Enalapril and low protein reverse chronic puromycin aminonucleoside nephropathy

Enalapril and low protein reverse chronic puromycin aminonucleoside nephropathy. The effects of dietary protein and converting enzyme inhibition (CEI) on chronic puromycin aminonucleoside nephropathy (PAN) were studied. PAN was induced with seven SQ injections of puromycin aminonucleoside 20 mg/kg over 10 weeks in male Sprague-Dawley rats. The rats were divided into a 22.5% protein diet group (Gr 1), a 6% protein diet group (Gr 2), and an enalapril-treated group on 22.5% protein diet (Gr 3). Group 4 animals served as age-matched controls. Both diets were isocaloric and had the same phosphorus content. Rats from groups 1, 2, and 4 were sacrificed at 12, 18 and 24 weeks. Five rats of group 3 were sacrificed at 12 weeks, and the others were divided in subgroups 3A (diet changed to 6% protein) and 3B (no changes); half of each subgroup was sacrificed at 18 and 24 weeks, respectively. Group 2 had significantly less proteinuria than group 1 at all times. Group 3 had the same proteinuria as group 1 until 12 weeks and then began to decrease. In group 3A proteinuria decreased to group 2 levels, while in group 3B the decrease was slower but still prominent. Early lesions of focal and segmental glomerular sclerosis/hyalinosis (FSH) were present in groups 1, 2, 3 at 12 weeks (16 ± 1.2%, 15 ± 1.3%, 7 ± 1.3%, respectively, versus 1.3 ± 0.4% in controls), but by 18 weeks a reversal in FSH was seen in groups 2 and 3A/B (3 ± 1.6%, 2 ± 0.4%, and 3 ± 0.9%, respectively, vs. 14 ± 1.5% in group 1). This reversal persisted at 24 weeks (5 ± 2.5%, 3 ± 0.8%, 4 ± 0.8% vs. 18 ± 2.6%). At 24 weeks mean glomerular diameter was significantly less in group 2 compared to group 1, 100.7 ± 2.0 µ versus 112.2 ± 2.7 µ, P = 0.009. In summary, both low protein diet and CEI for 24 weeks reversed both proteinuria and early FSH lesions in chronic PAN after cessation of PA injections

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 x 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 ΔGFR (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

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 x 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 ΔGFR (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