Educational Objective: Diagnose IgG4-related interstitial nephritis.
Key Point
IgG4-related disease is characterized by infiltration of different organs by
lymphoplasmacytic infiltrates of IgG4-positive plasma cells with resultant fibrosis associated with elevated serum IgG4 levels.
The most likely diagnosis is IgG4-related interstitial nephritis. This patient has a history of autoimmune pancreatitis and now presents with acute kidney injury. Her urinalysis is most consistent with a tubulointerstitial pattern, with mild proteinuria and the presence of inflammatory cells. This history and clinical presentation suggest the possibility of IgG4-related interstitial nephritis. Systemic IgG4-related disease is an uncommon disorder characterized by infiltration of different organs by lymphoplasmacytic
infiltrates of IgG4-positive plasma cells with resultant fibrosis associated with elevated serum IgG4 levels. Autoimmune pancreatitis is one form of IgG-related disease, although other organs such as the kidney may be affected, most commonly as interstitial nephritis. IgG4-related interstitial nephritis may present with acute or chronic kidney failure as well as renal mass–like lesions on imaging. As with other IgG4-related diseases, almost all patients with IgG4-related kidney disease will have elevated serum IgG4 levels, and the kidneys may be diffusely enlarged on imaging due to cellular infiltration. Definitive diagnosis requires kidney biopsy with staining for IgG4-positive plasma cells. Treatment is similar to other IgG4-related diseases using immunosuppression with glucocorticoids.
ANCA-associated vasculitis and anti–glomerular basement membrane antibody disease typically cause rapidly progressive glomerulonephritis with significant
proteinuria and hematuria in the sediment, occasionally with erythrocyte casts, none of which is present in this patient.
Lupus nephritis is primarily a glomerular lesion with significant proteinuria in the context of other clinical findings suggestive of systemic lupus erythematosus. This patient's clinical presentation is therefore less consistent with this diagnosis.
Question 25
A 46-year-old woman is evaluated in the emergency department for fatigue and weakness of 5 days' duration. The patient also reports recurrent lower extremity swelling. She is vague when asked about medication or drug use.
On physical examination, blood pressure is 108/62 mm Hg, pulse rate is 98/min, and respiration rate is 16/min. Upon standing, systolic blood pressure decreases by 15 mm Hg, and pulse rate increases by 10/min. BMI is 26. The remainder of the examination is unremarkable, with no evidence of lower extremity edema.
Laboratory studies:
Serum bicarbonate 29 mEq/L (29 mmol/L) Serum creatinine 1.2 mg/dL (106.1 µmol/L) Serum potassium 3.1 mEq/L (3.1 mmol/L) Urine chloride 53 mEq/L (53 mmol/L) Urine potassium 25 mEq/L (25 mmol/L) Urine sodium 42 mEq/L (42 mmol/L)
Which of the following is the most appropriate diagnostic test to perform next?
A
24-Hour urine free cortisol excretion B
Plasma aldosterone-plasma renin ratio C
Serum thyroid-stimulating hormone level D
Urine diuretic screening
Answer & Critique Correct Answer: D
Educational Objective: Diagnose diuretic-related metabolic alkalosis.
Key Point
Diuretic use can mimic the metabolic alkalosis findings of inherited kidney disorders of sodium and chloride handling such as Bartter and Gitelman syndromes.
Urine diuretic screening is appropriate for this patient. The first step when assessing a patient with metabolic alkalosis is to clinically assess the patient's volume status. This patient has metabolic alkalosis as implied by the elevated serum bicarbonate and is hypovolemic as evidenced by the orthostatic blood pressure and pulse changes. Such a patient would be expected to have low urine concentrations of sodium and chloride.
However, this patient's urine electrolytes show increased excretion of sodium and chloride despite the evident hypovolemia. These findings suggest the presence of active diuretic use or a renal tubular defect that impairs handling of sodium and chloride, such as Bartter and Gitelman syndromes. These rare autosomal recessive genetic disorders of renal sodium and chloride transporters clinically mimic loop diuretic and thiazide diuretic use, respectively, but should be considered only after diuretic use has been eliminated with negative urine diuretic screening.
Measurement of 24-hour urine free cortisol excretion is a standard test for diagnosing Cushing syndrome, which is characterized by proximal muscle weakness,
hypokalemia, hypertension, and diabetes mellitus. These findings are not present in this patient.
Plasma aldosterone-plasma renin ratio is unlikely to be helpful in this situation.
Although primary hyperaldosteronism is characterized by hypokalemia and metabolic alkalosis, the absence of hypertension makes this diagnosis unlikely. Finally, diuretics and Gitelman and Bartter syndromes are associated with various degrees of volume contraction and secondary hyperaldosteronism. Plasma aldosterone and renin activity levels will not differentiate these disorders.
Thyroid dysfunction is not associated with acid-base abnormalities and may be associated with hypokalemia only in rare and severe cases such as thyrotoxic periodic paralysis, in which attacks of profound generalized weakness occur suddenly with preserved consciousnes
Question 26
A 77-year-old woman is evaluated 4 months following a left middle cerebral artery ischemic stroke. The severity of her stroke required prolonged initial hospitalization and a 3-month stay in a rehabilitation center before returning home. Residual deficits include dense right-sided hemiparesis and dysphagia requiring oral feeding with thickened liquids. Medical history is otherwise significant for hypertension and diabetes mellitus. Current medications are aspirin, chlorthalidone, lisinopril, tolterodine, and insulin.
On physical examination, temperature is 37.2 °C (99.0 °F), blood pressure is 136/86 mm Hg, and pulse rate is 86/min. BMI is 18. The general medical examination is unremarkable. Neurologic examination reveals dysarthria, left-sided facial droop, 1/5 strength in the right arm and leg, and bilateral distal sensory neuropathy.
Laboratory studies:
Hemoglobin A1c 7.2%
Albumin 2.4 g/dL (24 g/L) Blood urea
nitrogen 12 mg/dL (4.3 mmol/L) (4 months ago: 28 mg/dL [10 mmol/L]) Creatinine 0.8 mg/dL (70.7 µmol/L) (4 months ago: 1.4 mg/dL [123.8
µmol/L]) Urinalysis Normal