Pretransplant Diabetes Mellitus Research Articles

Fracture risk and mortality post-kidney transplantation.

Fractures are associated with high morbidity and economic costs. There is a paucity of information on fractures after kidney transplantation outside the United States. Data were obtained from the Hospital Episode Statistics database on kidney transplants performed in England between 2001 and 2013 and post-transplant fracture-related hospitalization. Mortality data were obtained from the Office for National Statistics. In total, 21 769 first kidney transplant procedures were analyzed with 112 512 patient-years follow-up. Overall, 836 (3.8%) kidney allograft recipients developed a fracture requiring hospitalization. Event rate was 9.99 for any fracture and 1.54 for a hip fracture per 1000 patient-years. Accounting for the competing risk of mortality, increasing age, female gender, white ethnicity, and a history of pre-transplant diabetes mellitus or previous fracture were associated with increased fracture risk post-kidney transplantation. Death occurred in 2407 (11.1%) kidney allograft recipients, with 173 deaths occurring post-fracture. In an extended Cox model, hip fracture as a time-varying factor was independently associated with an increased risk of death (hazard ratio, 3.288; 95% confidence intervals, 2.513-4.301; p < 0.001). Fracture rates in English kidney transplant recipients are lower than previously reported in US cohorts. Sustaining a hip fracture is associated with an increased mortality risk. Our results can be used to power future fracture prevention trials.

New onset of diabetes after transplantation is associated with improved patient survival after liver transplantation due to confounding factor

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

Abstract #202: Independent and Additive Prognostic Value of Pretransplant Diabetes Mellitus for Early Cardiovascular Complications after Orthotropic Liver Transplantation

Abstract #202: Independent and Additive Prognostic Value of Pretransplant Diabetes Mellitus for Early Cardiovascular Complications after Orthotropic Liver Transplantation

Clinical Significance of Multidetector Coronary Computed Tomography Angiography to Evaluate the Prevalence and Severity of Coronary Artery Disease in Asymptomatic Kidney Transplantation Recipients

BackgroundCoronary artery disease (CAD) is one of the leading causes of mortality in kidney transplantation (KT) recipients. Noninvasive coronary angiography with the use of multidetector computerized tomography (MDCT) is feasible with high sensitivity and negative predictive value to evaluate CAD. However, few studies have been conducted to elucidate the applicability of MDCT in KT. This study was designed to evaluate the prevalence and severity of CAD with the use of MDCT angiography in asymptomatic KT recipients. MethodsFrom September 2011 to November 2013, MDCT angiography was performed on 90 renal transplant recipients who had no pre-transplantation CAD history and stabilized post-transplantation renal function for 6–18 months. According to the MDCT results, we divided our study population into 2 groups: The no-CAD group (n = 36; 40.0%) and the CAD group (n = 54; 60.0%). Severity of CAD was categorized as follows: mild CAD, 1 vessel obstructive, 2 vessels obstructive (or in the proximal left anterior descending), and 3 vessels obstructive (or left main). ResultsAmong the risk factors, pre-transplantation diabetes mellitus and lower levels of high-density lipoprotein, higher parathyroid hormone levels, higher coronary artery calcification scores, and rejection episodes were independent factors for CAD. Thirty-two (59.3%) of the CAD group had mild obstructive lesions and 22 (40.7%) had obstructive lesions in >1 vessel according to MDCT angiography. ConclusionsMDCT angiography is a useful and noninvasive method for detecting CAD even in asymptomatic KT recipients.

Simultaneous pancreas and kidney transplantation for liver transplant recipients with diabetes and uremia

Chronic kidney disease (CKD) has become a critical problem due to immunosuppressant related nephrotoxicity in liver transplant (LTx) recipients, especially in patients with pre-transplant risk factors. LTx recipients with uraemia and diabetes have poor prognosis even when treated with dialysis and insulin. Simultaneous pancreas and kidney transplantation (SPK) has been proven to be an effective treatment for patients with diabetic uraemia, but rarely performed in patients after LTx. Two cases of SPK after LTx were performed in our centre and we present our experience here. Two patients received LTx because of HBV related liver cirrhosis; both of them had pre-transplant diabetes mellitus (DM), which worsened after the administration of immunosuppressive drugs. These two patients suffered from CKD and developed uraemia due to diabetic nephropathy and immunosuppressive drugs induced renal toxicity years after LTx. They relied on dialysis and insulin injection. SPK were performed years after LTx and the clinical data was retrospectively analyzed. SPK was successfully performed in these two patients. Pancreatic fluid drainage was achieved via a side-to-side duodenojejunostomy into the proximal jejunum. No serious surgical complications, including pancreatitis or pancreatic fistula were observed postoperatively. In both cases, kidney and pancreatic grafts were functioning well as evidenced by euglycemia without the need for insulin injections and normal serum-creatinine level 7days after the operation. One of the patients presented with renal graft impairment 1week after the operation. FK506 was tapered and rapamycin was used when the renal graft biopsy indicated drug toxicity. The patient's kidney graft function recovered gradually after the adjustment. Both patients have good function of liver, kidney and pancreas grafts during a 60-month and 30-month period of follow up. SPK could serve as an effective option for patients with diabetes and uremia after LTx. Perioperative management, especially the immunosuppressive strategy is crucial to improve the outcome of this procedure.

Prevalence and risk factors of obesity, hypertension, dyslipidemia and diabetes mellitus before and after adult living donor liver transplantation.

The development of metabolic abnormalities after liver transplantation (LTx) contributes to cardiovascular events and mortality. We analyzed the prevalence and risk factors of obesity, hypertension, dyslipidemia and diabetes mellitus (DM) after adult living donor liver transplantation. Fifty-four adult recipients with a minimum follow up of 6 months receiving living donor liver transplantation between 2001 and 2012 at the Tohoku University Hospital were retrospectively analyzed. The prevalence of hypertension increased from 18.5% before transplantation to 35.2% post-transplantation, and new-onset hypertension after transplantation was 57.9% of post-transplant hypertension. Univariate analysis showed that risk factors of post-transplant hypertension were age (>50 years, P = 0.0023), pretransplant body mass index (BMI) of 25 or more (P = 0.0123), pretransplant hypertension (P = 0.0012) and cyclosporin A (61.5% vs tacrolimus 25.0%, P = 0.0248). The incidence of obesity, dyslipidemia and DM did not change from before to after transplantation. LTx was curative in 77.8% of cases of pretransplant dyslipidemia and 20% of cases of pretransplant DM. Primary biliary cirrhosis cases comprised 85.7% of cases of pretransplant dyslipidemia that were cured by LTx. In univariate analysis, pretransplant BMI of 25 or more was the only risk factor of post-transplant dyslipidemia (P = 0.0098). The incidence of new-onset DM after transplantation was 20%. Risk factors of post-transplant DM were male sex (P = 0.0156), pretransplant DM (P < 0.0001), alcohol abuse (P = 0.0248) and mycophenolate mofetil (P = 0.0181) by univariate analysis. The prevalence of hypertension increased after LTx and pretransplant obesity was associated with several post-transplant metabolic abnormalities.

Evolution of Coronary Artery Calcification in Renal Transplant Recipients.

Introduction Cardiovascular diseases are common complications in renal transplant (RTx) recipients. Coronary artery calcification (CAC) is a hallmark of CVD. The current study aimed to elucidate the evolution and determinants of CAC in renal transplant recipients. Methods RTx recipients were randomly selected for a 3-year prospective study. CAC score (CACS) was measured by MDCT scan. Patients were stratified into progressors and nonprogressors according to the definition proposed by Sevrukov et al, 2005. Results A total of 157 RTx patients were enrolled. At initiation, 47.8% had negligible CACS while 12.4% had CACS>1000. A higher CACS was associated with age (p=0.001), pretransplant diabetes mellitus (p=0.017), waist circumference (p=0.014) and body weight (p=0.037). A follow-up MDCT scan was available in 101 cases at 2 years. CAC was progressed in 23.8% and regressed in 7.9% patients. Progressors had significantly higher basal serum creatinine (1.74±0.66 vs 1.40±0.49 mg/dl, p=0.007), more hypertension (84.0% vs 66.4%, p=0.066) and diabetes mellitus (33.3% vs 18.1%, p=0.095). Multivariate regression analysis revealed that serum creatinine was the only predictor of CAC progression. Conclusion The majority of CAC in RTx recipients could be stabilized in a 2-year follow-up and, in a small proportion, CAC even regressed.

The Impact of Pretransplant Diabetes Mellitus, New-Onset Diabetes Mellitus After Transplant, and Acute Rejection On Kidney Transplant Outcomes.

The Impact of Pretransplant Diabetes Mellitus, New-Onset Diabetes Mellitus After Transplant, and Acute Rejection On Kidney Transplant Outcomes.

Risk Factors for Development of New-Onset Diabetes Mellitus and Progressive Impairment of Glucose Metabolism After Living-Donor Liver Transplantation

BackgroundNew-onset diabetes mellitus (NODM) has a negative impact on graft and patient survivals. Hepatitis C virus (HCV) infection, high body mass index, increased donor and recipient ages, and calcineurin inhibitor (CNI) type have been identified as risk factors for the development of NODM. We aimed to elucidate the risk factors for the development of NODM and those for progressive glucose intolerance in adult living-donor liver transplant (LDLT) recipients. MethodsWe collected data from 188 primary liver transplant recipients (age > 16 years) who underwent LDLT from June 1991 to December 2011 at Hiroshima University Hospital. Risk factors for NODM and progressive impairment of glucose metabolism in pre-transplantation diabetes mellitus (DM) recipients were examined. ResultsPre-transplantation DM was diagnosed in 32 recipients (19.3%). The overall incidence of NODM was 6.0% (8/134 recipients). Multivariate analysis revealed that old recipient age (≥55 years) is a unique predictive risk factor for developing NODM. The incident of pre-transplantation DM was significantly higher in recipients with HCV infection than in those without HCV. A high pre-transplantation triglyceride level was an independent risk factor for progressive impairment of glucose tolerance among 32 LDLT recipients with pre-transplantation DM. All of the NODM patients were being treated with tacrolimus at the time of diagnosis. Switching the CNI from tacrolimus to cyclosporine allowed one-half of the patients (4/8) to withdraw from insulin-dependent therapy. NODM and post-transplantation glucose intolerance had no negative impact on patient and graft outcomes. ConclusionsOlder age of the recipient (≥55 years) was a significant risk factor for NODM. Hypertriglyceridemia in the recipients with DM is an independent risk factor for post-transplantation progressive impairment of glucose metabolism. NODM had no negative impact on outcomes in the LDLT recipients.

(818) - Prevalence and Predictors of Diabetes After Lung Transplantation

Diabetes mellitus (DM) is common following lung transplantation (LTx) and is an independent risk factor for mortality. No studies to date have definitively established pre-transplant DM status using oral glucose tolerance tests (OGTT) and then prospectively determined the prevalence of post Tx DM at pre-specified time points. Identifying risk factors for persistent DM following LTx would help target patients requiring more intensive follow up.

Diagnosing hepatitis C virus and improved outcomes in overall and kidney graft survival among simultaneous liver-kidney transplant recipients in the post-MELD era.

We compared survival outcomes among simultaneous liver-kidney transplants after model for end-stage liver disease (MELD) according to their specific diagnosis and hepatitis C virus versus nonhepatitis C virus. Clinical data review was performed for all patients who underwent combined liver-kidney transplants at Johns Hopkins Hospital from January 31, 1995, to October 31, 2012. Differences in demographics and characteristics among 2 groups were compared using independent samples t test. Survival analysis and distributions were calculated using Kaplan-Meier and Mantel-Cox log-rank test. Of 48 combined liver-kidney transplants, 31 simultaneous liver-kidney transplants cases were included; nonsimultaneous liver-kidney transplants and patients with prior transplants were excluded. Proportions of age, sex, ethnicity, pre-MELD score, pretransplant renal replacement therapy requirement, hypertension, diabetes mellitus, and follow-up were similar in both groups. Median follow-up was 30 months. Overall and graft survival rates among simultaneous liver-kidney transplants recipients in the pre-MELD era were significantly superior to simultaneous liver-kidney transplants patients in the post-MELD era (P = .0473). However, overall and graft survival rates among simultaneous liver-kidney transplants recipients who had hepatitis C virus and non-hepatitis C virus causes were not statistically different. We demonstrated a statistically significant difference in overall and kidney graft survival between the post-MELD era and the pre-MELD era. Subgroup analyses of this group showed no statistically significant difference in overall and kidney-graft survival when compared with their specific diagnosis of hepatitis C virus. This must be further studied and verified in a larger cohort of patients to fully identify the effect of hepatitis C virus infection in this group of patients because it can affect both liver and kidney grafts after transplant.

Association Between 276G/T Adiponectin Gene Polymorphism and New-Onset Diabetes After Kidney Transplantation

New-onset diabetes after transplantation (NODAT) is a well-recognized complication of kidney transplantation and is associated with poor outcomes. Both adiponectin and chemokine ligand 5 (CCL5) proteins are related to glucose metabolism and genetic variations in their genes can lead to development of NODAT. The aim of this study was to investigate the association of adiponectin and CCL5 genes polymorphisms with NODAT in a population of Caucasian kidney transplant recipients. Two hundred seventy Caucasian kidney transplant recipients (83 with NODAT and 187 without NODAT) were included in a nested case-control study. Patients with pretransplantation diabetes mellitus and multiorgan transplantation were excluded. NODAT diagnosis was determined by American Diabetes Association criteria. Subjects were genotyped for 276G/T adiponectin gene polymorphism (rs1501299) and rs2280789 and rs3817655 CCL5 gene polymorphisms by real-time polymerase chain reaction. The TT genotype of 276G/T adiponectin gene polymorphism was significantly more frequent in NODAT than non-NODAT patients compared with GG/GT genotypes (recessive model; P=0.031). TT genotype was identified as an independent risk factor for NODAT in Caucasian kidney transplant recipients after adjusting for age at transplantation, pretransplantation body mass index, and use of tacrolimus (TT vs. GG/GT, hazard ratio=1.88, 95% confidence interval=1.03-3.45, P=0.041). There were no differences in genotype distribution and allele frequency of rs2280789 and rs3817655 CCL5 gene polymorphisms between NODAT and non-NODAT groups. The 276G/T adiponectin gene polymorphism is associated with NODAT in Caucasian kidney transplant recipients.

Preoperative left ventricular hypertrophy is associated with reduced patient survival after liver transplantation

Left ventricular hypertrophy (LVH) has been described in the context of cirrhotic cardiomyopathy. The influence of LVH on survival of liver transplant (LT) recipients has not been clarified. Therefore, we evaluated the effect of LVH on survival in LT recipients. In total, data from 352 LT patients were analyzed. LVH was diagnosed by echocardiographic measurement of left ventricular wall thickness before LT. Patients were followed up for a mean of 4.2 yr. LVH was diagnosed in 135 (38.4%) patients. Patients with LVH had significantly more frequently male gender (p = 0.046), diastolic dysfunction (p < 0.001), and hepatocellular carcinoma (HCC; p = 0.004). Furthermore, LVH patients were older (p < 0.001) and had a higher body mass index (BMI; p = 0.001). There was no difference in frequency of arterial hypertension, pre-transplant diabetes mellitus, or etiology of liver cirrhosis. Patients without LVH had a better survival (log rank: p = 0.05) compared with LVH patients. In a multivariate Cox regression LVH (p = 0.031), end-stage renal disease (ESRD; p = 0.003) and lack of arterial hypertension (p = 0.004) but not MELD score (p = 0.885) were associated with poorer survival. LVH is frequently diagnosed in patients on the waiting list and influences survival after LT.

Infection-related mortality is higher for kidney allograft recipients with pretransplant diabetes mellitus

The risk of infection-related mortality in kidney allograft recipients with pre-existing diabetes mellitus is unknown. We determined the risk of infection-related mortality after kidney transplantation in a population-based cohort stratified by diagnosis of pre-existing diabetes mellitus. We linked data between two national registries (Hospital Episode Statistics and the Office for National Statistics) to select all mortality events after kidney transplantation in England between April 2001 and March 2012. The primary outcome measure was infection-related mortality after transplantation comparing diabetic with non-diabetic recipients. A total of 19,103 kidney allograft recipients were analysed; 2,968 (15.5%) were known to have diabetes before kidney transplantation. After transplantation, 2,085 deaths (10.9%) occurred (median follow-up 4.4 years [interquartile range 2.2-7.3]), with 434 classified as secondary to infection (20.8% of all deaths). Risk of overall (16.0% vs 10.0%, p < 0.001) and infection-related (3.3% vs 2.1%, p < 0.001) mortality after kidney transplantation was higher for diabetic than non-diabetic recipients, respectively. No cytomegalovirus-related deaths occurred in diabetic recipients compared with 5.7% in non-diabetic recipients (p < 0.007), with a trend towards more unspecified sepsis in diabetic recipients (30.6% vs 22.6%, respectively, p = 0.070). Diabetes at the time of transplantation was an independent risk factor predicting infection-related mortality in kidney allograft recipients after transplantation (HR 1.71 [95% CI 1.36, 2.15], p < 0.001). Infection-related mortality is more common in kidney allograft recipients with pre-existing diabetes mellitus. Further work is required to determine whether attenuated immunosuppression is beneficial for diabetic kidney allograft recipients.

621 Treatment of HCV Recurrence After Liver Transplant: A Review of Early Virologic Responses Using Telaprevir, A Single Center Experience of 24 Patients

two groups were compared using independent-samples t-test. Survival analysis and the distributions were calculated using Kaplan-Meier method and Mantel-Cox log-rank test. Results: Out of total 43 combined liver-kidney transplants, 30 SLK cases (24 post-MELD and 6 pre-MELD) were included. Proportions of age, gender, ethnicity, pre-transplant MELD score; pre-transplant renal replacement therapy requirement, hypertension, diabetes mellitus and follow-up period were similar in two groups. Median follow up period was 30 months. Both overall and kidney-graft survival in pre-MELD era were 50%, but improved to 91.7% in post-MELD era (p=0.02). When compared according to HCV diagnosis, there was no statistical significance in overall and kidney-graft survival between 9 HCV and 15 non-HCV groups in post-MELD era (p=0.67 and p=0.4, respectively). Conclusion: Literature suggests lower risk of liver graft loss in SLK compared to LTA, but not much information is available regarding the specific diagnosis of the underlying liver disease, HCV vs non-HCV.Our study demonstrated that overall and kidney graft survival has significantly improved post-MELD as compared to pre-MELD era. Additionally, our study showed that there was no statistical difference in overall and kidney-graft survival between HCV and non-HCV groups. This observation needs to be further studied and verified in larger cohort to fully identify the impact of Hepatitis C infection on liver and kidney grafts, post transplantation.

A Canadian national retrospective chart review comparing the long term effect of cyclosporine vs. tacrolimus on clinical outcomes in patients with post-liver transplantation hepatitis C virus infection

The transition from regular use of cyclosporine to the newer calcineurin-inhibitors, such as tacrolimus, has been suggested as a contributing factor to the “era effect” of worsening outcomes of post-transplant HCV recurrence. This retrospective medical chart review of 458 patients was undertaken to evaluate the role of immunosuppressant choice (cyclosporine vs. tacrolimus) in determining virologic response and clinical outcomes of post-liver transplant HCV infection recurrence. Our results showed that patients undergoing interferon-based treatment taking cyclosporine have significantly better odds (OR: 2.59, P = 0.043) of presenting a sustained viral response (66.7%) compared to tacrolimus (52.8%). This did not result in a significant effect on post-liver transplantation clinical events including HCV-related deaths, graft loss, fibrosing cholestatic hepatitis, hepatocellular carcinoma or graft rejection. Other variables, which showed a significant relationship with the achievement of sustained viral response included donor age (OR 0.96, P = 0.001) and HCV genotype 1 infection (OR 0.05, P < 0.001). The observed significant increase in the odds of acute/hyperacute (OR 6.49, P = 0.001) and chronic rejection (OR 10.45, P < 0.001) in the cyclosporine to tacrolimus switch group, accompanied by an increase in the odds of HCV-related death (OR 2.30, P < 0.047) compared to tacrolimus merits further study. A significant increase (P < 0.044) in new-onset diabetes mellitus with tacrolimus (28.3%) compared to cyclosporine (18.7%) was also observed. Pre-transplant diabetes mellitus was associated with a significantly increased likelihood of graft fibrosis (HR 1.95, P = 0.003).

Patients with Persistent New-Onset Diabetes after Transplantation Have Greater Weight Gain after Kidney Transplantation

The purpose of the present study was to evaluate the difference in BMI pattern between patients with persistent new-onset diabetes after transplantation (P-NODAT) and without new-onset diabetes after transplantation (N-NODAT) in a retrospective matched case-control (1:3) analysis. Thirty-six patients who developed P-NODAT were identified among 186 adult renal transplant recipients with no evidence of pretransplant diabetes mellitus who underwent kidney transplantation from September 1997 to March 2008 and were treated with a triple regimen including tacrolimus. The controls were selected to match the patients for pretransplant BMI, age at transplantation (± 5 yr), and date of transplantation (± 12 months). Finally, 20 P-NODAT patients and 60 N-NODAT patients were selected. The pre- and posttransplant BMI data were collected every 16 weeks for up to 80 weeks. The clinical characteristics did not differ between the P-NODAT group and N-NODAT group. BMI increased faster in the P-NODAT group than in the N-NODAT group. The mixed-model analysis showed that patients with P-NODAT exhibited a faster increase in BMI. P-NODAT is associated with posttransplant weight gain. The risk of P-NODAT should be considered in patients with rapid weight gain after transplantation.

An unexpectedly high prevalence of undiagnosed diabetes in patients awaiting lung transplantation

Diabetes mellitus (DM) is a common complication after lung transplantation but its prevalence prior to transplantation has not been determined. We sought to determine the prevalence of and risk factors for DM in adults awaiting lung transplantation and to determine whether pre-transplant DM could be diagnosed by hemoglobin A1c (HbA1c) alone. All patients wait-listed for lung transplantation over a 2-year period had HbA1c measured. Those not known to have DM also underwent an oral glucose tolerance test (OGTT) with insulin levels. Of 190 patients listed for lung transplantation, 30 (16%) had been diagnosed previously with DM. Twelve patients received transplants and 1 came off the waiting list before having an OGTT. The remaining patients underwent OGTT: 14 were newly diagnosed with DM and 29 with pre-diabetes. One patient vomited during the test and was excluded from analyses. Thus, 41% of all screened waiting list patients had DM (known or newly diagnosed) or pre-diabetes. Neither age, BMI, prednisolone dose nor family history correlated with dysglycemia. Patients with newly diagnosed DM and pre-diabetes were more insulin-resistant than those with normoglycemia. HbA(1c) correlated poorly with OGTT. Patients awaiting lung transplantation have unexpectedly high rates of DM and pre-diabetes despite close medical follow-up. Screening for DM with an OGTT will allow early intervention, which may improve outcomes after transplantation.

Medication Errors and Adverse Drug Events in Kidney Transplant Recipients: Incidence, Risk Factors, and Clinical Outcomes

To determine the incidence, risk factors, and clinical outcomes associated with clinically significant medication errors or adverse drug events in kidney transplant recipients. Retrospective observational study. Transplant center at an academic medical center. A total of 476 adults who received kidney transplants between June 2006 and July 2009. Severe or significant medication errors and adverse drug events (medication-related problems [MRPs]) were identified by medical record review. Only patient-induced medication errors (e.g., took wrong dose or frequency of drug, took drug not prescribed) were captured. Clinical outcomes included patient and graft survival, infections (including cytomegalovirus), readmissions, and acute rejection episodes. Thirty-seven (8%) of the 476 patients developed a clinically significant MRP. Univariate and confirmatory multivariate analyses revealed that female sex, African-American race, pretransplantation diabetes mellitus, delayed graft function, and retransplant recipients were independent risk factors for developing an MRP. Patients with MRPs had significantly higher rates of acute rejection (11% vs 30%, p=0.004), cytomegalovirus infection (15% vs 30%, p=0.033), and 30-day readmissions (5% vs 16%, p=0.018). Graft survival was also significantly lower in patients who had MRPs (p<0.001). Patient-induced medication errors and associated adverse drug events were common in kidney transplant recipients. General and transplant-specific risk factors were associated with the development of these MRPs, and MRPs were associated with increased risk of rejection and graft loss.

Is the Diagnosis of HCV a Predisposing Factor in Simultaneous Liver Kidney Transplant Compared to Kidney after Liver Transplantation?

Purpose: The number of simultaneous liver-kidney transplants (SLK) has increased in the U.S. since the United Network for Organ Sharing (UNOS) implemented MELD score in regulating liver and kidney graft allocation in 2002. Recently, unfavorable outcomes of SLK have been reported with predisposing factors such as HCV infection and delayed kidney graft function. However, initial studies have shown that survival in SLK is greater than that of liver transplant alone. There is no study, to date, which compares the survival between SLK and KALT (kidney after liver transplantation). Our study is aimed to compare the survival among SLK and KALT patients with HCV infection. Methods: In this IRB-approved retrospective study, clinical data review was performed in all patients who underwent combined liver-kidney (CLK) transplants at Johns Hopkins Hospital from January 1, 1993 to January 1, 2012. Total 43 (6 KALT and 37 SLK) patients were identified. Non-HCV cases and cases with prior liver/kidney transplants were excluded. 4 KALT cases with HCV infection were included in the study after exclusion of 2 cases with prior liver/kidney transplants. Similarly, 10 SLK patients with HCV infection were included after exclusion of 22 non-HCV cases and 5 cases with prior liver/kidney transplants. Results: Proportions of age, gender, ethnicity, MELD score, pre-transplant renal replacement therapy (RRT) requirement, hypertension, diabetes mellitus and follow-up period were similar in two groups. Median follow-up period was 26 months (range 6 months-228 months). While 25% of HCV patients with KALT had RRT prior to their kidney transplantation, the percentage of prior RRT was 50% in HCV SLK group. 1-year overall survival in KALT and SLK group were 75% and 90%, respectively (p=0.595). 1-year kidney graft survival among two groups was also the same as overall survival. Conclusion: Studies have shown that recurrent HCV within 1 year after SLK correlated with early kidney graft failure. In our limited observation, no statistical significance was noted when 1-year patient and graft survival were compared according to the timing of kidney transplantation, simultaneous versus following liver transplantation. Since viral replication is anticipated to be increased in the presence of heightened immunosuppression following kidney transplant, one can predict that with KALT, increased viral replication can cause more graft dysfunction both in liver and kidney grafts. This preliminary study suggests no viral advantage of SLK to KALT and needs to be verified with further studies in larger cohort of patients.