Ischaemia imaging in type 2 diabetic kidney transplant candidates--is coronary angiography essential?

BACKGROUND: Coronary artery disease (CAD) remains the leading cause of death in type 2 diabetes mellitus (DM) patients undergoing renal transplantation. There is a high prevalence of silent CAD in these patients. Controversy exists regarding the role of dobutamine stress echocardiography (DSE) in detection of CAD. Our purpose was to compare DSE with coronary angiography (CA) for the detection of CAD in type 2 diabetic patients undergoing evaluation for renal transplantation. METHODS: Forty (36 male, four female) type 2 diabetic patients with end-stage renal disease (ESRD) were subjected to DSE followed by CA as a part of their pre-renal transplant evaluation. The ability of DSE to predict 70% stenosis in one or more coronary arteries as determined by CA was evaluated. Mean age of the patients was 49.2 +/- 5 years (range 39-60 years). RESULTS: DSE was positive in 10 (25%) patients, while 19 patients (48%) had a more than 70% lesion in at least one epicardial vessel on CA (six patients had single vessel, three had double vessel and 10 had triple vessel disease). The sensitivity and specificity in identifying CAD was 47.3 and 95.2%, respectively, while positive predictive value and negative predictive value was 90% and 66%. Accuracy of DSE was 72.5%. All four patients with diffuse diabetic coronary artery disease had negative DSE. CONCLUSION: DSE is a poor predictor of coronary artery disease in type 2 DM patients being evaluated for renal transplantation. CA should be included in evaluation of type 2 diabetic patients who are renal transplant candidates.     

Simultaneous pancreas-kidney transplantation reduces excess mortality in type 1 diabetic patients with end-stage renal disease

BACKGROUND: Diabetic renal disease continues to be the most significant cause of end-stage renal disease (ESRD) in the United States. Renal transplantation improves diabetic ESRD patient survival; however, the diabetic state remains associated with poor patient survival. Simultaneous pancreas-kidney (SPK) transplantation can restore normoglycemia and thus may improve outcomes. METHODS: We assessed the impact of SPK on age-range-matched type 1 diabetic patients who underwent renal transplantation at a single center. The observed/expected life span and annual mortality rates (AMRs) were used as measures of survival. A Cox proportional hazards analysis was used to analyze the impact of potential variables on mortality in SPK recipients. RESULTS: SPK transplantation (N = 335) increased the observed/expected life span compared with diabetic cadaveric (DM-Cad, N = 147) and live-donor (DM-Live, N = 160) transplant recipients (P = 0.004) and significantly reduced the AMRs (SPK, 1. 5%; DM-Cad, 6.27%; DM-Live, 3.65%, P = 0.008, SPK vs. other DM). Moreover, the SPK observed/expected life span and AMR were not significantly different from that of age-range-matched nondiabetic transplant recipients (N = 492). The only variable that was significantly associated with patient survival was discharge serum creatinine (relative risk 1.16, P < or = 0.0154). CONCLUSION: These data demonstrate that SPK improves the ability for type 1 diabetic patients to live more of their expected life span. This suggests that glycemic control, even as a late intervention in a diabetic patient's lifetime, may beneficially affect survival.     

Organ transplantation in diabetics patients with ESRD

Because of the increased incidence of end-stage renal disease (ESRD) secondary to diabetes mellitus (DM, organ transplantation in this population is a growing issue. Renal transplantation is the best therapeutic option. Patient survival for both Type I and type II DM patients, is improved by organ transplantation compared to dialysis. For type I DM, this improvement is also observed after combined kidney-pancreas transplantation (KPT). These results have been obtained by the improvement of surgical technique and immunosuppressive treatments. The characteristics of transplantation for DM patients are: 1. The need for early pre-transplantation evaluation with a special attention for ischemic cardiopathy. 2. The possibility of SPK for Type I or Type II DM patients if they are young, non-obese and with a marked endogenous insulin secretion decrease. The perspective for organ transplantation in diabetic patients with ESRD is islet transplantation. This technique has proven its efficacy for patients with no renal disease. Recent results show that islet transplantation may be successful in patients after renal transplantation.     

Surgical complications and renal function after kidney alone or simultaneous pancreas-kidney transplantation: a matched comparative study.

BACKGROUND: In selected type 1 diabetic (T1DM) patients with end-stage renal disease (ESRD), simultaneous pancreas-kidney transplantation (SPKT) offers higher long-term graft and patient survival, but also higher initial morbidity and mortality than cadaveric kidney transplantation alone (CKTA). The development of new immunosuppressive regimens and surgical approach has improved this initial outcome, but little is known about their effect on short-term renal function and surgical complications related to the renal graft. METHODS: We analysed retrospectively the short-term follow-up of 45 T1DM patients consecutively transplanted during 42 months (20 SPKT and 25 CKTA) in order to compare short-term (6 months) renal allograft function and surgical complications related to the renal allograft in both groups. RESULTS: There were no differences in donor characteristics. SPKT recipients had a significantly shorter time on dialysis and cold ischaemia time, with a higher number of HLA mismatches. There was no difference in acute rejection incidence, but delayed kidney graft function was less frequent in SPKT (5% vs 32%; P<0.05). Plasma creatinine level at discharge and 6 months was significantly lower in SPKT (1.1+/-0.3 vs 1.6+/-0.7; P<0.005 and 1.1+/-0.3 vs 1.5+/-0.6; P<0.05, respectively). There were no differences in surgical renal complications (haemorrhage, thrombosis or arterial stenosis, ureter leaks or stricture, lymphoceles or dehiscences). Two SPKT patients needed reintervention on the renal allograft and only one CKTA patient. CONCLUSIONS: In the modern transplant era, SPKT in ESRD diabetic patients, offers a slightly better short-term kidney allograft function without significant increase in surgical morbidity, compared with CKTA.     

Serum C-peptide concentrations poorly phenotype type 2 diabetic end-stage renal disease patients

BACKGROUND: A homogeneous patient population is necessary to identify genetic factors that regulate complex disease pathogenesis. In this study, we evaluated clinical and biochemical phenotyping criteria for type 2 diabetes in end-stage renal disease (ESRD) probands of families in which nephropathy is clustered. C-peptide concentrations accurately discriminate type 1 from type 2 diabetic patients with normal renal function, but have not been extensively evaluated in ESRD patients. We hypothesized that C-peptide concentrations may not accurately reflect insulin synthesis in ESRD subjects, since the kidney is the major site of C-peptide catabolism and would poorly correlate with accepted clinical criteria used to classify diabetics as types 1 and 2. METHODS: Consenting diabetic ESRD patients (N = 341) from northeastern Ohio were enrolled. Clinical history was obtained by questionnaire, and predialysis blood samples were collected for C-peptide levels from subjects with at least one living diabetic sibling (N = 127, 48% males, 59% African Americans). RESULTS: Using clinical criteria, 79% of the study population were categorized as type 1 (10%) or type 2 diabetics (69%), while 21% of diabetic ESRD patients could not be classified. In contrast, 98% of the patients were classified as type 2 diabetics when stratified by C-peptide concentrations using criteria derived from the Diabetes Control and Complications Trial Research Group (DCCT) and UREMIDIAB studies. Categorization was concordant in only 70% of ESRD probands when C-peptide concentration and clinical classification algorithms were compared. Using clinical phenotyping criteria as the standard for comparison, C-peptide concentrations classified diabetic ESRD patients with 100% sensitivity, but only 5% specificity. The mean C-peptide concentrations were similar in diabetic ESRD patients (3.2 +/- 1.9 nmol/L) and nondiabetic ESRD subjects (3.5 +/- 1.7 nmol/L, N = 30, P = NS), but were 2.5-fold higher compared with diabetic siblings (1.3 +/- 0.7 nmol/L, N = 30, P < 0.05) with normal renal function and were indistinguishable between type 1 and type 2 diabetics. Although 10% of the diabetic ESRD study population was classified as type 1 diabetics using clinical criteria, only 1.5% of these patients had C-peptide levels less than 0.20 nmol/L, the standard cut-off used to discriminate type 1 from type 2 diabetes in patients with normal renal function. However, the criteria of C-peptide concentrations> 0.50 nmol/L and diabetes onset in patients who are more than 38 years old identify type 2 diabetes with a 97% positive predictive value in our ESRD population. CONCLUSIONS: Accepted clinical criteria, used to discriminate type 1 and type 2 diabetes, failed to classify a significant proportion of diabetic ESRD patients. In contrast to previous reports, C-peptide levels were elevated in the majority of type 1 ESRD diabetic patients and did not improve the power of clinical parameters to separate them from type 2 diabetic or nondiabetic ESRD subjects. Accurate classification of diabetic ESRD patients for genetic epidemiological studies requires both clinical and biochemical criteria, which may differ from norms used in diabetic populations with normal renal function.     

Effect of renal transplantation on biomarkers of inflammation and oxidative stress in end-stage renal disease patients

BACKGROUND: Chronic kidney disease patients have a high prevalence of inflammation and oxidative stress, and this has been associated with the excess cardiovascular morbidity and mortality observed in this population. Because maintenance hemodialysis is ineffective in controlling these factors, we hypothesized that restoration of kidney function by transplantation would be required to improve uremic inflammation and oxidative stress. METHODS: This was a prospective cohort study evaluating time-dependent changes in biomarkers of inflammation and oxidative stress before and after renal transplantation. Nineteen end-stage renal disease (ESRD) patients (age 38.3+/-13.7 years, 58% male, 95% white, 21% diabetic) undergoing living-donor renal transplantation were enrolled. C-reactive protein (CRP), interleukin (IL)-6, IL-10, tumor necrosis factor (TNF)-alpha, protein-associated carbonyl content, and F2-isoprostanes were assessed at 1 week pretransplantation and at 1 week and 2 months posttransplantation. RESULTS: Pretransplant levels of the pro-inflammatory proteins IL-6, TNF-alpha, and CRP, as well as the oxidative stress markers plasma protein carbonyls and F2-isoprostanes, were significantly elevated in ESRD patients compared with healthy control subjects. We observed rapid and significant declines in all of these biomarkers after transplantation that persisted for 2 months. CONCLUSIONS: Our findings indicate that restoration of renal function by transplantation improves the chronic inflammation and increased oxidative stress associated with uremia, which may contribute to the improved survival afforded to ESRD patients by renal transplantation.     

Transplantation in Diabetic Kidney Failure Patients: Modalities,Outcomes, and Clinical Management

Diabetes mellitus (DM) is a common and devastating disease, affecting up to 19.3 million Americans. It is the leading cause of chronic kidney disease (CKD) and end‐stage renal disease (ESRD) in the United States. Diabetic patients with ESRD have a high incidence of cardiovascular disease and death. For those kidney transplant patients with no history of DM prior to transplantation, the development of new onset diabetes after transplantation (NODAT) also poses a serious threat to both graft and patient survival. Kidney transplantation is the best renal replacement option for diabetic ESRD and has the potential to halt the progression of cardiovascular diseases. Early referral for transplant evaluation is essential for pre‐emptive or early kidney transplantation in this cohort of patients. In type 1 DM patients with ESRD, simultaneous pancreas and kidney transplantation (SPK) should be encouraged; and in patients facing prolonged waiting time for SPK transplantation but with an available living donor, living donor kidney transplantation followed by pancreas after kidney transplantation (PAK) is a suitable alternative. Islet transplantation in type 1 diabetics is deemed experimental by Medicare, and easy access to this modality remains restricted to qualified patients enrolled in clinical trials or with private insurance. The optimal management of kidney transplant patients with pre‐existent DM or NODAT involves a multi‐pronged approach consisting of pharmacological and nonpharmacological intervention to address all potential cardiovascular risk factors such as glycemic and lipid control, blood pressure control, weight loss, and smoking cessation. Finally, re‐transplantation should be recommended in suitable kidney transplant patients when the kidney allograft demonstrates continuous and progressive decline in function.     

Improved survival in patients with type 1 diabetes mellitus after renal transplantation compared with hemodialysis: a case-control study

BACKGROUND: Diabetes mellitus is the leading cause of renal failure worldwide. The question of which treatment modality-hemodialysis versus renal transplantation-is associated with the lowest risk of cardiovascular morbidity and mortality in the diabetic end-stage renal disease (ESRD) population has not yet been investigated in a controlled trial. METHODS: We therefore conducted a case-control study of patients with ESRD caused by type 1 diabetes mellitus. The case patients were diabetics who received a renal graft between 1978 and 1997, whereas the controls were registered for renal transplantation but stayed on maintenance hemodialysis without ever undergoing transplantation. The groups were matched for age, sex, duration of diabetes, length of hemodialysis (up to the registration), and date of registration for renal transplantation. RESULTS: Kaplan-Meier life table analysis, based on 46 case patients and 46 controls, demonstrated a highly significant (P=0.0001) poorer survival in the control group compared with the case group. Logistic regression showed that hemodialysis was a significant risk factor for death (P=0.0002) and cardiovascular morbidity (P=0.0023). Patients with cardiovascular complications such as coronary artery and peripheral vascular events were significantly more frequent in the control group. Additionally tested risk factors for cardiovascular complications (serum cholesterol, arterial blood pressure, number of antihypertensive drugs, serum calcium, serum phosphate, and glucose control [hemoglobin A(1c)]) showed no significant correlation to survival or morbidity in either group by logistic regression. CONCLUSIONS: Renal transplantation is associated with a significantly improved survival compared with hemodialysis in patients with ESRD caused by type 1 diabetes mellitus. This seems to be a result of a reduced incidence of cardiovascular complications after renal transplantation.     

Association between attributed cause of end-stage renal disease and risk of death in Brazilian patients receiving renal replacement therapy

BACKGROUND: Studies conducted in several countries have indicated that the survival of patients undergoing renal replacement therapy (RRT) depends on the attributed cause of end-stage renal disease (ESRD). OBJECTIVES: This study was conducted to evaluate the association between attributed cause of ESRD and mortality risk in RRT patients in Brazil. METHODS: We analyzed 88,881 patients from the Brazilian Ministry of Health Registry who were undergoing RRT between April 1997 and July 2000. Cox proportional hazards models were used to estimate the relative risk (RR) of death in patients with ESRD secondary to diabetes mellitus (DM), polycystic kidney disease (PKD), and primary glomerulopathies (GN) compared with a reference group comprised of patients with ESRD caused by hypertensive nephropathy. Patient's age, gender, and length of time (years) in RRT before inclusion in the registry (vintage) were included in the adjusted Cox model. RESULTS: Compared with the reference group, the mortality risk was 27% lower in patients with PKD (RR=0.73, 95% CI: 0.65-0.83, p<0.0001); 29% lower in patients with GN (RR=0.71, 95% CI: 0.68-0.74, p<0.0001); and 100% greater in DM patients (RR=2.00, 95% CI: 1.92-2.10, p<0.0001). These relative risks remained statistically significant after adjustment for age, gender, and length of time in RRT before inclusion in the registry. CONCLUSIONS: Our data indicate that compared with the patients with hypertensive nephrosclerosis as attributed cause of ESRD, patients undergoing RRT in Brazil with idiopathic glomerulopathy and polycystic kidney disease have a lower risk of mortality, and patients with diabetes mellitus have a greater risk of mortality.     

Diabetic kidneys can safely expand the donor pool

BACKGROUND: The demand for organs has increased exponentially with a new name added to the United States waiting list every 16 min. As such, kidneys from medically marginal donors are being considered for transplantation more frequently, including kidneys from individuals already at risk for renal disease, e.g., diabetic donors. METHODS: We compared outcomes when using kidneys from donors with type 1 diabetes mellitus (D1) or type 2 diabetes mellitus (D2) at our center as a function of time. All patients with available data who underwent renal transplantation were evaluated (n=2013). RESULTS: Forty-two individuals were recipients of D1 or D2 donor kidneys. Thirty of these individuals did not have diabetes (R0). All patients received quadruple sequential immunosuppression with cyclosporine (CsA) or tacrolimus (FK506). Donor serum creatinine (Scr) values were not significantly different. D2 kidneys came from older donors (mean age, 56+/-10.4 years; P< or =0.01 vs. D1 and D0 donors). Mean discharge Scr was greater in nondiabetic D2 recipients (D2/R0, 2.45+/-1.3 mg/dl; P=0.0016 vs. D0/R0), and transplantation of D1 or D2 kidneys was associated with a significantly increased frequency of posttransplant proteinuria (P=0.0089). Interestingly, R0 recipients of D1 or D2 kidneys were more likely to initiate oral hypoglycemic therapy after transplant (P=0.04). However, rejection episodes were not significantly different among groups, and long-term graft survival and patient survival were similar among groups. CONCLUSIONS: These data suggest that diabetic kidneys can be safely used without risk to patient or graft survival. Preexisting diabetic injury in the donor may increase the risk for proteinuria, compromised renal function, and posttransplant glucose intolerance.     

Analysis of clinical manifestations and outcomes of idiopathic membranous nephropathy compared with diabetic nephropathy in patients with type 2 diabetes

Objective To evaluate the predictive factors and renal outcomes of idiopathic membranous nephropathy (IMN) in patients with type 2 diabetes (T2DM). Methods In this retrospective study, clinical data of 101 IMN patients with T2DM and 96 patients with diabetic nephropathy (DN) were consecutively collected. Logistic regression was used to assess potential clinical factors indicating IMN and COX regression was employed to analyze risks of IMN in developing to end-stage renal disease (ESRD), as compared with that of DN, in patients with T2DM. Results In a multivariate model, age≥55 years old, presence of nephrotic syndrome, estimated glomerular filtration rate (eGFR)＞60 ml?min-1?(1.73 m2)-1, duration of diabetes≤5 years and absence of diabetic retinopathy, were associated with IMN, as compared with DN, in patients with T2DM. In T2DM patients presented with nephrotic syndrome, age≥55 years old, eGFR＞60 ml?min-1?(1.73 m2)-1, duration of diabetes≤5 years and absence of diabetic retinopathy, were also associated with IMN, as compared with DN. Receiver operating characteristic curve (ROC) showed eGFR 65.5 ml?min-1?(1.73 m2)-1 was an optimal cutoff in differentiating DN and IMN. DN was associated with 16.8 times as high risk of incident ESRD as compared with IMN in T2DM patients. Conclusions In patients with T2DM, age≥55 years, presence of nephrotic syndrome, early stage of CKD, duration of diabetes≤5 years and absence of retinopathy, may indicate IMN rather than DN. T2DM patients with IMN have much better renal prognosis as compared with DN.     

Cytomegalovirus disease after kidney transplantation: clues to accurate diagnosis

BACKGROUND: The clinical diagnosis of cytomegalovirus (CMV) disease after kidney transplantation is often not accurate. We evaluated the factors associated with a correct diagnosis of CMV disease in these patients. MATERIALS AND METHODS: This retrospective study of all renal transplant patients between 2004 and 2005 with a clinical diagnosis of CMV disease included both donors and recipients who were seropositive for CMV at transplantation. We assessed the rate and correlated factors with a correct diagnosis. RESULTS: Among 127 cases, the 30 (23.6%) patients who had a correct diagnosis of CMV disease. Showed higher ages at transplantation (48.8 +/- 15.3 vs. 39.8 +/- 14.4 years; P=.004) and a shorter interval between transplantation and symptom presentation (9.7 +/- 20.7 vs. 25.6 +/- 33.6 days; P=.048). Diabetes mellitus (DM) was the cause of end-stage renal disease (ESRD) in 41% of patients with a correct diagnosis, whereas it was the cause in 11% of CMV disease-negative patients (P<.001). A multiple logistic regression model showed that DM as the cause of ESRD (P=.001; odds ratio [OR] 16.331), >5 months duration between transplantation and the presence of symptoms (P=.001; OR, 0.060), and age at transplantation >55 years (P=.022; OR, 3.833) were predictors of a correct diagnosis of CMV disease (chi(2)=46.45; P<.001). CONCLUSION: The results herein showed that considering some variables significantly improved the accuracy of a correct diagnosis of CMV disease after kidney transplantation.     

Outcomes of renal transplantation after end-stage renal disease due to diabetic nephropathy: a single-center experience

Background

Diabetic nephropathy is the most common cause of end-stage renal disease (ESRD) worldwide. However, data on renal transplantation outcomes in diabetic nephropathy among Japanese remain inadequate. This retrospective study was conducted to summarize our renal transplantation experience in diabetic ESRD patients.

Methods

We retrospectively studied 462 patients who underwent kidney transplantation between 1989 and 2011, including 23 with diabetic ESRD (DM group) and 439 with nondiabetic ESRD (NDM group). We compared demographic and clinical variables between these 2 groups.

Results

Mean age was higher in the DM group (48.0 vs 38.2 years; P < .001), and there was no significant difference in gender or donor source. The 1-, 3-, and 5-year graft survival rates in the DM and NDM groups were 100% vs 98.3% (ns), 82.4% vs 94.9% (P < .05), and 66.7% vs 90.3% (P < .01), respectively. The 1-, 3-, and 5-year patient survival rates were 95.0% vs 96.5% (ns), 88.2% vs 95.2% (ns), and 84.6% vs 92.9% (ns), respectively. One patient (4.3%) in the DM group and 6 (1.4%) in the NDM group died from cardiovascular disease during the follow-up period (ns). The incidence of rejection did not differ between the DM and NDM groups. There were no significant differences in the total infection rate or the urinary tract infection rate.

Conclusions

Renal transplantation in diabetic ESRD patients yields good results in terms of patient survival and complications, suggesting that renal transplantation can be performed in these patients and should become a more established treatment option.     

Neuropathy in type 1 diabetic renal transplanted patients

This study was undertaken to study the changes in neuropathy in type 1 diabetic patients with end-stage renal disease (ESRD) after renal transplantation. From April 2007 to June 2010, 30 renal transplanted patients with type 1 diabetes mellitus (RT) and 30 type 1 diabetic patients with ESRD were enrolled in this study. Electroneurodiagnostic tests of peroneal, sural, ulnar, and median nerves were performed. Nerve conduction velocity (NCV), compound motor action potentials (CMAPs), and sensory nerve action potentials (SNAPs) were analyzed at 6, 12, and 18 months after renal transplantation. The NCV improved in the RT group in 18 months of the follow-up period (P <0.01 versus baseline). This parameter worsened significantly in the control group throughout the study period (P = 0.03), but in the cross-sectional analysis between the groups, we could not find any remarkable differences (P = 0.07). Both SNAP and CMAP amplitudes improved in the RT (SNAP Sural = 0.04, SNAP Median = 0.01 and CAMP Peroneal = 0.03, CAMP Ulnar = 0.02) but worsened in the control group (SNAP Sural < 0.001, SAP Median < 0.01 and CAMP Peroneal < 0.01, CAMP Ulnar < 0.01). Comparison of both groups did not show any significant statistical changes. Electroneurodiagnostic values improved after renal transplantation in type 1 diabetic patients with ESRD, but cross-sectional analysis did not reveal statistically significant differences between the studied groups.     

Sickle cell nephropathy at end-stage renal disease in the United States: patient characteristics and survival

BACKGROUND: The patient characteristics, including age at presentation to end-stage renal disease (ESRD) and mortality associated with sickle cell nephropathy (SCN) have not been characterized for a national sample of patients. METHODS: 375,152 patients in the United States Renal Data System were initiated on ESRD therapy between January 1, 1992 and June 30, 1997 and analyzed in an historical cohort study of SCN. RESULTS: Of the study population, 397 (0.11%) had SCN, of whom 93% were African-American. The mean age at presentation to ESRD was 40.68+/-14.00 years. SCN patients also had an independently increased risk of mortality (hazard ratio 1.52, 95% CI: 1.27-1.82) even after adjustment for placement on the renal transplant waiting list, diabetes, hematocrit, creatinine, and body mass index. However, when receipt of renal transplantation was also included in the model, SCN was no longer significant (p = 0.51, HR = 1.10, 95% CI: 0.82-1.48). SCN patients were much less likely to be placed on the renal transplant waiting list or receive renal transplants in comparison to age and race matched controls, and results of survival analysis were similar in this model. CONCLUSIONS: SCN patients were much less likely to be listed for or receive renal transplantation than other comparable patients with ESRD. SCN patients were at independently increased of mortality compared with other patients with ESRD, including those with diabetes, but this increased risk did not persist when models adjusted for their low rates of renal transplantation.     

Diabetes as the cause of end-stage renal disease affects the pattern of post kidney transplant rehospitalizations

INTRODUCTION: Although there are reports that link diabetes-induced end-stage renal disease (ESRD) with several post renal transplantation complications and conditions, few studies have directly focused on this issue. This study compared the pattern of rehospitalizations after renal transplantation among diabetic versus nondiabetic ESRD patients, measuring causes, length of stay, outcomes and costs. METHODS: We retrospectively reviewed 366 randomly selected rehospitalization records of kidney transplant recipients between 1994 and 2006, including 69 who underwent renal transplantation due to diabetic nephropathy and 297, due to nondiabetic ESRD. We compared the two groups with respect to demographic and clinical variables: donor source, readmission pattern, rehospitalization cause, time interval between transplantation and hospitalization (T-H time), length of hospital stay (LOS), and intensive care unit (ICU) admission, hospital charges, and inpatient outcomes of graft loss and mortality. RESULTS: The diabetes group, compared with nondiabetic group, had a greater mean age (53 +/- SD vs. 39 +/- SD years), proportion of admissions due to infections (44.9% vs. 32%) or renal dysfunction (14.5% vs. 29.6%), mean hospital charges ($5056 vs. $3046), and hospital mortality (18% vs. 4.3%; P<.05). Diabetic patients were readmitted sooner after transplantation than nondiabetic patients (11 vs. 18 months; P<.05). There was no difference between the groups with regard to gender, donor source, LOS, ICU admission, and graft loss. CONCLUSION: The etiology of ESRD should be considered for scheduling post renal transplantation follow-up. Renal transplant recipients with diabetes-induced ESRD need further attention in follow-up programs.     

Kidney transplantation in type 2 diabetic patients: a comparison with matched non-diabetic subjects.

BACKGROUND: Because they generally are older and frequently have co-morbidities, patients with type 2 diabetes mellitus and end-stage renal disease seldom are selected for renal transplantation. Thus, information on transplantation results from controlled studies in this high-risk category of patients is scarce. We have compared the results of kidney transplantations in type 2 diabetic patients with carefully matched non-diabetic subjects. METHODS: All first cadaveric renal transplants performed in type 2 diabetic patients from January 1, 1988 to December 31, 1998 in our centre were included. Non-diabetic controls were individually matched with diabetic patients with respect to year of transplantation, sex, age, selected immunological parameters, and graft cold ischaemia. RESULTS: We included 64 type 2 diabetic and 64 non-diabetic patients who were followed for a mean period of 37+/-27 and 41+/-31 months, respectively, after renal transplantation. Patient survival at 1 and 5 years post-transplant was 85 and 69 vs 84 and 74% (P=0.43, NS), while graft survival rates censored for patient death were 84 and 77 vs 82 and 77% for diabetic and non-diabetic subjects, respectively (P=0.52, NS). With graft survival results not censored for death with functioning graft, no significant change was seen (diabetic vs non-diabetic group: 77 and 54 vs 73 and 61%, P=0.19, NS). Age, but not the presence of diabetes, was the only factor significantly affecting patient survival when both patient groups were pooled. With regard to post-transplant complications requiring hospitalization, there was a significant difference only in the number of patients who had amputations (diabetic vs non-diabetic group: 8 vs 0, P=0.01). CONCLUSIONS: Patient and graft survival after kidney transplantation was similar in type 2 diabetic and matched non-diabetic subjects, with more amputations occurring in the diabetic group. Thus, at a single-centre level renal transplantation results almost equivalent to those in non-diabetic patients may be achieved in type 2 diabetes mellitus.     

Predictive value of cytokine gene polymorphisms for the development of end-stage renal disease

BACKGROUND: Cytokines play a crucial role in different immunopathological conditions. Cytokine secretion is reported to be determined by polymorphisms in the cytokine genes. Since TNF-alfa and IL-10 are involved in regulation of inflammation, and TGF-beta 1 can induce fibrosis and renal insufficiency - dominant features of end-stage renal disease (ESRD), we explored the hypothesis that polymorphisms of these cytokine genes may be possible genetic susceptibility factors for the progression of renal failure. METHODS: We studied the IL-10 (-1082), TNF-alfa (-308), TGF-beta 1 (codon 10;25) gene single nucleotide polymorphisms in 118 healthy donors and 103 patients with ESRD (44 hemodialysis patients with diabetic nephropathy and 59 hemodialysis patients with glomerulonephritis) using PCR-SSP. RESULTS: Significant associations of ESRD with the TGF-beta 1 (codon 10) TT (odds ratio [OR] = 5.31; 95% confidence interval [95% CI], 3.77-7.02; p<0.001) and IL-10 (-1082) GG (OR=2.35; 95% CI, 1.67-3.15; p<0.01) genotypes were found. Statistical analysis of genotype frequencies made separately for the underlying renal disease (diabetes or glomerulo-nephritis) revealed the same linkage trend: TGF-beta 1 (codon 10) TT and IL-10 (-1082) GG were associated with type 2 diabetic nephropathy (p<0.001 and p<0.05, respectively) and chronic glomerulonephritis (p<0.001 and p<0.01, respectively). No significant differences in the TNF-alfa , TGF-beta 1 (codon 25) genotype distribution between healthy controls and patients with diabetic nephropathy- or glomerulonephritis-associated ESRD were detected. CONCLUSIONS: Carriage of the TGF-beta 1 (codon 10) TT and IL-10 (-1082) GG genotypes may increase susceptibility to ESRD in German patients with type 2 diabetes or glomerulonephritis.     

Estimating the benefits of solitary pancreas transplantation in nonuremic patients with type 1 diabetes mellitus: a theoretical analysis

BACKGROUND: The goal of early pancreas transplantation in type 1 diabetes mellitus is to achieve euglycemia and thereby prevent the renal, retinal, and vascular complications of this disease. The purpose of this analysis was to examine the conditions and assumptions that would make early solitary pancreas a viable therapeutic option. METHODS: A Markov model was constructed to compare outcomes for patients with type 1 diabetes mellitus and early overt nephropathy assigned to either standard insulin therapy or solitary pancreas transplantation. Probabilities for development of end stage renal disease (ESRD), blindness, mortality, and direct health care costs were taken from the literature. Utility scores for the relevant health states were determined by the standard gamble method on 16 type 1 diabetic patients suitable for pancreas transplantation. RESULTS: Assuming a baseline graft life expectancy for the pancreas of 10 years, early pancreas transplantation could provide 0.42 more life years and 2.2 more quality adjusted life years (discounted at 3%) to patients above standard insulin therapy. The model was sensitive to estimates of pancreas graft life expectancy (<8 years being inadequate to extend patient life), timing of pancreas transplantation with respect to rate of progression to ESRD, and drug nephrotoxicity rates. The incremental costs (charges) for early pancreas transplantation over standard therapy were estimated to be modestly high (about $56,600/quality adjusted life year for the baseline case). Pancreas transplant costs were also a very sensitive parameter in the cost utility analysis. CONCLUSIONS: The success of early solitary pancreas transplantation may well be at the stage to consider a trial in selected type 1 diabetic patients at risk for renal and retinal disease.     

Trends in incidence of treated end-stage renal disease, overall and by primary renal disease, in persons aged 20-64 years in Europe, Canada and the Asia-Pacific region, 1998-2002

AIMS: To determine if rates of diabetic and non-diabetic end-stage renal disease (ESRD), which had been rising in young and middle-aged adults in all populations up to the mid-1990s, had started to decline, and if so, whether improvement had occurred in respect of each of the principal primary renal diseases causing ESRD. METHODS: Poisson regression of age- and sex-standardized incidence of ESRD for persons aged 20-64 years in 18 populations from Europe, Canada and the Asia-Pacific region, for 1998-2002. RESULTS: In persons from 12 European descent (Europid) populations combined, there was a small downward trend in all-cause ESRD (-1.7% per year, P = 0.001), with type 1 diabetic ESRD falling by 7.8% per year (P < 0.001), glomerulonephritic ESRD by 3.1% per year (P = 0.001), and 'all other non-diabetic' ESRD by 2.5% per year (P = 0.02). The reductions in ESRD attributed to hypertensive (-2.2% per year) and polycystic renal disease (-1.5% per year) and unknown diagnosis (-0.2% per year) were not statistically significant. On the other hand, the incidence of type 2 diabetic ESRD rose by 9.9% per year (P < 0.001) in the combined Europid population, although that of (principally type 2) diabetic ESRD remained unchanged in the pooled data from the four non-Europid populations. CONCLUSION: Recent preventive strategies, probably chiefly modern renoprotective treatment, appear to have been effective for tertiary prevention of ESRD caused by the proteinuric nephropathies other than type 2 diabetic nephropathy, for which the continuing increase in Europid populations represents a failure of prevention and/or a change in the nephropathic potential of type 2 diabetes.