Suphamai Bunnapradist

Fluid retention is associated with cardiovascular mortality in patients undergoing long-term hemodialysis.

Background— Patients with chronic kidney disease (stage 5) who undergo hemodialysis treatment have similarities to heart failure patients in that both populations retain fluid frequently and have excessively high mortality. Volume overload in heart failure is associated with worse outcomes. We hypothesized that in hemodialysis patients, greater interdialytic fluid gain is associated with poor all-cause and cardiovascular survival. Methods and Results— We examined 2-year (July 2001 to June 2003) mortality in 34 107 hemodialysis patients across the United States who had an average weight gain of at least 0.5 kg above their end-dialysis dry weight by the time the subsequent hemodialysis treatment started. The 3-month averaged interdialytic weight gain was divided into 8 categories of 0.5-kg increments (up to ≥4.0 kg). Eighty-six percent of patients gained >1.5 kg between 2 dialysis sessions. In unadjusted analyses, higher weight gain was associated with better nutritional status (higher protein intake, serum albumin, and body mass index) and tended to be linked to greater survival. However, after multivariate adjustment for demographics (case mix) and surrogates of malnutrition-inflammation complex, higher weight-gain increments were associated with increased risk of all-cause and cardiovascular death. The hazard ratios (95% confidence intervals) of cardiovascular death for weight gain <1.0 kg and ≥4.0 kg (compared with 1.5 to 2.0 kg as the reference) were 0.67 (0.58 to 0.76) and 1.25 (1.12 to 1.39), respectively. Conclusions— In hemodialysis patients, greater fluid retention between 2 subsequent hemodialysis treatment sessions is associated with higher risk of all-cause and cardiovascular death. The mechanisms by which fluid retention influences cardiovascular survival in hemodialysis may be similar to those in patients with heart failure and warrant further research.

Intravenous immune globulin treatment inhibits crossmatch positivity and allows for successful transplantation of incompatible organs in living-donor and cadaver recipients.

Background. Sensitization to human leukocyte antigens (HLA) is a significant barrier to transplantation. Currently, no proven therapy exists to improve access to transplantation for highly sensitized patients. Here, we report a novel approach using intravenous immune globulin to modulate anti-HLA antibody and improve the chances for successful transplantation. Patients and methods. Forty-five highly HLA-sensitized patients presented as candidates for living-donor kidney transplantation (n=28), cadaveric kidney transplantation (n=15), or heart transplantation (n=2). All patients had a positive CDC crossmatch (CMX) with their donors. In living-donor recipients, intravenous immune globulin (IVIG) was added to the CMX evaluation to determine whether blocking antibodies present in IVIG could inhibit cytotoxicity. For those who showed in vitro inhibition with IVIG (n=26), IVIG was administered (usually as a single dose, 2 g/kg) and the CDC CMX was repeated against the prospective donor immediately after IVIG infusion. If negative, the patient underwent transplantation with their living-donor kidney within 24 to 72 hr. A similar but modified protocol was performed for cadaver donor candidates, all of whom were highly sensitized and had had CMX positivity with multiple donors, negating transplantation. Reductions in CMX positivity, posttransplantation serum creatinine level, number and severity of rejection episodes, and patient and graft survival rates were determined. Results. Forty-two patients underwent transplantation. IVIG treatment completely abrogated the donor-specific CMXs in 35 of 42 patients. In the remaining 7 patients, the CDC CMX was inhibited, but flow cytometry CMXs remained positive. A total of 13 (31%) of 42 recipients developed rejection episodes 3 to 49 days after transplantation. Three grafts (7%) were lost to rejection. Mean serum creatinine level at 24 months was 1.4±0.4 mg/dL. Patient and graft survival rates were 97.6% and 89.1%, respectively, at 24 months. Conclusions. The in vitro IVIG CMX technique predicts the ability of IVIG to reduce anti-HLA antibody levels in highly sensitized patients. Subsequent in vivo IVIG treatment of responders eliminates the positive CDC CMX and allows for successful transplantation. Thus a positive CMX result is not necessarily a contraindication for transplantation and allows access to transplantation for patients for whom it was previously contraindicated.

Hepatitis C virus antibody status and survival after renal transplantation: Meta-analysis of observational studies

The natural history of hepatitis C virus (HCV) among patients after renal transplantation (RT) remains incompletely defined. We conducted a systematic review of the published medical literature on the impact of hepatitis C antibody status on survival of patients who received RT. We used the random effects model of DerSimonian and Laird to generate a summary estimate of the relative risk (RR) for mortality and graft loss with HCV seropositivity across the published studies.

Post-transplant diabetes mellitus and HCV seropositive status after renal transplantation: Meta-analysis of clinical studies

Hepatitis C virus (HCV) infection has a detrimental role on patient and graft survival after renal transplantation (RT). Some studies have also implicated HCV in the development of post‐transplant diabetes mellitus (PTDM). We conducted a systematic review of the published medical literature of the relationship between anti‐HCV seropositive status and DM after RT. The risk of DM occurrence in anti‐HCV‐positive and ‐negative patients after RT was regarded as the most reliable outcome end‐point. We used the random effects model of DerSimonian and Laird to generate a summary estimate of the Odds Ratio (OD) of new onset DM in HCV‐positive and ‐negative patients after kidney transplantation. Ten studies involving 2502 unique RT recipients were identified. The incidence of PTDM after RT ranged between 7.9% and 50%. The summary estimate for adjusted OR was 3.97 with a 95% confidence interval (CI) of 1.83–8.61 (p‐value for homogeneity <0.0473). Thus, pooling of study results demonstrated the presence of a significant link between anti‐HCV seropositive status and DM after RT. This relationship provides one potential explanation for the adverse effects of HCV on patient and graft survival after RT.

Meta‐analysis: interferon for the treatment of chronic hepatitis C in dialysis patients

Background : The efficacy of interferon monotherapy in dialysis patients with chronic hepatitis C remains unclear, although a number of small clinical trials have been published addressing this issue.

Outcomes of Kidney Transplantation From Older Living Donors to Older Recipients

BACKGROUND More than half the newly wait-listed patients for kidney transplantation in 2005 were older than 50 years, and 13% were older than 65 years. As waiting times for a deceased donor kidney increase, these older candidates are disadvantaged by rapidly deteriorating health, often resulting in death or removal from the wait list before transplantation. STUDY DESIGN An observational cohort study was conducted using data from the Organ Procurement Transplant Network/United Network for Organ Sharing. SETTING & PARTICIPANTS All adult kidney-only transplantations performed in recipients 60 years and older from 1996 to 2005 were included. PREDICTOR The recipient cohort was stratified into 4 groups based on donor source: older living donor (OLD: living donor age > 55 years), younger living donor (YLD: living donor age </= 55 years), standard criteria deceased donor (SCD), and expanded criteria deceased donor (ECD). OUTCOMES & MEASUREMENTS Early posttransplantation outcomes, graft survival, patient survival, renal function 1 year posttransplantation, and relative risk of graft loss and patient death were compared. RESULTS Of 23,754 kidney transplantations performed in recipients 60 years and older, 7,006 were living donor transplantations (1,133 were > 55 years [OLD] and 5,873 were <or= 55 years [YLD]), 12,197 from SCDs, and 4,551 from ECDs. Early posttransplantation outcomes were best in YLD transplantations, followed by SCD and OLD transplantations. OLD transplantations were associated with inferior 3-year graft survival rates (85.7%), but similar 3-year patient survival rates (88.4%) compared with YLD (3-year graft survival, 83.4%; patient survival, 87.4%) and had superior graft survival compared with all deceased donor options. Compared with OLD transplantations, ECD transplantations were associated with a greater risk of graft loss (hazard ratio, 2.36; 95% confidence interval, 1.18 to 4.74). LIMITATIONS Observational retrospective studies using registry data are subject to inherent limitations, including the possibility of selection bias. CONCLUSIONS With superior graft and patient survival in recipients of transplants from OLDs compared with SCDs and ECDs, OLDs may be an important option for elderly transplantation candidates and should be considered for older patients with a willing and suitable older donor.

Mycophenolate mofetil dose reductions and discontinuations after gastrointestinal complications are associated with renal transplant graft failure.

Background. Mycophenolate mofetil (MMF) use in renal transplantation has steadily increased since 1995 because of its ability to lower the risks of rejection and chronic allograft nephropathy. However, significant gastrointestinal (GI) complications may lead to MMF dose reductions and discontinuations. Little is known of the association between MMF dose reductions and discontinuations following GI complications and graft survival. Methods. Using the United States Renal Data System, we identified 3,675 adult recipients (age ≥18) with a diagnosed GI complication who were prescribed MMF at the time of first GI diagnosis and had Medicare as their primary insurer. MMF doses were ascertained from Medicare payment records. We estimated risk of graft loss associated with MMF dose adjustments after GI diagnosis: dosage unchanged (reference), reduced <50%, reduced ≥50%, and MMF discontinued. Patients were followed until graft loss, death, last recorded immunosuppression prescription, or 3 years posttransplant. Results. Compared to those with no MMF dose reductions or discontinuations, the risk of graft failure increased with MMF doses reduction ≥50% (HR=2.36, 95% CI 1.23–4.54) and those with MMF discontinuation (2.72, CI 1.60–4.64). Conclusion. Renal transplant recipients who underwent MMF dose reduction or withdrawal following GI diagnosis are associated with increased risk of graft failure.

Risk factors for development of new-onset diabetes mellitus after kidney transplantation.

Background. New-onset diabetes mellitus after kidney transplantation (NODM) is an important co morbid condition that is associated with inferior graft and patient survival. The objective of this study was to identify donor, recipient and transplant factors, and choices of immunosuppression associated with development of NODM using Organ Procurement Transplant Network/United Network of Organ Sharing database (OPTN/UNOS). Methods. From January 2004 to December 2005, 15,309 adult kidney transplants alone with at least one follow-up report as of March 2006 were identified in the OPTN/UNOS database. Among these, 1,581 patients developed NODM during the follow-up period. We examined the risk factors of NODM using multivariate Cox regression analysis using the time to diagnosis of NODM as a time-varying end point. Other events such as graft loss, patient death, and lost to follow-up were censored. Results. NODM was reported in 10% in our study population with mean follow-up time of 306 days. After adjusting for other known factors, independent factors associated with the development of NODM included recipient age (29% increase of relative risk [RR] for every 10-year age increment), obesity (RR=1.39 for body mass index [BMI] 25–30 and RR=1.85 for BMI>30 vs. BMI<25), tacrolimus use (RR=1.50), hepatitis C virus (HCV) positivity (RR=1.42), and African-American recipients (RR=1.32). Alemtuzumab was associated with a lower risk of NODM (RR=0.52). Discussion. Using OPTN/UNOS database, we identified risk factors for development of NODM. Some of these factors are potentially modifiable, including obesity, HCV infection, and the use of tacrolimus. Clinical trials are needed to assess whether modifying these “modifiable risk factors” will indeed prevent NODM.

Meta-analysis: Effect of hepatitis C virus infection on mortality in dialysis.

Background : The natural history of hepatitis C virus infection among patients on long‐term dialysis treatment remains incompletely understood. Efforts to elucidate the natural history of hepatitis C virus in this population are difficult because of the slowly progressive nature of hepatitis C virus with often an unrecognized onset in patients whose life‐expectancy is substantially diminished by end‐stage renal disease.

A Retrospective Analysis of Immunosuppression Compliance, Dose Reduction and Discontinuation in Kidney Transplant Recipients

We describe factors associated with poor compliance and dose reductions and examine the relative impact of compliance, dose reduction and discontinuation on graft outcome.