Altered kidney graft high-energy phosphate metabolism in kidney-transplanted end-stage renal disease type 1 diabetic patients : a cross-sectional analysis of the effect of kidney alone and kidney-pancreas transplantation

OBJECTIVE - Diabetes, hypertension, dyslipidemia, obesity, nephrotoxicity of certain immunosuppressive drugs, and the persistence of a chronic alloimmune response may significantly affect graft survival in end-stage renal disease (ESRD) type 1 diabetic patients who have undergone kidney transplant. The aim of this study was to ascertain the impact of kidney alone (KD) or combined kidney-pancreas (KP) transplantation on renal energy metabolism. RESEARCH DESIGN AND METHODS - We assessed high-energy phosphates (HEPs) metabolism by using, in a cross-sectional fashion, 31P-magnetic resonance spectroscopy in the graft of ESRD type 1 diabetic transplanted patients who received KD (n = 20) or KP (n = 20) transplant long before the appearance of overt chronic allograft nephropathy (CAN). Ten nondiabetic microalbuminuric kidney transplanted patients and 10 nondiabetic kidney transplanted patients with overt CAN were chosen as controls subjects. RESULTS - Simultaneous KP transplantation patients showed a higher \u3b2-ATP/inorganic phosphorus (Pi) ratio (marker of the graft energy status) versus the other groups, and a positive correlation between \u3b2-ATP/Pi phosphorus ratio and A1C was found. In the analysis limited to the subgroup of normoalbuminuric patients, the difference in \u3b2-ATP/Pi was still detectable in KP patients compared with KD transplantation. CONCLUSIONS - KP transplantation was associated with better HEPs than in KD transplantation, suggesting that restoration of \u3b2-cell function positively affects kidney graft metabolism

Islet transplantation is associated with improvement of renal function among uremic patients with type I diabetes mellitus and kidney transplants

The potential effects of islet transplantation on the renal function of 36 patients with type I diabetes mellitus and kidney transplants were studied with 4 yr of follow-up monitoring. Kidney-islet recipients were divided into two groups, i.e., patients with successful islet transplants (SI-K group) (n = 24, fasting C-peptide levels of >0.5 ng/ml for >1 yr) and patients with unsuccessful islet transplants (UI-K group) (n = 12, fasting C-peptide levels of <0.5 ng/ml). Kidney graft survival rates and function, urinary albumin excretion rates, and sodium handling were compared. Na+/K+-ATPase activity in protocol kidney biopsies and in red blood cells was cross-sectionally analyzed. The SI-K group demonstrated better kidney graft survival rates (100, 83, and 83% at 1, 4, and 7 yr, respectively) than did the UI-K group (83, 72, and 51% at 1, 4, and 7 yr, respectively; P = 0.02). The SI-K group demonstrated reductions in exogenous insulin requirements and higher C-peptide levels, compared with the UI-K group, whereas GFR values were similar. Microalbuminuria (urinary albumin index) increased significantly in the UI-K group only (UI-K, from 92.0 \ub1 64.9 to 183.8 \ub1 83.8, P = 0.05; SI-K, from 108.5 \ub1 53.6 to 85.0 \ub1 39.0, NS). In the SI-K group, but not in the UI-K group, natriuresis decreased at 2 and 4 yr (P < 0.01). The SI-K group demonstrated greater Na+/K+-ATPase immunoreactivity in renal tubular cells (P = 0.05) and higher activity in red blood cells (P = 0.03), compared with the UI-K group. The Na+/K+-ATPase activity in red blood cells was positively correlated with circulating C-peptide levels but not with glycated hemoglobin levels. Successful islet transplantation was associated with improvements in kidney graft survival rates and function among uremic patients with type I diabetes mellitus and kidney grafts

Selective intra-graft apoptosis and down-regulation of lymphocyte bcl-2, iNOs and CD95L expression in kidney-pancreas transplanted patients after anti-Thymoglobulin induction

Intra-graft infiltrating cells apoptosis was evaluated in 20 consecutive kidney-pancreas transplanted (KP) patients without kidney rejection. Two fine-needle aspirated biopsy (FNAB) and two peripheral blood lymphocytes (PBL) samples were obtained 14 days after transplantation. Immunosuppression was based on anti-Thymoglobulins (ATG) induction for 7 days and cyclosporine/mofetil mycophenolate as maintenance therapy. Ten matched healthy subjects were chosen as controls for PBL. Lymphocyte phenotypes and activation markers, apoptotic rate and lymphocyte expression of pro/anti-apoptotic molecules were analysed by flow cytometry analysis (FACS). Lymphocyte phenotypes and activation markers: higher levels of CD8 and CD4DR were evident in the graft (p < 0.05) than in PBL, CD3CD25 in PBL were higher in transplanted patients than in controls. Apoptotic rate and lymphocyte expression of pro- and anti-apoptotic molecules: a higher expression of annexin V, together with reduced lymphocytes CD95L, iNOs and Bcl-2 expression (PBL = 97.7+/-1.1% vs FNAB = 81.9+/-15.1%; p < 0.05) were evident in the graft than in PBL. In KP patients intra-graft apoptosis and reduced anti-apoptotic molecules were evident after ATG induction

Kidney-Pancreas transplantation Is associated with near-normal sexual function in uremic type 1 diabetic patients

Background. Sexual function is altered in patients with type 1 diabetes (T1D) and end-stage renal disease (ESRD), thus affecting quality of life. The present study aimed to analyze sexual function in patients with T1D and ESRD (T1D + ESRD) who received a simultaneous kidney-pancreas (KP) or kidney-alone (KD) transplantation. Methods. Ten KP, 10 KD, 9 T1D + ESRD patients and 11 healthy control subjects were evaluated according to the following parameters: (1) medical/sexual history and physical examination; (2) International Index of Erectile Function; (3) Beck's inventory for depression; (4) assessment of hormonal profile; (5) quantitative sensory testing of both hand and penile sensory thresholds; and (6) hemodynamic penile assessment. Results. Controls and KP patients showed a higher rate of self-reported satisfactory erectile function as compared with KD and T1D + ESRD patients. Circulating androgens level resulted lower in both groups of transplanted patients and in patients with T1D + ESRD compared with healthy controls, albeit a relatively better profile was observed in KP. Both transplanted and T1D + ESRD patients showed peripheral hyposensitivity; however, healthy controls and KP showed better penile hemodynamic parameters compared with KD and T1D + ESRD. Conclusions. Our study demonstrates that sexual function, circulating sex steroids milieu, penile sensitivity, and hemodynamics are near-normalized for the most part in KP transplantation. Further studies are needed to assess the beneficial role and the overall impact of KP transplantation on sexual function in a long-term setting and a larger cohort of patients

31P-magnetic resonance spectroscopy (31P-MRS) detects early changes in kidney high-energy phosphate metabolism during a 6-month Valsartan treatment in diabetic and non-diabetic kidney-transplanted patients

P-31-magnetic resonance spectroscopy (P-31-MRS) is a non-invasive tool to study high-energy phosphate (HEP) metabolism. We evaluate whether P-31-MRS can detect early changes in kidney HEP metabolism during a 6-month trial with Valsartan. Twenty consecutive stable and normotensive kidney-transplanted patients were enrolled. Nine of them received short-term low-dose Valsartan treatment (80 mg/day) for 6 months, while 11 controls received no medication. Kidney HEP metabolism was evaluated both at baseline and after treatment by P-31-MRS with a 1.5 T system (Gyroscan Intera Master 1.5 MR System; Philips Medical Systems, Best, The Netherlands). Valsartan-treated patients (n = 9) showed a significant increase in beta-ATP/Pi ratio, a marker of kidney HEP metabolism (baseline = 1.03 +/- 0.08 vs. 6 months = 1.26 +/- 0.07, p = 0.03). In contrast, the beta-ATP/Pi ratio in the control group (n = 11) did not change (baseline = 0.85 +/- 0.10 vs. 6 months = 0.89 +/- 0.08, ns). The improvement in the beta-ATP/Pi ratio was not associated with a reduction in arterial blood pressure or in urinary albumin excretion. Kidney-localized P-31-MRS can detect early changes in kidney HEP metabolism during a short-term low-dose Valsartan treatment in stable normotensive kidney-transplanted patients

Islet transplantation is associated with an improvement of cardiovascular function in type 1 diabetic kidney transplant patients

OBJECTIVE - Cardiovascular mortality and morbidity are major problems in type 1 diabetic patients with end-stage renal disease (ESRD). The aim of this study was to determine whether islet transplantation can improve cardiovascular function in these patients. RESEARCH DESIGN AND METHODS - We assessed various markers of cardiac function at baseline and 3 years later in a population of 42 type 1 diabetic patients with ESRD who received a kidney transplant. Seventeen patients then received an islet transplant that had persistent function as defined by long-term C-peptide secretion (kidney-islet group). Twenty-five patients did not receive a functioning islet transplant (kidney-only group). RESULTS - GHb levels were similar in the two groups, whereas the exogenous insulin requirement was lower in the kidney-islet group with persistent C-peptide secretion. Overall, cardiovascular parameters improved in the kidney-islet group, but not in the kidney-only group, with an improvement of ejection fraction (from 68.2 \ub1 3.5% at baseline to 74.9 \ub1 2.1% at 3 years posttransplantation, P < 0.05) and peak filling rate in end-diastolic volume (EDV) per second (from 3.87 \ub1 0.25 to 4.20 \ub1 0.37 EDV/s, P < 0.05). Time to peak filling rate remained stable in the kidney-islet group but worsened in the kidney-only group (P < 0.05). The kidney-islet group also showed a reduction of both QT dispersion (53.5 \ub1 4.9 to 44.6 \ub1 2.9 ms, P < 0.05) and corrected QT (QTc) dispersion (67.3 \ub1 8.3 to 57.2 \ub1 4.6 ms, P < 0.05) with higher erythrocytes Na +-K+-ATPase activity. In the kidney-islet group only, both atrial natriuretic peptide and brain natriuretic peptide levels decreased during the follow-up, with a stabilization of intima-media thickness. CONCLUSIONS - Our study showed that type 1 diabetic ESRD patients receiving a kidney transplant and a functioning islet transplant showed an improvement of cardiovascular function for up to 3 years of follow-up compared with the kidney-only group, who experienced an early failure of the islet graft or did not receive an islet graft