Test your medicine knowledge with the MKSAP challenge, in partnership with the American College of Physicians.
A 53-year-old woman is evaluated during a routine follow-up visit. Medical history is significant for hypertension and chronic active hepatitis B infection. Her hepatitis B infection has been treated with tenofovir for the past 5 years with suppression of her serum hepatitis B DNA levels. She currently notes mild generalized weakness but otherwise feels well. Medications are ramipril and tenofovir.
On physical examination, temperature is 37.0 °C (98.6 °F), blood pressure is 136/79 mm Hg, pulse rate is 70/min, and respiration rate is 14/min. BMI is 22. Abdominal examination shows a normal-sized liver and no splenomegaly. The remainder of the examination is normal.
Laboratory studies:
| Bicarbonate | 21 mEq/L (21 mmol/L) |
| Creatinine | 1.2 mg/dL (106.1 µmol/L) (3 years ago: 0.8 mg/dL [70.7 µmol/L]) |
| Glucose | 87 mg/dL (4.8 mmol/L) |
| Phosphorus | 2.2 mg/dL (0.71 mmol/L) |
| Urinalysis | 1+ protein; 2+ glucose; no cells or casts |
Which of the following is the most likely cause of this patient’s kidney findings?
A. Hypertensive nephropathy
B. Membranoproliferative glomerulonephritis
C. Membranous glomerulopathy
D. Tubulointerstitial disease
MKSAP Answer and Critique
The correct answer is D. Tubulointerstitial disease.
This patient has tubulointerstitial disease, likely due to long-standing exposure to tenofovir. Evidence for a tubulointerstitial process includes a slowly progressive course without a clear inciting event, subnephrotic proteinuria, bland urine sediment, and a kidney ultrasound showing atrophic kidneys. History and physical examination should focus on conditions associated with tubulointerstitial disease and a careful review of medications, because numerous medications may induce tubulointerstitial disease. An associated characteristic that may be present with tubulointerstitial disease is abnormal tubular handling of glucose, amino acids, uric acid, phosphate, and bicarbonate (termed Fanconi syndrome); renal tubular acidosis is also common. Patients may also have concentrating defects and may present with nocturia and polyuria. With more advanced disease, anemia may be present due to the destruction of erythropoietin-producing cells in the kidney. This patient’s findings are consistent with tubulointerstitial disease with Fanconi syndrome, indicated by glucosuria in the context of normoglycemia, trace proteinuria, and hypophosphatemia. Because tenofovir has been associated with tubulointerstitial disease, it is the likely cause in this patient.
Hypertensive nephropathy involves damage to the vascular structures, glomeruli, and tubulointerstitial regions of the kidney. It may cause progressive kidney failure, often with elevated protein excretion (less than 1000 mg/24 h). However, the rapid progression of kidney dysfunction and the presence of tubular dysfunction (Fanconi syndrome) characteristic of tubulointerstitial disease make hypertensive nephropathy less likely in this patient.
Membranoproliferative glomerulonephritis may also be associated with chronic hepatitis B infection and involves immune complex deposition in the glomeruli. It typically presents with hematuria (often with dysmorphic erythrocytes and/or erythrocyte casts), variable degrees of proteinuria, and a reduced glomerular filtration rate. This would not be a consistent finding in this patient with a bland urine sediment.
Membranous glomerulopathy is common in patients with chronic hepatitis B infection and appears to be related to subendothelial and mesangial immune deposits in the glomeruli. Because it primarily affects the glomeruli, it is associated with high levels of proteinuria, usually in the nephrotic range, and would not be expected to present with tubular dysfunction and Fanconi syndrome as seen in this patient.
Key Point
- Kidney disease with a tubulointerstitial process is characterized by a slowly progressive course without a clear inciting event, subnephrotic proteinuria, bland urine sediment, and a kidney ultrasound showing atrophic kidneys.
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