A 40-year-old woman comes to the office for follow-up. She received a living-related donor kidney transplant a year ago for membranoproliferative glomerulonephritis. The patient feels well and has been consistent with follow-up and medications. Other medical issues include hypertension and diet-controlled type 2 diabetes mellitus. Current medications include tacrolimus, prednisone, mycophenolate mofetil, lisinopril, and amlodipine, as well as fluconazole for recurrent vaginal candidiasis.
Temperature is 36.9 C (98.4 F), blood pressure is 152/100 mm Hg, and pulse is 82/min. Physical examination reveals mild cushingoid features. The abdomen is soft with no graft tenderness.
Laboratory results are as follows:
The patient's creatinine was 1.4 mg/dL 3 months ago. Which of the following is the most likely cause of the acute renal dysfunction in this patient?

Question

A 40-year-old woman comes to the office for follow-up.  She received a living-related donor kidney transplant a year ago for membranoproliferative glomerulonephritis.  The patient feels well and has been consistent with follow-up and medications.  Other medical issues include hypertension and diet-controlled type 2 diabetes mellitus.  Current medications include tacrolimus, prednisone, mycophenolate mofetil, lisinopril, and amlodipine, as well as fluconazole for recurrent vaginal candidiasis.
Temperature is 36.9 C (98.4 F), blood pressure is 152/100 mm Hg, and pulse is 82/min.  Physical examination reveals mild cushingoid features.  The abdomen is soft with no graft tenderness.
Laboratory results are as follows:
 The patient's creatinine was 1.4 mg/dL 3 months ago.  Which of the following is the most likely cause of the acute renal dysfunction in this patient?

Quizplus · Accepted Answer

11ec193a_9901_eb8c_853d_2fafa0e49537_MD0002_00 This patient has acute kidney injury and electrolyte abnormalities while on tacrolimus and fluconazole; this should raise suspicion for calcineurin inhibitor nephrotoxicity. Calcineurin inhibitors (eg, tacrolimus, cyclosporine) are common immunosuppressants used in organ transplantation; toxicity may be due to medication-induced vasoconstriction leading to renal ischemia. Patients can have declining glomerular filtration rates and a variety of metabolic abnormalities, including hyperkalemia, hyperuricemia, hypophosphatemia, hypomagnesemia, hypercalciuria, and possibly metabolic acidosis. Significant hypertension may also be present. Toxicity is dose-dependent. Calcineurin inhibitors are metabolized by cytochrome P450 3A4; levels are increased by other drugs that are metabolized by this enzyme (eg, azole antifungals, macrolides, non-dihydropyridine calcium channel blockers). Biopsy is often required to rule out acute rejection; histologic findings are nonspecific, but calcineurin inhibitor nephrotoxicity is suggested by the absence of signs of acute rejection (eg, interstitial inflammation, intimal arteritis, tubulitis). Acute calcineurin inhibitor toxicity is usually reversible with drug cessation, although some patients develop residual chronic renal dysfunction. (Choice A) Although this patient has diabetes and an elevated blood glucose possibly indicating suboptimal control, diabetic nephropathy is typically slowly progressive over a period of years (as opposed to the acute change in this patient) and is associated with proteinuria. (Choice B) Acute graft rejection most commonly occurs within the first 6 months post-transplant, unless the patient is noncompliant with immunosuppression. In addition, significant proteinuria (>1 g) is often present. (Choice C) Hypertensive nephrosclerosis usually presents with a long history of hypertension, slowly rising creatinine, and mild proteinuria. Although this patient has hypertension, the elevated blood pressure is more likely due to tacrolimus rather than primary hypertension, given the electrolyte abnormalities. (Choice E) Recurrence of membranoproliferative glomerulonephritis could cause progressive renal failure and hypertension, but urinalysis would likely show hematuria, red blood cell casts, and proteinuria. Educational objective: Calcineurin inhibitors (eg, cyclosporine, tacrolimus) can cause nephrotoxicity that presents with declining glomerular filtration rates and metabolic abnormalities. Toxicity is dose-dependent; drugs metabolized by cytochrome P450 3A4 can increase toxicity. __________ References: Calcineurin inhibitor nephrotoxicity. (http://www.ncbi.nlm.nih.gov/pubmed/19218475)

A 40-Year-Old Woman Comes to the Office for Follow-Up