Nondiabetic Kidney Transplant Patients Research Articles

Update on Sodium Glucose Cotransporter Type 2 Inhibitors Use in Kidney Transplant Patients

Sodium glucose cotransporter type 2 inhibitors are a new class of drugs that act on the cardiovascular system, kidneys and metabolism in a multiple ways. Indeed, even though their principal action involves the transport of sodium and glucose in the convoluted distal tubule, they have multiple actions, such as antifibrotic and endothelial protective effects. Their principal mechanism consists of the loss of sodium and glucose. Therefore, they affect blood pressure and glucose metabolism. Their first use was in the diabetic general population; later, some studies documented their activity in the nondiabetic general population and in heart failure in chronic kidney disease patients. Only in recent years have several small studies documented the efficacy of these drugs in diabetic and nondiabetic kidney transplant patients; relatively large studies are rare, very recent, and open new routes for the development of these drugs.

#2502 THE FREQUENCY AND RISK FACTORS OF NODAT AND ELECTROLYTE DISORDERS IN KIDNEY TRANSPLANT PATIENTS

Abstract Background and Aims The purpose of the study is to investigate at the incidence and risk factors for post-transplant diabetes mellitus (PTDM) in non-diabetic kidney transplant patients (KTrs). Method The study included 120 KTRs who did not have diabetes in the pretransplant period. The diagnosis of PTDM was made according to the 2003 ADA DM diagnostic criteria. The relationship between PTDM and clinical and laboratory data on the 0th, 1st, 3rd, 6th, 12th and 24th months was investigated. Results The mean age of the patients was 33.3±11.5 years, 65% (78) of them were male. PTDM was developed in 29.1% (35) and 80% of PTDM at first 3 months. The risk factors for PTDM were found to be older (4.4%), family history of diabetes mellitus (5.24 times), beta-blocker use (2.55 times). KTRs with and without PTDM; Pretransplant dialysis type (Hemodialysis (P=0.822) and Peritoneal dialysis (P = .583)), living donor (101/84.2%)/cadaveric donor (19/ 15.8%), donor age and gender were similar. Serum magnesium and potassium were different only in the first month between the groups with and without PTDM (P = .019 and 0.008 respectively). The negative effect of PTDM on GFR was not observed in the 2-year follow-up. Conclusion It can be predicted that diabetes mellitus may develop with a family history of diabetes, advanced age and the use of beta-blockers. The risk of developing PTDM is higher in the first 3 months and hypomagnesemia in the first month may contribute to diabetes development.

A Comparative Study on Graft and Overall Survival Rates Between Diabetic and Nondiabetic Kidney Transplant Patients Through Survival Analysis.

Patients with diabetes mellitus (DM) have worse graft and overall survival, but recent evidence suggests that the difference is no longer significant. To compare the outcomes between patients with end-stage kidney disease due to DM (ESKD-DM) and ESKD due to nondiabetic etiology (ESKD-non-DM) who underwent kidney transplantation (KT) up to 10 years of follow-up. Survival analysis of a retrospective cohort. All patients who underwent KT at the Hospital Universitario San Ignacio, Colombia, between 2004 and 2022. Overall and graft survival in ESKD-DM and ESKD-non-DM who received KT. Patients who died with functional graft were censored for the calculation of kidney graft survival. Log-rank test, Cox proportional hazards model, and competing risk analysis were used to compare overall and graft survival in patients with ESKD-DM and ESKD-non-DM who underwent KT. A total of 375 patients were included: 60 (16%) with ESKD-DM and 315 (84%) with ESKD-non-DM. Median follow-up was 83.3 months. Overall survival was lower in patients with ESKD-DM at 5 (75.0% vs 90.8%, P < .001) and 10 years (55.0% vs 86.7%, P < .001). Cardiovascular death was higher in patients with diabetes (27.3% vs 8.2%, P = .021). Death-censored graft survival was similar in both groups (96.7% vs 93.3% at 5 years, P = .324). On multivariate analysis, the factors associated with global survival were DM (hazard ratio [HR] = 2.11, 95% confidence interval [CI] = 1.23-3.60, P = .006), recipient age (HR = 1.05, 95% CI = 1.02-1.08, P < .001), delayed graft function (HR = 2.07, 95% CI = 1.24-3.46, P = .005), and donor age (HR = 1.03, 95% CI = 1.01-1.05, P = .002). In the competing risk analysis, DM was associated with mortality only in the cardiovascular death group (sub-hazard ratio [SHR] = 6.06, 95% CI = 1.01-36.4, P = .049). Change in diabetes treatment received over time and adherence to glycemic targets were not considered. The sample size is relatively small, which limits the precision of our estimates. The Kidney Donor Profile Index and the occurrence of treated acute rejection were not included in the regression models. Overall survival is lower in patients with diabetes, possibly due to older age and cardiovascular comorbidities. Therefore, patients with diabetes should be followed more closely to control cardiovascular risk factors. However, there is no difference in graft survival.

OGTT 2-hour serum C-peptide index as a predictor of post-transplant diabetes mellitus in kidney transplant recipients.

The high incidence of post-transplant diabetes mellitus (PTDM) necessitates the identification of new factors to explain its pathogenesis. This study aimed to clarify the association between the C-peptide index (CPI) and PTDM. A total of 290 non-diabetic kidney transplant patients were analyzed. All subjects underwent a 75 g oral glucose tolerance test (OGTT). Plasma glucose concentrations, serum C-peptide levels, hemoglobin A1c (HbA1c), and other biochemical indicators were measured. CPI was calculated as the ratio of serum C-peptide to plasma glucose. Among the 290 patients, 36 (12.4%) developed PTDM at the end of 1 year. Patients with PTDM had older age (P<0.001), higher levels of body mass index (BMI) (P=0.004) and HbA1c (P=0.001), a higher proportion of deceased donors (P=0.045), and lower levels of 2 h-CPI (P=0.02) than those without PTDM. The OGTT 2 h-CPI was positively correlated with BMI, HbA1c, type of calcineurin inhibitor, albumin, and triglyceride. Multivariate logistic regression and Cox hazard model analysis showed that pre-transplant OGTT 2 h-CPI was an independent predictor for the development of PTDM, together with age, BMI, and HbA1c. Of the pre-transplant factors studied, OGTT 2 h-CPI proved to be an independent predictor of PTDM.

Effect of Calcineurin Inhibitor on Blood Glucose Level in Non-Diabetic Kidney Transplant Patients

Effect of Calcineurin Inhibitor on Blood Glucose Level in Non-Diabetic Kidney Transplant Patients

Effect of Calcineurin Inhibitor on Blood Glucose Level in Non-Diabetic Kidney Transplant Patients

Background Calcineurin inhibitor (CNI) is a class of immunosuppressant agent used in kidney transplant management, known to pose risk for new-onset diabe­tes after transplant (NODAT). Tacrolimus and cyclo­sporine cause NODAT through multiple mechanisms, such as decreasing insulin secretion, increasing in­sulin resistance, and a direct effect on the pancreatic beta cell. Method This is a retrospective study on pa­tients receiving immunosuppressant agents for kidney transplant patients in Surabaya. The immunosuppres­sant agents studied were CNI (tacrolimus and cyclo­sporine) in combination with mycophenolate mofetil (MMF) or azathioprine (Aza) and steroid. The blood glucose measured were fasting blood glucose (FBD) and 2-hour postprandial blood glucose (2PPBG). Ob­jective Aim of this study is to determine the effect of calcineurin inhibitor (CNI) on glucose regulation in the nondiabetic renal transplant patient. Result Fifty-six subjects were included in the study, divided into two groups. One group of 28 patients (50%) received tac­rolimus-MMF-MP and the other group received cyc­losporine-MMF-MP. A significant increase in fasting blood glucose (pre-intervention level 86 ± 6 mg/dl vs post-intervention level 109 ± 34 mg/dl with p = 0.01) and 2-hour postprandial blood glucose (pre-interven­tion level 117 ± 20 mg/dl vs post-intervention level 150 ± 43 mg/dl with p &lt; 0.001) was found in the tacro­limus group. A significant increase was also found in the cyclosporine group, both in fasting blood glucose (pre-intervention value 85 ± 7 mg/dl vs post-interven­tion value 97 ± 22 mg/dl with p = 0.002) and 2-hour postprandial blood glucose (pre-intervention value 119 ± 18 mg/dl vs post-intervention value 148 ± 55 mg/dl with p = 0.001). Tacrolimus was found to have a relative risk of NODAT up to 1.2 fold compared to cy­closporine. Conclusion Tacrolimus poses 1.29 relative risk of NODAT compared to cyclosporine. However, both drugs significantly increase fasting blood glucose and 2-hour postprandial blood glucose in non-diabetic patients receiving kidney transplantation.

Arterial stiffness is associated with visceral fat mass in kidney transplanted patients—A nationwide cohort study

Arterial stiffness, visceral fat, and hyperglycemia are acknowledged risk factors for adverse outcomes after transplantation, but whether arterial stiffness is associated with visceral adipose tissue and hyperglycemia is unknown. We studied 162 non-diabetic kidney transplant recipients 8-10weeks after transplantation. Arterial stiffness was measured as pulse wave velocity (PWV) by SphygmoCor and visceral fat using a validated software applied on DXA scans. Also a standard oral glucose tolerance test was performed. Median PWV was 8.6m/s (IQR 7.3-10.4m/s). Patients in the upper quartile of PWV had 31%-106% higher visceral fat percentage (P<0.001), they were older (P<0.001) and had a fasting plasma glucose of 5.8mmol/L that was higher than in the other quartiles (P=0.006). In univariate analysis, visceral fat percentage and age were the parameters strongest associated with PWV (P<0.001), but cholesterol and glucose were also significant (P<0.05). In multivariate analysis, visceral fat was the only significant predictor of PWV along with age (P<0.001). In conclusion, arterial stiffness is significantly associated with visceral fat but not hyperglycemia in non-diabetic kidney transplant patients. We identified age and VAT as risk variables for arterial stiffness. A potential reversibility of arterial wall stiffness with reduction in VAT needs further study.

Association of Inflammation prior to Kidney Transplantation with Post-Transplant Diabetes Mellitus

Background/Objective: Post-transplant diabetes mellitus (PTDM) is both common and associated with poor outcomes after kidney transplantation. Our objective was to examine relationships of uremia-associated inflammation and adiponectin with PTDM. Methods: Nondiabetic kidney transplant patients were enrolled with donor controls. Inflammatory cytokines and adiponectin were measured before and after transplantation. Adipose tissue was obtained for gene expression analysis. Glucose transport was quantified in vitro in C2C12 cells following cytokine exposure. The patients were monitored up to 12 months for PTDM. Results: We studied 36 controls and 32 transplant patients, of whom 11 (35%) developed PTDM. Compared to controls, plasma TNFα, IL-6, MCP-1, and CRP levels were higher in transplant patients (p < 0.01). In multivariable analysis, TNFα plasma levels before transplantation were associated with development of PTDM (OR = 2.03, p = 0.04). Visceral adipose tissue TNFα mRNA expression was higher in transplant patients than controls (fold change 1.33; p < 0.05). TNFα mRNA expression was also higher in patients who developed PTDM than in those who did not (fold change 1.42; p = 0.05), and adiponectin mRNA expression was lower (fold change 0.48; p < 0.05). The studies on the C2C12 cells demonstrated an increase in glucose uptake following exposure to adiponectin and no significant change after exposure to TNFα alone. Concomitant TNFα and adiponectin exposure blunted adiponectin-induced glucose uptake (11% reduction; p < 0.001). Conclusion: Our in vitro and clinical observations suggest that TNFα could contribute to PTDM through an effect on adiponectin. Our study proposes that inflammation is involved in glucose regulation after kidney transplantation.

Nutritional research and intensive nutritional counselling of the chronic kidney disease patients after kidney transplantation

Background: Dietology treatment is the one of the foundation stones in the complex treatment of the chronic kidney disease (CKD) patients together with all other treatments. The dietary intervention plays an important role to determine the effects to a decrease of metabolic abnormalities. Aim: The aim of the long-term study was to monitor nutritional parameters in the post-transplant period. Subjects and methods : We studied 28 clinically stable consecutive nondiabetic kidney transplant patients: 12 males at the age of 42.8 ± 16.1 years, and 16 females at the age of 47.0 ± 14.9 years. Intensive nutritional counselling and dietary consultation by a dietitian were carried out for all the studied patients during one and a half years after the kidney transplantation. Initial data were compared with the results obtained at the end of the study. During the 3-days dietary records analysis and counselling of CKD patients, giving answers to their questions about their food and portion sizes, the dietitian used the standards portion book with many photographs. Results: The consumption of vegetables and fruit was modest compared to Estonian food and nutrition recommendations. The food frequency questionnaire revealed that the patients consumed different foodstuffs at different frequencies, but there was a tendency to excessive consumption of foodstuffs rich in proteins and carbohydrates. To consumption of fat-rich foodstuffs a tendency of decrease was found. Conclusion: An intensive nutritional counselling and healthy diet, avoiding excessive amounts of alcohol as well as regular exercise can help to reduce the chance of developing of chronic transplant nephropathy.

Glucose Tolerance in Non-Diabetic Kidney Transplant Patients Before and 6 Months After Transplantation Compared to Healthy Controls.

Purpose. Evaluating the effect of living kidney transplantation (Tx) on insulin sensitivity (IS) in non-diabetic uremic patients (ptt). Methods. Nine non-diabetic ptt awaiting Tx and six age and BMI matched healthy controls (Ctrl) examined with an oral glucose tolerance test before Tx. Furthermore, a 3 hour hyperinsulinaemic euglycaemic clamp was performed before and 6 months after Tx. Immunosuppression with simulect induction, cyclosporine (n=4)/prograf (n=5), MMF and steroids (one without steroids). Results. Fasting plasma glucose (FPG) (Tx: 5.1±0.7, Ctrl: 5.0±0.3 mmol/L) and HbA1c (Tx: 33±4, Ctrl: 33±2 mmol/mol) were comparable before Tx and HbA1c increased after Tx (FPG: 5.5±0,4 mmol/L (P=NS) and HbA1c: 35±3 mmol/mol (P=0.04)). All exept two Tx ptt with prediabetes had both normal FPG and normal glucose tolerance (mean 2h glucose Tx: 6.9±1.0 Ctrl: 5.5±1.5 mmol/L, P = 0.06). Insulin sensitivity measured as the total amount of glucose utilized during the clamp (GIR area under the curve) was lower in Tx patients before Tx (Tx: 490±164, Ctrl: 786±256 mg/kg, P = 0.02) and further reduced after Tx (319±131 mg/kg, P = 0.01).Figure: No Caption available.The weighted average of plasma glucose (AUC/180 min) during the clamp was comparable (Tx-before: 4.9±0.2 mmol/L Ctrl: 4.9±0.1 mmol/L and Tx-after: 5.1±0.2 mmol/L). Fasting insulin levels tended to be higher in Tx ptt (Tx: 62±34, Ctrl: 37±17 pmol/l, P = 0.2) and increased further after Tx (82±51 pmol/l, (P = 0.28)). Conclusion. Insulin sensitivity is impaired in non-diabetic Tx ptt as compared to healthy controls before Tx and IS deteriorates further after Tx. Uremia pre-Tx and immunosuppression post-Tx may contribute to this.

Regression of cardiac growth in kidney transplant recipients using anti-m-TOR drugs plus RAS blockers: a controlled longitudinal study.

BackgroundLeft ventricular hypertrophy (LVH) is common in kidney transplant (KT) recipients. LVH is associated with a worse outcome, though m-TOR therapy may help to revert this complication. We therefore conducted a longitudinal study to assess morphological and functional echocardiographic changes after conversion from CNI to m-TOR inhibitor drugs in nondiabetic KT patients who had previously received RAS blockers during the follow-up.MethodsWe undertook a 1-year nonrandomized controlled study in 30 non-diabetic KT patients who were converted from calcineurin inhibitor (CNI) to m-TOR therapy. A control group received immunosuppressive therapy based on CNIs. Two echocardiograms were done during the follow-up.ResultsNineteen patients were switched to SRL and 11 to EVL. The m-TOR group showed a significant reduction in LVMi after 1 year (from 62 ± 22 to 55 ± 20 g/m2.7; P = 0.003, paired t-test). A higher proportion of patients showing LVMi reduction was observed in the m-TOR group (53.3 versus 29.3%, P = 0.048) at the study end. In addition, only 56% of the m-TOR patients had LVH at the study end compared to 77% of the control group (P = 0.047). A significant change from baseline in deceleration time in early diastole was observed in the m-TOR group compared with the control group (P = 0.019).ConclusionsSwitching from CNI to m-TOR therapy in non-diabetic KT patients may regress LVH, independently of blood pressure changes and follow-up time. This suggests a direct non-hemodynamic effect of m-TOR drugs on cardiac mass.

Metabolic Syndrome, Vitamin D Deficiency and Hypoadiponectinemia among Nondiabetic Patients Early after Kidney Transplantation

Background and Aims: Metabolic syndrome (MetS) is common among kidney transplant patients. We studied the relationship between MetS, vitamin D deficiency/insufficiency and hypoadiponectinemia early posttransplantation and their impact on clinical outcomes. Methods: Seventy-four previously nondiabetic kidney transplant patients were enrolled in a prospective cohort study between February and November 2008. Participants underwent a 2-hour oral glucose tolerance test and had their plasma levels of 25-hydroxyvitamin D (25[OH]D), adiponectin, insulin, intact parathyroid hormone and lipids measured at 11 weeks posttransplantation. Clinical events including cardiovascular events, new-onset diabetes after transplantation, acute rejection, graft loss and death were recorded during the follow-up to December 2012. Results: Thirty-four study patients (45.9%) had MetS. Patients with MetS had lower plasma concentrations of 25[OH]D (20.5 ± 7.2 vs. 24.8 ± 11.1 ng/ml, p = 0.049) and adiponectin (8.2 ± 4.5 vs. 14.6 ± 8.0 μg/ml, p < 0.0001) early on, and higher composite clinical event rate (61.8 vs. 27.5%, p = 0.003) during the follow-up. Multivariate analysis showed that the presence of MetS early after transplantation was independently associated with 25[OH]D deficiency/insufficiency (OR: 14.0, 95% CI: 1.8, 107.5; p = 0.011), depressed plasma adiponectin levels (β -6.39, r² 0.195, p < 0.0001) and increased risk for clinical events (OR: 5.6, 95% CI: 1.9, 16.5; p = 0.002). Conclusion: Kidney transplant patients with MetS early after transplantation had lower levels of 25[OH]D and adiponectin, and unfavorable clinical outcomes.

Post-transplantation diabetes mellitus

To determine the prevalence of post-kidney transplantation diabetes (PTDM) and to assess its risk factors, we retrospectively studied 92 non-diabetic kidney transplant patients. The immunosuppressive drugs used to prevent rejection included prednisone, a calcineurin inhibitor (cyclosporine or tacrolimus) and an antimetabolite (azathioprine or mycofenolate mofetil). Diabetes was defined according to the WHO criteria and the American Diabetes Association. The mean age of our patients was 35.8 ± 10.5 years, and there was a clear male predominance (56 men and 36 women). The graft was from living related donor in 71/92 (76%) patients. The prevalence of diabetes in post-kidney transplant was 15.2%. The factors increasing the occurrence of PTDM included advanced age, high doses of steroids and cyclosporine. Management of PTDM included diet modification, oral anti-diabetic and insulin. We conclude that the prevalence of PTDM is significant in our transplant population and risk factors for its development are multiple and require aggressive multifaceted management.

Association of transcription factor 7-like 2 (TCF7L2) gene polymorphism with posttransplant diabetes mellitus in kidney transplant patients medicated with tacrolimus

New onset posttransplant diabetes mellitus (PTDM) has a high incidence after kidney transplantation in patients medicated with tacrolimus. PTDM can adversely affect patient and graft survival. The pathophysiology of PTDM closely mimics type 2 diabetes mellitus (T2DM). One of the possible genetic factors predisposing individuals to PTDM might be a polymorphism in the transcription factor 7-like 2 gene (TCF7L2). This polymorphism has previously been associated with increased risk of T2DM in the general population. Therefore, the present study aimed to evaluate TCF7L2 polymorphisms in PTDM in kidney transplant patients medicated with tacrolimus. Non-diabetic kidney transplant patients medicated with tacrolimus (n=234) were genotyped for the presence of TCF7L2 gene variants (rs12255372 and rs7903146) using TaqMan probes. Of the 234 patients, 66 patients had developed PTDM and 168 had not. Frequencies of the studied single nucleotide polymorphisms (SNPs) did not differ significantly between the study groups. Moreover, haplotype analyses failed to detect any associations between TCF7L2 haplotypes and PTDM. However, in late-onset PTDM (developed later that 2 weeks from transplantation), frequencies of the rs7903146 TT genotype and T minor allele were significantly increased compared to non-PTDM controls (17.9% vs. 5.9%, p=0.017, OR: 4.13, 95% CI: 1.19–14.33 for TT genotype, 39.3% vs. 25.9%, p=0.038 for T allele). If the application of TCF7L2 rs7903146 SNPs as a marker for PTDM is confirmed by further independent studies, replacing tacrolimus with other immunosuppressants could be warranted in patients at high risk of PTDM, as diagnosed by TCF7L2 genotyping.

New-Onset Diabetes Mellitus in Kidney Transplant Recipients Discharged on Steroid-Free Immunosuppression

New-onset diabetes after transplant (NODAT) is a serious complication after kidney transplantation. We studied the relationship between steroid-free maintenance regimens and NODAT in a national cohort of adult kidney transplant patients. A total of 25,837 previously nondiabetic kidney transplant patients, engrafted between January 1, 2004, and December 31, 2006, were included in the study. Logistic regression analysis was used to compare the risk of developing NODAT within 3 years after transplant for patients discharged with and without steroid-containing maintenance immunosuppression regimens. The effect of transplant program-level practice regarding steroid-free regimens on the risk of NODAT was studied as well. The cumulative incidence of NODAT within 3 years of transplant was 16.2% overall; 17.7% with maintenance steroids and 12.3% without (P<0.001). Patients discharged with steroids had 42% greater odds of developing NODAT compared with those without steroids (adjusted odds ratio [AOR]=1.42, 95% confidence interval [CI]=1.27-1.58, P<0.001). The maintenance regimen of tacrolimus and mycophenolate mofetil or mycophenolate sodium was associated with 25% greater odds of developing NODAT (AOR=1.25, 95% CI=1.08-1.45, P=0.003) than the regimen of cyclosporine and mycophenolate mofetil or mycophenolate sodium. Several induction therapies also were associated with lower odds of NODAT compared with no induction. Patients from programs that used steroid-free regimens for a majority of their patients had reduced odds of NODAT compared with patients from programs discharging almost all of their patients on steroid-containing regimens. The adoption of steroid-free maintenance immunosuppression at discharge from kidney transplantation in selected patients was associated with reduced odds of developing NODAT within 3 years.

Association of calpain-10 gene polymorphism and posttransplant diabetes mellitus in kidney transplant patients medicated with tacrolimus.

New-onset, posttransplant diabetes mellitus (PTDM) has a high incidence after kidney transplantation in patients medicated with tacrolimus, and may adversely affect the patient and graft survival. The pathophysiology of PTDM closely mimics that of type II diabetes mellitus (T2DM). One of possible genetic factors predisposing to PTDM might be polymorphism in calpain-10 gene (CAPN10), previously associated with increased risk of T2DM in general population. Therefore, the present study was aimed at evaluation of CAPN10 gene polymorphisms in PTDM in kidney transplant patients medicated with tacrolimus. A total of 214 nondiabetic kidney transplant patients medicated with tacrolimus (56 patients with PTDM and 158 patients without PTDM were genotyped for the presence of CAPN10 gene variants (SNP-43: rs3792267:G>A, SNP-19: rs3842570 ins/del and SNP-63: rs5030952:C>T) using PCR-based assays. Frequency of SNP-63 minor allele was slightly increased in PTDM patients (P=0.056), and an association of SNP-63 heterozygosity and the risk of PTDM (odds ratios (OR)=2.45, P=0.023) was observed. An increased odds for PTDM development in patients carrying 1-1-2 haplotype (rs3792267:G-rs3842570:ins-rs5030952:T) compared to noncarriers was also noted (OR=2.35, P=0.026). Patients' higher body mass index and SNP-63 minor T allele carrier status were identified as independent PTDM risk factors, confirmed by multivariate regression analysis. This is the first study of CAPN10 polymorphism in relation to PTDM risk. However, the application of SNP-63 (rs5030952:C>T) as a marker of PTDM should be verified by further independent studies.

Do Anti-CD25 Monoclonal Antibodies Potentiate Posttransplant Diabetes Mellitus?

Anti-CD25 monoclonal antibodies (MAbs) are directed against the IL-2 (CD-25) receptor, which is associated with the pathogenesis of diabetes mellitus (DM). Measuring CD25 on peripheral blood lymphocytes could be a new immunologic marker to identify patients with prediabetes. Objective The study aimed to analyze whether administration of anti-CD25 MAbs was an independent risk factor for posttransplant diabetes mellitus (PTDM) in kidney transplant (KT) patients at 3 months after transplantation. Patients and methods Seventy-four stable, nondiabetic KT patients were included in the study. The overall sex distribution was 70% men and mean overall age, 52 ± 10 years. Thirty-eight subjects where treated with anti-CD25 antibodies (basiliximab). The diagnosis of PTDM was made if patients required insulin or oral antidiabetic drugs and/or had glycemia >200 mg/dL at 120 minutes after an oral glucose tolerance test (75 g glucose). We determined the age, weight, body mass index, acute rejection, chronic hepatitis C virus ( HCV) infection, and type of calcineurin inhibitor. Results Thirty-four percent of patients developed PTDM. Patients treated with anti-CD25 antibodies were older ( P = .022) and showed a greater incidence of PTDM ( P = .041). The logistic regression analysis (dependent variable: PTDM; independent variables: age, anti-CD25, tacrolimus vs cyclosporine) showed that treatment with anti-CD25 is an independent risk factor for PTDM ( P = .041; OR 3.28; CI 95% 1.04–10.31). Conclusion Patients treated with anti-CD25 MAbs showed greater incidence of PTDM.

L-arginine-induced vasodilation of the renal vasculature is preserved in uremic type 1 diabetic patients after kidney and pancreas but not after kidney-alone transplantation.

In uremic type 1 diabetic patients, kidney and pancreas transplantation (KP) and kidney-alone transplantation (KD) provide full restoration of normal renal function; however, only KP, i.e., curing diabetes, is expected to prevent endothelial damages. Our aim was to study L-arginine-induced vasodilation of the renal vasculature in uremic type 1 diabetic patients after KP or KD using magnetic resonance (MR). MR quantitative flow measurements were performed in 15 KP patients (mean age 39.0 +/- 1.7 years, 10 men and 5 women), in 11 KD patients (mean age 47.3 +/- 1.9 years, 7 men and 4 women), and in 8 nondiabetic kidney transplant patients (mean age 44.0 +/- 4.8 years, 7 men and 1 woman), who were used as control subjects, to measure renal blood flow and velocity and renal vascular resistance before and immediately after infusion of L-arginine. Renal blood flow and velocity were not different at baseline in KP, KD, and control subjects. In contrast, during L-arginine administration renal blood flow increased significantly in KP subjects (basal 8.4 +/- 0.6 vs. post 9.6 +/- 0.8 ml/s, Delta 14.3 +/- 4.4%, P < 0.05) and in control subjects (basal 9.3 +/- 0.8 vs. post 9.1 +/- 0.8 ml/s, Delta 17.3 +/- 6.2%, P < 0.01), while it remained unchanged in KD subjects (basal 10.0 +/- 0.8 vs. post 11.6 +/- 0.9 ml/s, Delta -1.36 +/- 6.9%, NS). Parallel results have been achieved for renal blood velocity (KP subjects: 20.1 +/- 4.9%, P < 0.01; control subjects: 23.0 +/- 7.99%, P < 0.01; and KD subjects: -0.3 +/- 6.5%; NS). A reduction in renal vascular resistance in response to L-arginine was evident in KP and control subjects but not in KD patients. L-Arginine vasodilatory response was successfully assessed with MR quantitative flow measurements. KP patients and control subjects, but not those with KD, showed a preserved L-arginine-induced vasodilation of the renal vasculature.

Insulin resistance and insulin deficiency in the pathogenesis of posttransplantation diabetes in man.

Although steroids can induce insulin resistance, it is not known whether additional defects in insulin secretion are necessary for the development of diabetes. To address this question, we measured insulin sensitivity (euglycemic insulin clamp in combination with indirect calorimetry and infusion of tritiated glucose) and insulin secretion (hyperglycemic clamp) in three groups of subjects: (1) 10 kidney transplant patients with normal oral glucose tolerance, (2) 14 patients who developed diabetes after kidney transplantation, and (3) 10 healthy controls. Glucose utilization, primarily storage of glucose as glycogen, was reduced by 34% in kidney transplant patients with normal glucose tolerance when compared with healthy control subjects (18.2 +/- 2.9 vs. 27.5 +/- 2.7 microM/L; P less than 0.05). Insulin secretion was normal in relation to the degree of insulin resistance in transplanted non-diabetic patients, thus maintaining a normal oral glucose tolerance. Development of transplantation diabetes was associated with only minor further deterioration of glucose storage (14.7 +/- 2.7 microM/L; P less than 0.001 vs. control subjects), whereas first-phase, second-phase, and glucagon-stimulated insulin secretion measured during hyperglycemic clamping (incremental area under the insulin curve 287 +/- 120, 1275 +/- 419, and 3515 +/- 922 pM) became impaired as compared with nondiabetic kidney transplant patients (769 +/- 216, 3084 +/- 545, and 6293 +/- 533 pM; P less than 0.05). We conclude that both insulin resistance and insulin deficiency are necessary for the development of diabetes in kidney transplant patients.