Gerald C. Groggel

Randomized Trial of Single-Dose Versus Divided-Dose Rabbit Anti-Thymocyte Globulin Induction in Renal Transplantation : An Interim Report

Background. The optimal dosing protocol for rabbit anti-thymocyte globulin (rATG) induction in renal transplantation has not been determined, but evidence exists that rATG infusion before renal allograft reperfusion improves early graft function. Infusing a large rATG dose over a short interval has not previously been evaluated for its effect on renal function and allograft nephropathy in a prospective, randomized comparison against conventional rATG induction. Methods. Between April 20, 2004 and December 26, 2007 we enrolled renal transplant patients into a prospective, randomized, nonblinded trial of two rATG dosing protocols (single dose, 6 mg/kg vs. divided doses, 1.5 mg/kg every other day×4; target enrollment=160) followed after 6 months by calcineurin-inhibitor withdrawal. Primary endpoints are renal function by calculated glomerular filtration rate (GFR) and chronic allograft nephropathy at protocol biopsy. We now present the early GFR data of all 160 patients and safety and efficacy data of the first 142 patients with 6 months follow up and before calcineurin inhibitor withdrawal (average follow up=23.3±11.6 months). Results. There were no differences between groups in rATG-related adverse events, patient and graft survival, acute rejection, or chronic allograft nephropathy rate at 6 months. Calculated &Dgr;GFR (POD 1–4) was significantly better in the single-dose group (P=0.02), with a trend toward improved renal function from months 2 to 6 in recipients of deceased donor kidneys (P=0.08). Conclusions. This study demonstrates that administering 6 mg/kg of rATG over 24 hr is safe and is associated with improved early renal function compared with administering rATG in alternate-day doses.

Dyslipidemia Can Be Controlled in Diabetic as well as Nondiabetic Recipients after Kidney Transplant

Background. Patients with diabetes have been reported to have greater dyslipidemia after kidney transplant (KTX). Because postKTX management of diabetes has changed markedly since those reports, we hypothesized that lipids can be controlled as well in diabetic as in nondiabetic recipients. Methods. We compared lipid levels up to 2 years after KTX (n=192) between diabetic and nondiabetic recipients. The cohort was subdivided into nondiabetic (nonDM-K; n=123), type 2 (DM2-K; n=33), or type 1 diabetes after KTX (DM1-K; n=14), or type 1 after kidney-pancreas transplant (DM1-KP; n=22). Results. Mean age and body mass index of DM2-K were greater than the others (P<0.01), and diabetes groups had a higher pretransplant A1C than nonDM-K (P<0.001). After KTX, lipid levels were not higher in diabetic than in nondiabetic recipients, and did not increase in any group. Total and low-density lipoprotein cholesterol levels decreased in DM1-K (P<0.001), high-density lipoprotein levels decreased in DM1-KP (P=0.02), and triglyceride levels were unchanged after KTX for all groups. A1C improved in DM1-K and DM1-KP (P<0.0001). There was less improvement in lipid levels with tacrolimus-sirolimus immunosuppression than with other steroid-containing regimens (P<0.05). Conclusions. Multiple mechanisms may contribute to better lipid levels in both groups as well as the lack of difference between diabetic and nondiabetic recipients compared with what has been reported previously: greater use of and more effective lipid-lowering agents, no significant weight gain, no difference in renal function between groups, and better control of glucose in the diabetic group. Thus, overall, lipids can be controlled as well in diabetic as in nondiabetic KTX recipients.

Association of vascular risk factors with carotid intima media thickness after kidney transplant

Background. Vascular risk remains the greatest cause of mortality after kidney transplant (KTX). Carotid intima media thickness (CIMT) has not been studied after KTX. We have analyzed a cross section of KTX recipients to determine which risk factors best correlate with CIMT, representing vascular risk. Methods. All recipients 6 or more months after KTX with estimated glomerular filtration rate (GFR) ≥30 mL/min were invited to participate. Biomarkers of vascular risk were compared with CIMT. Results. A total of 342 recipients (192 men/150 women) with mean age of 52.3±0.6 years (±standard error of the mean) were studied 5.9±0.3 years since KTX (range: 0.5–33.7 years). Diabetes (P<0.01), smoking (P=0.01), and donor status (deceased vs. living) (P=0.04) were associated with CIMT. Age (P<0.0001), body mass index (BMI, P=0.0026), systolic blood pressure (P=0.0013), and pulse pressure (P<0.0001) were positively and diastolic pressure was negatively correlated with CIMT (P=0.0002) and pulse pressure (P=0.007). In multivariate analysis, race/ethnicity, GFR, as well as age, BMI, diabetes status, systolic and diastolic blood pressures, and pulse pressure were all independently associated with CIMT (P<0.05). There was no correlation between CIMT and lipids, homocysteine, high-sensitive C-reactive protein, 25-hydroxyvitamin D, or parathyroid hormone (PTH). Conclusions. In the largest study of CIMT after KTX, diastolic blood pressure was negatively correlated with vascular risk, whereas age, diabetes, BMI, systolic blood pressure, race/ethnicity, and GFR independently correlated with CIMT after KTX confirming the value of CIMT as a noninvasive means to assess vascular risk and factors unique to this patient population.