Outcomes After Simultaneous Pancreas and Kidney Transplantation and the Discriminative Ability of the C-peptide Measurement Pretransplant Among Type 1 and Type 2 Diabetes Mellitus

Background

Earlier studies reporting outcomes after pancreas transplantation have included a combination of C-peptide cutoffs and clinical criteria to classify type 2 diabetes mellitus (T2DM). However, because the kidney is the major site for C-peptide catabolism, C-peptide is unreliable to discriminate the type of diabetes in patients with kidney disease.

Methods

To improve the discriminative power and better classify the type of diabetes, we used a composite definition to identify T2DM: presence of C-peptide, negative glutamic acid decarboxylase antibody, absence of diabetic ketoacidosis, and use of oral hypoglycemics. Additionally among T2DM patients with end-stage renal disease (ESRD), body mass index of <30 kg/m² and use of <1 u/kg of insulin per day were selection criteria for suitablity for simultaneous pancreas and kidney transplantation (SPKT). We compared graft and patient survival between T1DM and T2DM after SPKT.

Results

Our study cohort consisted of 80 patients, 10 of whom were assigned as T2DM based on our study criteria. Approximately 15% of patients with T1DM had detectable C-peptide. Cox regression survival analyses found no significant differences in allograft (pancreas and kidney) or patient survival between the 2 groups. The mean creatinine clearance at 1 year estimated by the modification of Diet in Renal Disease (MDRD) equation was not significantly different between the 2 groups. Among those with 1 year of follow-up, all patients with T2DM had glycosylate hemoglobin of <6.0 at 1 year versus 92% of those with T1DM.

Conclusion

SPKT should be considered in the therapeutic armamentarium for renal replacement in selected patients with T2DM and ESRD. Use of C-peptide measurements for ESRD patients can be misleading as the sole criterion to determine the type of diabetes.     

Prevalence, severity and predictors of HOMA-estimated insulin resistance in diabetic and nondiabetic patients with end-stage renal disease

BACKGROUND: Prevalence of insulin resistance (IR) is increased in type 2 diabetes and in end-stage renal disease (ESRD). IR is associated with advanced atherosclerosis and is an independent predictor for cardiovascular disease in diabetes and ESRD patients. We investigated prevalence, severity, predictors and relation to vascular diseases by the homeostasis model assessment (HOMA-IR) in diabetic and nondiabetic ESRD patients. METHODS: ESRD patients with type 2 diabetes (n = 27) and nondiabetic ESRD patients (n = 35) were included in the study. IR was assessed with the HOMA-IR using fasting glucose and insulin levels. Additionally, serum levels of C-peptide, HbA1c, triglycerides, cholesterol and C-reactive protein and blood pressure were assessed. RESULTS: Median HOMA-IR was significantly higher in the diabetic ESRD patients than in the nondiabetic ESRD patients (6.3 [range 0.7-61.7] vs. 2.4 [range 0.3-5.7]; p < 0.001). Systolic blood pressure and triglycerides were significantly higher in patients with higher HOMA-IR, whereas HDL cholesterol was significantly lower in those patients. Only nondiabetic patients with increased HOMA-IR had significantly higher C-peptide levels than those with lower HOMA-IR (14.9 + 5.7 vs. 9.0 + 4.3, p = 0.004). Vascular disease prevalence was significantly higher in diabetic patients with higher HOMA-IR than in those with lower HOMA-IR. CONCLUSIONS: Prevalence and severity of HOMA-IR was greater in diabetic ESRD patients than in those without diabetes. In diabetic patients low HDL cholesterol was the only predictor for higher HOMA-IR, whereas in nondiabetic patients a high C-peptide level was the only predictor for higher HOMA-IR. The prevalence of vascular diseases is associated with higher HOMA-IR in ESRD patients.     

The utility of the C-peptide in the phenotyping of patients candidates for pancreas transplantation

It is not unusual for simultaneous pancreas and kidney transplantation (SPK) to be performed in patients with type 2 diabetes (T2D), clinically classified as having type 1 diabetes (T1D). C-peptide determination is useful to identify these patients. We describe the prevalence and characteristics of patients with C-peptide levels >3 ng/mL, classified with T2D in 172 patients referred for SPK from 1998-2006. Nine patients (5.2%) fulfilled this criteria (mean free C-peptide 9.08 ng/mL) and were older at diabetes onset (23.5 vs. 12 yr, p < 0.001) and at assessment (42.2 vs. 37.6 yr, p = 0.047) with shorter time between diabetes onset and renal failure (17.8 vs. 22.7 yr, p = 0.3) compared with T1D patients (mean free C-peptide 0.24 ng/mL). In our experience the prevalence of T2D in candidates for SPK is not negligible. Despite some clinical differences with T1D these T2D patients can phenotypically be confounded with T1D in the absence of C-peptide determination.     

Classification of diabetes in patients with end-stage renal disease. Validation of clinical criteria according to fasting plasma C-peptide.

An epidemiologic study of end-stage diabetic nephropathy in France (Uremidiab) was performed, aiming to establish the prevalence of both types of diabetes in dialysis patients. Because discrimination between type I and type II diabetes remains mostly clinical, our aim was to evaluate what the most fitted clinical criteria were. We studied 494 hemodialyzed diabetic patients. A first classification (Cn) was offered by the nephrologist. Clinical data of 472 patients (22 patients of the 494 have been excluded) were then collected with a standardized questionnaire, allowing one diabetologist of us to establish the diagnosis of type of diabetes (classification Cd). Plasma C-peptide at this stage of the disease was expected to be very discriminative, measured in 88 patients and defined classification Ccp (< or = 0.6 ng/ml = "negative C-peptide" = type I, > 0.6 ng/ml = "positive C-peptide" = type II). Classification Cd observed 98 type I and 374 type II diabetes. Cn overestimated type I diabetes, 37% of type II diabetes being misclassified because insulin-treated. Classification Ccp observed 74 positive C-peptide patients, classified as type II, among whom 45 were insulin-treated. Only 3 patients were discordant for classification Cd and Ccp. Predictive value of "negative C-peptide" and "positive C-peptide" were 100% and 96% respectively. Multiple regression analysis of the Ccp classification was performed with the clinical criteria and showed very significant correlation with: age at the time of diagnosis of diabetes (AGE), maximal body mass index ever reached (BMI MAX) and delay between diagnosis and consistent insulin use (DI).(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparison of type II and type I diabetics treated for end-stage renal disease in a large prepaid health plan population

From 1978 through 1984, the incidence of treated end-stage renal disease (ESRD) secondary to diabetic nephropathy increased from 3 to 19 per million population among the membership of the Kaiser Permanente Medical Care Program in Northern California. Forty-eight percent had type II diabetes. Among 66 type II diabetics retinopathy was less severe and hypertension was more frequent than among 50 type I diabetics. Blacks were represented in a higher proportion than expected from their proportion of the health plan membership. Among type II diabetics who developed ESRD, once proteinuria occurred, nephropathy progressed at the same rate observed in type I diabetics. This observation suggests that the clinical progression of diabetic nephropathy may be similar for both types of diabetes after the development of proteinuria, but requires prospectively collected data for confirmation.     

Perceived health-related quality of life and comorbidity in diabetic patients starting dialysis (CALVIDIA study)

BACKGROUND: Diabetes mellitus (DM) is a widespread prevalent illness, currently the main cause of end-stage renal disease (ESRD). MATERIAL AND METHODS: In a longitudinal, prospective study we compared two cohorts of patients starting dialysis therapy, diabetic and non-diabetic ESRD patients. Perceived health was measured by the Medical Outcomes Study Short-Form 36 (SF-36) questionnaire, functional status by the Karnofsky scale and comorbidity by the Charlson age-comorbidity index. A broad spectrum of variables in relation to diabetes, ESRD, comorbidity and renal replacement therapy (RRT) were studied, as well as the distribution of comorbidity frequencies at dialysis start. RESULTS: Thirty-four Spanish centers included 232 diabetic patients, 43 type 1 and 189 type 2, mean diabetes duration 18 +/- 9 yrs, and five centers included 121 non-diabetic patients. Out of the 232 diabetic patients, 187 patients (81%) started hemodialysis (HD) and 45 patients (19%) started peritoneal dialysis (PD) (vs. 82% and 18%, respectively in non-diabetic patients). Transient vascular access (VA) for starting RRT was required in 54% of the diabetic patients vs. 53% in the nondiabetic patients. When both study groups were compared, diabetic patients required antihypertensive drugs more frequently than non-diabetic patients and showed higher systolic blood pressure (BP), as well as higher cardiovascular (CV) complication incidences, poorer SF-36 physical component summary scores and mental component summary scores and worse Karnofsky scale scores, with the Charlson age-comorbidity score being higher. CONCLUSION: Diabetic patients starting dialysis in Spain are more often type 2 diabetics, have worse perceived health-related quality of life (HRQoL) in relation to non-diabetic patients, worse functional status and higher incidences of prognostic mortality markers.     

Circulating TNF receptors 1 and 2 predict ESRD in type 2 diabetes

Levels of proinflammatory cytokines associate with risk for developing type 2 diabetes but whether chronic inflammation contributes to the development of diabetic complications, such as ESRD, is unknown. In the 1990s, we recruited 410 patients with type 2 diabetes for studies of diabetic nephropathy and recorded their characteristics at enrollment. During 12 years of follow-up, 59 patients developed ESRD (17 per 1000 patient-years) and 84 patients died without ESRD (24 per 1000 patient-years). Plasma markers of systemic inflammation, endothelial dysfunction, and the TNF pathway were measured in the study entry samples. Of the examined markers, only TNF receptors 1 and 2 (TNFR1 and TNFR2) associated with risk for ESRD. These two markers were highly correlated, but ESRD associated more strongly with TNFR1. The cumulative incidence of ESRD for patients in the highest TNFR1 quartile was 54% after 12 years but only 3% for the other quartiles (P<0.001). In Cox proportional hazard analyses, TNFR1 predicted risk for ESRD even after adjustment for clinical covariates such as urinary albumin excretion. Plasma concentration of TNFR1 outperformed all tested clinical variables with regard to predicting ESRD. Concentrations of TNFRs moderately associated with death unrelated to ESRD. In conclusion, elevated concentrations of circulating TNFRs in patients with type 2 diabetes at baseline are very strong predictors of the subsequent progression to ESRD in subjects with and without proteinuria.     

Impact of Nitric Oxide Synthase Glu298Asp Polymorphism on the Development of End-Stage Renal Disease in Type 2 Diabetic Egyptian Patients

Abstract

Background: Nitric oxide is an important regulator of renal hemodynamics. This study aimed to investigate the role of endothelial nitric oxide synthase (eNOS) gene polymorphism in type 2 diabetic patients with end-stage renal disease (ESRD) and to elucidate any alteration of nitric oxide synthase (NOS) activity caused by this polymorphism. Methods: The study included 80 patients with type 2 diabetes of >10 years duration (40 with diabetes-derived ESRD, 40 without nephropathy) and 20 healthy controls. Plasma nitrate/nitrite level, and serum NOS activity were measured and eNOS Glu298Asp genotypes were determined. Results: The frequency of Glu/Glu (GG) genotype in diabetics with ESRD was lower than controls. However, the frequency of Asp/Asp (TT) genotype was increased in diabetics with ESRD as compared to those without nephropathy and controls. Diabetics with ESRD had significantly lower nitrate/nitrite level and NOS activity than those without nephropathy. Diabetic patients with TT genotype are at a significant risk for ESRD. Moreover, subjects carrying TT genotype had lower nitrate/nitrite level and NOS activity than those carrying GG genotype. In diabetics with ESRD, creatinine clearance was positively correlated with both nitrate/nitrite level and NOS activity. Conclusions: These results imply that TT genotype of eNOS may be associated with an increased risk of ESRD in Egyptian type 2 diabetics. It could represent a useful genetic marker to identify diabetics at high risk for the development of ESRD. However, larger future prospective studies are required to confirm the role of eNOS gene polymorphism in the progression of diabetic nephropathy to ESRD.     

Management of Latent Autoimmune Diabetes in Adults: A Consensus Statement From an International Expert Panel

A substantial proportion of patients with adult-onset diabetes share features of both type 1 diabetes (T1D) and type 2 diabetes (T2D). These individuals, at diagnosis, clinically resemble T2D patients by not requiring insulin treatment, yet they have immunogenetic markers associated with T1D. Such a slowly evolving form of autoimmune diabetes, described as latent autoimmune diabetes of adults (LADA), accounts for 2–12% of all patients with adult-onset diabetes, though they show considerable variability according to their demographics and mode of ascertainment. While therapeutic strategies aim for metabolic control and preservation of residual insulin secretory capacity, endotype heterogeneity within LADA implies a personalized approach to treatment. Faced with a paucity of large-scale clinical trials in LADA, an expert panel reviewed data and delineated one therapeutic approach. Building on the 2020 American Diabetes Association (ADA)/European Association for the Study of Diabetes (EASD) consensus for T2D and heterogeneity within autoimmune diabetes, we propose “deviations” for LADA from those guidelines. Within LADA, C-peptide values, proxy for β-cell function, drive therapeutic decisions. Three broad categories of random C-peptide levels were introduced by the panel: 1) C-peptide levels <0.3 nmol/L: a multiple-insulin regimen recommended as for T1D; 2) C-peptide values ≥0.3 and ≤0.7 nmol/L: defined by the panel as a “gray area” in which a modified ADA/EASD algorithm for T2D is recommended; consider insulin in combination with other therapies to modulate β-cell failure and limit diabetic complications; 3) C-peptide values >0.7 nmol/L: suggests a modified ADA/EASD algorithm as for T2D but allowing for the potentially progressive nature of LADA by monitoring C-peptide to adjust treatment. The panel concluded by advising general screening for LADA in newly diagnosed non–insulin-requiring diabetes and, importantly, that large randomized clinical trials are warranted.     

胰岛细胞及肾联合移植治疗胰岛素依赖型糖尿病合并尿毒症四例

目的　观察成人胰岛细胞及肾联合移植治疗胰岛素依赖型糖尿病合并尿毒症的临床效果。方法　对 4例胰岛素依赖型糖尿病合并尿毒症的患者施行成人胰岛细胞及肾联合移植。肾移植为常规术式 ,在移植肾开放血液循环后 ,将分离、纯化、培养好的胰岛细胞注入门静脉中。移植后监测患者的空腹血糖、基础C 酞、糖化血红蛋白及肾功能的变化 ,并与其术前各项指标比较。结果　 4例患者术后在观察期间内胰岛素的用量均较术前减少超过 2 5 % ,且持续 3个月以上 ;空腹血糖基本保持在正常水平 ,基础C 酞也基本维持在正常水平 ,糖化血红蛋白于术后降至正常水平 ;4例患者的移植肾功能良好 ,3例患者已恢复正常工作。结论　成人尸体胰岛细胞及肾联合移植治疗胰岛素依赖型糖尿病合并尿毒症的临床效果较好 ,具有操作简单、安全等优点     

The fatty acid-binding protein-2 A54T polymorphism is associated with renal disease in patients with type 2 diabetes

The intestinal fatty-acid binding protein-2 (FABP2) gene codes a protein responsible for the absorption of long-chain fatty acids. To test whether FABP2 is a candidate gene for renal disease in patients with type 2 diabetes, a functional A54T polymorphism was genotyped in 1,042 Brazilians with type 2 diabetes. Patients were classified as having normoalbuminuria (urinary albumin excretion [UAE] <20 microg/min; n = 529), microalbuminuria (UAE 20-199 microg/min; n = 217), or proteinuria (UAE >199 microg/min; n = 160). Patients with end-stage renal disease (ESRD) (n = 136) were also included. The prevalence of the TT genotype was higher in patients with renal involvement compared with those with normoalbuminuria (odds ratio [95% CI] 2.4 [1.1-5.4]) following adjustment for type 2 diabetes duration, BMI, hypertension, A1C, and cholesterol levels. The risk was similar considering different stages of renal involvement. In a second independent patient sample (483 type 2 diabetic Caucasians residing in Massachusetts), a significant association was also observed between the TT genotype and proteinuria or ESRD (2.7 [1.0-7.3]; P = 0.048). This study thus provides evidence that FABP2 confers susceptibility to renal disease in type 2 diabetic patients.     

Risk factors for renal replacement therapy in the Early Treatment Diabetic Retinopathy Study (ETDRS), Early Treatment Diabetic Retinopathy Study Report No. 26

BACKGROUND: Diabetes is a leading cause of end-stage renal disease (ESRD). The purpose of this study is to assess the risk factors for renal replacement therapy (RRT) in the Early Treatment Diabetic Retinopathy Study (ETDRS). METHODS: We examined demographic, clinical, and laboratory characteristics of the 2226 subjects with complete laboratory data enrolled in the ETDRS. The primary renal variable evaluated was the time to development of renal replacement therapy, defined as the need for dialysis or transplantation. Multivariable Cox proportional hazards regression was used to assess risk factors for type 1 and type 2 diabetes separately. RESULTS: The 5-year estimated incidence of RRT in the entire ETDRS population was 10.2% and 9.8% for patients with type 1 and type 2 diabetes, respectively. Of those patients with complete data, 127 of 934 (14%) of patients with type 1 diabetes, and 150 of 1292 (12%) patients with type 2 diabetes required RRT during the study. Baseline risk factors common to type 1 and type 2 diabetes included elevated total cholesterol, and serum creatinine; and low serum albumin and anemia. Other risk factors significant in type 1 diabetes included body mass index (BMI), shorter duration of diabetes, elevated hemoglobin A(1c) (HbA(1c)), elevated systolic blood pressure, and the development of proliferative diabetic retinopathy. Risk factors significant in type 2 diabetes, but not type 1 diabetes, included younger age, proteinuria, and elevated triglycerides. CONCLUSION: In this study, major modifiable risk factors such as hypertension, dyslipidemia, and hyperglycemia were found to be predictive of RRT. Other predictors were markers of vascular pathology and inflammation, proteinuria, hypoalbuminemia, and increased serum creatinine. Controlled clinical trials with treatment strategies that improve serum lipid levels, systemic blood pressure, glycemic control, and markers of inflammation may be important in furthering our knowledge on the pathogenesis of diabetic complications such as nephropathy and ESRD.     

Prevalence of LADA and frequency of GAD antibodies in diabetic patients with end-stage renal disease and dialysis treatment in Austria.

BACKGROUND: The prevalence of individuals with latent autoimmune diabetes in adults (LADA) among diabetic patients with end-stage renal disease is unknown. Furthermore, there are no references in the literature about the persistence of glutamic acid decarboxylase antibodies (GADA) in uraemic LADA patients. The aim of the study, therefore, was to evaluate the prevalence of LADA, classified according to special features, in diabetic patients undergoing dialysis therapy as well as to find out the frequency of GADA in these patients. In addition, we investigated vascular risk factors and the prevalence of vascular diseases in each type of diabetes. METHODS: 538 patients undergoing chronic dialysis therapy from 37 Austrian dialysis centres were analysed in the study. Patients were divided into three groups: patients with type 1 or type 2 diabetes and patients with LADA. The classification of the different types of diabetes was based on the guidelines of the German Diabetes Society. We measured GADA and estimated the baseline data with reference to body mass index (BMI), age at onset of diabetes and at initiating dialysis therapy, the actual values of haemoglobin (Hb) A1c and cholesterol and the prevalence of vascular diseases by using a structured questionnaire. RESULTS: Type 1 diabetes was classified in 52 patients, type 2 diabetes in 434 and LADA in 52 (9.7%). The prevalence of positive GADA was 17.3% in the type 1 diabetic patients and 26.9% in the LADA patients. There was no positive GADA in the type 2 diabetic subjects. Age at the onset of diabetes and age at the start of dialysis were approximately the same in the LADA and the type 2 diabetic patients, while the age of the subjects with type 1 diabetes was significantly lower (P<0.001). BMI was significantly lower (25+/-3 vs 27+/-5 kg/m2) in the LADA patients than in the type 2 diabetic patients. The mean HbA1c value in the LADA patients was significantly higher than in the subjects with type 2 diabetes (P<0.01). Blood pressure (BP) was similar between LADA and type 1 or type 2 diabetes, though diastolic BP tended to be lower in the LADA patients than in the type 1 diabetics. The cholesterol levels were comparably high in each type of diabetes. In the LADA patients, the prevalence of retinopathy was lower than in the type 1 diabetics and the prevalence of stroke and angina pectoris was lower than in the type 2 diabetic patients, but the differences were not significant. CONCLUSIONS: The prevalence of LADA in diabetic patients on maintenance dialysis was 9.7%. This value is comparable to the frequency of LADA at onset of diabetes. The frequency of persisting GAD autoantibodies was 27% in the LADA patients and 17% in the type 1 diabetic patients. BMI was significantly lower in the LADA patients than in the type 2 diabetic patients, while diastolic BP only tended to be lower in the LADA patients than in the type 1 diabetics. The prevalence of vascular diseases was not significantly different between LADA and types 1 or 2 diabetes. According to our data it can be assumed that only a few uraemic patients with LADA are suitable for simultaneous pancreas-kidney transplantation.     

Geographic, ethnic, age-related and temporal variation in the incidence of end-stage renal disease in Europe, Canada and the Asia-Pacific region, 1998-2002.

BACKGROUND: Only unbiased estimates of end-stage renal disease (ESRD) incidence and trends are useful for disease control-identification of risk factors and measuring the effect of intervention. METHODS: Age- and sex-standardized incidences (with trends) were calculated for all-cause and diabetic/non-diabetic ESRD for persons aged 0-14, 15-29, 30-44 and 45-64 years in 13 populations identified geographically, and six populations identified by ethnicity. RESULTS: The incidence of ESRD varied most with age, ethnicity and prevalence of diabetes. All non-Europid populations had excess ESRD, chiefly due to rates of type 2 diabetic ESRD that were greater than accounted for by community prevalences of diabetes. Their rates of non-diabetic ESRD also were raised, with contributions from most common primary renal diseases except type 1 diabetic nephropathy and polycystic kidney disease. The ESRD rates generally were low, and more similar than different, in Europid populations, except for variable contributions from type 1 (high in Finland, Sweden, Denmark and Canada) and type 2 (high in Austria and Canada) diabetes. In Europid populations during 1998-2002, all-cause ESRD declined by 2% per year in persons aged 0-44 years, and all non-diabetic ESRD by a similar amount in persons aged 45-64 years, in whom diabetic ESRD had increased by 3% per year. CONCLUSIONS: Increased susceptibility to type 2 diabetes and to kidney disease progression characterizes excess ESRD in non-Europid peoples. The decline in all-cause ESRD in young persons, and non-diabetic ESRD in the middle-aged, probably reflects improving management of progressive renal disease.     

Increased prevalence of renal biopsy findings other than diabetic glomerulopathy in type II diabetes mellitus.

It is a widely held view that when a patient with type I diabetes mellitus and diabetic retinopathy or neuropathy develops renal impairment the renal lesion will be diabetic glomerulonephropathy. This has been extrapolated to apply to type II diabetes. We have performed a retrospective study of the clinical data of patients with diabetes mellitus who have had a renal biopsy between November 1980 and December 1990. Seventy-one patients were biopsied, data were available on 68. Nineteen of 22 type I diabetics had diabetic glomerulopathy, two had diabetic glomerulopathy in addition to another lesion only one patient did not have diabetic glomerulopathy. Twenty-three of 46 type II diabetics had diabetic glomerulopathy alone 22 having an alternative diagnosis. Eight further patients were identified who were not known to be diabetic at the time of renal biopsy, but whose biopsies revealed diabetic glomerulopathy. These data suggest that patients with type II diabetes and renal impairment should have a renal biopsy as part of their investigation.     

A genome-wide association study for diabetic nephropathy genes in African Americans

A genome-wide association study was performed using the Affymetrix 6.0 chip to identify genes associated with diabetic nephropathy in African Americans. Association analysis was performed adjusting for admixture in 965 type 2 diabetic African American patients with end-stage renal disease (ESRD) and in 1029 African Americans without type 2 diabetes or kidney disease as controls. The top 724 single nucleotide polymorphisms (SNPs) with evidence of association to diabetic nephropathy were then genotyped in a replication sample of an additional 709 type 2 diabetes-ESRD patients and 690 controls. SNPs with evidence of association in both the original and replication studies were tested in additional African American cohorts consisting of 1246 patients with type 2 diabetes without kidney disease and 1216 with non-diabetic ESRD to differentiate candidate loci for type 2 diabetes-ESRD, type 2 diabetes, and/or all-cause ESRD. Twenty-five SNPs were significantly associated with type 2 diabetes-ESRD in the genome-wide association and initial replication. Although genome-wide significance with type 2 diabetes was not found for any of these 25 SNPs, several genes, including RPS12, LIMK2, and SFI1 are strong candidates for diabetic nephropathy. A combined analysis of all 2890 patients with ESRD showed significant association SNPs in LIMK2 and SFI1 suggesting that they also contribute to all-cause ESRD. Thus, our results suggest that multiple loci underlie susceptibility to kidney disease in African Americans with type 2 diabetes and some may also contribute to all-cause ESRD.     

New clinical trials with vitamin D and analogs in renal disease

Two new clinical trials highlight refinements in the use of vitamin D and its analogs in the treatment of secondary hyperparathyroidism in end-stage renal disease (ESRD), and the treatment of proteinuria in diabetics. In patients with ESRD, alfacalcidol is as effective as paricalcitol in suppressing parathyroid hormone; the occurrence of hypercalcemia and hyperphosphatemia is infrequent and similar with the two analogs. Oral cholecalciferol reduces albuminuria and urinary transforming growth factor-β1 in patients with type 2 diabetes mellitus and proteinuria.     

Successful long-term kidney-pancreas transplants regardless of C-peptide status or race

BACKGROUND: We have previously shown that our patient population of 60% minority races has end-stage renal disease primarily as a result of diabetes mellitus and hypertension. It therefore was logical to explore the restoration of normal insulin production and renal function by simultaneous pancreas-kidney (SPK) transplantation, without regard to race. This study represents new analyses integrating race with C-peptide status and reports the outcome of 136 SPK transplantations performed over the last 10 years. RESULTS: Of the 49 African-Americans with diabetes mellitus and end-stage renal disease, 60% were type I and 40% were type II, based on C-peptide levels. In comparison, only 16% of Caucasians were type II. The average age at onset of diabetes mellitus was 15.7 years for type I compared with 20.7 years for type II (P>0.05). The actuarial 10-year survival rates for the 136 SPKs were 91.79% (patient), 85.07% (pancreas), and 83.58% (kidney). The type I and type II survival rates were similar in the two diabetic groups. CONCLUSIONS: The data strongly suggest that pretransplant C-peptide status does not influence the outcome of SPK transplantation in patients with renal failure from diabetes mellitus. SPK transplants should be offered to all suitable diabetic patients with renal failure regardless of C-peptide status or race.     

Comparison of lipids, apoproteins and associated enzyme activities between diabetic and nondiabetic end-stage renal disease.

Lipids, apoproteins and associated enzyme activities in type 2 diabetic end-stage renal disease (ESRD) were compared with that in nondiabetic ESRD and normal controls. Of the 40 uremic patients with non-insulin-dependent diabetes mellitus, 20 patients were receiving stable continuous hemodialysis treatment (CHT). Of the 39 patients with nondiabetic ESRD, 21 were undergoing CHT. Patients with nondiabetic ESRD exhibited elevated levels of serum triglyceride and a marked reduction in high-density-lipoprotein (HDL) cholesterol. Concentrations of serum apolipoprotein (Apo) C-3 were higher than in controls, whereas mean levels of serum Apo E were lower. The concentrations of serum Apo A-1 and Apo A-2 decreased with diminished lecithin: cholesterol acyltransferase activity. Lipoprotein lipase activity decreased in undialysed patients, and hepatic triglyceride lipase activity decreased significantly throughout the observation. Patients with diabetic ESRD exhibited elevated serum Apo B and normal serum Apo E levels, besides the lipid and Apo abnormalities observed in nondiabetic ESRD. Moreover, a prominent reduction in serum Apo A-1 was found in dialysed diabetic patients. The Apo B/Apo A-1 ratio was significantly higher in diabetic ESRD than in nondiabetic patients undergoing CHT. These results indicate that lipid abnormalities are accelerated in diabetic ESRD and may constitute a serious risk for the development of atherosclerosis.     

Underdiagnosis of diabetes mellitus in chronic dialysis patients on the renal transplant waiting list

In diabetic patients long-term patient and graft survival after renal transplantation is reduced compared to nondiabetic graft recipients. Incidence and prevalence of diabetic patients on dialysis is rising continuously; however, there is a surprisingly low prevalence of patients with known diabetes mellitus on our local renal transplant waiting list. In a retrospective study we clarified the underestimation of diabetic dialysis patients on the transplant waiting list. Our local waiting list includes 46 diabetic patients among 377 (12.2%) candidates. Nine patients had type 1 diabetes and 37 type 2 diabetes. Surprisingly, only 20 of 37 patients (ie, 54%) were initially (at the time of wait-listing) classified as (type 2 diabetes mellitus). Primary renal disease in these 17 diabetic patients was classified in only eight patients, whereas the remaining nine were considered as chronic glomerulonephritis (not biopsy-proven and diabetic nephropathy not excluded). We conclude that among uremic patients on the renal transplant waiting list, the prevalence of diabetes mellitus and the number of patients with diabetic nephropathy are notably underdiagnosed.