Impact of cold ischemia time on the outcomes of kidneys with Kidney Donor Profile Index ≥85%: mate kidney analysis - a retrospective study.

The new kidney allocation system recommends local and regional sharing of deceased donor kidneys (DDK) with 86-100% Kidney Donor Profile Index (KDPI) to minimize discard. Regional sharing can increase cold ischemia time (CIT) which may negatively impact transplant outcomes. Using a same donor mate kidney model, we aimed to define a CIT that should be targeted to optimize outcomes. Using Organ Procurement and Transplant Network/United Network for Organ Sharing database, we identified recipients of DDK from 2000 to 2013 with ≥85% KDPI. From this cohort, three groups of mate kidney recipients were identified based on CIT: group 1 (≥24 vs. ≥12 to <24 h), group 2 (≥24 vs. <12 h), and group 3 (≥12 to <24 vs. <12 h). Adjusted delayed graft function (DGF), and graft and patient survivals were compared for mate kidneys. DGF risk was significantly lower for patients with CIT <12 vs. ≥24 h in group 2 (adjusted OR: 0.25, 95% CI: 0.12-0.57, P < 0.001) while trending lower for CIT ≥12 to <24 vs. ≥24 h in group 1 (adjusted OR: 0.78, 95% CI: 0.59-1.03, P = 0.08) and CIT <12 vs. ≥12 to <24 h in group 3 (adjusted OR: 0.74, 95% CI: 0.55-1.0, P = 0.05). Adjusted graft and patient survivals were similar between mate kidneys in all groups. Minimizing CIT improves outcomes with regional sharing of marginal kidneys.

Changes in the small bowel of symptomatic kidney transplant recipients converted from mycophenolate mofetil to enteric-coated mycophenolate sodium.

BACKGROUND/AIMS: Gastrointestinal (GI) symptoms in renal transplant recipients may be caused due to mycophenolic acid (MPA) toxicity. Using small bowel capsule endoscopy (SBCE) we examined the impact of conversion from Mycophenolate Mofetil (MMF) to enteric-coated formulation of Mycophenolate Sodium (EC-MPS) given to treat GI mucosal lesions. METHODS: Adult kidney-only recipients at least 30 days after transplant, presenting with GI symptoms while receiving MMF completed a Gastrointestinal Symptom Rating Scale (GSRS) questionnaire, underwent SBCE, and had MMF substituted by EC-MPS. After 30 days, GSRS and SBCE were repeated and findings were compared to baseline values. Patients who were still on EC-MPS 6-24 months post-conversion were contacted for completing a follow-up GSRS questionnaire and SBCE. RESULTS: Eighteen out of 23 subjects completed the first part of the study. Subjects' median ages and post-transplant time were 47.5 years old and 4.5 months, respectively. Tacrolimus, MMF and prednisone was the main regimen (94%), with a median MMF dose of 750 mg BID. The average baseline GSRS was 2.99 ± 0.81; it significantly decreased to 2.19 ± 0.8 at 30 days post-conversion. At baseline, 50 had gastric and 89% had small bowel lesions. At 30 days, 29 and 62% of the SBCE were still showing gastric and small bowel lesions, respectively. Of 5 patients in the study extension, 4 had abnormal SBCE findings but have been reporting improvement in their symptoms. CONCLUSION: Stomach and small bowel mucosal lesions are common in kidney recipients with GI symptoms when treated with MMF. Conversion to EC-MPS for 30 days significantly alleviated the GI symptoms; however, no evident correlation with SBCE findings was found.

Induction Therapy and Outcomes following Kidney Transplantation in Recipients of Previous Heart or Liver Transplants.

Introduction: Optimal induction for kidney transplantation in patients with previous nonrenal organ transplantation is unclear. We aimed to evaluate the impact of induction therapy on the outcomes following kidney transplantation in patients who underwent prior heart or liver transplantation. Methods: Using the UNOS database, patients who underwent isolated heart or liver transplant from 2000 to 2016 followed by subsequent kidney transplant and maintained on calcineurin inhibitor (CNI)/mycophenolic acid (MPA) regimen were identified and stratified into three groups according to the induction used for kidney transplant: No induction, induction with interleukin-2 receptor antibody (IL-2RA), or T-cell depleting induction with Thymoglobulin. The outcomes were compared between no induction vs. IL-2RA and T-cell depleting induction, and IL-2RA vs. T-cell depleting induction. Results: Adjusted risk for delayed graft function was significantly higher for T-cell depleting vs. no induction (OR 4.56, 95% CI 1.14-18.3, P = 0.03) and trended higher for IL-2RA vs. no induction (OR 2.96, 95% CI 0.84-10.33, P = 0.08) among kidney after heart group and significantly higher for T-cell depleting vs. no induction (OR 2.88, 95% CI 1.40-5.95, P = 0.004) and IL-2RA induction (OR 1.88, 95% CI 1.12-3.17, P = 0.02) among kidney after liver patients. Adjusted graft failure and patient death risks were similar in patients who got IL-2RA or depleting inductions vs. no induction and IL-2RA vs. depleting induction groups in kidney after heart and kidney after liver groups. Conclusions: The use of induction was not associated with graft or patient survival benefits for kidney transplantation in patients who had prior heart or liver transplants and maintained on CNI and MPA regimen.

Outcomes of renal transplantation in recipients with Wegener's granulomatosis.

Wegener's granulomatosis (WG) is the leading cause of rapidly progressive glomerulonephritis-induced end-stage renal disease (ESRD). In this study, we compared transplant outcomes between recipients with ESRD caused by WG to recipients with ESRD secondary to other causes. Using OPTN/UNOS data from 1996 to 2007, 919 recipients with WG were identified. Post-transplant outcomes included rates of delayed graft function, acute rejection within one-yr post-transplant, overall and death-censored graft survival, and patient survival and were compared between recipients with ESRD secondary to WG versus ESRD from other causes. Recipients with ESRD because of WG had superior unadjusted and adjusted rates of graft loss, patient death, and functional graft loss (adjusted hazard ratio [HR] 0.711, 0.631, and 0.625 respectively, p < 0.001). When we compared the WG cohort to a non-WG, non-diabetic population, the HR for graft loss was still significant, but patient death and death-censored graft loss were not. Subgroup analysis of recipients aged over 60 confirmed that WG recipients had better unadjusted outcomes. This study supports the notion that renal transplantation is an effective treatment option for patients with ESRD secondary to WG. They fare similarly, if not better, than other patients.

Induction therapy in pediatric kidney transplant recipients discharged with a triple drug immunosuppressive regimen.

We evaluated the effectiveness of induction therapy on transplant outcomes during 2004-2007 in the United States. We retrospectively reviewed OPTN/UNOS registry and selected kidney pediatric (<21-yr) recipients that received no induction (NoIND), IL-2RA, or rabbit anti-THY and were discharged with a triple drug immunosuppressive maintenance regimen, including steroids. Of 2932 recipients, 20%, 36%, and 43% were in NoIND, THY, and IL-2RA groups, respectively. The majority received tacrolimus (88%) and MMF (89%) at discharge. There was no association of induction with the risk of acute rejection even after adjusting for known cofounders. Compared to NoIND, IL2-RA, but not THY, had a modest decrease (3%) in absolute rate of graft loss and was associated with a risk reduction ratio of 0.51 (95% CI, 0.31-0.84) in one-yr graft loss. At three yr, no induction agent was associated with decreased graft loss. In conclusion, induction agents were used in 80% of pediatric kidney recipients discharged with a triple drug immunosuppressive maintenance regimen between 2004-2007 in the United States. Neither THY nor IL-2RA was associated with reduced rejection episodes. The use of induction therapy was not associated with improvement in three-yr graft survival.

Chronic obstructive pulmonary disease as a risk factor for suicide: A systematic review and meta-analysis.

BACKGROUND: Patients living with chronic obstructive pulmonary disease (COPD) commonly present several limitations in their daily activities, high depression rates, and low quality of life, which makes this population a risk group for suicide. This study aims to systematically assess the literature on the association between CPOD and the likelihood of suicide. METHODS: The protocol was registered in PROSPERO (CRD42018096618). The Latin-American and Caribbean Health Sciences Literature (LILACS), PubMed, SciELO, Scopus, LIVIVO, Web of Science, and PsychNET databases were used as primary study sources. OpenThesis and OpenGrey were used to partially capture the "grey literature". A manual search was also performed through a systematized analysis of the references of eligible articles. The risk of bias among the studies included was assessed with the Joanna Briggs Institute Critical Appraisal Tools for Systematic Reviews. A random effects meta-analysis was performed to estimate the variation in odds ratio (OR) and 95% confidence intervals (95% CI). RESULTS: The search provided 4762 results, from which only seven met the eligibility criteria and were ultimately included in the qualitative assessment of the review. The studies were published from 2002 to 2015. All studies presented low risk of bias. The total sample included 1390 suicide cases of COPD patients. The meta-analysis, which was based on five eligible case control studies, found that people with history of COPD are more likely to commit suicide (OR = 1.90; 95% CI = 1.27-2.48; p = 0.002). CONCLUSION: COPD patients are 1.9 times more likely to commit suicide than people without COPD.

Depleting Antibody Induction and Kidney Transplant Outcomes: A Paired Kidney Analysis.

BACKGROUND: Induction immunosuppression decreases the risk for acute rejection and improves graft outcomes in kidney transplant recipients (KTRs). We aimed to compare the outcomes of induction with Thymoglobulin and alemtuzumab in KTRs through paired-kidney analysis. METHODS: Using Organ Procurement and Transplantation Network/United Network for Organ Sharing database from 2003 to 2013, we identified recipients of deceased donor kidneys from the same donor in such a way that 1 patient received Thymoglobulin induction and recipient of the mate kidney underwent alemtuzumab induction. All patients were discharged on maintenance immunosuppression with tacrolimus and mycophenolate mofetil with/without steroids. Outcomes were compared between the groups in an adjusted model. RESULTS: Study cohort included 1149 patients each in alemtuzumab and Thymoglobulin groups. Incidence of delayed graft function (25.8% vs 28.6%, P = 0.12), and 1-year rejection (5.7% vs 4.5%, P = 0.97) were similar for alemtuzumab versus Thymoglobulin groups. Adjusted overall graft (hazard ratio, 0.97; 95% confidence interval, 0.82-1.48; P = 0.52) and patient (hazard ratio, 0.86; 95% confidence interval, 0.69-1.05) survivals were also similar for alemtuzumab versus Thymoglobulin groups. Median hospital length of stay was significantly shorter in alemtuzumab group (4 days vs 5 days, P < 0.001). Similar findings were observed in a subgroup of high immune risk patients. There was evidence for clustering of alemtuzumab use within transplant centers which did not impact long-term outcomes. CONCLUSIONS: Depleting antibody induction therapy with alemtuzumab and Thymoglobulin appear equally effective in deceased donor KTRs maintained on tacrolimus/mycophenolate mofetil-based regimen along with steroid. Alemtuzumab induction is beneficial in reducing hospital length of stay.

Renal dysfunction in end-stage liver disease and post-liver transplant.

Renal dysfunction is a frequent complication in patients with end-stage liver disease awaiting orthotopic liver transplantation and in the post-liver transplant period. Although the stereotypical form of renal dysfunction is the hepatorenal syndrome, other causes of acute kidney injury in this population include prerenal azotemia and acute tubular necrosis. Renal injury in a patient with cirrhosis is associated with a poor prognosis.

Renal Transplant Outcomes in Waitlist Candidates with a Previous Inactive Status Due to Being Temporarily Too Sick.

BACKGROUND: In 2003, the United Network for Organ Sharing (UNOS) changed its policy to allow candidates with 'inactive' status to accrue time on the waitlist. In this study, we assessed the transplant outcomes among deceased donor kidney transplant (DDKT) recipients who were temporarily inactive specifically due to medical reason, i.e., being temporarily too sick (reason 7). METHODS: Using the UNOS database, adult DDKT recipients were divided into two groups: those who had never been inactivated (active group) and those with a history of being inactive due to reason 7 (reason 7 group). Patient and graft survival, 3-year risk of death, and graft failure were examined and compared. RESULTS: After 3 years of follow-up, patient survival in the reason 7 group was significantly lower than that of the active group (88.14% versus 91.93%, p < 0.01). The reason 7 group had a 20% increased risk of death (hazard ratio, HR 1.20, confidence interval, CI 1.04 - 1.38), a 16% increase in graft failure (HR 1.16, CI 1.06-1.28), and a 15% decrease in death-censored graft failure (HR 1.15, CI 1.01-1.31). CONCLUSION: Recipients with a history of reason 7 have lower patient and graft survival when compared to the active group. Nonetheless, the margins of difference are minimal. Candidates with a history of reason 7 should not be discouraged from transplantation once they return to active status. Standardized criteria for placing candidates on inactive status should be developed to reduce disparities among transplant centers.

Genetic polymorphisms of the transcription factor NFATc4 and development of new-onset diabetes after transplantation in Hispanic kidney transplant recipients.

Transcription factors of the nuclear factor of activated T cells (NFAT) family regulate both immune activation and insulin production. Calcineurin inhibitors (CNIs) target NFAT activation. Hence, CNIs not only prevent organ transplant rejection but also contribute to the development of new-onset diabetes after transplantation (NODAT). Given individual variation in the susceptibility to NODAT, we hypothesized that polymorphisms in the cytoplasmic NFAT (NFATc)4 gene, which is expressed in pancreatic islets, may be associated with NODAT. Haplotype-tagging single-nucleotide polymorphisms (SNPs) of the NFATc4 gene were genotyped in Hispanic renal transplant patients. Cumulative incidences of NODAT were compared between recipients of different NFATc4 genotypes and haplotypes. The Cox proportional hazard model was used to examine risks for NODAT. Nongenetic and genetic characteristics were included in the multivariate risk model. The SNP (rs10141896) T allele was associated with a lower cumulative incidence of NODAT (P=0.02). This is a tagging SNP for one of the five dominant NFATc4 haplotypes, T-T-T-T-G, and CNI-treated recipients with this haplotype had a reduced adjusted risk for NODAT (hazard ratio: 0.45; 95% confidence interval: 0.19-1.01). Conversely, patients homozygous for the C-C-C-G-G haplotype were at an increased risk (hazard ratio: 2.13; 95% confidence interval: 1.01-4.46) for NODAT in subanalysis. Of the nongenetic factors, use of tacrolimus, sirolimus, and older age were associated with increased risk for NODAT. Polymorphisms in the NFATc4 gene may confer certain protection or predisposition for NODAT.

Association of pretransplant serum phosphorus with posttransplant outcomes.

BACKGROUND AND OBJECTIVES: Serum phosphorus levels are associated with mortality, cardiovascular disease, and renal function loss in individuals with and without chronic kidney disease. The association of pretransplant serum phosphorus levels with transplant outcomes is not clear. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Data of the Scientific Registry of Transplant Recipients (SRTR) up to June 2007 were linked to the database (2001 through 2006) of one of the U.S.-based large dialysis organizations (DaVita). The selected 9384 primary kidney recipients were divided into five groups according to pretransplant serum phosphorus levels (mg/dl): <3.5, 3.5 to <5.5 (reference group), 5.5 to <7.5, 7.5 to <9.5, and ≥9.5. Unadjusted and multivariate adjusted risks for transplant outcomes were compared. RESULTS: Patients were 48 ± 14 years old and included 37% women and 27% African Americans. After multivariate adjustment, all-cause and cardiovascular death hazard ratios were 2.44 (95% confidence interval: 1.28 to 4.65) and 3.63 (1.13 to 11.64), respectively, in recipients in the ≥9.5 group; allograft loss hazard ratios were 1.42 (1.04 to 1.95) and 2.36 (1.33 to 4.17) in recipients with 7.5 to >9.5 and ≥9.5, respectively. No significant association with delayed graft function was found. CONCLUSIONS: Pretransplant phosphorus levels 7.5 to <9.5 mg/dl and ≥9.5 mg/dl were associated with increased risk of functional graft failure and increased risk of all-cause and cardiovascular deaths, respectively, when compared with 3.5 to <5.5 mg/dl. Additional studies are needed to examine whether more aggressive control of pretransplant serum phosphorus may improve posttransplant outcomes.

Intermediate-term outcomes associated with kidney transplantation in recipients 80 years and older: an analysis of the OPTN/UNOS database.

BACKGROUND: An increasing number of patients 80 years and older have received a kidney transplant in the United States, but their outcomes are not well described. Using Organ Procurement and Transplantation Network/United Network of Organ Sharing data, outcomes of recipients 80 years and older were evaluated. METHODS: Thirty-one thousand one hundred seventy-nine elderly recipients defined by age 60 years and older receiving kidney transplants from 2000 to 2008 were stratified: ages 60 to 69 years (n=24,877), 70 to 79 years (n=6,103), and 80 years and older (n=199). Cox regression models were used to compare patient, graft, and death-censored graft survival. RESULTS: The majority of recipients 80 years and older was male (82.9%), white (87.9%), and less likely to have diabetes or coronary artery disease. More expanded criteria donor (ECD) but fewer living donor transplants were performed among 80 years and older compared with those younger than 80 years. Perioperative mortality, defined as death within 30 days posttransplant, was rare (60-69 years: 1.4%; 70-79 years: 1.5%; and ≥80 years: 2.5%) but tended to be higher among those 80 years and older compared with recipients 60 to 69 years (hazard ratio [HR] 1.67; 95% confidence interval [CI] 0.69-4.05). At 2 years, survival was lower for 80 years and older (73%; HR 2.42; 95% CI 1.91-3.06) and 70 to 79 years (86%; HR: 1.42; 95% CI: 1.34-1.51) compared with recipients 60 to 69 years (89%). There was a greater risk of graft loss among recipients 80 years and older compared with those 60 to 69 years (HR 1.78; 95% CI 1.42-2.23); however, no difference in death-censored graft survival was observed (0.89; 0.57-1.39). Among recipients 80 years and older, no difference in survival was observed between standard criteria donor and ECD recipients. CONCLUSION: Although perioperative mortality was uncommon among elderly recipients (1.5%), a trend toward higher perioperative mortality was observed in recipients 80 years and older. There was no difference in survival among standard criteria donor and ECD recipients.

Alemtuzumab versus interleukin-2 receptor antibodies induction in living donor kidney transplantation.

BACKGROUND: Alemtuzumab use has been increasing in kidney transplantation. We aimed to compare posttransplantation outcomes between alemtuzumab and interleukin-2 receptor antibodies (IL-2RA) in living donor kidney transplant recipients in the United States. METHODS: Organ Procurement Transplant Network/United Network of Organ Sharing data, as of August 2007, were used to identify all living donor kidney transplants performed in adults in the United States from 2003 to 2006 where induction therapy with alemtuzumab or IL-2RA (daclizumab or basiliximab) was used. Primary outcomes included incidence of acute rejection, graft survival, and patient survival. RESULTS: One thousand nine hundred thirteen recipients received alemtuzumab and 7011 received IL-2RA. There were few significant differences in baseline characteristics. The incidence of acute rejection at discharge was lower in the alemtuzumab group, when compared with that in the IL-2RA group (0.8% vs. 4.4%, respectively, P<0.001), but it was similar by 1 year posttransplant (9.8% vs. 11%, respectively). After adjusting for confounding factors, those in alemtuzumab group had a higher adjusted relative risk of graft loss (hazard ratios 1.23, 95% CI 1.03-1.48) in 4 years. Patient survival was comparable between the study groups. A higher rate of acute rejection and graft failure was seen in the recipients who used triple regimen (calcineurin-mycophenolate-steroid) in association with alemtuzumab. CONCLUSION: The incidence of acute rejection at discharge was lower with alemtuzumab but was comparable with IL-2RA up to 1 year posttransplant. There was no difference in patient survival, but the risk of graft loss among patients who received alemtuzumab was higher compared with those who received IL-2RA induction.