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1
Question:

A 56-year-old man comes to the clinic for follow-up.  The patient has a history of end-stage renal disease due to hypertensive nephropathy and underwent renal transplantation 2 weeks ago.  The surgery had no complications and he had good initial graft function.  The patient has no other medical conditions.  His immunosuppression medications include prednisone, tacrolimus, and mycophenolate sodium.  The patient does not use tobacco, alcohol, or illicit drugs.  Vital signs are normal.  BMI is 31.8 kg/m2.  Physical examination shows a healing lower abdominal surgical scar with no erythema or drainage.  Fasting serum chemistry reveals the following:

Sodium136 mEq/L
Potassium4.6 mEq/L
Chloride102 mEq/L
Bicarbonate22 mEq/L
Blood urea nitrogen14 mg/dL
Creatinine1.4 mg/dL
Glucose102 mg/dL
Calcium9.8 mg/dL

Which of the following is this patient at greatest risk of developing within the next several months?

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Explanation:

The risk of new-onset diabetes mellitus (DM) is increased following renal transplant and highest within the first few months.  The cause of the increased risk is likely multifactorial and related to the following:

  • Immunosuppression medication adverse effects:  Following renal transplant, patients are typically maintained on a multidrug regimen that can consist of glucocorticoids (eg, prednisone), calcineurin inhibitors (eg, tacrolimus, cyclosporine), and antimetabolic agents (eg, mycophenolate).  Glucocorticoids cause weight gain and decreased insulin sensitivity, and calcineurin inhibitors cause reversible toxicity to pancreatic islet cells, leading to impaired insulin secretion.
  • Improved renal function:  The healthy, transplanted kidney causes increased insulin excretion and is capable of increased gluconeogenesis.

Many cases of new-onset DM following renal transplant likely represent patients with preexisting susceptibility to type 2 DM.  Risk factors include increased age (eg, >45), BMI >30 kg/m2, and family history of DM.  The development of new-onset DM following renal transplant has been shown to both increase patient mortality and shorten graft survival time.

(Choice B)  There are increased rates of subclinical hypothyroidism following renal transplant, likely related to adverse effects of glucocorticoids.  However, the rates of hyperthyroidism are not significantly increased.

(Choice C)  The incidence of nephrolithiasis in renal transplant recipients is not increased and may be decreased compared to the general population; the reasons are unclear.

(Choice D)  The risk of osteoporosis is increased following renal transplant, likely due to adverse effects of both glucocorticoids and calcineurin inhibitors on bone metabolism.  However, over the next several months the development of osteoporosis is less likely than DM in this overweight male patient.

(Choice E)  The lifetime risk of renal cell carcinoma (RCC) of the native kidneys is significantly increased in renal transplant recipients.  This is likely due to immunosuppression and may also be related to structural changes that occur in the native kidneys during the period of advanced renal disease that precedes renal transplant.  However, cancer is slow growing and the risk of developing RCC within the first few months following transplant is low.

Educational objective:
The risk of new-onset diabetes mellitus is increased following renal transplant, predominantly in the first few months.  The cause of this increased risk is likely multifactorial, related to adverse effects of immunosuppression medications (eg, glucocorticoids, calcineurin inhibitors) as well as increased insulin excretion and gluconeogenesis by the healthy, transplanted kidney.