Natural History of Kidney Graft Survival, Hypertrophy, and Vascular Function in End-Stage Renal Disease Type 1 Diabetic Kidney-Transplanted Patients

Abstract

OBJECTIVE -Diabetes, hypertension, infections, and nephrotoxicity of certain immunosuppressive drugs (i.e., calcineurin inhibitors) can reduce functional survival of the kidney graft. Our aim was to evaluate survival, hypertrophy, and vascular function of the kidney graft in end-stage renal disease (ESRD) type 1 diabetic patients after transplant. RESEARCH DESIGN AND METHODS -The study population consisted of 234 ESRD type 1 diabetic patients who underwent kidney-pancreas (KP; 166 patients), successful kidney-islet (KI-s; 24 patients), and kidney (KD; 44 patients) transplant. Kidney size, graft survival, vascular function, and microalbuminuria were evaluated prospectively yearly for 6 years. Sixty-eight protocol kidney biopsies were performed routinely between 1993 and 1998 cross-sectionally (3.2 Ϯ 0.3 years from kidney transplant).RESULTS -The KP and KI-s groups had better cumulative kidney graft survival at 6 years than did the KD group (KP: 73%; KI-s: 86%; KD: 42%, P Ͻ 0.01). The KP group but not the KI-s/KD groups showed a persistent kidney graft hypertrophy up to 6 years of follow-up. A significant increase in creatinine levels from baseline to year 6 was evident in the KD group (1.58 Ϯ 0.08 to 2.78 Ϯ 0.44 mg/dl, P Ͻ 0.05) but not in the KP/KI-s groups. The KP/KI-s groups only showed a reduction of renal resistance index from baseline to year 6 (KP at baseline: 0.74 Ϯ 0.01 to 0.68 Ϯ 0.01%, P Ͻ 0.01; KI-s at baseline: 0.72 Ϯ 0.02 to 0.69 Ϯ 0.02%, P Ͻ 0.05). At year 6, an increase from baseline in urinary albumin excretion was observed only in the KD group (31.4 Ϯ 9.0 to 82.9 Ϯ 33.6 mg/l, P Ͻ 0.05). Preliminary data suggested that graft nitric oxide (NO) expression was higher in the KP/KI-s groups than in the KD group (data not shown).CONCLUSIONS -In ESRD type 1 diabetic patients, KP and KI-s compared with KD resulted in enhanced kidney graft survival, hypertrophy, and vascular function. Diabetes Care 28:1303-1310, 2005N ephropathy is one of the most common and most serious complications in type 1 diabetes (1,2). Glomerular hyperfiltration is the first feature of renal involvement and can be observed soon after diabetes onset, accompanied by a loss of renal functional reserve (3). Microalbuminuria appears later, as do morphological changes such as thickening of the glomerular basement membrane and mesangial expansion (4).Nephrosclerosis or glomerulosclerosis of the transplanted kidney in end-stage renal disease (ESRD) type 1 diabetic kidney transplant patients may result from the interaction of diabetes, hypertension, obesity, smoking, and dyslipidemia and from nephrotoxicity of certain immunosuppressive drugs (calcineurin inhibitors but not only) (5-6), leading to a reduction in the intrarenal vascular surface area and an increase in vascular resistance (7-10).Pancreas and islet transplantation can confer insulin independence in type 1 diabetic transplant patients, thus preventing the progression to diabetic nephropathy, improving graft survival, and ameliorating diabetic macro-/microangiopathy (6,(11)(12)(1...

Kidney Function After Islet Transplant Alone in Type 1 Diabetes

“…However, immunosuppression consisted of only one potentially nephrotoxic drug (i.e., cyclosporine), and insulin independence was prolonged for a decade. In patients who underwent simultaneous pancreas-kidney or islet-kidney transplantation, improved cumulative survival, kidney graft size, and function were reported in the group with a functioning pancreas or islets (9). Furthermore, insulin independence was not required for a positive effect on kidney function (8), supporting the EDIC finding that patients with type 1 diabetes with residual C-peptide function have a lower risk of diabetic nephropathy (2).…”

“…In patients with type 1 diabetes, pancreas or islet transplantation has improved kidney graft survival (8,9), whereas the positive impact of pancreas transplantation on the native kidney has been counterbalanced by the nephrotoxicity of immunosuppressants, namely calcineurin inhibitors (10,11).…”

Gliquidone decreases urinary protein by promoting tubular reabsorption in diabetic Goto-Kakizaki rats

“…*P!0.05, **P!0.01 vs DN group. (Fiorina et al 2003(Fiorina et al , 2005. Recent studies have indicated that C-peptide produced by islet cells might help to prevent and treat diabetic microvascular lesions (Cotter et al 2003, Forst & Kunt 2004, Hills et al 2010.…”

Bone Marrow-Derived Stem Cell Transplantation for the Treatment of Insulin-Dependent Diabetes

“…Also, a positive impact of islet transplantation on the progression of diabetes complications has been reported. Although, most of the studies showing reduced complications were small-scale and nonrandomized [9][10][11][12][13][14][15][16].…”