Better Management Needed to Lower Cardiovascular Risks After Kidney Transplant

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Even with protocols in place to improve compliance, many kidney transplant patients did not achieve risk factor targets for cardiovascular disease, a leading cause of graft failure and of death after transplantation, according to study results presented at the American Transplant Congress in Philadelphia in early May. But as time went on after transplantation, the modifiable risk factors of hypertension, hyperlipidemia, and diabetes mellitus could become better controlled, said lead author Rakesh Kumar, MD, of the State University of New York at Buffalo.

Although advances in immunosuppressive therapy can prevent immune-mediated damage to transplanted kidneys and improve short-term allograft survival,

Even with protocols in place to improve compliance, many kidney transplant patients did not achieve risk factor targets for cardiovascular disease, a leading cause of graft failure and of death after transplantation, according to study results presented at the American Transplant Congress in Philadelphia in early May. But as time went on after transplantation, the modifiable risk factors of hypertension, hyperlipidemia, and diabetes mellitus could become better controlled, said lead author Rakesh Kumar, MD, of the State University of New York at Buffalo.

Although advances in immunosuppressive therapy can prevent immune-mediated damage to transplanted kidneys and improve short-term allograft survival, the same factors that increase cardiovascular risk—hypertension, dyslipidemia, and diabetes—also affect the function and survival of grafts. Cardiovascular disease in itself accounts for up to 25 percent of patient deaths in the long term.

In this single-center retrospective chart review study performed at the university-affiliated Erie County Medical Center Kidney-Pancreas Transplant Unit, the researchers assessed blood pressure and levels of LDL cholesterol and hemoglobin A1c (HbA1c) annually, starting 1 year after transplant. Data were collected for 1–5 years (2005–2009) depending on the date of the transplant.

Uncontrolled blood pressure was defined as readings above 130/80 mm Hg on three or more occasions over 5 years. The results were compared with the Kidney Disease: Improving Global Outcomes (KDIGO) recommended guidelines of blood pressure no greater than 130/80 mm Hg, LDL cholesterol less than or equal to 100 mg/dL, and HbA1c less than or equal to 7.5 percent. The immunosuppressive regimen was alemtuzumab induction with tacrolimus and mycophenolate maintenance.

The 128 patients (44 women) in the study had a mean age of 51 years; 6 percent were white, 44 percent had a history of diabetes, 83 percent had dyslipidemia at the time of the study, and 96 percent were hypertensive. Thirty-four percent were taking three or more antihypertensive medications.

Results

In general, blood pressure appeared to improve over time. One year after transplantation, 41 percent of patients had controlled hypertension. “After 5 years of transplant, 55 percent of patients had blood pressure less than 130/80,” Kumar reported. “There was a greater decline in eGFR [estimated glomerular filtration rate] among patients with uncontrolled hypertension compared with patients with controlled hypertension, although it did not reach a significant level.”

At 1 and 5 years, eGFR was 59.2 and 55.1 mL/min, respectively, among patients with controlled hypertension and 52.9 and 45.3 mL/min, respectively, for patients with uncontrolled hypertension. At 1 year, 76 percent of 106 patients had an LDL cholesterol reading at or below 100 mg/dL, and at 5 years, the figure was 91 percent of 12 patients. Seventy percent of 78 patients had HbA1c levels at or below the desired level of 7.5 percent at 1 year, and by 5 years the figure increased to 81 percent of 9 patients for whom there was a reading. Kumar summarized his findings, saying that hypertension was the most prevalent cardiovascular risk factor in this cohort of renal transplant patients and that eGFR declined faster in the presence of uncontrolled blood pressure. Some patients were fairly refractory to the multiple antihypertensive therapies prescribed. “Forty percent of patients with uncontrolled hypertension and 35 percent of patients with controlled hypertension were on three or more antihypertensive medications,” Kumar said.

Although compliance with KDIGO guidelines for blood pressure, LDL cholesterol, and HbA1c improved over time, a substantial proportion of transplant recipients missed some of the routine screenings for cardiovascular risk factors, and 30–60 percent of patients failed to reach risk factor goals in the first year after transplant. “Evidence-based guidelines alone were insufficient to uniformly drive ideal care,” Kumar concluded, and he said that better strategies are needed to meet treatment objectives.

Session moderator Vinay Nair, DO, a transplant nephrologist at Mt. Sinai Medical School in New York, told ASN Kidney News that continued improvement in KDIGO parameters over the years would not be expected. “If anything, when you go further years you’d expect some graft deterioration. It’s very common with transplantation,” he said. “A lower GFR should mean worse blood pressure control if anything. So it is a little bit surprising” that blood pressure control improved over time but that eGFR was declining.

He agreed that better strategies are needed if outcomes are to improve, but that first it is important to know how well patients do with chronic kidney disease but without transplantation, and how the general population compares. He asked that if patients who have received transplants are doing worse, “are we as transplant nephrologists not doing a good enough job, or it is something with the medications that makes them harder to treat and control?”

Nair also noted Kumar’s statement that calcium channel blockers were the majority of first-line antihypertensive medications used for the study patients. However, “JNC 7 [Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure 7] suggests that the first medication is a diuretic. We’re often, initially at least, reluctant to give diuretics because of rises and falls in creatinine, or ACE [angiotensin converting enzyme] inhibitors,” Nair explained. He said that clinicians have historically tended to prescribe calcium channel blockers because some previous data suggested that they may reverse the effects of calcineurin inhibitors on blood pressure, but more recent data have called that idea into question.

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