Kidney transplantation is the gold standard therapeutic alternative for patients with end-stage renal disease; nevertheless, it is not without potential complications leading to considerable morbidity and mortality such as post-transplant diabetes mellitus (PTDM). This narrative review aims to comprehensively evaluate PTDM in terms of its diagnostic approach, underlying pathophysiological pathways, epidemiological data, and management strategies.

Articles were retrieved from electronic databases using predefined search terms. Inclusion criteria encompassed studies investigating PTDM diagnosis, pathophysiology, epidemiology, and management strategies.

PTDM emerges as a significant complication following kidney transplantation, influenced by various pathophysiological factors including peripheral insulin resistance, immunosuppressive medications, infections, and proinflammatory pathways. Despite discrepancies in prevalence estimates, PTDM poses substantial challenges to transplant. Diagnostic approaches, including traditional criteria such as fasting plasma glucose (FPG) and HbA1c, are limited in their ability to capture early PTDM manifestations. Oral glucose tolerance test (OGTT) emerges as a valuable tool, particularly in the early post-transplant period. Management strategies for PTDM remain unclear, within sufficient evidence from large-scale randomized clinical trials to guide optimal interventions. Nevertheless, glucose-lowering agents and life style modifications constitute primary modalities for managing hyperglycemia in transplant recipients.

The complex interplay between PTDM and the transplant process necessitates individualized diagnostic and management approaches. While early recognition and intervention are paramount, modifications to maintenance immunosuppressive regimens based solely on PTDM risk are not warranted, given the potential adverse consequences such as increased rejection risk. Further research is essential to refine management strategies and enhance outcomes for transplant recipients.

Renal transplant recipients have a high peri-operative risk for cardiovascular events. The post-transplantation period also carries a risk of myocardial infarction (MI). Coronary artery disease (CAD) is a leading cause of death in these patients. We aimed to assess the risk of MI, the specific morbidity profile of MI after transplantation as well as the long-term prognosis after MI in renal transplantation (RT) patients regarding cardiovascular (CV) death and all-cause death.

From a French national medical information database, all of the patients seen in French hospitals in 2013 with at least 5-years follow-up were retrospectively identified and patients without transplantation but with previous dialysis at baseline were excluded. There were 17,526 patients with RT and 3,288,857 with no RT.

Among these patients, 1020 in the RT group (5.8%), and 93,320 in the non-RT group (2.8%) suffered acute MI during a median follow-up of 5.4 years. After multivariable adjustment, risk of MI was higher in RT patients than in non-RT patients (HR 1.45, IC 95% 1.35-1.55). The mean age was 59.5 years for transplant patients with MI, and 70.6 years for the reference population with MI (p < 0.0001). MI patients with RT (vs. non RT patients) were more likely to have hypertension, diabetes dyslipidemia, and peripheral artery disease (76.0% vs. 48.1%, 38.7% vs. 25.2%, 33.2% vs. 23.2%, and 31.2% vs. 17.3%, respectively, p < 0.0001). Incidence of non ST-elevation MI (NSTEMI) was higher in RT patients while incidence of ST-elevation MI (STEMI) was higher in patients without RT. In unadjusted analysis, risk of all-cause death and CV death within the first month after MI were higher in patients without RT (18% vs. 11.1% p < 0.0001 and 12.3% vs. 7.8%, p < 0.0001, respectively). However, multivariable analysis indicated that risk of all-cause death was higher in patients with RT than in those with no RT (adjusted HR 1.15 IC 95% 1.03-1.28).

MI is not an uncommon complication after RT (incidence of around 5.8% after 5 years). RT is independently associated with a 45% higher risk of MI than in patients without RT, with a predominance of NSTEMI. MI in patients with RT is independently associated with a 15% higher risk of all-cause death than that in patients with MI and no RT.

Kidney transplantation is the gold-standard treatment for many patients with end-stage renal disease. Renal transplant recipients (RTRs) remain at an increased risk of fatal and non-fatal cardiovascular (CV) events compared to the general population, although rates are lower than those patients on maintenance haemodialysis. Death with a functioning graft is most commonly due to cardiovascular disease (CVD) and therefore this remains an important therapeutic target to prevent graft failure. Conventional CV risk factors such as diabetes, hypertension and renal dysfunction remain a major influence on CVD in RTRs. However it is now recognised that the morbidity and mortality from CVD are not entirely accounted for by these traditional risk-factors. Immunosuppression medications exert a deleterious effect on many of these well-recognised contributors to CVD and are known to exacerbate the probability of developing diabetes, graft dysfunction and hypertension which can all lead on to CVD. Non-traditional CV risk factors such as inflammation and anaemia have been strongly linked to increased CV events in RTRs and should be considered alongside those which are classified as conventional. This review summarises what is known about risk-factors for CVD in RTRs and how, through identification of those which are modifiable, outcomes can be improved. The overall CV risk in RTRs is likely to be multifactorial and a complex interaction between the multiple traditional and non-traditional factors; further studies are required to determine how these may be modified to enhance survival and quality of life in this unique population.

The influence of NODAT on survival of liver transplant recipients has not been clarified. Therefore, we evaluated the effect of NODAT on survival in LT recipients.

Data from 352 LT patients were totally analyzed. 97 patients with pretransplant diabetes mellitus were excluded, and 255 patients without diabetes mellitus at time of transplantation were included.

NODAT was diagnosed in 41 patients (16.1%). There was no difference in frequency of NODAT according to the etiology of liver cirrhosis. NODAT was associated with a higher body weight (p=0.004) and BMI (p=0.002) 5years after LT, but not with weight gain (p=0.201) or increase in BMI (p=0.335) 5years after LT. HbA1c 5years after LT was significantly higher in patients with NODAT (p=0.001), but mean HbA1c still remained lower than 6.5% (6.4(±1.2) %). Patients with NODAT showed better survival rates (log rank: p=0.002) compared to LT recipients without diabetes. According to all existing knowledge of diabetes mellitus (DM) better survival cannot be a direct effect of this disease. Our results are rather influenced by an not known confounding factor (possibly recovery from cachexia) associated with better survival and NODAT, while complications of NODAT will not appear during the relatively short postoperative time and observation period (mean follow up 6.08 (±2.67) years).

NODAT is frequently diagnosed in LT recipients and is associated with an improved 5year survival after LT due to a not exactly known confounding factor.

New Onset Diabetes after Transplantation (NODAT) is defined as sustained hyperglycemia developing in patients without diabetes history before transplantation. A cohort study was performed to access the effects of tacrolimus on insulin secretion and insulin sensitivity and consequently in the development of NODAT in kidney transplant recipients. Then, we further investigated the association between NODAT and single-nucleotide polymorphisms of IRS-1 and IRS-2 in renal allograft recipients. One hundred and fifty-eight kidney transplant patients, receiving tacrolimus as the base immunosuppressant, were divided into two groups: with or without NODAT. Plasma levels of fasting insulin concentration (FINS) and C-peptide were determined by enhanced chemiluminescence immunoassay and ADVIA Centaur C peptide assay, respectively. The genotypes of Gly1057Asp in IRS-2 and Gly972Arg in IRS-1 were detected through polymerase chain reaction fragment length polymorphism in NODAT and non-NODAT patients. It was found that the concentrations of fasting plasma insulin and C-peptide in NODAT and non-NODAT patients treated with tacrolimus were higher than that in healthy volunteers (p < 0.05). Fasting plasma insulin concentration in NODAT was significantly elevated compared with than that in non-NODAT group (p < 0.05). But there are no statistical differences in fasting plasma C-peptide concentrations between NODAT and non-NODAT groups. The allele and genotype frequencies of IRS-2 Gly1057Asp and IRS-1 Gly972Arg in NODAT patients were not significantly different from non-NODAT patients (p > 0.05). In conclusion, insulin resistance is the primary cause of tacrolimus-induced NODAT. The IRS-2 Gly1057Asp and IRS-1 Gly972Arg genotypes are not related to NODAT.

Tacrolimus (FK506) use has been suggested as a risk factor for post-transplantation diabetes mellitus (PTDM) because it can impair insulin secretion. This association warrants further investigation. This study aimed to examine the prevalence of PTDM and its association with FK506 use in kidney transplant recipients. The study also aimed to examine the relationship of FK506 use and diabetes-related biologic markers.

A retrospective chart review was used to collect data at a medical center in northern Taiwan from September 2003 to February 2012. PTDM was defined with the use of the criteria of the American Diabetes Association.

Among 166 patients included in the analysis, PTDM was reported in 49 patients (29.5%). A total of 93 patients used the FK506 regimen, of whom 34 (36.6%) were PTDM cases. Logistic regression showed that FK506 use (odds ratio [OR], 2.71; 95% confidence interval [CI], 1.20-6.11; P = .016) and older age (OR,1.08; 95% CI, 1.03-1.13; P = .001) were significant risk factors for PTDM. In addition, FK506 use in PTDM cases was associated with a significantly higher hemoglobin A1c level (7.55 vs 5.81; P = .01) and a borderline significantly higher insulin resistance index (3.24 vs 1.92; P = .053) than was FK506 use without the presence of PTDM.

Older age and an FK506 regimen were important predictors of the prevalence of PTDM. Greater early detection and prevention efforts for PTDM are needed for older transplant recipients. PTDM patients with an FK506 regimen had higher hemoglobin A1c levels and insulin resistance index than did patients who did not use FK506. The association of serum indicators with FK506 use in the prevalence of PTDM warrants further investigation.

Cardiovascular risk in hemodialysis patients is enhanced, resulting in a higher mortality rate compared with the general population, yet the average wait time for renal transplantation in Germany is 5-7 years. The age of wait-listed patients has risen progressively. The aim of this study was to evaluate the prevalence of cardiovascular disease in patients on the waiting list in our center before and after renal transplantation as well as the extent to which invasive treatment was required in these patients.

The study investigated 2 groups: 350 patients on the renal transplantation waiting list at our center in 2008 and 324 patients who underwent renal transplantation at the same center in the years 2003-2007.

In 2008, 141 women and 209 men with a mean age of 48.6 years (range 13-71 years) were on the waiting list. In the years 2003-2007, 98 women and 226 men with a mean age of 54.3 years (range 16-78 years) received renal transplants. One hundred six patients on the waiting list for renal transplantation had to undergo coronary angiography. There is no upper age limit for donors or recipients in our program. Mean age at admission on the waiting list was 48.6 years (range 13-71 years). Mean age at transplantation was 54.3 years (range 16-78 years) in our center. Most of these patients were asymptomatic but presented a risk profile that included diabetes mellitus, severe general atherosclerosis, a pathologic ergometric test, or abnormal myocardial scintigraphy. Only in 1 case could coronary heart disease be excluded. Seventy patients (20%) suffered from mild to moderate coronary heart disease without the need for intervention. In 5 patients (1.4%) coronary bypass surgery was necessary due to severe 3-vessel coronary heart disease. In 2 cases (0.6%) replacement of the aortic valve was performed because of aortic valvular stenosis. Coronary angioplasty without implantation of stents was done in 2 patients (0.6%). Twenty-two patients (6.8%) were treated with implantation of bare metal stents and 6 patients (1.7%) with drug-eluting stents. After renal transplantation, 22 patients (6.8%) suffered from peripheral arterial occlusive disease. In 58 patients, coronary heart disease was documented by angiography. 16 patients (4.9%) had 1-vessel disease, 23 patients (7%) 2-vessel disease, and 19 patients (5.8%) 3-vessel disease. Myocardial infarction was documented in 18 patients (5.5%) before and in 5 patients (1.5%) after renal transplantation. Bare metal stent implantation was performed in 6 patients (1.8%) after transplantation. One patient received a drug-eluting stent after renal transplantation. In the years 2003-2007, 22 patients underwent coronary bypass surgery before kidney transplantation.

The prevalence of coronary heart disease is high in patients on the waiting list and after renal transplantation. The majority of these patients are clinically asymptomatic. One-third of the patients with coronary heart disease had to be treated invasively. Nevertheless, many diabetic patients are very sick from multiple complications after the waiting time, making theme unsuitable for transplantation.

To assess the incidence, risk factors and outcomes of PTDM, a total of 61 non-diabetic children (24 girls, 37 boys, age: 14.5 +/- 2.1 yr) were examined after their first kidney transplantation (37.3 +/- 21.6 months) with an OGTT. At baseline, 16 (26.2%) patients had IGT, 45 (73.8%) had NGT, and no patient had PTDM. No significant difference was shown between TAC- and CSA-treated patients in terms of IGT. Higher BMI z-scores (p = 0.011), LDL-cholesterol (p < 0.05) and triglyceride levels (p < 0.01), HOMA-IR (p = 0.013) and lower HOMA-%beta (p = 0.011) were significantly associated with IGT. Fifty-four patients were re-evaluated after six months; eight patients with baseline IGT (50%) improved to NGT, three (19%) developed PTDM requiring insulin therapy, five (31%) remained with IGT, and four patients progressed from NGT to either IGT (two) or PTDM (two). These 12 progressive patients had significantly higher total cholesterol (p < 0.05), triglycerides (p < 0.05), HOMA-IR (p < 0.01) and lower HOMA-%beta (p < 0.0) than non-progressive patients at baseline. We can conclude that post-transplantation glucose abnormalities are common in Turkish pediatric kidney recipients, and higher BMI z-scores and triglyceride concentrations are the main risk factors. Considering that the progressive patients are significantly more insulin resistant at baseline, we suggest that the utility of both HOMA-IR and HOMA-%beta in predicting future risk of PTDM and/or IGT should be evaluated in children.

At present, there is some controversy about the impact of diabetes mellitus on heart transplant patients. The effect of the disease on mortality and on other complications, such as infection or rejection, is unclear. The objective of this study was to investigate these factors in our heart transplant patients.

We studied 365 consecutive patients who underwent heart transplantation between November 1987 and May 2003. We divided them in three groups according to whether they had pretransplantation diabetes (group 1), de novo diabetes (group 2), or no diabetes (group 3). Baseline variables and the development of complications were recorded, and findings were analyzed using Student's t test, chi squared test, and Kaplan-Meier survival analysis.

There was no difference in the 1-year or 5-year survival rate between the groups (P=.24 and P=.32, respectively). Patients with pretransplantation and de novo diabetes were older (54.6 years vs 54.9 years vs 50.6 years, P=.04), had a higher prevalence of hypertension (48% vs 36% vs 23%, P=.001), and had more frequently been treated with tacrolimus (10% vs 12% vs 4%, P=.04) or steroids (92% vs 86% vs 70%, P=.001). The incidence of rejection during follow-up was greater in these two groups (64% vs 70% vs 45%, P=.001).

Neither pretransplantation diabetes nor de novo diabetes had a negative impact on survival in our heart transplant patients. The disease's presence was associated with treatment with steroids and tacrolimus. In these patients it would be preferable to individualize immunosuppressive therapy.

The clinical impact of new-onset diabetes mellitus (NODM) is frequently underestimated by clinicians. NODM occurs in approximately 15-20% of renal transplant patients and 15% of liver transplant recipients. Diabetes after transplantation is a leading risk factor for cardiovascular events, with a higher prognostic value than in the non-transplant population. NODM also appears to have a negative influence on graft function, and graft survival rates after renal transplantation are significantly lower in patients who develop diabetes than in controls. Patient mortality following renal transplantation is generally found to be higher in patients with NODM, due to increased cardiovascular and peripheral vascular disease, accelerated graft deterioration and diabetes-related complications, notably infection. A renal registry analysis has reported an increase of 87% in risk of death following onset of NODM. There is also limited evidence that NODM is associated with increased risk of death in liver transplant patients. The relative incidence and severity of diabetic complications in transplant recipients have not been assessed rigorously in a clinical trial but registry data indicate that 20% of renal transplant patients with NODM experience at least one clinically significant diabetic complication within three years. Financially, the additional healthcare costs incurred over the first two years following onset of NODM amount to 21,500 dollars. Routine pre-transplant assessment of diabetic risk, with requisite modification of lifestyle, glycaemic monitoring and immunosuppressive regimens, and coupled with standardized, aggressive hypoglycaemic management as necessary, offers an important opportunity to alleviate the burden of NODM for transplant patients.

We hypothesized that the use of HbA1c testing would help identify postrenal transplant diabetes (PTDM).

In all, 199 adult kidney transplant recipients at least 3 months posttransplant without previous history of diabetes or elevated fasting blood sugar were studied. Medical history, a fasting blood glucose, calcineurin inhibitor blood level, and HbA1c were obtained. Primary outcome was the incidence of subjects with HbA1c > or =6.1%. The covariates were use of cyclosporine or tacrolimus, time posttransplant, body mass index (BMI) at transplant and change since transplant, current steroid dose, history of graft rejection, current fasting glucose, age, and race. Proportions were compared between HbA1c <6 and > or =6.1% using Fisher's exact test. Means were compared using Student's t test. Logistic regression was used to identify risk factors associated with elevated HbA1c.

Twenty subjects (10.1%) had an elevated HbA1c. High normal fasting glucose (P=0.003) and African American race (P=0.08, marginally significant) were found to be associated with an elevated HbA1c. Subjects with normal and abnormal HbA1c levels were otherwise similar. There was no difference in HbA1c in tacrolimus versus cyclosporine treated subjects or in the percent of subjects with elevated HbA1c between these groups.

HbA1c levels were found to be more a more sensitive test than fasting blood glucose levels in PTDM, with 10.1% of all patients and 19.4% of blacks found to have an elevated HbA1c. HbA1c testing should be considered as a screening test for PTDM, especially in African Americans.

Posttransplantation diabetes (PTD) contributes to cardiovascular disease and graft loss in renal transplant recipients (RTR). Current recommendations advise fasting blood glucose (FBG) as the screening and diagnostic test of choice for PTD. This study sought to determine (1) the predictive power of FBG with respect to 2-h blood glucose (2HBG) and (2) the prevalence of PTD using FBG and 2HBG compared with that using FBG alone, in prevalent RTR. A total of 200 RTR (mean age 52 yr; 59% male; median transplant duration 6.6 yr) who were > 6 mo posttransplantation and had no known history of diabetes were studied. Patients with FBG < 126 mg/dl (7.0 mmol/L; n = 188) underwent an oral glucose tolerance test (OGTT). Receiver operating characteristic analyses evaluated the optimal level of FBG predictive of PTD (2HBG > or = 200 mg/dl [11.1 mmol/L]) and impaired glucose tolerance (IGT; 2HBG 140 to 200 mg/dl [7.8 to 11.0 mmol/L]). An abnormal OGTT was reported in 79 (42%) nondiabetic RTR: PTD (n = 22) and IGT (n = 57). The optimal FBG that was predictive of PTD was 101 mg/dl (5.6 mmol/L; area under the curve 0.70; sensitivity 64%, specificity 67%, positive predictive value 20%, negative predictive value 93%). The optimal FBG that was predictive of IGT was less well defined (area under the curve 0.54). The prevalence of PTD was higher by OGTT than by FBG alone (17 versus 6%; P < 0.001). FBG may not be the optimal screening or diagnostic tool for PTD or IGT in RTR. Consideration should be given to introducing the OGTT as a routine posttransplantation investigation, although the implications of a pathologic OGTT are still to be determined in this population.

The prevalence of diabetes mellitus (DM) in the Gulf region is among the highest in the world. In the general population of Oman, the rate is approximately 11.7% with an additional 6.1% of the population having an abnormal glucose tolerance. This study reviewed the data for 162 adults who received kidney transplants between 2001 and 2004. The immunosuppression regimen was cyclosporine, mycophenolate mofetil (MMF), and steroids. The mean age of the group was 40.2 years. Twenty-two patients (13.6%) had DM prior to transplantation. Within the first 2 months after transplantation, 45 (32%) of the remaining 140 patients required insulin, and 10 (7.1%) required oral agents. A further 16 patients (11.4%) displayed blood glucose levels >11 mmol/L, but required only a special diet for control. The data indicate that 50% of recent adult kidney recipients in Oman receiving cyclosporine develop posttransplantation DM. This major problem in our transplant population requires special attention. Protocols with minimal steroid use and/or steroid withdrawal may be beneficial for the Oman kidney recipient population.

Obesity is a frequent and important consideration to be taken into account when assessing patient suitability for renal transplantation. In addition, posttransplant obesity continues to represent a significant challenge to health care professionals caring for renal transplant recipients. Despite the vast amount of evidence that exists on the effect of pretransplant obesity on renal transplant outcomes, there are still conflicting views regarding whether obese renal transplant recipients have a worse outcome, in terms of short- and long-term graft survival and patient survival, compared with their non-obese counterparts. It is well established that any association of obesity with reduced patient survival in renal transplant recipients is mediated in part by its clustering with traditional cardiovascular risk factors such as hypertension, dyslipidaemia, insulin resistance and posttransplant diabetes mellitus, but what is not understood is what mediates the association of obesity with graft failure. Whether it is the higher incidence of cardiovascular comorbidities jeopardising the graft or factors specific to obesity, such as hyperfiltration and glomerulopathy, that might be implicated, currently remains unknown. It can be concluded, however, that pre- and posttransplant obesity should be targeted as aggressively as the more well-established cardiovascular risk factors in order to optimize long-term renal transplant outcomes.

New-onset diabetes melittus (NODM) is a serious complication following transplantation. Recent studies suggest an association between hepatitis C virus (HCV) infection and DM both in nontransplant settings as well as after liver transplantation (LT). The aim of this study was to assess the prevalence of NODM among Brazilian LT recipients, analyzing possible risk factors including HCV infection. We conducted a cross-sectional study to evaluate the prevalence of NODM in 82 LT recipients with a posttransplant follow-up > or =1 year including 29 HCV-positive patients and 53 with other causes for liver disease. Patients were considered to meet the criteria for DM if they had two consecutive fasting glucose values > or =126 mg/dL or if they were taking insulin or oral hypoglycemic agents at the time of the study. The overall prevalence of NODM was 18.29% with a median interval of 20 months between LT and diagnosis of DM. The age, sex, and race distribution, immunosuppressive regimen, number of rejection episodes treated with pulse therapy, and family history of DM were similar in both groups. However, the frequency of BMI > or = 30 in the pre- and posttransplant periods was higher among patients who developed NODM (P = .02). Upon multivariate analysis of the entire cohort, HCV infection was the only significant predictor of NODM (OR = 4.31, CI = 1.17 to 15.84, P = .02). In conclusion, our study confirmed an association between HCV infection and NODM among Brazilian liver transplant recipients, suggesting that HCV infection may have a potential role in the pathogenesis of posttransplantation DM.

The complications concerning liver and intestinal transplant surgery have relevance for the field of intensive care because they share some characteristics with those following complex long-term surgery. Thus, in this article we shall try to describe complications that are specific to liver and multivisceral transplants. A review of the existing literature on this topic reveals a large number of studies dedicated to early as well as late surgical complications, and immunosuppressive treatment, while there are far fewer contributions describing complications exclusively concerning intensive care. We shall thus attempt to focus on certain aspects where, besides the literature data, we have personal experience. In particular we want to underline the implications of failure in the functional recovery of the graft; alterations in water, electrolyte, and glycemic balance; as well as neurological, respiratory, renal, nutritional, and infective complications.

Recent evidence suggests that new-onset diabetes after transplant (NODAT) adversely affects orthotopic liver transplant (OLTX) patient and graft survival. The objective of this study is to evaluate the effect of hepatitis C infection on the natural history of NODAT.

A retrospective review of 492 OLTX recipients at a single center was conducted from January 1993 to January 2003. Patients were followed for a minimum of 12 months (range 12 months-10 years). The study population consisted of 444 OLTX recipients who were either HCV positive (n = 206) or HCV negative (n = 238). NODAT was defined by the need for antidiabetic medication for at least 7 days starting anytime after OLTX. Statistical analysis was performed by using the Student t test, Kaplan-Meier survival, and chi-square tests.

The overall incidence of NODAT was 33% (146/444). There was a significant difference in the development of NODAT between the HCV-positive group (82/206, 40%) and the HCV-negative group (64/238, 27%) (P < .001). Other independent risk factors for development of NODAT were male gender and age >50 years.

Hepatitis C infection contributes to the development of diabetes mellitus in OLTX recipients. The mechanisms behind HCV infection and associated NODAT in HCV-positive OLTX recipients warrant further investigation.

Posttransplant diabetes mellitus (PTDM) is a frequent complication in renal-transplant recipients (RTRs). We conducted a prospective study to assess the potential role of PTDM in the development of atherosclerotic events (AE) in RTRs.

Three hundred fifty-seven consecutive RTRs were enrolled in this study. The incidence of various AE were assessed with respect to the presence of PTDM and a number of cardiovascular (CV) risk factors.

The patients were followed for a mean duration of 60+/-14 months. Thirty-nine (11%) patients had PTDM. Fifty AE occurred in 48 (13.4%) patients. Although AE were more frequent in RTRs with PTDM compared with nondiabetic patients (33% vs. 8.8%; P=0.007), PTDM was only modestly associated with AE in the multivariate Cox regression analysis (relative risk [RR] 1.34; 95% confidence interval [CI], 1.04-2.18), mostly caused by significant interactions between PTDM and three confounding variables that were independently associated with AE: age, serum C-reactive protein (CRP) level, and serum high-density lipoprotein cholesterol concentration. Patients with high levels of homocysteine showed a significantly increased risk of AE (RR 4.67; 95% CI 1.82-15.87), as did those with high serum levels of CRP (RR 2.57; 95% CI 1.57-6.23).

Our study shows a significant association between PTDM and AE. Nevertheless, a large amount of the excess risk of posttransplant diabetic RTR is explained by the coexistence of other CV risk factors. Moreover, high serum levels of CRP and hyperhomocystinemia were found to be among the nontraditional factors contributing to AE in our patients.

The risk and predictors of post-kidney transplantation myocardial infarction (PTMI) are not well described. Registry data collected by the United States Renal Data System were used to investigate retrospectively PTMI among adult first renal allograft recipients who received a transplant in 1995 to 2000 and had Medicare as the primary payer. PTMI events were ascertained from billing and death records, and participants were followed for up to 3 yr after transplant or until the end of observation (December 31, 2000). Extended Cox's hazards analysis was used to identify independent clinical correlates of PTMI (hazard ratio [HR]) and to examine PTMI as an outcomes predictor. Among 35,847 eligible participants, the cumulative incidence of PTMI was 4.3% (95% confidence interval [CI], 4.1 to 4.5%), 5.6% (95% CI, 5.3 to 5.8%), and 11.1% (95% CI, 10.7 to 11.5%) at 6, 12, and 36 mo, respectively. Risk factors for PTMI included older recipient age, pretransplantation comorbidities (diabetes, angina, peripheral vascular disease, and MI), transplantation from older donors and deceased donors, and delayed graft function. Women, blacks, Hispanics, and employed recipients experienced reduced risk. The hazard of PTMI rose after a diagnosis of posttransplantation diabetes (HR, 1.60; 95% CI, 1.35 to 1.88) and markedly increased after graft failure (HR, 2.78; 95% CI, 2.41 to 3.19). In separate analyses, PTMI predicted death-censored graft failure (HR, 1.89; 95% CI, 1.63 to 2.20) and strongly predicted death in a manner that declined with time after PTMI. Risk factors for PTMI include potentially modifiable posttransplantation complications. Because PTMI in turn predicts graft failure and death, reducing the risk for PTMI may improve outcomes after kidney transplantation.

Statins have anti-inflammatory effects, modify endothelial function and improve peripheral insulin resistance. We hypothesized that statins influence the development of new-onset diabetes mellitus in renal transplant recipients. The records of all previously non-diabetic adults who received an allograft in Toronto between January 1, 1999 and December 31, 2001 were reviewed with follow-up through December 31, 2002. All patients receiving cyclosporine or tacrolimus, mycophenolate mofetil and prednisone were included. New-onset diabetes was diagnosed by the Canadian Diabetic Association criteria: fasting plasma glucose > or =7.0 mmol/L or 2-h postprandial glucose > or =11.1 mmol/L on more than two occasions. Statin use prior to diabetes development was recorded along with other variables. Cox proportional hazards models analyzing statin use as a time-dependent covariate were performed. Three hundred fourteen recipients met study criteria, of whom 129 received statins. New-onset diabetes incidence was 16% (n = 49). Statins (p = 0.0004, HR 0.238[0.109-0.524]) and ACE inhibitors/ARB (p = 0.01, HR 0.309[0.127-0.750]) were associated with decreased risk. Prednisone dose (p = 0.0001, HR 1.007[1.003-1.010] per 1 mg/d at 3 months), weight at transplant (p = 0.02, HR 1.022[1.003-1.042] per 1 kg), black ethnicity (p = 0.02, HR 1.230[1.023-1.480]) and age > or =45 years (p = 0.01, HR 2.226[1.162-4.261]) were associated with increased diabetes. Statin use is associated with reduced new-onset diabetes development after renal transplantation.