A 38-year-old woman comes to the office with 2 weeks of mild headache and nausea. She has a history of end-stage renal disease secondary to lupus nephritis and had an allograft renal transplant a year ago. Her medications include tacrolimus, azathioprine, and prednisone. The patient has also been taking lansoprazole for indigestion for the past 3 weeks. She does not use tobacco, alcohol, or illicit drugs. To take better care of herself, she has begun eating plenty of fruits and green vegetables and drinking grapefruit juice.
The patient is afebrile. Her blood pressure was 120/70 mm Hg a month ago and is now 150/90 mm Hg. Examination shows clear lung fields, normal heart sounds, and a soft and nontender abdomen. She has mild bilateral hand tremor without muscle weakness or sensory loss. There is no lower extremity edema.
Laboratory results are as follows:

Urinalysis shows clear urine with no protein, blood, cells, or casts. Renal ultrasound shows no abnormalities of the transplanted kidney with no urinary leak or obstruction.
Which of the following is the most likely cause of this patient's renal failure?

Question

A 38-year-old woman comes to the office with 2 weeks of mild headache and nausea.  She has a history of end-stage renal disease secondary to lupus nephritis and had an allograft renal transplant a year ago.  Her medications include tacrolimus, azathioprine, and prednisone.  The patient has also been taking lansoprazole for indigestion for the past 3 weeks.  She does not use tobacco, alcohol, or illicit drugs.  To take better care of herself, she has begun eating plenty of fruits and green vegetables and drinking grapefruit juice.
The patient is afebrile.  Her blood pressure was 120/70 mm Hg a month ago and is now 150/90 mm Hg.  Examination shows clear lung fields, normal heart sounds, and a soft and nontender abdomen.  She has mild bilateral hand tremor without muscle weakness or sensory loss.  There is no lower extremity edema.
Laboratory results are as follows:

Urinalysis shows clear urine with no protein, blood, cells, or casts.  Renal ultrasound shows no abnormalities of the transplanted kidney with no urinary leak or obstruction.
Which of the following is the most likely cause of this patient's renal failure?

Quizplus · Accepted Answer

11ec193a_990d_ab76_853d_d39dfdecfa1b_MD0002_00 Tacrolimus and cyclosporine are calcineurin inhibitors that antagonize interleukin-2 and other cytokines to decrease T cell activity. Both drugs are extensively metabolized by hepatic cytochrome P450 and excreted into bile. As a result, compounds interacting with hepatic cytochrome P450 can alter the drug's level and effect. This patient recently started both lansoprazole and grapefruit juice and most likely has tacrolimus toxicity. Patients most commonly develop nephrotoxicity, which presents with an acute rise in serum creatinine, tubular dysfunction, and bland urinalysis. Other side effects include hypertension, neurotoxicity (eg, tremor, headache, visual difficulties), and metabolic abnormalities (eg, hyperglycemia, hyperkalemia, hypomagnesemia). Drug levels should be obtained periodically with dose adjustments to prevent toxicity. tacrolimus toxicity (Choice A) Acute transplant rejection usually presents early after surgery or within the first 6 months due to noncompliance or overaggressive reduction in immunosuppression. Patients can be asymptomatic or develop graft pain/tenderness, fever, hypertension, oliguria, acute renal failure, pyuria, proteinuria, and increased graft size on imaging. This patient's normal renal ultrasound and normal urinalysis make this less likely. (Choice B) BK virus infection in transplant patients typically presents within the first year after transplant with tubulointerstitial nephritis, acute or progressively rising creatinine, and abnormal urinalysis (eg, proteinuria, hematuria, casts). This patient's urinalysis is normal. (Choice C) Hypertensive nephrosclerosis is due to a long history of uncontrolled hypertension and typically presents with slowly rising creatinine and mild proteinuria. This patient has an acute rise in blood pressure and normal urinalysis. (Choice D) Lupus nephritis recurs in <10% of kidney transplant patients. Laboratory studies in recurrent disease usually show increased creatinine, new proteinuria, and hematuria. Educational objective: Tacrolimus and cyclosporine are calcineurin inhibitors that antagonize interleukin-2 and other cytokines to decrease T cell activity. Because both drugs are extensively metabolized by hepatic cytochrome P450, compounds that interact with cytochrome P450 can increase or decrease drug levels. Patients can develop nephrotoxicity (most common), hypertension, neurotoxicity, and metabolic abnormalities. __________ References: Calcineurin inhibitor nephrotoxicity. (http://www.ncbi.nlm.nih.gov/pubmed/19218475)

A 38-Year-Old Woman Comes to the Office with 2 Weeks