Retrospective analysis of the impact of severe obesity on kidney transplant outcomes.

BACKGROUND: The prevalence of obesity among kidney transplant recipients is rising. We sought to determine the association between recipient body mass index (BMI) and post-transplant complications. METHODS: Single-center, retrospective cohort study of all adult kidney transplant recipients from 2004 to 2020. Recipients were stratified into four BMI categories: normal-weight (BMI 18.5-24.9 kg/m2, n = 1020), overweight (BMI 25-29.9 kg/m2, n = 1002), moderately obese (BMI 30-34.9 kg/m2, n = 510) and severely-to-morbidly obese (BMI ≥35 kg/m2, n = 274). Logistic regression was used to estimate the association between BMI category and surgical site infections (SSIs). RESULTS: Recipients with BMI ≥35 kg/m2 had significantly higher rates of SSIs (P < .0001) compared with recipients in all other categories. On multivariable analysis, recipients with BMI ≥35 kg/m2 had increased odds of SSIs compared with normal-weight recipients [odds ratio (OR) 3.34, 95% confidence interval (CI) 1.55-7.22, P = .022). On multivariable and Kaplan-Meier analyses, no BMI groups demonstrated increased odds for death-censored graft failure. CONCLUSION: Severe obesity in kidney transplant recipients is associated with increased SSIs, but not kidney allograft failure.

Tocilizumab for the treatment of chronic antibody mediated rejection in kidney transplant recipients.

BACKGROUND: Chronic active antibody-mediated rejection (CAAMR) constitutes a dominant form of late allograft failure. Several treatment strategies directed at CAAMR have been attempted but proven ineffective at delaying kidney function decline or reducing donor-specific antibodies (DSA). We describe our single-center experience using tocilizumab in patients with CAAMR. METHODS: This is a retrospective analysis using electronic medical records. 38 kidney transplant recipients at Columbia University Irving Medical Center who had been prescribed tocilizumab and followed for at least 3 months between August 2013 through December 2019 were included. RESULTS: Tocilizumab use was associated with a decrease in the rate of estimated glomerular filtration rate (eGFR) decline in the 6 months following treatment initiation as compared to the 3 months before tocilizumab was initiated (difference between slopes before and after initiation of treatment = 2.6 mL/min/1.73 m2 (SE = .8, p = .002) per month for up to 6 months following Tocilizumab initiation). Allograft biopsies showed significant improvement in interstitial inflammation scores (score 1(0,1) to 0 (0,1), p = .03) while other histologic scores remained stable. There was no significant change in proteinuria or DSA titers post-treatment with tocilizumab. CONCLUSIONS: Treatment of CAAMR with tocilizumab was associated with a decrease in the rate of eGFR decline and a reduction in interstitial inflammation scores in patients with CAAMR.

Donor-derived cell-free DNA and renal allograft rejection in surveillance biopsies and indication biopsies.

To evaluate the role of circulating dd-cfDNA in allograft surveillance in immunologically high-risk patients, a retrospective cross-sectional study of 261 kidney transplant recipients who underwent outpatient allograft biopsy at our center between September 2020 and August 2021 was performed. Of the 236 dd-cfDNA results included, 37 samples were obtained at the time of a surveillance biopsy in sensitized recipients and 199 at the time of a clinically indicated biopsy. The median serum creatinine at the time of the biopsy was 1.3 mg/dl and 2.1 mg/dl for surveillance biopsies and clinically indicated biopsies, respectively (P < .001). Rejection was diagnosed in 27% of surveillance biopsies and 29% of clinically indicated biopsies. Among surveillance biopsies, sensitivity and specificity to detect rejection were 0% and 89%, respectively, and among clinically indicated biopsies they were 28% and 96%, respectively. The sensitivity and specificity to detect antibody-mediated rejection were 0% and 91% among surveillance biopsies and 50% and 94% among clinically indicated biopsies. Nine biopsies without rejection findings had corresponding dd-cfDNA of ≥1%. Our data does not support dd-cfDNA as a biomarker for kidney allograft rejection, even in immunologically high-risk patients in the absence of graft dysfunction.

Successful Use of Arteriovenous Graft for Hemodialysis Access After Left Ventricular Assist Device Placement.

Kidney replacement therapy is required in up to one-third of patients after left ventricular assist device (LVAD) placement. A subset of these patients requires long-term maintenance hemodialysis and therefore needs durable vascular access but the ideal access in such patients has not been established. We present a series of 3 patients in whom arteriovenous grafts (AVGs) were successfully used for long-term kidney replacement therapy after LVAD placement. The maximum time from AVG placement to first successful AVG use was 40 days, and the longest AVG use duration was more than 2 years. 2 patients required AVG excision due to infection but both had successful placement of a second AVG. Total time on kidney replacement therapy was 993, 1,055, and 956 days for the 3 cases, of which dialysis catheter use was required for only 23%, 6.5%, and 27%, respectively. These cases suggest that AVG placement is a viable option for dialysis access in patients with LVADs.

Cystatin C- Versus Creatinine-Based Assessment of Renal Function and Prediction of Early Outcomes Among Patients With a Left Ventricular Assist Device.

BACKGROUND: Estimated glomerular filtration rate (eGFR) based on serum creatinine (sCr) improves early after left ventricular assist device (LVAD) implantation but subsequently declines. Although sCr is a commonly accepted clinical standard, cystatin C (CysC) has shown superiority in assessment of renal function in disease states characterized by muscle wasting. Among patients with an LVAD, we aimed to (1) longitudinally compare CysC-eGFR and sCr-eGFR, (2) assess their predictive value for early postoperative outcomes, and (3) investigate mechanisms which might explain potential discrepancies. METHODS: A prospective cohort (n=116) with CysC and sCr concurrently measured at serial time points, and a retrospective cohort (n=91) with chest computed tomography performed within 40 days post-LVAD were studied. In the prospective cohort, the primary end point was a composite of in-hospital mortality, renal replacement therapy, or severe right ventricular failure. In the retrospective cohort, muscle mass was estimated using pectoralis muscle area indexed to body surface area (pectoralis muscle index). RESULTS: In the prospective cohort, sCr-eGFR significantly improved early post-LVAD and subsequently declined, whereas CysC-eGFR remained stable. CysC-eGFR but not sCr-eGFR predicted the primary end point: odds ratio per 5 mL/(min·1.73 m2) decrease 1.16 (1.02-1.31) versus 0.99 (0.94-1.05). In retrospective cohort, for every 5 days post-LVAD, a 6% decrease in pectoralis muscle index was observed (95% CI, 2%-9%, P=0.003). After adjusting for time on LVAD, for every 1 cm2/m2 decrease in pectoralis muscle index, there was a 4% decrease in 30-day post-LVAD sCr (95% CI, 1%-6%, P=0.004). CONCLUSIONS: Initial improvement in sCr-eGFR is likely due to muscle wasting following LVAD surgery. CysC may improve assessment of renal function and prediction of early postoperative outcomes in patients with an LVAD.

High rate of renal recovery in survivors of COVID-19 associated acute renal failure requiring renal replacement therapy.

INTRODUCTION: A large proportion of patients with COVID-19 develop acute kidney injury (AKI). While the most severe of these cases require renal replacement therapy (RRT), little is known about their clinical course. METHODS: We describe the clinical characteristics of COVID-19 patients in the ICU with AKI requiring RRT at an academic medical center in New York City and followed patients for outcomes of death and renal recovery using time-to-event analyses. RESULTS: Our cohort of 115 patients represented 23% of all ICU admissions at our center, with a peak prevalence of 29%. Patients were followed for a median of 29 days (2542 total patient-RRT-days; median 54 days for survivors). Mechanical ventilation and vasopressor use were common (99% and 84%, respectively), and the median Sequential Organ Function Assessment (SOFA) score was 14. By the end of follow-up 51% died, 41% recovered kidney function (84% of survivors), and 8% still needed RRT (survival probability at 60 days: 0.46 [95% CI: 0.36-0.56])). In an adjusted Cox model, coronary artery disease and chronic obstructive pulmonary disease were associated with increased mortality (HRs: 3.99 [95% CI 1.46-10.90] and 3.10 [95% CI 1.25-7.66]) as were angiotensin-converting-enzyme inhibitors (HR 2.33 [95% CI 1.21-4.47]) and a SOFA score >15 (HR 3.46 [95% CI 1.65-7.25). CONCLUSIONS AND RELEVANCE: Our analysis demonstrates the high prevalence of AKI requiring RRT among critically ill patients with COVID-19 and is associated with a high mortality, however, the rate of renal recovery is high among survivors and should inform shared-decision making.