme pigment nephropathy is associated with a positive urine dipstick for blood in the absence of erythrocytes and the presence of pigmented granular casts.

A 42-year-old diabetic woman with vomiting and ketones; what’s her acid-base status?

A. Anion gap metabolic acidosis B. Metabolic alkalosis C. Mixed anion gap metabolic acidosis and metabolic alkalosis D. Mixed anion gap metabolic acidosis and non-anion gap metabolic acidosis E. Non-anion gap metabolic acidosis and metabolic alkalosis

C. Mixed anion gap metabolic acidosis and metabolic alkalosis
A. Anion gap metabolic acidosis
B. Metabolic alkalosis
D. Mixed anion gap metabolic acidosis and non-anion gap metabolic acidosis
E. Non-anion gap metabolic acidosis and metabolic alkalosis

A 42-year-old woman presents with a 5-day history of weakness, polyuria, polydipsia, and frequent vomiting. She is insulin-dependent and diabetic. A physical exam reveals a pale, ill-appearing woman in moderate distress. Vital signs are as follows: blood pressure is 85/55 mm Hg; pulse is 130/min; respiratory rate is 18/min; temperature is 37.3°C. Head, eyes, ears, nose, and throat (HEENT) exam reveals dry mucous membranes. Her neck is supple. Her lungs are clear, and other than tachycardia, the cardiac exam is unremarkable. The abdomen is diffusely tender in the epigastric area. The rectal exam is heme-negative. A room air blood gas shows:

pH 7.01 (7.38–7.46)
PCO2 19 mm Hg (32–45)
PO2 85 mm Hg (83–116)
Glucose 33 mmol/L (3.3‐5.8)
Sodium 131 mmol/L (135‐145)
Chloride 85 mmol/L (98‐106)
Bicarbonate 10 mmol/L (24‐30)
Urea nitrogen (BUN) 10 mmol/L (2.5‐8.0)

Her serum is positive for ketones. What best describes this patient’s acid-base status?

Clarification:

The correct answer is C. The patient is presenting with signs of diabetic ketoacidosis (DKA) with positive ketones and a glucose of 33 mmol/L.
Anion gap (AG) is calculated by the equation AG = [Na] – ([Cl] + [HCO3]) = 12 (+/-4). Evaluation of this patient’s anion gap [(131 – [85 + 10]) = 36] reveals an anion gap metabolic acidosis.
To evaluate if there is a mixed acid-base problem occurring, evaluation of the changes in AG in relation to the changes in the HCO3 is helpful. The delta AG ratio normally ranges from 1.0 – 1.6, and it is calculated as: delta anion gap = (anion gap – 10) / (24 – HCO3-).
In patients with otherwise normal respiratory function, there will be a respiratory alkalosis in response to any metabolic acidosis. A delta AG ratio greater than 1.6 or less than 1 suggests mixed disorders. A value of less than 1 indicates the presence of non-anion gap metabolic acidosis. A value of 1 – 1.6 is indicative of high-anion-gap metabolic acidosis without additional acid-base disorder. A value greater than 1.6 indicates that there is a simultaneous metabolic alkalosis present or a compensated chronic respiratory acidosis.
In this patient, the delta AG ratio is [(36 – 10) / (24 – 10)] = 1.85. The delta AG ratio is greater than 1.6; this suggests a mixed acid-base disorder—anion gap metabolic acidosis with metabolic alkalosis or a mixed anion gap acidosis plus chronic respiratory acidosis (high baseline HCO3). In this case, the protracted vomiting indicates the former.
The most frequent causes of increased production of organic acids are lactic acidosis, ketoacidosis, uremia, and drug intoxication (especially methanol, ethanol, ethylene glycol, and salicylates). Ketoacidosis may be diabetic, starvation, or alcoholic in origin.

Why Other Choices Are Incorrect:

A. Anion gap metabolic acidosis: This is part of the picture, but it does not account for the elevated delta AG ratio (>1.6), which indicates an additional metabolic alkalosis from vomiting.
B. Metabolic alkalosis: Metabolic alkalosis is created by factors that increase the HCO3 concentration or reduce H+ concentration. Patients with uncompensated metabolic alkalosis have an increased pH and an increased HCO3 concentration, unlike this patient with a pH of 7.01.
D. Mixed anion gap metabolic acidosis and non-anion gap metabolic acidosis: Mixed anion gap metabolic acidosis and non-anion gap metabolic acidosis will have a delta AG ratio value of less than 1, not >1.6 as seen here.
E. Non-anion gap metabolic acidosis and metabolic alkalosis: Evaluation of this patient’s anion gap [(131 – [85 + 10]) = 36] reveals an anion gap metabolic acidosis as part of her problem, ruling out a non-anion gap metabolic acidosis and metabolic alkalosis etiology as her sole acid-base problem.

Medical Conclusion:

To evaluate if there is a mixed acid-base problem occurring, evaluation of the changes in AG in relation to the changes in the HCO3 is helpful. The delta AG ratio normally ranges from 1.0 – 1.6, and it is calculated as: delta anion gap = (anion gap – 10) / (24 – HCO3-). A value >1.6, as in this case, indicates a mixed disorder with anion gap acidosis and metabolic alkalosis.

A 43-year-old woman with bilateral leg edema and weight gain; what’s the next diagnostic step?

A. Renal biopsy B. Fasting lipid profile C. Hepatitis serology panel D. Brain natriuretic peptide E. Random urine protein/creatinine ratio

E. Random urine protein/creatinine ratio
A. Renal biopsy
B. Fasting lipid profile
C. Hepatitis serology panel
D. Brain natriuretic peptide

A 43-year-old female presents to the family physician’s office complaining of one week of bilateral lower extremity edema. She denies dyspnea on exertion and orthopnea, but she does report an 8-pound (3.6 kg) weight gain in the last week. Physical examination reveals a well-appearing female with bilateral pitting lower extremity edema to the tibial plateaus. Cardiac, pulmonary, and abdominal examinations are normal. Which of the following studies is the most appropriate next step in determining the diagnosis?

A. Renal biopsy B. Fasting lipid profile C. Hepatitis serology panel D. Brain natriuretic peptide E. Random urine protein/creatinine ratio

E. Random urine protein/creatinine ratio
A. Renal biopsy
B. Fasting lipid profile
C. Hepatitis serology panel
D. Brain natriuretic peptide

Clarification:

The correct answer is E. New-onset edema, particularly in the lower extremities, is the most common presenting symptom of nephrotic syndrome (NS). Depending on disease severity, patients may have edema extending to the proximal lower extremities, lower abdomen, or genitalia. Ascites, periorbital edema, hypertension, and pleural effusion are also possible presenting features. Patients may report foamy urine, exertional dyspnea or fatigue, and significant fluid-associated weight gain.
The diagnostic criteria for NS are listed in Table. Confirmation of proteinuria via 24-hour urine collection is cumbersome for patients, and the specimen can be collected incorrectly. The protein-to-creatinine ratio from a single urine sample is commonly used to diagnose nephrotic-range proteinuria. Although this spot test has limited accuracy in patients who exercise heavily, are gaining or losing muscle mass, or have similar factors, in general, it is sufficient for diagnosing heavy proteinuria.

Why Other Choices Are Incorrect:

A. Renal biopsy: The role of renal biopsy in patients with NS is controversial, and there are no evidence-based guidelines regarding indications for biopsy. Whether a biopsy is performed often depends on the preferences of consulting nephrologists. In patients with NS from a known secondary cause and who are responding to treatment appropriately, the biopsy will likely add little to treatment. The biopsy may be more useful for treatment and prognosis in patients with idiopathic NS of an unknown histologic disease type or with suspected underlying systemic lupus erythematosus or other renal disorders.
B. Fasting lipid profile: In addition to proteinuria, low serum albumin levels (less than 25g per dL [2.5g per L]) and severe hyperlipidemia are also typical features of nephrotic syndrome. In one study of persons with nephrotic syndrome, 53 percent had a total cholesterol level greater than 7.77 mmol per L (300 mg per dL) and 25 percent had a total cholesterol level greater than 10.36 mmol per L (400 mg per dL). Because hyperlipidemia is not present in all persons with nephrotic syndrome, and proteinuria is present in all cases, the protein-to-creatinine ratio is the better answer.
C. Hepatitis serology panel: Hepatitis B or C may be a secondary cause of nephrotic syndrome for the patient in the clinical scenario above. However, to establish the diagnosis of nephrotic syndrome, the degree of proteinuria must be measured using a urine protein/creatinine ratio or a 24-hour urine collection. Additionally, the patient in the clinical scenario above has a normal abdominal examination, making cirrhosis (secondary to hepatitis) a less likely cause of her lower extremity edema.
D. Brain natriuretic peptide: Brain natriuretic peptide (BNP) is a substance secreted from the ventricles or lower chambers of the heart in response to changes in pressure that occur when heart failure develops and worsens. The level of BNP in the blood increases when heart failure symptoms worsen and decreases when the heart failure condition is stable. The BNP level in a person with heart failure — even someone whose condition is stable — is higher than in a person with normal heart function. The patient in the clinical scenario above does not have dyspnea on exertion or orthopnea, which are clinical symptoms of congestive heart failure, and her cardiac examination is normal.

Medical Conclusion:

Typical clinical (progressive lower extremity edema, weight gain, and fatigue without symptoms of heart failure or cirrhosis) and laboratory (proteinuria, hypoalbuminemia) features of nephrotic syndrome are sufficient to establish the diagnosis of nephrotic syndrome. A random urine protein/creatinine ratio is sufficient to estimate the degree of proteinuria.

A 35-year-old man with body aches and dark urine after alcohol use; what’s the best management?

A. Give calcium gluconate 1 g intravenous B. Consult nephrology for initiation of dialysis C. Give intravenous fluids to target a urine output of 200-300 ml/h D. Give intravenous sodium bicarbonate to target a urine pH 7.5

C. Give intravenous fluids to target a urine output of 200-300 ml/h
A. Give calcium gluconate 1 g intravenous
B. Consult nephrology for initiation of dialysis
D. Give intravenous sodium bicarbonate to target a urine pH 7.5

A 35-year-old man presents to the emergency department for evaluation of body aches and generalized weakness. He reports the body aches are diffuse and started two days ago, after a week of heavy alcohol use. He has noted that his urine is the color of tea. A physical exam reveals an ill-appearing man with normal lung sounds and normal findings on the neurological exam.
Vitals are blood pressure 125/70 mm Hg, pulse 110 /min, and temperature 37.8°C (100.1°F). Lab results show:

Serum
Sodium 135 mmol/L (135‐145)
Potassium 4.9 mmol/L (3.5‐5.0)
Total calcium 1.75 mmol/L (2.18‐2.58)
Creatinine 221 μmol/L (70‐120)
Creatine kinase 12000 U/L (5‐130)

Which of the following is the most appropriate management?

Clarification:

The correct answer is C. Aggressive IV rehydration is the mainstay of treatment for rhabdomyolysis. Therapy can be initiated with an initial bolus of crystalloid fluids followed by an infusion of fluids to maintain a urine output of 200–300 mL/h or 3–4 mL/kg/h.
Rhabdomyolysis is the destruction of skeletal muscle caused by any injury that results in damage to the myocytes. The most common causes of rhabdomyolysis in adults are drugs and alcohol, medications, trauma, seizures, immobility, infection, muscle diseases, strenuous physical activity, and heat-related illnesses. The effects of rhabdomyolysis are due to the release of intracellular contents, specifically myoglobin, creatine kinase (CK), aspartate aminotransferase, and potassium.
Symptoms typically include myalgias, weakness, malaise, and dark-colored urine. Tachycardia, vomiting, and low-grade fever may be present as well. An elevated serum CK of fivefold or greater above the upper threshold of normal (approximately 800 to 1,000 U/L) is generally required for a diagnosis of rhabdomyolysis. CK is the most sensitive indicator of muscle injury and begins to rise 2–12 hours after the onset of injury and peaks at 24–72 hours. Myoglobinuria often precedes CK elevation and causes urine discoloration seen in this patient. It can be detected on a urinalysis that is positive for blood but that has zero or few red blood cells seen on microscopy. Treatment is aimed at early, aggressive fluid resuscitation and treatment of electrolyte abnormalities, particularly hyperkalemia.

Why Other Choices Are Incorrect:

A. Give calcium gluconate 1 g intravenous: Calcium gluconate would be indicated if the patient has severe hyperkalemia, particularly with ECG changes. Hypocalcemia can occur early in the course of an illness but will generally improve with fluid resuscitation.
B. Consult nephrology for initiation of dialysis: This patient has elevated creatinine that will likely respond to aggressive fluid administration. Dialysis is not indicated emergently unless the patient has severe hyperkalemia not responsive to treatment.
D. Give intravenous sodium bicarbonate to target a urine pH 7.5: Alkalinization of the urine with sodium bicarbonate has been proposed as a treatment for rhabdomyolysis, but no prospective controlled studies have demonstrated any benefit.

Medical Conclusion:

Once the patient is in the emergency department, continue aggressive IV rehydration for the next 24 to 72 hours. One method is the rapid correction of the fluid deficit with IV crystalloids followed by infusion of 2.5 mL/kg/h, with the goal of maintaining a minimum urine output of 2 mL/kg/h. Another method is a goal of 200 to 300 mL of urine output each hour, as in rhabdomyolysis.

A 58-year-old woman with persistent fever after pyelonephritis treatment; what’s the likely cause?

A. Cholecystitis B. Drug fever C. Infective endocarditis D. Renal abscess E. Urinary infection with resistant organism

D. Renal abscess
A. Cholecystitis
B. Drug fever
C. Infective endocarditis
E. Urinary infection with resistant organism

A 58-year-old woman with type 2 diabetes mellitus returns to the physician due to continued fever and abdominal discomfort. She was initially seen 5 days ago for fever, chills, right flank pain, and back pain. At that time, urinalysis showed positive leukocyte esterase and 15-20 white blood cells/high power field, and she was started on oral levofloxacin. Her temperature is 38.1 C (100.5 F), blood pressure is 130/84 mm Hg, and pulse is 84/min. Examination shows right costovertebral angle tenderness and mild right upper quadrant tenderness. No murmurs are heard on cardiac examination. Breath sounds are mildly decreased at the right lung base. There are no skin rashes. Laboratory testing shows a leukocyte count of 14 ×109/L (3.5–10.5), creatinine of 123 µmol/L (50-90), and normal liver function tests. Repeat urinalysis shows trace leukocyte esterase and nitrites as well as 10-15 white blood cells/hpf. Which of the following is the most likely cause of this patient’s current condition?

A. Cholecystitis B. Drug fever C. Infective endocarditis D. Renal abscess E. Urinary infection with resistant organism

D. Renal abscess
A. Cholecystitis
B. Drug fever
C. Infective endocarditis
E. Urinary infection with resistant organism

Clarification:

Persistent fever and symptoms >48-72 hours after the initiation of antibiotic therapy for pyelonephritis suggest a renal/perinephric abscess. Patients should be evaluated promptly with either ultrasound or computed tomography (CT scan) of the abdomen (preferred). Complications of abscess formation include rupture in the renal collecting system or extension into nearby muscles (psoas), the peritoneal cavity, the subphrenic space (subphrenic abscess), or the lung (with decreased breath sounds at the base, as noted in this patient).

Why Other Choices Are Incorrect:

A. Cholecystitis: Cholecystitis usually presents with right upper quadrant pain and fever. Sometimes, it can also present with costovertebral angle and flank pain. However, normal liver function tests make cholecystitis less likely.
B. Drug fever: Drug fever can present as a persistent fever (sometimes with rash) following treatment for a bacterial infection, but it is a diagnosis of exclusion after evaluating for infectious causes. This patient’s persistent symptoms, lack of rash, and abnormal urinalysis also make this unlikely.
C. Infective endocarditis: Infective endocarditis typically presents with fever, evidence of embolic phenomena, cardiac murmur, and valvular vegetations on echocardiogram. This is less likely given this patient’s normal cardiac examination and abnormal urinalysis.
E. Urinary infection with resistant organism: Infection with a resistant organism should be considered once renal/perinephric abscess and obstructive uropathy are excluded. This patient was treated with an appropriate first-line antimicrobial agent for pyelonephritis (e.g., levofloxacin).

Medical Conclusion:

The correct answer is D, as a renal abscess is the most likely cause of this patient’s persistent fever and symptoms following treatment for pyelonephritis.

A 16-year-old boy with microscopic hematuria and family history; what’s the likely diagnosis?

A. Alport syndrome B. Autosomal dominant polycystic kidney disease C. Thin basement membrane nephropathy D. IgA nephropathy E. Medullary sponge kidney

C. Thin basement membrane nephropathy
A. Alport syndrome
B. Autosomal dominant polycystic kidney disease
D. IgA nephropathy
E. Medullary sponge kidney

A 16-year-old boy is evaluated for microscopic hematuria discovered on a sports physical examination. He has never had bloody urine and he has no known medical problems. His father was told in the past that he had a urine abnormality but is otherwise in good health. His mother suffered from breast cancer at age 42 and underwent mastectomy. There is no history of renal failure in the family. On further evaluation, a 10-year-old male sibling has been found to have microscopic hematuria. However, his female sibling is in good health. His blood pressure is 121/68 mm Hg and his pulse is 72/min. His physical examination is within normal limits. Laboratory results are as follows:

Serum
Sodium 140 mmol/L (135-145)
Potassium 4.0 mmol/L (3.5-5.0)
Chloride 100 mmol/L (98-106)
Bicarbonate 24 mmol/L (24-30)
Blood urea nitrogen 7 mmol/L (2.5-8.0)
Creatinine 72 µmol/L (70-120)

Urinalysis
Specific gravity 1.020
Protein none
Blood negative
White blood cells 1-2/hpf
Red blood cells 10-15/hpf (dysmorphic)
Casts none

Which of the following is the most likely diagnosis?

A. Alport syndrome B. Autosomal dominant polycystic kidney disease C. Thin basement membrane nephropathy D. IgA nephropathy E. Medullary sponge kidney

C. Thin basement membrane nephropathy
A. Alport syndrome
B. Autosomal dominant polycystic kidney disease
D. IgA nephropathy
E. Medullary sponge kidney

Clarification:

The correct answer is C. Recurrent asymptomatic microscopic hematuria in children is classified as either glomerular or non-glomerular. Glomerular disease is suggested by microscopic hematuria, red blood cell casts, dysmorphic red blood cells (> 30% of total), > 5% acanthocytes, or proteinuria > 100 mg/m2. This patient’s dysmorphic red blood cells suggest glomerular disease, and thin basement membrane nephropathy (TBMN) is the most common condition presenting solely with microscopic hematuria. Benign familial hematuria (another term for TBMN) is due to gene mutations in type IV collagen causing thin glomerular basement membranes.
Thin basement membrane nephropathy is autosomal dominant with 30-50% of patients having a family history, nearly 50% of first-degree relatives having hematuria, and frequent father-to-son transmission. Macroscopic hematuria, flank pain, hypertension, and proteinuria are less common. Diagnosis is made clinically, but renal biopsy is performed in patients with proteinuria to exclude other causes. It rarely progresses to chronic kidney disease. Treatment involves routine monitoring and ACE inhibitors or angiotensin receptor blockers in patients with proteinuria.

Why Other Choices Are Incorrect:

A. Alport syndrome: Alport syndrome (hereditary nephritis) is X-linked and results from gene mutations in type IV collagen. Patients typically present with hematuria (usually macroscopic), proteinuria, progressive loss of renal function, and sensorineural hearing loss. This patient’s normal hearing, microscopic hematuria, and family history of hematuria (with father-to-son transmission) make this less likely.
B. Autosomal dominant polycystic kidney disease: Autosomal dominant polycystic kidney disease presents with an increased size and number of kidney cysts with renal failure in mid- to late-life. Macroscopic hematuria with flank pain may occur with cyst rupture, but it is less likely in this asymptomatic teenager.
D. IgA nephropathy: IgA nephropathy usually presents with macroscopic hematuria, red blood cell casts, and proteinuria after upper respiratory or gastrointestinal infections. There is usually not a strong family history of renal disease, as seen in this patient.
E. Medullary sponge kidney: Medullary sponge kidney typically presents with medullary cysts with linear and rounded calcifications, hypercalciuria with recurrent painful nephrolithiasis, and secondary urinary tract infections leading to chronic kidney disease. Asymptomatic microscopic hematuria is not usually seen in this condition.

Medical Conclusion:

Asymptomatic microscopic hematuria is common in children and can be either glomerular or non-glomerular. Glomerular disease is suggested by red cell casts, dysmorphic red cells, or proteinuria. Thin basement membrane nephropathy is the most common glomerular cause without other organ involvement; it rarely progresses to chronic kidney disease.

An 80-year-old man with fever, rash, and rising creatinine; what’s the likely diagnosis?

A. Myeloma cast nephropathy B. ANCA-associated glomerulonephritis C. Proliferative lupus nephritis D. Minimal change glomerulopathy E. Anti-glomerular basement membrane antibody disease

B. ANCA-associated glomerulonephritis
A. Myeloma cast nephropathy
C. Proliferative lupus nephritis
D. Minimal change glomerulopathy
E. Anti-glomerular basement membrane antibody disease

An 80-year-old man is evaluated for a week’s history of poor appetite, myalgia, fatigue, arthralgia, and low-grade fever. He was previously healthy and active. His only medication is acetaminophen, as needed. On physical examination, the patient is afebrile. Blood pressure is 155/95 mmHg, and pulse rate is 80/min; there are no orthostatic changes. There is a trace of lower extremity edema. A faint red-blue reticular rash is present over the lower extremities. Laboratory studies:

Hemoglobin 120 g/L (125–170)
Calcium 2.5 mmol/L (2.18-2.58)
Creatinine
Current 274 μmol/L (70-120)
Baseline 2 months ago 79.6 μmol/L
Urinalysis
Blood 3+
Protein 2+
Dysmorphic erythrocytes 20-30/hpf
Leukocytes 5-10/hpf

Chest radiograph shows no acute infiltrates. Kidney ultrasound shows no masses or obstruction. Which of the following is the most likely diagnosis?

A. Myeloma cast nephropathy B. ANCA-associated glomerulonephritis C. Proliferative lupus nephritis D. Minimal change glomerulopathy E. Anti-glomerular basement membrane antibody disease

B. ANCA-associated glomerulonephritis
A. Myeloma cast nephropathy
C. Proliferative lupus nephritis
D. Minimal change glomerulopathy
E. Anti-glomerular basement membrane antibody disease

Clarification:

The most likely diagnosis is ANCA-associated glomerulonephritis (pauci-immune crescentic glomerulonephritis). This patient’s clinical picture suggests rapidly progressive glomerulonephritis (RPGN), with an acute and steep rise in serum creatinine accompanied by hematuria and proteinuria. ANCA-associated glomerulonephritis accounts for more than half of all RPGN cases and has a particularly high prevalence in patients >65 years of age presenting with acute kidney injury and active urine sediment.

Why Other Choices Are Incorrect:

A. Myeloma cast nephropathy: Kidney dysfunction is found in 29% of patients with multiple myeloma, often due to cast nephropathy, a condition in which excess monoclonal free light chains precipitate in the distal tubules. Patients will typically have concomitant anemia and hypercalcemia. These findings are absent in this patient.
C. Proliferative lupus nephritis: Proliferative lupus nephritis is a cause of RPGN that is usually limited to the pediatric and young adult patient population.
D. Minimal change glomerulopathy: Minimal change glomerulopathy is characterized by sudden-onset nephrotic syndrome. It can be associated with acute kidney injury in elderly patients, but the presentation is one of severe nephrotic syndrome without significant hematuria.
E. Anti-glomerular basement membrane antibody disease: Anti-GBM antibody disease is a rarer form of RPGN. More than half of patients present with concomitant alveolar hemorrhage that may progress to life-threatening respiratory failure. These findings are not present in this patient.

Medical Conclusion:

The correct answer is B, as ANCA-associated glomerulonephritis is the most likely diagnosis given this patient’s vasculitis symptoms, rash, and rapidly progressive kidney injury.

Patient with C-ANCA positive; what’s the best initial treatment?

A. High-dose steroids and cyclophosphamide B. Cyclosporine C. Cystoscopy D. Plasma-exchange therapy E. Refer for surgical lobectomy/pneumonectomy

A. High-dose steroids and cyclophosphamide
B. Cyclosporine
C. Cystoscopy
D. Plasma-exchange therapy
E. Refer for surgical lobectomy/pneumonectomy

An antibody panel is positive for antiproteinase 3 antibodies or C-ANCA. What is the best initial treatment of this patient’s condition?

A. High-dose steroids and cyclophosphamide B. Cyclosporine C. Cystoscopy D. Plasma-exchange therapy E. Refer for surgical lobectomy/pneumonectomy

A. High-dose steroids and cyclophosphamide
B. Cyclosporine
C. Cystoscopy
D. Plasma-exchange therapy
E. Refer for surgical lobectomy/pneumonectomy

Clarification:

The correct answer is A: Presence of antibodies against proteinase 3 (circulating anti-neutrophil cytoplasmic antibody (C-ANCA) and clinical presentation distinguish granulomatosis with polyangiitis from other vasculitides. Untreated, granulomatosis with polyangiitis is uniformly fatal. With the initiation of steroids and cyclophosphamide therapy, however, the prognosis is excellent, and complete remission is achieved in 75 % of cases.

Why Other Choices Are Incorrect:

B. Cyclosporine: Cyclosporine is a potent drug used for immunosuppression in transplant recipients. It is not the initial treatment for granulomatosis with polyangiitis.
C. Cystoscopy: Cystoscopy is useful to identify bladder pathology in patients with hematuria. However, it is not the best initial treatment for this patient who presents with both hematuria and hemoptysis.
D. Plasma-exchange therapy: Plasma-exchange therapy is the cornerstone of treatment for Goodpasture syndrome. Based on this patient’s history of upper airway involvement and antibody pattern, a diagnosis of granulomatosis with polyangiitis is more likely than Goodpasture syndrome.
E. Refer for surgical lobectomy/pneumonectomy: Patients with granulomatosis with polyangiitis may have severe hemoptysis due to arteriovenous malformations that may necessitate surgical exploration for emergent control of hemorrhage. However, this patient’s hemoglobin level is normal, and her hemoptysis is low volume, which argues against the immediate need for surgery.

Medical Conclusion:

Granulomatosis with polyangiitis is an autoimmune vasculitis characterized by the classic pattern of upper and lower airway involvement, renal manifestations, and granuloma formation. Antiproteinase 3 antibody (C-ANCA) is very specific for this condition. The treatment of choice is with steroids and cyclophosphamide.

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