Renal Function Declines in Heart Tx Patients for Decades

TORONTO – Heart-transplant recipients experience a steady decline in kidney function for at least 20 years, with the most rapid deterioration occurring in the first year post-transplant, a study has confirmed.

In a cohort of 306 patients who received heart transplants from 1983 to 2012, researchers found that their average estimated glomerular filtration rate (eGFR) fell from 62.3 mL/min/1.73 m2 preoperatively to approximately 57 mL/min/1.73 m2 at one year post-transplant, 52 mL/min/1.73 m2 at five years, and 43 mL/min/1.73 m2 at 20 years.

The main risk factors for kidney-function decline at one year were increased age, female sex, low pre-transplant eGFR, elevated systolic blood pressure and being on a corticosteroid-free regimen. At five years the same set of risk factors prevailed except higher prednisone doses had taken the place of a corticosteroid-free anti-rejection regimen.

The team members are somewhat puzzled by the results, particularly those relating to steroid regimen, but have a working hypothesis to explain them.

“At one year we think that patients not taking prednisone may have higher doses or concentrations of CNIs [calcineurin inhibitors, which are known to be nephrotoxic] to maintain immunosuppression, while at five years those that have already experienced significant renal dysfunction may have been switched from CNIs to prednisone, which has adverse effects that could aggravate the renal dysfunction,” said PhD candidate Kim Lachance, BPharm, who presented the results at the 2012 Canadian Cardiovascular Congress.

The goal of the team, led by Simon de Denus, MSc (Pharm), PhD, Beaulieu-Saucier Chair of Pharmacogenomics at the University of Montreal, was to investigate the causes and hence possible remedies for complications in the management of heart-transplant patients. These complications are becoming more common with increased population age and higher rates of comorbidities such as obesity and diabetes.

At baseline, the 306 patients, 79.7% of whom were male, had an average age of 47.2 years. Half had ischemic heart disease, 25.5% had dilated cardiomyopathy, and 24.2% had another form of heart disease. Diabetes was present in 9.5% of the patients and 17% had hypertension. The donors' average age was 31.3 years, and two-thirds were male.

The recipients' eGFR increased for the first six months post-transplant and then began to decline. It fell sharply in the next six months and subsequently dropped more slowly.

The researchers then performed analyses to determine what causes most of the eGFR decline and found that increased age, female gender, low pre-transplant eGFR, elevated systolic blood pressure, and being on a corticosteroid-free regimen accounted for 39% of the inter-patient variability in eGFR at one year. At five years 40% of the overall eGFR variability was accounted for by the first four factors plus taking higher prednisone doses.

“The goal when trying to identify risk factors for post-transplantation renal dysfunction is to design strategies to preserve patient kidney function,” said Lachance said. “While many of the risk factors are non-modifiable, we can use them to predict renal function in patients. And we can also exert control over the modifiable factors such as by trying to optimize management of hypertension and adapt the immunosuppressive protocols for each patient such as through careful tapering of corticosteroids.”

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