Disappearance of Nephrotic Syndrome in Type 1 Diabetic Patients Following Pancreas Transplant Alone

Abstract

Diabetic nephropathy affects approximately 40% of diabetic patients and is the leading cause of kidney disease in patients starting renal replacement therapy (1, 2). It increases the risk of death, mainly from cardiovascular causes, and is defined by increased urinary albumin excretion in the absence of other renal diseases (1, 2). Nephrotic syndrome, characterized by massive proteinuria (≥2.5–3.0 g/24h), dysproteinemia/hypoalbuminemia, hyperlipidemia and edema, may be a devastating clinical manifestation of diabetic nephropathy (3). Pancreas transplant alone (PTA) can be effective in significantly improving the quality of life of type 1 diabetic patients, and can also eliminate diabetes acute complications, such as hypoglycemic and/or hyperglycemic episodes (4). In addition, evidence is growing to show that pancreas transplantation alone may have positive effects on chronic diabetes complications (4). We have recently observed that this procedure reduced urinary protein excretion in a group of type 1 diabetic patients (5). Here we describe the effects of pancreas transplant alone on the course of nephrotic syndrome in six type 1 diabetic patients (four females and two males, aged 35.3±3.7 years at the time of transplantation, with a diabetes duration of 24.1±7.5 years) with histologically documented diabetic nephropathy. Patients were evaluated before and after successful PTA (28.0±6.9 months of follow-up, with a range of 3–36 months), and results were compared with those obtained from a group of five matched type 1 diabetic patients (four females and one male, aged 26±5 years, with a diabetes duration of 18±3 years, and 28.0±5.6 months of follow-up, with a range of 3–36 months), who were evaluated for pancreas transplantation but did not accept to undergo the procedure. All the transplanted patients received portal drainage of endocrine pancreas secretions. Induction immunosuppression therapy consisted of basiliximab and steroids, and maintainance therapy consisted of tacrolimus (given at doses to achieve blood through levels of 10–15 ng/ml during the first month posttransplant, and 8–12 ng/ml thereafter), mycophenolate mophetil and steroids (tapered to 5 mg per day after 3 months) (6). Pancreas transplantation restored sustained normoglycemia, without exogenous insulin administration (plasma glucose levels: from 238±123 to 98±1.5 mg/dl; A1c values: from 9.52±2.26% to 5.6±0.41%, both P<0.01 of last posttransplant control vs. pretransplant measurements). Under these conditions, edema disappeared in all the patients, and urinary protein excretion decreased (Fig. 1A), with values from 6.3±3.5 before transplantation to 0.50±0.18 g/24h at the end of follow-up (P<0.01). Conversely, no significant change occurred in non-transplanted patients (Fig. 1B). As shown in Table 1, serum protein levels normalized in transplanted patients, whereas, again, no major change was observed in the control group (Table 1). Furthermore, in PTA patients serum total and LDL cholesterol decreased significantly (Table 1) in the absence of antidyslipidemic therapy modifications. These improvements occurred without any significant change of creatinine clearance values (from 84±19 ml/min pretransplantation to 78±28 ml/min posttransplantation, P=0.47).FIGURE 1.: Course of proteinuria in transplanted (A) and nontransplanted (B) patients.TABLE 1: Some biochemical parameters of transplanted and nontransplanted patientsThis study demonstrates for the first time that in type 1 diabetic patients, successful pancreas transplant alone determines the disappearance of nephrotic syndrome, as documented by disappearance or significant improvement of the clinical signs of this condition. These effects were accompanied by no change of creatinine clearance. Routine native kidney biopsies of pancreas transplant alone recipients are not performed in our centre for ethical reasons. Nevertheless, the beneficial actions of PTA that we observed are unlikely to be due to anatomical changes in the kidneys, because it has been previously demonstrated that reversal of diabetic renal lesions occurred many years after pancreas grafting (7). Rather, diabetes “curing” by PTA is likely to have played the major role, by normalization of circulating glucose levels and restoration of endogenous insulin and C-peptide secretion. These data suggest that the beneficial effects of PTA may be more evident than currently appreciated. Alberto Coppelli Rosa Giannarelli Ugo Boggi Stefano Del Prato Gabriella Amorese Fabio Vistoli Franco Mosca Piero Marchetti Department of Endocrinology and Metabolism University of Pisa Pisa, Italy