BRCU Sample Question 3

A 52-year-old woman with type-2 diabetes mellitus, hypertension, osteoarthritis, and HIV infection presents for
routine care. She is a former injection drug user. Medications include metformin, amlodipine, naproxen, and Stribild
(elvitegravir, cobicistat, emtricitabine, and tenofovir disoproxil fumurate). Physical examination is normal, and BP is
135/85 mm Hg. Laboratory tests:

Sodium 134 mEq/L

Potassium 3.3 mEq/L
Chloride 106 mEq/L
Total CO2 17 mEq/L
Serum creatinine 2.3 mg/dL (6 months ago, 1.5 mg/dL)
Glucose 88 mg/dL
Albumin 3.4 g/dL
Hemoglobin 10.1 g/d
Spot urine protein/creatinine ratio 1.05 g/g

Urinalysis is notable for 1+ protein, 3+ glucose, and no cellular elements. Viral load is undetectable and CD4 count
330/mm3.

Which is the MOST likely cause of this clinical picture?

A. Naproxen-associated kidney injury

B. Metformin-associated kidney injury
C. Antiretroviral-associated kidney injury
D. Progression of diabetic kidney disease
E. HIV-associated nephropathy (HIV-AN)

Answer: C

Explanation:
Kidney disease in HIV patients can be due to HIV (e.g., HIV-AN, immune complex disease or thrombotic
microangiopathy) or from combined anti-retroviral therapy (cART). The patient does not exhibit any sign of
glomerular disease (proteinuria/hematuria) or systemic signs of microangiopathy. The combination of a
tubulointerstitial disease with renal glycosuria (Fanconi syndrome) suggests nephrotoxicity from cART. Tenofovir is
a nucleotide reverse-transcriptase inhibitor that is used in many effective cART regimens. Proximal tubular injury
with components of Fanconi syndrome (renal glycosuria, phosphate wasting, hypouricemia), hypokalemia, and
metabolic acidosis and renal insufficiency have been described (≥4% in patients treated with tenofovir versus those
with other regimens). The diagnosis is proximal tubular injury from tenofovir. Kidney biopsy may show abnormal
mitochondria that can confirm the diagnosis. Naproxen can cause AKI and type-4 RTA, but not a Fanconi
syndrome. Metformin causes lactic acidosis in at risk patients. The course is not consistent with progression of
diabetic nephropathy.

References:
Tourret J, Deray G, Isnard-Bagnis C. Tenofovir effect on the kidneys of HIV-infected patients: A double-edged
sword? J Am Soc Nephrol 24(10): 1519–1527, 2013.

Kumar N, Perazella MA. Differentiating HIV-associated nephropathy from antiretroviral drug-induced nephropathy:
A clinical challenge. Curr HIV/AIDS Rep 11(3): 202–211, 2014.

Register for BRCU today, and face the boards with confidence:
www.asn-online.org/BRCU