IdeS (Imlifidase): A Novel Agent That Cleaves Human IgG and Permits Successful Kidney Transplantation Across High-strength Donor-specific Antibody.

OBJECTIVES: The presence of a donor-specific positive crossmatch has been considered to be a contraindication to kidney transplantation because of the risk of hyperacute rejection. Desensitization is the process of removing hazardous preformed donor-specific antibody (DSA) in order to safely proceed with transplant. Traditionally, this involves plasmapheresis and intravenous immune globulin treatments that occur over days to weeks, and has been feasible when there is a living donor and the date of the transplant is known, allowing time for pre-emptive treatments. For sensitized patients without a living donor, transplantation has been historically difficult. SUMMARY OF BACKGROUND DATA: IdeS (imlifidase) is an endopeptidase derived from Streptococcus pyogenes which has specificity for human IgG, and when infused intravenously results in rapid cleavage of IgG. METHODS: Here we present our single-center's experience with 7 highly sensitized (cPRA98-100%) kidney transplant candidates who had DSA resulting in positive crossmatches with their donors (5 deceased, 2 living) who received IdeS within 24 hours prior to transplant. RESULTS: All pre-IdeS crossmatches were positive and would have been prohibitive for transplantation. All crossmatches became negative post-IdeS and the patients underwent successful transplantation. Three patients had DSA rebound and antibody-mediated rejection, which responded to standard of care therapies. Three patients had delayed graft function, which ultimately resolved. No serious adverse events were associated with IdeS. All patients have functioning renal allografts at a median follow-up of 235 days. CONCLUSION: IdeS may represent a groundbreaking new method of desensitization for patients who otherwise might have no hope for receiving a lifesaving transplant.

Quantitative evaluation of acute renal transplant dysfunction with low-dose three-dimensional MR renography.

PURPOSE: To assess prospectively the ability of quantitative low-dose three-dimensional magnetic resonance (MR) renography to help identify the cause of acute graft dysfunction. MATERIALS AND METHODS: This HIPAA-compliant study was approved by the institutional review board, and written informed consent was obtained. Between December 2001 and May 2009, sixty patients with transplanted kidneys (41 men and 19 women; mean age, 49 years; age range, 22-71 years) were included. Thirty-one patients had normal function and 29 had acute dysfunction due to acute rejection (n = 12), acute tubular necrosis (ATN) (n = 8), chronic rejection (n = 6), or drug toxicity (n = 3). MR renography was performed at 1.5 T with three-dimensional gradient-echo imaging. With use of a multicompartment renal model, the glomerular filtration rate (GFR) and the mean transit time (MTT) of the tracer for the vascular compartment (MTT(A)), the tubular compartment (MTT(T)), and the collecting system compartment (MTT(C)) were calculated. Also derived was MTT for the whole kidney (MTT(K) = MTT(A) + MTT(T) + MTT(C)) and fractional MTT of each compartment (MTT(A/K) = MTT(A)/MTT(K), MTT(T/K) = MTT(T)/MTT(K), MTT(C/K) = MTT(C)/MTT(K)). These parameters were compared in patients in the different study groups. Statistical analysis was performed by using analysis of covariance. RESULTS: There were significant differences in GFR and MTT(K) between the acute dysfunction group (36.4 mL/min ± 20.8 [standard deviation] and 177.1 seconds ± 46.8, respectively) and the normal function group (65.9 mL/min ± 27.6 and 140.5 seconds ± 51.8, respectively) (P < .001 and P = .004). The MTT(A/K) was significantly higher in the acute rejection group (mean, 12.7% ± 2.9) than in the normal function group (mean, 8.3% ± 2.2; P < .001) or in the ATN group (mean, 7.1% ± 1.4; P < .001). The MTT(T/K) was significantly higher in the ATN group (mean, 83.2% ± 9.2) than in the normal function group (mean, 72.4% ± 10.2; P = .031) or in the acute rejection group (mean, 69.2% ± 6.1; P = .003). CONCLUSION: Low-dose MR renography analyzed by using a multicompartmental tracer kinetic renal model may help to differentiate noninvasively between acute rejection and ATN after kidney transplantation.

Kidney function: glomerular filtration rate measurement with MR renography in patients with cirrhosis.

PURPOSE: To assess the accuracy of glomerular filtration rate (GFR) measurements obtained with low-contrast agent dose dynamic contrast material-enhanced magnetic resonance (MR) renography in patients with liver cirrhosis who underwent routine liver MR imaging, with urinary clearance of technetium 99m ((99m)Tc) pentetic acid (DTPA) as the reference standard. MATERIALS AND METHODS: This HIPAA-compliant study was institutional review board approved. Written informed patient consent was obtained. Twenty patients with cirrhosis (14 men, six women; age range, 41-70 years; mean age, 54.6 years) who were scheduled for routine 1.5-T liver MR examinations to screen for hepatocellular carcinoma during a 6-month period were prospectively included. Five-minute MR renography with a 3-mL dose of gadoteridol was performed instead of a routine test-dose timing examination. The GFR was estimated at MR imaging with use of two kinetic models. In one model, only the signal intensities in the aorta and kidney parenchyma were considered, and in the other, renal cortical and medullary signal intensities were treated separately. The GFR was also calculated by using serum creatinine levels according to the Cockcroft-Gault and modification of diet in renal disease (MDRD) formulas. All patients underwent a (99m)Tc-DTPA urinary clearance examination on the same day to obtain a reference GFR measurement. The accuracies of all MR- and creatinine-based GFR estimations were compared by using Wilcoxon signed rank tests. RESULTS: The mean reference GFR, based on (99m)Tc-DTPA clearance, was 74.9 mL/min/1.73 m(2) ± 27.7 (standard deviation) (range, 10.3-120.7 mL/min/1.73 m(2)). With both kinetic models, 95% of MR-based GFRs were within 30% of the reference values, whereas only 40% and 60% of Cockcroft-Gault- and MDRD-based GFRs, respectively, were within this range. MR-based GFR estimates were significantly more accurate than creatinine level-based estimates (P < .001). CONCLUSION: GFR assessment with MR imaging, which outperformed the Cockcroft-Gault and MDRD formulas, adds less than 10 minutes of table time to a clinically indicated liver MR examination without ionizing radiation. SUPPLEMENTAL MATERIAL: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.11101338/-/DC1.

Decreasing Incidence of Acute Kidney Injury in Patients with COVID-19 Critical Illness in New York City.

INTRODUCTION: Reports from the United States suggest that acute kidney injury (AKI) frequently complicates coronavirus disease 2019 (COVID-19), but understanding of AKI risks and outcomes is incomplete. In addition, whether kidney outcomes have evolved during the course of the pandemic is unknown. METHODS: We used electronic medical records to identify patients with COVID-19 with and without AKI admitted to 3 New York Hospitals between March 2 and August 25, 2020. Outcomes included AKI overall and according to admission week, AKI stage, the requirement for new renal replacement therapy (RRT), mortality, and recovery of kidney function. Logistic regression was used to assess associations of patient characteristics and outcomes. RESULTS: Of 4732 admissions, 1386 (29.3%) patients had AKI. Among those with AKI, 717 (51.7%) had stage 1 disease, 132 (9.5%) had stage 2 disease, 537 (38.7%) had stage 3 disease, and 237 (17.1%) required RRT initiation. In March, 536 of 1648 (32.5%) patients developed AKI compared with 15 of 87 (17.2%) in August (P < 0.001 for monthly trend), whereas RRT initiation was required in 6.9% and 0% of admissions in March and August, respectively. Mortality was higher with than without AKI (51.6% vs. 8.6%) and was 71.9% in individuals requiring RRT. However, most patients with AKI who survived hospitalization (77%) recovered to within 0.3 mg/dl of baseline creatinine. Among those surviving to discharge, 62% discontinued RRT. CONCLUSIONS: AKI impacts a high proportion of admitted patients with COVID-19 and is associated with high mortality, particularly when RRT is required. AKI incidence appears to be decreasing over time and kidney function frequently recovers in those who survive.

Outcomes among Hospitalized Chronic Kidney Disease Patients with COVID-19.

Background: Patients with CKD ha ve impaired immunity, increased risk of infection-related mortality, and worsened COVID-19 outcomes. However, data comparing nondialysis CKD and ESKD are sparse. Methods: Patients with COVID-19 admitted to three hospitals in the New York area, between March 2 and August 27, 2020, were retrospectively studied using electronic health records. Patients were classified as those without CKD, those with nondialysis CKD, and those with ESKD, with outcomes including hospital mortality, ICU admission, and mortality rates. Results: Of 3905 patients, 588 (15%) had nondialysis CKD and 128 (3%) had ESKD. The nondialysis CKD and ESKD groups had a greater prevalence of comorbidities and higher admission D-dimer levels, whereas patients with ESKD had lower C-reactive protein levels at admission. ICU admission rates were similar across all three groups (23%-25%). The overall, unadjusted hospital mortality was 25%, and the mortality was 24% for those without CKD, 34% for those with nondialysis CKD, and 27% for those with ESKD. Among patients in the ICU, mortality was 56%, 64%, and 56%, respectively. Although patients with nondialysis CKD had higher odds of overall mortality versus those without CKD in univariate analysis (OR, 1.58; 95% CI, 1.31 to 1.91), this was no longer significant in fully adjusted models (OR, 1.11; 95% CI, 0.88 to 1.40). Also, ESKD status did not associate with a higher risk of mortality compared with non-CKD in adjusted analyses, but did have reduced mortality when compared with nondialysis CKD (OR, 0.57; 95% CI, 0.33 to 0.95). Mortality rates declined precipitously after the first 2 months of the pandemic, from 26% to 14%, which was reflected in all three subgroups. Conclusions: In a diverse cohort of patients with COVID-19, we observed higher crude mortality rates for patients with nondialysis CKD and, to a lesser extent, ESKD, which were not significant after risk adjustment. Moreover, patients with ESKD appear to have better outcom es than those with nondialysis CKD.

Renal Considerations in COVID-19: Biology, Pathology, and Pathophysiology.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has emerged into a worldwide pandemic of epic proportion. Beyond pulmonary involvement in coronavirus disease 2019 (COVID-19), a significant subset of patients experiences acute kidney injury. Patients who die from severe disease most notably show diffuse acute tubular injury on postmortem examination with a possible contribution of focal macro- and microvascular thrombi. Renal biopsies in patients with proteinuria and hematuria have demonstrated a glomerular dominant pattern of injury, most notably a collapsing glomerulopathy reminiscent of findings seen in human immunodeficiency virus (HIV) in individuals with apolipoprotein L-1 (APOL1) risk allele variants. Although various mechanisms have been proposed for the pathogenesis of acute kidney injury in SARS-CoV-2 infection, direct renal cell infection has not been definitively demonstrated and our understanding of the spectrum of renal involvement remains incomplete. Herein we discuss the biology, pathology, and pathogenesis of SARS-CoV-2 infection and associated renal involvement. We discuss the molecular biology, risk factors, and pathophysiology of renal injury associated with SARS-CoV-2 infection. We highlight the characteristics of specific renal pathologies based on native kidney biopsy and autopsy. Additionally, a brief discussion on ancillary studies and challenges in the diagnosis of SARS-CoV-2 is presented.

Acute Peritoneal Dialysis During the COVID-19 Pandemic at Bellevue Hospital in New York City.

Background: The COVID-19 pandemic strained hospital resources in New York City, including those for providing dialysis. New York University Medical Center and affiliations, including New York City Health and Hospitals/Bellevue, developed a plan to offset the increased needs for KRT. We established acute peritoneal dialysis (PD) capability, as usual dialysis modalities were overwhelmed by COVID-19 AKI. Methods: Observational study of patients requiring KRT admitted to Bellevue Hospital during the COVID surge. Bellevue Hospital is one of the largest public hospitals in the United States, providing medical care to an underserved population. There were substantial staff, supplies, and equipment shortages. Adult patients admitted with AKI who required KRT were considered for PD. We rapidly established an acute PD program. A surgery team placed catheters at the bedside in the intensive care unit; a nephrology team delivered treatment. We provided an alternative to hemodialysis and continuous venovenous hemofiltration for treating patients in the intensive-care unit, demonstrating efficacy with outcomes comparable to standard care. Results: From April 8, 2020 to May 8, 2020, 39 catheters were placed into ten women and 29 men. By June 10, 39% of the patients started on PD recovered kidney function (average ages 56 years for men and 59.5 years for women); men and women who expired were an average 71.8 and 66.2 years old. No episodes of peritonitis were observed; there were nine incidents of minor leaking. Some patients were treated while ventilated in the prone position. Conclusions: Demand compelled us to utilize acute PD during the COVID-19 pandemic. Our experience is one of the largest recently reported in the United States of which we are aware. Acute PD provided lifesaving care to acutely ill patients when expanding current resources was impossible. Our experience may help other programs to avoid rationing dialysis treatments in health crises.

Comparison of heparin-coated and conventional split-tip hemodialysis catheters.

Catheter coatings have the potential to decrease infection and thrombosis in patients with chronic dialysis catheters. We report our midterm experience with a heparin-coated dialysis catheter. This retrospective, case-control study was approved by our Institutional Review Board. A total of 88 tunneled dialysis catheters were inserted over a 13-month period via the internal jugular vein. Thirty-eight uncoated split-tip catheters and 50 heparin-coated catheters were inserted. Primary catheter patency was compared between the two groups using the log rank test, with infection and/or thrombosis considered as catheter failures. Dialysis parameters during the first and last dialysis sessions, including pump speed, actual blood flow, and arterial port pressures, were compared using unpaired t-tests. Primary patency of the uncoated catheters was 86.0 +/- 6.5% at 30 days and 76.1 +/- 8.9% at 90 days. Primary patency of heparin-coated catheters was 92.0 +/- 6.2% at 30 days and 81.6 +/- 8.0% at 90 days (p = 0.87, log rank test). Infection requiring catheter removal occurred in four patients with uncoated catheters and two patients with heparin-coated catheters (p = 0.23). Catheter thrombosis requiring catheter replacement or thrombolysis occurred in one patient with an uncoated catheter and two patients with heparin-coated catheters (p = 0.9). No differences in catheter function during hemodialysis were seen between the two groups. In conclusion, the heparin-coated catheter did not show a significantly longer patency compared to the uncoated catheter. The flow characteristics of this device were comparable to those of the conventional uncoated catheter. A demonstrable benefit of the heparin-coated catheter in randomized trials is needed before a recommendation for routine implementation can be made.