Pulse pressure is an independent risk factor of cardiovascular disease in renal transplant patients

Elevated pulse pressure in the general population has been shown to be associated with cardiovascular disease, which is the main cause of death in renal transplant patients. We investigated the effects that a wide pulse pressure has on cardiovascular disease after renal transplantation in a cohort of 532 transplant patients with functioning grafts for more than one year. Patients were classified into two groups depending on whether the one-year pulse pressure was less than or greater than 65 mm Hg. We analyzed patient survival, posttransplant cardiovascular disease and principle causes of death. Five- and ten-year patient survival were lower among the group with higher pulse pressures. The main cause of death was vascular disease in both groups. The presence of posttransplant cardiovascular disease was higher among the group with higher pulse pressures (RR=1.73). In addition, the incidence of an elevated pulse pressure was directly associated with recipient age and posttransplant diabetes mellitus. In conclusion, pulse pressure represents an independent risk factor for increased cardiovascular morbidity and mortality in renal transplant patients.     

Autosomal-dominant polycystic kidney disease as a risk factor for diabetes mellitus following renal transplantation

BACKGROUND: Posttransplant diabetes mellitus is an important complication of renal transplantation that is associated with a significant impact on quality of life and an increase in long-term morbidity and mortality. Autosomal-dominant polycystic kidney disease (ADPKD) is a hereditary disease that commonly leads to end-stage renal disease (ESRD) in adulthood. The association between ADPKD and posttransplant diabetes mellitus has not been previously studied in a large cohort of patients. METHODS: To address this question, we studied a cohort of 135 patients with ADPKD who received a first renal-only transplant between January 1985 and December 1999. An age, race, and date of transplant-matched cohort of 135 non-ADPKD subjects were used as the control population. RESULTS: The cohorts were similar at baseline for gender distribution, body mass index (BMI), proportion of obese subjects (BMI greater than 30 kg/m(2)), family history of diabetes mellitus, and type of donor (deceased or living). At 12 months, the incidence of posttransplant diabetes mellitus was significantly higher in patients with ADPKD when compared to the controls (17% vs. 7.4%) (P= 0.016), despite no significant differences in the BMI, percent increase in BMI, number of acute rejections, prednisone dose at 3 and 6 months, use of diuretics or beta blockers, delayed graft function, or serum creatinine levels. The proportion of subjects requiring insulin was significantly higher in the ADPKD group (11.1% vs. 3%) (P= 0.009). Variables significantly associated with posttransplant diabetes mellitus at 1 year by bivariate analyses were the diagnosis of ADPKD (P= 0.02), BMI at transplant (P= 0.04), obesity at 12 months (P= 0.01), and delayed graft function (P= 0.02). Gender of recipient (P= 0.9), family history of diabetes (P= 0.3), prednisone dose at 3 months (P= 0.9) and 6 months (P= 0.7), acute rejection (P= 0.9), use of beta blockers or tacrolimus (P= 0.8), deceased donor transplant (P= 0.2), and serum creatinine at 1 year (P= 0.5) were not associated with posttransplant diabetes mellitus. A trend toward increased incidence of posttransplant diabetes mellitus was found with the use of diuretics post transplant (P= 0.054). By multivariable analyses, in patients with ADPKD, the adjusted (by all the variables listed above) relative risk for development of posttransplant diabetes mellitus was 2.87 (95% CI = 1.24-6.65) (P= 0.014). Only the diagnosis of ADPKD (RR = 2.9) (P= 0.01), obesity at 1 year (RR 2.5) (P= 0.017), and delayed graft function (RR 2.4) (P= 0.03) contributed significantly to the fit of a stepwise logistic regression model. Patient survival was significantly worse in the cohort of patients who developed posttransplant diabetes mellitus (median survival 109.3 vs. 121 months) (P= 0.008). CONCLUSION: In our study patients with ADPKD were at a threefold increased risk for development of posttransplant diabetes mellitus within the first year following renal transplantation. Development of posttransplant diabetes mellitus was associated with a significant detrimental impact on patient survival. Further studies are needed to provide insight into the mechanisms of the association between ADPKD and posttransplant diabetes mellitus.     

The effect of the American Heart Association step one diet on hyperlipidemia following renal transplantation

Cardiovascular disease is a frequent cause of morbidity and mortality following renal transplantation. The percentage of deaths due to ischemic cardiovascular disease and cerebrovascular accidents nearly equals that caused by infection among patients receiving their first transplant, according to data from the European Dialysis and Transplant Association Registry. Hypercholesterolemia is a risk factor for cardiovascular disease frequently identified following renal transplantation, and diets low in fat and cholesterol have been suggested as treatment. Previous studies have not reported the response of LDL cholesterol to dietary treatment, and it is this form of cholesterol that is most closely related to cardiovascular disease. The American Heart Association has provided nutritionists with guidelines for the treatment of hyperlipidemic patients which include the Step One Diet. Previous dietary studies of renal transplant recipients have allowed a slightly higher intake of fat than that currently recommended by the AHA. We wondered if an easily reproducible diet well known to nutritionists such as the AHA Step One Diet would be effective in lowering cholesterol levels in hyperlipidemic renal transplant recipients. The purpose of our study was not to define the mechanisms of posttransplant hyperlipidemia, but rather to assess the effectiveness of dietary intervention on hyperlipidemia following renal transplantation.     

Risk factors for the development of new-onset diabetes mellitus in a living related renal transplant program

New-onset diabetes mellitus is associated with considerable morbidity after transplantation. We evaluated 78 living related renal transplant recipients due to all causes except diabetic nephropathy a waiting a living related renal transplantation. We evaluated demographic characteristics, pretransplant glycemic profile, fasting C-peptide levels, plasma insulin levels, pretransplant insulin resistance, and immunosuppression protocols. Among the 16.7% of patients developing diabetes mellitus at the end of 1 year, age, family history, and impaired glucose tolerance at the time of transplantation corelated with the development of diabetes mellitus in the posttransplant period.     

Posttransplant diabetes mellitus in liver transplant recipients

CONTEXT: Approximately 20% of liver transplant recipients develop posttransplant diabetes mellitus. Hepatitis C, a leading indication for liver transplantation, has been identified as a risk factor for posttransplant diabetes mellitus and is an observation that is not well described. OBJECTIVE: To evaluate the incidence of posttransplant diabetes mellitus and risk factors associated with this condition. DESIGN: A retrospective chart review. SETTING: A large urban transplant center. PATIENTS: One hundred fifteen liver transplant recipients who received a transplant between January 1, 1998, and August 31, 2001. RESULTS: The rate of posttransplant diabetes mellitus, calculated at 3-month intervals in the first year after liver transplantation, ranged from 19.4% to 24.6%, which is similar to the averages reported in most published studies. The cumulative rate of posttransplant diabetes mellitus, which includes all patients who developed this condition during the time studied, was 31.3%. Clinical and demographic factors, including immunosuppression regimens, were similar between patients with and without posttransplant diabetes mellitus. Two risk factors for posttransplant diabetes mellitus were identified: hepatitis C, which was the leading indication for transplantation in this group (54.8%), and cytomegalovirus infection during the first year after transplantation. Other clinical and demographic variables, such as gender, age, ethnicity, rejection episodes, body mass index, and immunosuppression, were not identified as risk factors for posttransplant diabetes mellitus in liver transplant recipients.     

Cardiovascular morbidity and mortality in patients with diabetes mellitus type I after kidney transplantation: a case-control study

BACKGROUND: The proportion of diabetics among patients requiring renal replacement therapy continues to increase in most western countries. The acceptance rate for renal transplantation varies among transplant centers and is influenced by the current opinion on the outcome of transplantation in diabetics. Controlled data on patient and graft survival in type I diabetics, however, are scarce. METHODS: We performed a retrospective case-control analysis on patient and graft survival and the cardiovascular morbidity of patients with type I diabetes after renal transplantation versus carefully matched non-diabetic transplant recipients. Match criteria were duration of previous hemodialysis, age and date of renal transplantation. Moreover, risk factors for cardiovascular disease in uremic patients were evaluated at the time of registration for renal transplantation and at the end of the observation period. RESULTS: Seventy-seven matched pairs were enclosed. Patient survival was significantly worse in the diabetic patients, graft survival was comparable in both groups, when graft loss because of patient's death was censored. In the diabetic patients, risk of death (odds ratio: 4.38) as well as the prevalence of cardiovascular morbidity (odds ratio: 4.47) were significantly higher than in the matched nondiabetic controls. Cox regression analysis showed that diabetes mellitus was an independent risk factor for patient survival; no association was found with hypertension, hyperlipidemia, hyperparathyroidism, calcium x phosphate product, body mass index and HbA1c. Cardiovascular morbidity, however, was already significantly higher in the diabetic group at the time of registration. CONCLUSIONS: Diabetes mellitus type I has a dominant impact on morbidity and mortality after renal transplantation and is associated with an approximately 4-fold higher risk of death. Cardiovascular disease accounts for the significantly worse long-term outcome of diabetic patients after renal transplantation.     

Cardiovascular complications after renal transplantation and their prevention

By the time of renal transplantation, end-stage renal disease patients have a huge burden of cardiovascular disease (CVD) and are heavily saturated with atherosclerotic risk factors. Worsening of preexisting risk factors or new CVD risk factors may develop in the posttransplant period consequent in part to the diabetogenic and atherogenic potential of immunosuppressive drugs. The annual risk of a fatal or non-fatal CVD event of 3.5 to 5% in kidney transplant recipients is 50-fold higher than the general population. Renal allograft dysfunction, proteinuria, anemia, moderate hyperhomocysteinemia and elevated serum C-reactive protein concentrations, each dependently confer greater risk of CVD morbidity and mortality in the posttransplant period. Long-term care of renal transplant recipients should programmatically incorporate the recommendations of the National Kidney Foundation Working Groups and European Best Practice Guidelines Expert Group on Renal Transplantations into the management of hypertension, dyslipidemia, smoking, and posttransplant diabetes mellitus. Timely utilization of coronary revascularization procedures should be undertaken as these treatments are equally effective in the kidney transplant population.     

Global cardiovascular risk under early corticosteroid cessation decreases progressively in the first year following renal transplantation

A primary reason to eliminate corticosteroids from immunosuppressive regimens in solid organ transplant recipients is improved cardiovascular risk profiles. Although a number of studies have documented that corticosteroid withdrawal (CSWD) regimens reduce hypertension, hyperlipidemia, diabetes, and weight gain, global assessments of cardiovascular risk under CSWD have not been reported. The purpose of this study was to document cardiovascular risk under CSWD using a global risk assessment by Framingham risk assessment. METHODS: Framingham global cardiovascular risk assessments were performed at baseline and 3, 6, and 12 months posttransplant on patients enrolled in prospective, IRB-approved early (<7 days of corticosteroids) CSWD trials. Framingham score was based on age, sex, presence of diabetes, HDL and total cholesterol, and systolic blood pressure. All patients were nonsmokers. Left ventricular hypertrophy assessment by EKG criteria was not available at all time points and therefore were not included. RESULTS: One hundred eighty-three patients were included in the analysis. Fourteen percent of patients had evidence of coronary heart disease (prior MI, CABG, PTCA, or significant cardiovascular disease as evidenced by angiography) prior to transplant. Complete information was available for 160 patients at baseline, 132 at 1, 3, and 6 months, and 93 at 12 months posttransplant. Mean 10-year risk (expressed as percent) for developing coronary heart disease decreased over time: 8.03 at baseline, 8.31 at 3 months, 7.40 at 6 months, and 7.20 at 12 months, indicating that global cardiovascular risk fell at 1 year posttransplant by about 10% in renal transplant recipients undergoing early CSWD. CONCLUSIONS: Estimation of cardiovascular risk by Framingham risk factor assessment allows incorporation of several cardiovascular risk factors into a single estimate, thereby accounting for differential effects of each individual factor on global cardiovascular risk. This experience indicates that global cardiovascular risk decreases by approximately 10% at 1 year posttransplant in renal transplant recipients who undergo early corticosteroid withdrawal (CSWD).     

Assessing the relative risk of cardiovascular disease among renal transplant patients receiving tacrolimus or cyclosporine

Calcineurin inhibitors potentially contribute to risk of cardiovascular events through the development of new-onset diabetes mellitus, hypertension and hyperlipidemia. The exact extent to which calcineurin inhibitors affect these risk factors is difficult to establish since pre-existing renal disease and concomitant immunosuppressive agents (such as steroids or TOR inhibitors) also exert an effect. Clinical trials have consistently shown a higher incidence of new-onset diabetes mellitus with tacrolimus, which has been borne out in large-scale registry analyses. However, the risk of hypertension is approximately 5% higher with cyclosporine than tacrolimus, as is the risk of hyperlipidemia. Statin therapy is effective in treating dyslipidemia and has significant benefits in renal transplant patients. An individualized approach to choice of calcineurin inhibitor, by which cyclosporine or tacrolimus are selected based on the patient's particular risk profile, may thus help to reduce the toll of cardiovascular mortality among renal transplant recipients in the future.     

The burden of new-onset diabetes mellitus after transplantation

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.     

Transplant-associated hyperglycemia

As patient survival after solid organ transplantation continues to improve, comorbidites associated with chronic hyperglycemia will assume increasing importance in limiting outcomes and quality of life. New-onset diabetes mellitus commonly occurs in the posttransplant setting and is associated with multiple complications including graft loss, cardiovascular disease, infection, and death. Furthermore, recent studies have begun to highlight the very high posttransplant prevalence and the significant cardiovascular implications of the prediabetic states of impaired fasting glucose and impaired glucose tolerance, indicating that the overall burden of transplantation-associated hyperglycemia is far greater than previously appreciated. Shared and distinct pathogenic factors and clinical repercussions exist among the organ-specific transplant scenarios. Diabetogenic immunosuppressive agents are common to all organ transplant settings, whereas glucose regulation is also strained by the restoration of failed hepatic and renal function. The atherogenic properties of hyperglycemia are particularly significant in the kidney transplant population, which has a marked predisposition to cardiovascular disease, whereas accelerated cardiac allograft vasculopathy and liver fibrosis have been associated with hyperglycemia in the heart and liver transplant settings, respectively. Aggressive screening will effectively detect transplant-associated hyperglycemia, whereas risk factor modification, lifestyle intervention and, where appropriate, drug therapy, may decrease its impact. Topics of future investigation should include the use of emerging diabetes therapies and avenues for the prevention and reversal of transplant-associated hyperglycemia.     

Lipid abnormalities in cyclosporine-prednisone-treated renal transplant recipients

Hyperlipidemia and hypertension, two major risk factors for accelerated atherosclerosis, undoubtedly contribute to the excessive cardiovascular morbidity and mortality experienced by renal transplant recipients. The present survey of posttransplant hyperlipidemia in 500 cyclosporine-treated patients documented a 37.6% incidence of hypercholesterolemia, which occurred within 6 months posttransplant in 82% of patients. An etiologic relation to corticosteroid therapy was suggested by the strong correlation between prednisone doses and cholesterol levels, by the reduced cholesterol levels in patients undergoing steroid withdrawal, and by the reduction in hypercholesterolemia to 13% by 3 years posttransplant when steroid doses were less than 10 mg daily. Hypertriglyceridemia, which was present in 14.7% of the patients, was more severe under CsA-prednisone compared with azathioprine-prednisone therapy. Hypertriglyceridemia, which occurred later in the posttransplant course than hypercholesterolemia, strongly correlated with an excessive percent relative weight and elevated serum creatinine but not with steroid or CsA doses. Increasing age, diabetes mellitus, beta-blockers and nephrotic syndrome contribute to posttransplant hyperlipidemia in the CsA-Pred era as they did in the azathioprine era of immunosuppression.     

Impact of obesity on renal transplant outcomes

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.     

Renal impairment and diabetes mellitus after liver transplant

INTRODUCTION: One of the major concerns in liver transplant patients who survive past 1 year posttransplant is the development of chronic diseases. AIM: We studied two important clinical conditions that can have a chronic course-renal impairment and diabetes mellitus-among long-term liver transplant survivors. METHODS: All adult patients transplanted and followed for at least 1 year were evaluated for clinical status, blood tests, and imaging studies. The occurrence and development of renal impairment, defined as a serum creatinine above 125 micromol/L or creatinine clearance less than 75 mL/min, or diabetes mellitus were evaluated for contributing factors. RESULTS: The 35 evaluated patients of mean age at transplant of 50 years had a mean follow-up duration of 45 months. The incidence of posttransplant renal impairment was 22.8% at 1 year and 47.6% at 3 years. This disorder was associated with pretransplant renal impairment and with a diagnosis of diabetes. Posttransplant diabetes mellitus was observed in 48.6% with 41.1% resolving over time. CONCLUSION: Posttransplant renal impairment appears to be a potential long-term problem. Although this relates to pretransplant conditions, longer follow-up is required to examine whether posttransplant factors contribute to its progression.     

Risk factors for cardiovascular events after successful renal transplantation

BACKGROUND: Cardiovascular disease is a frequent cause of morbidity after renal transplantation. The aims of this study were to evaluate the incidence of cardiovascular events and to identify the main risk factors for cardiovascular complications and mortality in 2071 white adults with a renal transplant functioning for at least 1 year. METHODS: Clinical events, routine biochemistry, and prescribed drugs at month 1, month 6, and yearly after transplantation were analyzed. RESULTS: The incidence of cardiovascular events increased over time. At 15 years after transplantation, only 47% of surviving patients had not experienced any cardiovascular event. Risk factors associated with cardiovascular complications were male gender (P=0.04), age (P<0.0001), arterial hypertension before transplantation (P<0.0001), longer pretransplant dialysis (P<0.0001), cardiovascular event before transplantation (P<0.0001), older era of transplantation (P=0.0009), center-specific effect (P=0.003), posttransplant diabetes mellitus (P=0.01), increased pulse pressure after transplantation (P=0.02), intake of corticosteroids (P=0.016), intake of azathioprine (P=0.016), lower serum albumin after transplantation (P=0.004), and higher serum triglyceride levels after transplantation (P=0.007). The risk of death was increased in patients with low or elevated hematocrit, while it was minimal with values around 38%. CONCLUSIONS: The occurrence of fatal and nonfatal cardiovascular events after successful renal transplantation not only relates to baseline cardiovascular risk factors present at transplantation, but also to immunosuppressive drugs and posttransplantation traditional and nontraditional risk factors.     

Predictors of cardiovascular events and associated mortality of kidney transplant recipients

BACKGROUND: Cardiovascular disease is the most common cause of death after renal transplantation. Furthermore, acute coronary syndrome (ACS) attributable to coronary artery disease (CAD) accounts for the majority of deaths due to cardiovascular disease posttransplant. Although renal transplantation is the treatment of choice for end-stage renal disease, understanding the causes of graft and patient loss is exceedingly important to improve outcomes. METHODS: This observational study included 1200 patients who underwent a kidney transplant between 1988 and 2003. The outcome was the occurrence of an ACS event within a maximum of 15 years after renal transplantation. RESULTS: Of all 215 deaths, 28.3% were caused by complications of CAD, the most common cause of death at our center. On multivariate analysis, diabetes (P = .005), prior transplant (P = .047), body mass index (BMI) at the time of transplant (P = .01), cholesterol level (P = .012), and low-density lipoprotein (LDL) level (P = .007) during 3 years after transplant were associated with early ACS. In conclusion, diabetes, prior transplant, BMI, cholesterol, and LDL were significantly associated with early ACS highlighting the importance of improved screening and perioperative management.     

Metabolic syndrome, insulin resistance, and chronic allograft dysfunction

Metabolic syndrome (MS) is a cluster of cardiovascular (CV) risk factors (hypertension, dyslipidemia, obesity, and glucose homeostasis alterations), and insulin resistance (IR) is suggested to be a common pathogenic background. In the general population, MS and IR have been proven to be risk factors for diabetes, CV disease, and chronic kidney disease. In the renal transplant setting, few studies have analyzed the relevance of MS and IR. According to the few data available, the prevalence of MS in renal transplant patients has been described as 22.6% at 12 months, 37.7% at 36 months, and 64% at 6 years after transplantation. Importantly, MS has been shown to be an independent risk factor for chronic allograft dysfunction (CAD), graft failure, new-onset diabetes, and CV disease. Also, persistent hyperinsulinemia during the first posttransplant year has been related to an increase in glomerular filtration rate, probably reflecting glomerular hyperfiltration as observed in prediabetes and early type 2 diabetes. Importantly, prediabetes (impaired fasting glucose and impaired glucose tolerance), a state hallmarked by IR, proved to be highly frequent among stable renal transplant recipients (30%), which is nearly three times its incidence in the general population. Posttransplant IR has been associated with subclinical atheromatosis as assessed by carotid intima-media thickness, and with chronic subclinical inflammation. In conclusion, MS and IR are important modifiable risk factors in renal transplant recipients, and prompt interventions to avoid its deleterious effects at the metabolic, CV, and graft function levels are needed.     

Posttransplant complications in cardiac transplant recipients at National Cardiovascular Center

We have performed 21 cases of heart transplantation at our institution. We retrospectively reviewed the complications and its incidence in those post transplant course. METHODS: Twenty-one heart transplant recipients (aged at transplant 14 to 61 year old, 16 male and 5 female, observation period: 4 to 99 months) were retrospectively reviewed. Transplant coronary artery disease (TxCAD) was defined as existence of severer than Stanford class IV maximum intimal thickness seen by intra-coronary ultrasound at their annual evaluation. The incidence of hypertension, diabetes, hyperlipidemia, renal dysfunction and malignancy were also reviewed. RESULT: One patient died after 4.3 year posttransplant due to systemic infections. Eight patients (38.1%) developed TxCAD, 4 patients (19%) developed hypertension, 2 patients (9.5%) developed diabetes, 1 patient (4.8%) developed hyperlipidemia. Renal insufficiency defined as serum creatinine level of greater than 1.5 mg/dl was seen in 2 patients (9.5%), however none of them showed severe renal dysfunction such as serum creatinine level of greater than 2.0 mg/dl or requiring dialysis. No malignancy was seen in our patients. Cellular rejection episodes requiring admission for treatment were seen in 3.1% of all biopsies performed. CONCLUSIONS: Survival rate of our cardiac transplant recipients was 95.2% at 8.3 years. TxCADs and renal insufficiency were seen in 38% and 9.5% of our patients respectively, however the incidences of these complications were lower than those in ISHLT 2006 registry. Even in Japan, long-term survivors after cardiac transplantation are increasing. Maintenance of not only the cardiac function but also other organ function is required in post transplant care.     

Bone disease after kidney transplantation

Kidney transplantation is the optimal form of renal replacement therapy for many with end-stage kidney disease. However, kidney transplantation comes with a unique set of medical complications, important among them is bone disease. Posttransplant bone disorders are manifestations of pathologic processes occurring posttransplant that are superimposed on preexisting disorders of bone and mineral metabolism secondary to kidney failure and/or diabetes mellitus. As a consequence of early rapid bone loss, which is seen commonly within the first 3 to 6 months of transplant, the fracture risk posttransplant increases and has been reported as high as 5% to 44%. Posttransplant fractures occur more commonly at peripheral than central sites. Patients with a history of diabetes mellitus are at particular risk for fracture. Parathyroid hormone (PTH) and osteocalcin levels generally decrease after transplantation. Alkaline phosphatase and urinary collagen cross-links are unpredictable. Bone histology varies. No single biomarker unequivocally distinguishes between the various bone disorders found on biopsy examination. Immunosuppression is a major cause of posttransplant bone disorders. Glucocorticoids lead to decreased bone formation whereas the calcineurin inhibitors appear to cause increased bone turnover. Evaluating and managing posttransplant bone disease is an integral part of posttransplant medical care.     

Diabetes mellitus following liver transplantation in patients with hepatitis C virus: risks and consequences

Recurrent hepatitis C virus (HCV) infection of the allograft occurs universally following liver transplantation. Longitudinal natural history studies have identified several pre- and posttransplant factors associated with more rapid fibrosis progression, including baseline host and viral factors, donor factors and posttransplant immunosuppression effects, such as metabolic syndrome. Evidence accumulated over the past two decades indicates that HCV has metabolic associations, in particular insulin resistance and diabetes mellitus. Approximately half of HCV-positive liver transplant recipients develop posttransplant diabetes mellitus (PTDM), which is associated with accelerated fibrosis progression and poorer graft and patient survival outcomes. This review summarizes the risks and consequences of insulin resistance and PTDM in HCV-positive liver transplant recipients. Risk for developing PTDM is one factor that should be considered when choosing the primary immunosuppressive regimen following liver transplantation. Comparative studies suggest that cyclosporine A-based immunosuppression may provide improved responses to antiviral therapy and reduced incidence of PTDM compared with tacrolimus-based immunosuppression. Addressing insulin resistance and PTDM in HCV-positive liver transplant recipients may have the potential to slow HCV complications and improve survival outcomes.