Tacrolimus and Cyclosporine Nephrotoxicity in Native Kidneys of Pancreas Transplant Recipients

Abstract

SummaryBackground and objectives Calcineurin inhibitors, while representing advances for solid organ transplantation, have nephrotoxic potential that reduces their net benefit. Tacrolimus has been considered less nephrotoxic than cyclosporine, but direct quantitative comparisons of the changes in renal structure from baseline to follow-up biopsies have not been done. To avoid the pitfalls of renal allograft studies, including rejection and disease recurrence, we compared the development of calcineurin lesions in the native kidneys of 14 tacrolimus-and 12 calcineurin-treated pancreas transplant alone recipients cured of type 1 diabetes.Design, setting, participants, & measurements Research renal biopsies obtained before and at 5 years after transplantation were studied using established morphometric methods. ResultsThe cyclosporine and tacrolimus groups had, respectively, on average, 33% versus 44% decline in GFR (ns), 27% versus 29% increase in cortical interstitial fractional volume (ns), 245% versus 347% increase in the fractional volume of cortical tubules that were atrophic (ns), and 291% versus 392% increase in the percent of globally sclerotic glomeruli (ns). Arteriolar hyalinosis did not change significantly in either group. ConclusionsThese studies indicate that the nephrotoxic potential of tacrolimus and cyclosporine are equivalent and support the development of strategies to reduce these negative effects.

Results of Pancreas Transplantation Alone with Special Attention to Native Kidney Function and Proteinuria in Type 1 Diabetes Patients

“…Similar rates of GFR loss after 5 years post-PTA have been recently reported, with no major difference, irrespective of which calcineurin inhibitor was used [17]. Interestingly, in the present study, the loss of renal function after PTA was less significant in patients with lower baseline GFR (< 90 ml/min) than in patients with higher pristine renal function (GFR > 90 ml/min).…”

Arteriolar Hyalinosis Predicts Increase in Albuminuria and GFR Decline in Normo- and Microalbuminuric Japanese Patients With Type 2 Diabetes

“…Previous studies in type 1 diabetes have shown that IAH did not change 5-10 years after pancreas transplantation, although glomerular changes returned to normal or near normal after surgery (24,25). However, Fioretto et al (26) showed that calcineurin inhibitors, which were used in that study, can induce renal arteriolar hyalinosis. Therefore, the potential histological reversibility of arteriolar hyalinosis with normoglycemia remains uncertain (25,26).…”

PharmGKB summary

“…For example, tacrolimus is more likely to cause alopecia [16], tremors [17], and new-onset diabetes mellitus [12], whereas cyclosporine is associated with hyperlipidemia [18], hypertrichosis, and gingival hyperplasia [19]. The idea that tacrolimus is less nephrotoxic than cyclosporine remains controversial [20], particularly as most studies of renal injury are based on evaluations in renal transplant patients, making it difficult to discriminate between drug-induced organ damage and other causes of organ dysfunction [21]. A recent study in pancreatic transplant recipients examined baseline kidney biopsies and 5-year post-transplant biopsies, and reported that the chronic nephrotoxic effects of tacrolimus and cyclosporine were similar [20].…”