Hypertension and obesity in living kidney donors.

Over the past few decades, the shortage in the kidney donor pool as compared to the increasing number of candidates on the kidney transplant waitlist led to loosening of kidney donors' acceptance criteria. Hypertension and obesity represent risk factors for chronic kidney disease, both in native kidneys and those in kidney transplant recipients. While great progress has been made in kidney transplantation from living donors to benefit the recipient survival and quality of life, progress has been slow to fully risk-characterize the donors. This review critically reassesses the current state of understanding regarding the risk of end-stage kidney disease in those donors with obesity, hypertension or both. Accurate risk assessment tools need to be developed urgently to fully understand the risk glomerular filtration rate compensation failure in the remaining kidney of the donors.

Clinical Outcomes of Older Kidney Transplant Recipients.

BACKGROUND: Older kidney transplant recipients (OKTR) are vulnerable to infections and AKI, often prompting hospitalization. This study elucidates etiology of hospitalizations, AKI, and outcomes in OKTR. METHODS: Retrospective study of 500 patients age ≥ 60, who underwent kidney transplantation from 2005-2015. Demographic, transplant, and outcomes data were collected. RESULTS: OKTR had mean age 66 years; 59% males and 50% African Americans. 62% had at least one hospitalization post-transplant. Predictors of hospitalization were DGF, DM, panel reactive antibodies (PRA), dialysis duration. Hospitalization was mostly due to infection and surgical complications. Average length of stay was 6.4 days. OKTR with at least one hospitalization had 84% higher risk for graft loss (p=0.001). 56% of older kidney transplant recipients had at least one AKI episode post-transplant. Predictors of AKI included DGF, older, African American donor, and tacrolimus variability. The most common etiologies for AKI were infection, dehydration, and GI complications. OKTR with at least one AKI episode had 2.6-fold higher risk for graft loss (p<0.001). CONCLUSIONS: Post-transplant hospitalization and AKI in OKTR significantly impact graft survival. Addressing comorbidities and risks in the pre-transplant and outpatient setting may help alleviate burden of hospitalization and risk of AKI in OKTR and improve graft outcomes.

Immunosuppression in kidney transplant recipients with COVID-19 infection - where do we stand and where are we heading?

The appropriate immunosuppressive regimen in kidney transplant recipients with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2/COVID-19) infection remains unclear. The impact of direct virus injury complicated by dysregulated hyperimmune response with overwhelming release of various cytokines in COVID-19 infected subjects contributes to the complexity of management. The largest concern of the practicing clinicians at current time is how to tailor maintenance immune-modulating therapy during active viral infection and the efficacy of the soon-to-be upcoming immunization for COVID-19. This targeted review aims to cover most of the current evidence on the effect of key maintenance immunosuppressive agents in COVID-19 infection and proposes a line of management to specific scenarios on this very rapidly evolving subject.

Preliminary assessment of safety and adherence to a once-daily immunosuppression regimen in kidney transplantation: Results of a randomized controlled pilot study.

Medication non-adherence is common after transplant and a major contributor to graft loss. The objective of this pilot study was to obtain preliminary safety and adherence data of a complete once-daily immunosuppression regimen of Extended-release-tacrolimus (LCP-tac), everolimus, and prednisone vs LCP-tac, mycophenolate Twice daily (BID), and prednisone through a randomized controlled pilot study of 40 patients (20 in each arm). At 3 ± 2 months post-transplant, patients were randomized to receive LCP-tac and everolimus once daily or LCP-tac and mycophenolate BID (control arm) for 6 months; 80 met eligibility, and 40 were randomized. Mean age was 51 ± 14 years, 33% were female, 45% African American, and 55% had a Calculated panel reactive antibody (cPRA) >20%. Both regimens were well-tolerated, and medication side effect burden tended to be less severe in the intervention group. Self-reported high medication adherence decreased in the control arm from baseline to 6 months (80%-59%), while remaining the same in the intervention arm throughout the study (45%-47%). For safety assessment, there was no rejection, graft loss, or death in either arm. These results provide preliminary evidence of the safety of a novel once-daily immunosuppression regimen. The impact of this once-daily regimen on medication adherence requires a larger long-term study.

Protocol-based nurse coordinator management of ambulatory tacrolimus dosing in de novo renal transplant recipients-A single-center experience with a large African American population.

INTRODUCTION: Transplant nurse (RN) coordinators review tacrolimus levels frequently and would be capable of making dose adjustments autonomously if not limited by their license. Collaborative practice agreements could be an answer; thus, the aim of this evaluation was to determine if an RN-driven protocol could be used safely and effectively to manage tacrolimus in ambulatory kidney transplant (KTX) recipients. METHODS: This was a retrospective review of all solitary adult KTX recipients between August 1, 2016, and July 29, 2017. The primary objective was to evaluate protocol adherence and frequency of use, and secondary objectives were to evaluate the utility of the protocol both overall and based on ethnicity. RESULTS: A total of 173 patients were included in the evaluation (59% African American [AA], 41% non-African American [non-AA). RN coordinators followed the protocol for 75% of tacrolimus adjustments; however, they only responded to 27% of the overall levels. There was no difference in 180-day tacrolimus-associated readmission (15% AA vs 5% non-AA, P = .06), biopsy-proven acute rejection (4% AA vs 7% non-AA, P = .363), or hyperkalemia (34% AA vs 32% non-AA, P = .87) between groups. CONCLUSIONS: Transplant nurse coordinators are capable of accurately following a protocol for tacrolimus dosage adjustment in a large, racially diverse kidney transplant center.

Development and future deployment of a 5 years allograft survival model for kidney transplantation.

AIM: Identifying kidney transplant patients at highest risk for graft loss prior to loss may allow for effective interventions to improve 5 years survival. METHODS: We performed a 10 years retrospective cohort study of adult kidney transplant recipients (n = 1747). We acquired data from electronic health records, United Network of Organ Sharing, social determinants of health, natural language processing data extraction, and real-time capture of dynamically evolving clinical data obtained within 1 year of transplant; from which we developed a 5 years graft survival model. RESULTS: Total of 1439 met eligibility; 265 (18.4%) of them experienced graft loss by 5 years. Graft loss patients were characterized by: older age, being African-American, diabetic, unemployed, smokers, having marginal donor kidneys and cardiovascular comorbidities. Predictive dynamic variables included: low mean blood pressure, higher pulse pressures, higher heart rate, anaemia, lower estimated glomerular filtration rate peak, increased tacrolimus variability, rejection and readmissions. This Big Data analysis generated a 5 years graft loss model with an 82% predictive capacity, versus 66% using baseline United Network of Organ Sharing data alone. CONCLUSION: Our analysis yielded a 5 years graft loss model demonstrating superior predictive capacity compared with United Network of Organ Sharing data alone, allowing post-transplant individualized risk-assessed care prior to transitioning back to community care.

Renal Function Variability: An Independent Risk Factor for Graft Loss and Death following Kidney Transplantation.

BACKGROUND: Several studies have been performed to evaluate surrogate markers of long-term allograft function in renal transplant recipients. These include serum creatinine, estimated glomerular filtration rate (eGFR), slope of eGFR, and more recently eGFR variability. The aim of this study was to measure eGFR slope while assessing the variability of this slope and if high variability occurring at any time post-transplant was predictive of poorer long-term outcomes in a large cohort of kidney transplant recipients. METHODS: Adult solitary kidney transplant recipients transplanted between July 1, 2005 and July 31, 2015 were included. The primary outcome was time to graft loss, defined as return to chronic dialysis, retransplant, or death. Secondary outcomes were death-censored graft loss and acute allograft rejection. Cox regression was utilized for primary and secondary outcomes. Multivariate logistic regression was used to determine baseline factors predictive of high eGFR variability. RESULTS: A total of 1,543 patients were included in the analysis. The percentage of patients who experienced an eGFR coefficient of variation of <30% was 79.6% (1,229/1,543), while 20.4% (314/1,543) patients had high eGFR variability (≥30%). Patients with high eGFR variability tended to be younger, African-American and female. Those with higher eGFR variability, accounting for confounding and other eGFR measures (peak and slope), had significantly lower overall patient and graft survival. CONCLUSION: This study provides a novel analysis of the utility of eGFR variability in a large cohort. The clinical use of the slope of eGFR and eGFR variability may aid in predicting long-term graft outcomes and facilitate early patient discussions to change the trajectory of allograft function.

Belatacept conversion in African American kidney transplant recipients with severe renal dysfunction.

OBJECTIVES: Conversion from calcineurin inhibitor-based maintenance immunosuppression to belatacept in kidney transplant recipients has been demonstrated to improve renal function while maintaining efficacy against rejection. However, conversion studies to date have excluded patients with an estimated glomerular filtration rate < 35 mL/min/1.73 m2. METHODS: We describe two patients with an estimated glomerular filtration rate < 30 mL/min/1.73 m2 who underwent conversion from maintenance calcineurin inhibitor to belatacept. RESULTS: Both patients experienced improvement in renal function following conversion. CONCLUSIONS: These results suggest that patients with more severe degrees of allograft impairment may benefit from conversion of maintenance calcineurin inhibitor to belatacept-based immunosuppression. Larger, randomized studies are warranted to evaluate the impact of such an approach.

The benefit of sirolimus maintenance immunosuppression and rabbit antithymocyte globulin induction in liver transplant recipients that develop acute kidney injury in the early postoperative period.

Published data are limited describing renal outcomes in orthotopic liver transplant (OLT) recipients prescribed sirolimus (SRL) maintenance immunosuppression (MIS) and rabbit antithymocyte globulin (rATG) induction. We investigated whether SRL MIS and rATG induction facilitated recovery of acute kidney injury in the early postoperative period. This retrospective descriptive study screened 308 consecutive OLTs performed between 2006 and 2009. All patients received rATG induction with steroid avoidance. MIS consisted of SRL or TAC with mycophenolate mofetil. A total of 197 patients were included: 168 (85%) received TAC and 29 (15%) received SRL for a median of 365 days. Demographics were similar between groups except for a higher incidence of pretransplant renal dysfunction in the SRL recipients (SRL 59% versus TAC 21%; P < 0.05). The eGFR was significantly (P < 0.05) higher for all time points in the TAC group with the exception of month 2. However, improvement in eGFR was significantly (P < 0.05) greater in the SRL group postoperatively. Our study suggests that rATG induction and SRL maintenance immunosuppression facilitate renal recovery for liver transplant recipients that develop acute kidney injury in the early postoperative period.

Improved detection of hepatitis C virus infection by transcription-mediated amplification technology in dialysis population.

BACKGROUND: Hepatitis C virus (HCV) infection remains common among patients undergoing maintenance dialysis and plays an adverse effect on survival in this population. Accurate detection of HCV viremia (HCV RNA) in dialysis patients requires a sensitive and specific diagnostic test. METHODS: The Versant HCV RNA Qualitative Assay, based on transcription-mediated amplification (TMA) technique, was prospectively evaluated in 112 dialysis patients. Performance characteristics of the Versant HCV TMA Assay were evaluated in comparison to the Amplicor((R)) 2.0 HCV test based on polymerase chain reaction (PCR) technique. In addition, anti-HCV serologic tests including third-generation enzyme immunoassay and Recombinant Immunoblot Assay were performed. RESULTS: Of the 112 specimens tested, 29 were reactive by Versant HCV TMA Assay, yielding an overall prevalence of HCV viremia of 25.9%. The concordance between TMA and PCR techniques was excellent [91% (101/112)]. Eleven specimens (10%) were invalid or equivocal by PCR due to interference phenomena; all 11 specimens had valid TMA results (2 patients being TMA reactive and 9 nonreactive). Four specimens [3.6% (4/112)] that tested PCR-negative and HCV TMA nonreactive were anti-HCV seropositive, consistent with resolved HCV infection. In the group of seronegative samples, one was reactive by TMA Assay [1.25% (1/80)]. CONCLUSIONS: The HCV TMA technology seems a highly sensitive tool for detecting HCV RNA in the dialysis population, with no evidence of specimen interference. One EIA-negative but HCV-RNA-positive patient by Versant HCV TMA Assay was identified. Prospective clinical trials are under way to assess the clinical impact related to the use of HCV TMA technology in dialysis population.

Association of hepatitis C with posttransplant diabetes in renal transplant patients on tacrolimus.

Posttransplant diabetes mellitus (PTDM) remains a common complication of immunosuppression. Although multiple risk factors have been implicated, none have been clearly identified as predisposing to the increased PTDM frequency observed in patients on tacrolimus. Hepatitis C virus (HCV) has been associated with diabetes and is a significant renal transplant comorbidity. In this study, records of 427 kidney recipients who had no known diabetes before transplantation were retrospectively examined. A multivariate logistic regression model was fit with covariates that had unadjusted relationships with PTDM to examine the independent relationship of HCV and the odds of development of PTDM by 12 mo posttransplant. A potential interaction between HCV and the use of tacrolimus as maintenance therapy on the odds of the development of PTDM was examined. Overall, PTDM occurred more frequently in HCV(+) than HCV(-) patients (39.4% versus 9.8%; P = 0.0005). By multivariate logistic regression, HCV (adjusted odds ratio [OR], 5.58; 95% confidence interval [CI], 2.63 to 11.83; P = 0.0001), weight at transplantation (adjusted OR 1.028; 95% CI, 1.00 to 1.05; P = 0.001), and tacrolimus (adjusted OR, 2.85; 95% CI, 1.01 to 5.28; P = 0.047) were associated with PTDM. A significant interaction (P = 0.0001) was detected between HCV status and tacrolimus use for the odds of PTDM. Among the HCV(+) cohort, PTDM occurred more often in tacrolimus-treated than cyclosporine A-treated patients (57.8% versus 7.7%; P < 0.0001). PTDM rates in HCV(-) patients were similar between the two calcineurin inhibitors (10.0% versus 9.4%; P = 0.521, tacrolimus versus cyclosporine A). In conclusion, HCV is strongly associated with PTDM in renal transplant recipients and appears to account for the increased diabetogenicity observed with tacrolimus.