Publications by authors named "Sumit Mohan"

165 Publications

Association Between Donor-Recipient Biological Relationship and Allograft Outcomes After Living Donor Kidney Transplant.

JAMA Netw Open 2021 Apr 1;4(4):e215718. Epub 2021 Apr 1.

Department of Medicine, Division of Nephrology, Columbia University Medical Center, New York, New York.

Importance: The proportion of living donor kidney transplants from donors unrelated to their recipients is increasing in the US.

Objective: To examine the association between donor-recipient biological relationship and allograft survival after living donor kidney transplant.

Design, Setting, And Participants: This retrospective cohort study used Organ Procurement and Transplantation Network data on US adult living donor kidney transplants (n = 86 154) performed from January 1, 2000, to December 31, 2014, excluding cases in which recipients previously received a kidney transplant (n = 10 342) or key data were missing (n = 2832). Last follow-up was March 20, 2020.

Exposures: Donor-recipient biological relationship.

Main Outcomes And Measures: The primary outcome was death-censored allograft failure. Univariate and multivariable time-to-event analyses were performed for death-censored allograft failure for the overall cohort, then separately for recipients with and without primary diagnoses of cystic kidney disease and for transplants from African American and non-African American donors.

Results: Among the 72 980 transplant donor and recipients included in the study (median donor age, 41 years; interquartile range [IQR], 32-50 years; 43 990 [60%] female; 50 014 [69%] White), 43 174 (59%) donors and recipients were biologically related and 29 806 (41%) were unrelated. Donors related to their recipients were younger (median [IQR] age, 39 [31-48] vs 44 [35-52] years) and less likely to be female (24 848 [58%] vs 19 142 [64%]) or White (26 933 [62%] vs 23 081 [77%]). Recipients related to their donors were younger (median [IQR] age, 48 [34-58] vs 50 [40-58] years), more likely to be female (18 035 [42%] vs 10 530 [35%]), and less likely to have cystic kidney disease (2530 [6%] vs 4600 [15%]). Related pairs had fewer HLA mismatches overall (median [IQR], 3 [2-3] vs 5 [4-5]). After adjustment for HLA mismatches, donor and recipient characteristics, and transplant era, donor-recipient biological relationship was associated with higher death-censored allograft failure (hazard ratio, 1.05; 95% CI, 1.01-1.10; P = .03). When stratified by primary disease, this association persisted only for recipients without cystic kidney disease. When stratified by donor race, this association persisted only for transplants from African American donors.

Conclusions And Relevance: In this cohort study, living donor kidney transplants from donors biologically related to their recipients had higher rates of allograft failure than transplants from donors unrelated to their recipients after HLA matching was accounted for. Further study is needed to determine which genetic or socioenvironmental factors are associated with this finding.
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http://dx.doi.org/10.1001/jamanetworkopen.2021.5718DOI Listing
April 2021

COVID-19 mortality among kidney transplant candidates is strongly associated with social determinants of health.

Am J Transplant 2021 Mar 23. Epub 2021 Mar 23.

Division of Nephrology, Department of Medicine, Columbia University Vagelos College of Physicians and Surgeons, New York, New York, USA.

The COVID-19 pandemic has affected all portions of the global population. However, many factors have been shown to be particularly associated with COVID-19 mortality including demographic characteristics, behavior, comorbidities, and social conditions. Kidney transplant candidates may be particularly vulnerable to COVID-19 as many are dialysis-dependent and have comorbid conditions. We examined factors associated with COVID-19 mortality among kidney transplant candidates from the National Scientific Registry of Transplant Recipients from March 1 to December 1, 2020. We evaluated crude rates and multivariable incident rate ratios (IRR) of COVID-19 mortality. There were 131 659 candidates during the study period with 3534 all-cause deaths and 384 denoted a COVID-19 cause (5.00/1000 person years). Factors associated with increased COVID-19 mortality included increased age, males, higher body mass index, and diabetes. In addition, Blacks (IRR = 1.96, 95% C.I.: 1.43-2.69) and Hispanics (IRR = 3.38, 95% C.I.: 2.46-4.66) had higher COVID-19 mortality relative to Whites. Patients with lower educational attainment, high school or less (IRR = 1.93, 95% C.I.: 1.19-3.12, relative to post-graduate), Medicaid insurance (IRR = 1.73, 95% C.I.: 1.26-2.39, relative to private), residence in most distressed neighborhoods (fifth quintile IRR = 1.93, 95% C.I.: 1.28-2.90, relative to first quintile), and most urban and most rural had higher adjusted rates of COVID-19 mortality. Among kidney transplant candidates in the United States, social determinants of health in addition to demographic and clinical factors are significantly associated with COVID-19 mortality.
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http://dx.doi.org/10.1111/ajt.16578DOI Listing
March 2021

Post-acute COVID-19 syndrome.

Nat Med 2021 Mar 22. Epub 2021 Mar 22.

Division of Cardiology, Department of Medicine, Vagelos College of Physicians and Surgeons, New York-Presbyterian/Columbia University Irving Medical Center, New York, New York, USA.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the pathogen responsible for the coronavirus disease 2019 (COVID-19) pandemic, which has resulted in global healthcare crises and strained health resources. As the population of patients recovering from COVID-19 grows, it is paramount to establish an understanding of the healthcare issues surrounding them. COVID-19 is now recognized as a multi-organ disease with a broad spectrum of manifestations. Similarly to post-acute viral syndromes described in survivors of other virulent coronavirus epidemics, there are increasing reports of persistent and prolonged effects after acute COVID-19. Patient advocacy groups, many members of which identify themselves as long haulers, have helped contribute to the recognition of post-acute COVID-19, a syndrome characterized by persistent symptoms and/or delayed or long-term complications beyond 4 weeks from the onset of symptoms. Here, we provide a comprehensive review of the current literature on post-acute COVID-19, its pathophysiology and its organ-specific sequelae. Finally, we discuss relevant considerations for the multidisciplinary care of COVID-19 survivors and propose a framework for the identification of those at high risk for post-acute COVID-19 and their coordinated management through dedicated COVID-19 clinics.
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http://dx.doi.org/10.1038/s41591-021-01283-zDOI Listing
March 2021

Factors that Influence Organ Donor Registration Among Asian American Physicians in Queens, New York.

J Immigr Minor Health 2021 Mar 22. Epub 2021 Mar 22.

Division of Nephrology, Department of Medicine, Columbia University Irving Medical Center, New York, NY, USA.

Organ donation rates in the United States are lowest among Asians. Physicians are highly respected in Asian communities and may be influential in promoting donor registration, but little is known about their organ donor registration attitudes. We assessed associations between knowledge, attitudes, personal/professional experience, cultural/religious beliefs surrounding organ donation and donor registration status using multivariable logistic regression. We surveyed 121 Asian physicians in Queens, New York; 22% were registered donors. Registered donors were more likely to discuss donation wishes with their family (OR 9.47, 95% CI 2.60-34.51), know that donor human leukocyte antigen does not need to match organ recipients (OR 6.47, 95% CI 1.66-25.28), and have experience advising patients about organ donation (OR 5.35, 95% CI 1.50-19.02). Culturally tailored educational materials providing updated information to promote family discussion about organ donation could potentially increase Asian physicians' level of comfort and expertise in discussing organ donor registration with patients.
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http://dx.doi.org/10.1007/s10903-021-01182-yDOI Listing
March 2021

Development and validation of prediction models for mechanical ventilation, renal replacement therapy, and readmission in COVID-19 patients.

J Am Med Inform Assoc 2021 Mar 11. Epub 2021 Mar 11.

Department of Biomedical Informatics, Columbia University, New York, New York, USA.

Objective: Coronavirus disease 2019 (COVID-19) patients are at risk for resource-intensive outcomes including mechanical ventilation (MV), renal replacement therapy (RRT), and readmission. Accurate outcome prognostication could facilitate hospital resource allocation. We develop and validate predictive models for each outcome using retrospective electronic health record data for COVID-19 patients treated between March 2 and May 6, 2020.

Materials And Methods: For each outcome, we trained 3 classes of prediction models using clinical data for a cohort of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2)-positive patients (n = 2256). Cross-validation was used to select the best-performing models per the areas under the receiver-operating characteristic and precision-recall curves. Models were validated using a held-out cohort (n = 855). We measured each model's calibration and evaluated feature importances to interpret model output.

Results: The predictive performance for our selected models on the held-out cohort was as follows: area under the receiver-operating characteristic curve-MV 0.743 (95% CI, 0.682-0.812), RRT 0.847 (95% CI, 0.772-0.936), readmission 0.871 (95% CI, 0.830-0.917); area under the precision-recall curve-MV 0.137 (95% CI, 0.047-0.175), RRT 0.325 (95% CI, 0.117-0.497), readmission 0.504 (95% CI, 0.388-0.604). Predictions were well calibrated, and the most important features within each model were consistent with clinical intuition.

Discussion: Our models produce performant, well-calibrated, and interpretable predictions for COVID-19 patients at risk for the target outcomes. They demonstrate the potential to accurately estimate outcome prognosis in resource-constrained care sites managing COVID-19 patients.

Conclusions: We develop and validate prognostic models targeting MV, RRT, and readmission for hospitalized COVID-19 patients which produce accurate, interpretable predictions. Additional external validation studies are needed to further verify the generalizability of our results.
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http://dx.doi.org/10.1093/jamia/ocab029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7989331PMC
March 2021

Continuous renal replacement therapy and the COVID pandemic.

Semin Dial 2021 Mar 11. Epub 2021 Mar 11.

Division of Nephrology, Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, USA.

Severe COVID-19 illness and the consequent cytokine storm and vasodilatory shock commonly lead to ischemic acute kidney injury (AKI). The need for renal replacement therapies (RRTs) in those with the most severe forms of AKI is considerable and risks overwhelming health-care systems at the peak of a surge. We detail the challenges and considerations involved in the preparation of a disaster response plan in situations such as the COVID-19 pandemic, which dramatically increase demand for nephrology services. Taking careful inventory of all aspects of an RRT program (personnel, consumables, and machines) before a surge in RRT arises and developing disaster contingency protocol anticoagulation and for shared RRT models when absolutely necessary are paramount to a successful response to such a disaster.
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http://dx.doi.org/10.1111/sdi.12962DOI Listing
March 2021

Left-digit bias and deceased donor kidney utilization.

Clin Transplant 2021 Mar 11:e14284. Epub 2021 Mar 11.

Department of Medicine, Division of Nephrology, Columbia University Medical Center, New York, NY, USA.

Cognitive biases shown to impact medical decision-making include left-digit bias, the tendency to focus on a continuous variable's leftmost digit. We hypothesized that left-digit bias impacts deceased donor kidney utilization through heuristic processing of donor age and creatinine. We used US registry data to identify 87 019 kidneys recovered (2015-2019) and compared the proportion around thresholds for donor age (69 vs. 70 years) and creatinine (1.9 vs. 2.0 mg/dl), then compared the risk of kidney discard. Kidneys from donors aged 70 vs. 69 years were more frequently discarded (77% vs. 65%, p < .001), with higher risk of discard even after adjusting for KDRI (adjusted RR 1.11, 95% CI 1.02-1.21, p = .018). Similarly, kidneys from donors with final creatinine 2.0 vs. 1.9 mg/dl were more frequently discarded (37% vs. 29%, p < .001), with higher risk of discard after adjusting for KDRI (adjusted RR 1.19, 95% CI 1.07-1.33, p = .001). However, no significant left-digit effect was found when examining other donor age (39/40, 49/50, 59/60 years) or creatinine (0.9/1.0, 2.9/3.0 mg/dl) thresholds. The findings suggest a possible left-digit effect affecting kidney utilization at specific thresholds. Additional investigations of the impact of this and other heuristics on organ utilization are needed to identify potential areas for decision-making interventions aimed at reducing kidney discard.
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http://dx.doi.org/10.1111/ctr.14284DOI Listing
March 2021

Managing Patients with Failing Kidney Allograft: Many Questions Remain.

Clin J Am Soc Nephrol 2021 Mar 10. Epub 2021 Mar 10.

Department of Medicine, University of Colorado, Aurora, Colorado

Patients who receive a kidney transplant commonly experience failure of their allograft. Transplant failure often comes with complex management decisions, such as when and how to wean immunosuppression and start the transition to a second transplant or to dialysis. These decisions are made in the context of important concerns about competing risks, including sensitization and infection. Unfortunately, the management of the failed allograft is, at present, guided by relatively poor-quality data and, as a result, practice patterns are variable and suboptimal given that patients with failed allografts experience excess morbidity and mortality compared with their transplant-naive counterparts. In this review, we summarize the management strategies through the often-precarious transition from transplant to dialysis, highlighting the paucity of data and the critical gaps in our knowledge that are necessary to inform the optimal care of the patient with a failing kidney transplant.
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http://dx.doi.org/10.2215/CJN.14620920DOI Listing
March 2021

Deceased-Donor Acute Kidney Injury and BK Polyomavirus in Kidney Transplant Recipients.

Clin J Am Soc Nephrol 2021 Mar 10. Epub 2021 Mar 10.

Division of Nephrology, Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, Maryland

Background And Objectives: BK polyomavirus (BKV) infection commonly complicates kidney transplantation, contributing to morbidity and allograft failure. The virus is often donor-derived and influenced by ischemia-reperfusion processes and disruption of structural allograft integrity. We hypothesized that deceased-donor AKI associates with BKV infection in recipients.

Design, Setting, Participants, & Measurements: We studied 1025 kidney recipients from 801 deceased donors transplanted between 2010 and 2013, at 13 academic centers. We fitted Cox proportional-hazards models for BKV DNAemia (detectable in recipient blood by clinical PCR testing) within 1 year post-transplantation, adjusting for donor AKI and other donor- and recipient-related factors. We validated findings from this prospective cohort with analyses for graft failure attributed to BKV within the Organ Procurement and Transplantation Network (OPTN) database.

Results: The multicenter cohort mean kidney donor profile index was 49±27%, and 26% of donors had AKI. Mean recipient age was 54±13 years, and 25% developed BKV DNAemia. Donor AKI was associated with lower risk for BKV DNAemia (adjusted hazard ratio, 0.53; 95% confidence interval, 0.36 to 0.79). In the OPTN database, 22,537 (25%) patients received donor AKI kidneys, and 272 (0.3%) developed graft failure from BKV. The adjusted hazard ratio for the outcome with donor AKI was 0.7 (95% confidence interval, 0.52 to 0.95).

Conclusions: In a well-characterized, multicenter cohort, contrary to our hypothesis, deceased-donor AKI independently associated with lower risk for BKV DNAemia. Within the OPTN database, donor AKI was also associated with lower risk for graft failure attributed to BKV.

Podcast: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2021_03_10_CJN18101120_final.mp3.
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http://dx.doi.org/10.2215/CJN.18101120DOI Listing
March 2021

Prevalence and Predictors of SARS-CoV-2 Antibodies among Solid Organ Transplant Recipients with Confirmed Infection.

Am J Transplant 2021 Feb 16. Epub 2021 Feb 16.

Center for Liver Disease and Transplantation, Columbia University College of Physicians & Surgeons, New York, NY, USA.

It remains uncertain whether immunocompromised patients including solid organ transplant (SOT) recipients will have a robust antibody response to SARS-CoV-2 infection. We enrolled all adult SOT recipients at our center with confirmed SARS-CoV-2 infection who underwent antibody testing with a single commercially available anti-nucleocapsid antibody test at least 7 days after diagnosis in a retrospective cohort. 70 SOT recipients were studied (56% kidney, 19% lung, 14% liver +/- kidney, and 11% heart +/- kidney recipients). 36 (51%) had positive anti-nucleocapsid antibody testing, and 34 (49%) were negative. Recipients of a kidney allograft were less likely to have positive antibody testing compared those who did not receive a kidney (p=0.04). In the final multivariable model, the years from transplant to diagnosis (OR 1.26, p=0.002) and baseline immunosuppression with more than 2 agents (OR 0.26, p=0.03) were significantly associated with the antibody test result, controlling for kidney transplantation. In conclusion, among SOT recipients with confirmed infection, only 51 % of patients had detectable anti-nucleocapsid antibodies, and transplant-related variables including the level and nature of immunosuppression are important predictors. These findings raise the concern that SOT recipients with COVID-19 may be less likely to form SARS-CoV-2 antibodies.
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http://dx.doi.org/10.1111/ajt.16541DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8014874PMC
February 2021

Failure to Advance Access to Kidney Transplantation over Two Decades in the United States.

J Am Soc Nephrol 2021 Feb 11. Epub 2021 Feb 11.

Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, Ohio.

Background: Extensive research and policies have been developed to improve access to kidney transplantation among patients with ESKD. Despite this, wide variation in transplant referral rates exists between dialysis facilities.

Methods: To evaluate the longitudinal pattern of access to kidney transplantation over the past two decades, we conducted a retrospective cohort study of adult patients with ESKD initiating ESKD or placed on a transplant waiting list from 1997 to 2016 in the United States Renal Data System. We used cumulative incidence models accounting for competing risks and multivariable Cox models to evaluate time to waiting list placement or transplantation (WLT) from ESKD onset.

Results: Among the study population of 1,309,998 adult patients, cumulative 4-year WLT was 29.7%, which was unchanged over five eras. Preemptive WLT (prior to dialysis) increased by era (5.2% in 1997-2000 to 9.8% in 2013-2016), as did 4-year WLT incidence among patients aged 60-70 (13.4% in 1997-2000 to 19.8% in 2013-2016). Four-year WLT incidence diminished among patients aged 18-39 (55.8%-48.8%). Incidence of WLT was substantially lower among patients in lower-income communities, with no improvement over time. Likelihood of WLT after dialysis significantly declined over time (adjusted hazard ratio, 0.80; 95% confidence interval, 0.79 to 0.82) in 2013-2016 relative to 1997-2000.

Conclusions: Despite wide recognition, policy reforms, and extensive research, rates of WLT following ESKD onset did not seem to improve in more than two decades and were consistently reduced among vulnerable populations. Improving access to transplantation may require more substantial interventions.
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http://dx.doi.org/10.1681/ASN.2020060888DOI Listing
February 2021

A deeper dive into the impact of multiple-organ transplant policy on kidney transplant candidate prognoses.

Am J Transplant 2021 Jan 29. Epub 2021 Jan 29.

Department of Medicine, Columbia University College of Physicians and Surgeons and New York Presbyterian Hospital, New York, New York.

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http://dx.doi.org/10.1111/ajt.16508DOI Listing
January 2021

COVID-19 infection in former living kidney donors.

Clin Transplant 2021 Jan 22:e14230. Epub 2021 Jan 22.

Division of Nephrology and Hypertension, Department of Medicine, Weill Cornell Medicine, New York, NY, USA.

The COVID-19 pandemic brought living donor kidney transplant programs across the United States to a near halt in March 2020. As programs have begun to reopen, potential donor candidates often inquire about their risk of a COVID-19 infection and its potential impact on kidney function after donation. To address their concerns, we surveyed 1740 former live kidney donors at four transplant centers located in New York and Michigan. Of these, 839 (48.2%) donors responded, their mean age was 46 ± 12.5 years, 543 (65%) were females, and 611 (73%) were white. Ninety-two donors (11%) had symptoms suggestive of a COVID-19 infection with fever (48%) and fatigue (43%) being the most common. Among those with symptoms, 42 donors underwent testing and 16 tested positive. Testing was more common among donors with private insurance, and a positive test result was more common among young black donors. Only one donor surveyed required hospitalization and none required dialysis. Fourteen donors have recovered completely and two partially. Our survey highlights that a COVID-19 infection in former donors results in a mild disease with good recovery. These data will be useful for transplant programs to counsel living donors who are considering kidney donation during this pandemic.
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http://dx.doi.org/10.1111/ctr.14230DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7995102PMC
January 2021

Contemporary incidence and risk factors of post transplant Erythrocytosis in deceased donor kidney transplantation.

BMC Nephrol 2021 Jan 12;22(1):26. Epub 2021 Jan 12.

Division of Nephrology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Background: Post-Transplant erythrocytosis (PTE) has not been studied in large recent cohorts. In this study, we evaluated the incidence, risk factors, and outcome of PTE with current transplant practices using the present World Health Organization criteria to define erythrocytosis. We also tested the hypothesis that the risk of PTE is greater with higher-quality kidneys.

Methods: We utilized the Deceased Donor Study which is an ongoing, multicenter, observational study of deceased donors and their kidney recipients that were transplanted between 2010 and 2013 across 13 centers. Eryrthocytosis is defined by hemoglobin> 16.5 g/dL in men and> 16 g/dL in women. Kidney quality is measured by Kidney Donor Profile Index (KDPI).

Results: Of the 1123 recipients qualified to be in this study, PTE was observed at a median of 18 months in 75 (6.6%) recipients. Compared to recipients without PTE, those with PTE were younger [mean 48±11 vs 54±13 years, p < 0.001], more likely to have polycystic kidney disease [17% vs 6%, p < 0.001], have received kidneys from younger donors [36 ±13 vs 41±15 years], and be on RAAS inhibitors [35% vs 22%, p < 0.001]. Recipients with PTE were less likely to have received kidneys from donors with hypertension [16% vs 32%, p = 0.004], diabetes [1% vs 11%, p = 0.008], and cerebrovascular event (24% vs 36%, p = 0.036). Higher KDPI was associated with decreased PTE risk [HR 0.98 (95% CI: 0.97-0.99)]. Over 60 months of follow-up, only 17 (36%) recipients had sustained PTE. There was no association between PTE and graft failure or mortality, CONCLUSIONS: The incidence of PTE was low in our study and PTE resolved in majority of patients. Lower KDPI increases risk of PTE. The underutilization of RAAS inhibitors in PTE patients raises the possibility of under-recognition of this phenomenon and should be explored in future studies.
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http://dx.doi.org/10.1186/s12882-021-02231-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7802150PMC
January 2021

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

PLoS One 2020 28;15(12):e0244131. Epub 2020 Dec 28.

Division of Nephrology, Department of Medicine, Columbia University Irving Medical Center, New York, NY, United States of America.

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.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0244131PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7769434PMC
January 2021

Greater complexity and monitoring of the new Kidney Allocation System: Implications and unintended consequences of concentric circle kidney allocation on network complexity.

Am J Transplant 2020 Dec 12. Epub 2020 Dec 12.

Department of Medicine, Division of Nephrology, Vagelos College of Physicians & Surgeons, Columbia University, New York, New York.

The deceased donor kidney allocation system in the United States has undergone several rounds of iterative changes, but these changes were not explicitly designed to address the geographic variation in access to transplantation. The new allocation system, expected to start in December 2020, changes the definition of "local allocation" from the Donation Service Area to 250 nautical mile circles originating from the donor hospital. While other solid organs have adopted a similar approach, the larger number of both kidney transplant centers and transplant candidates is likely to have different consequences. Here, we discuss the incredible increase in complexity in allocation, discuss some of the likely intended and unintended consequences, and propose metrics to monitor the new system.
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http://dx.doi.org/10.1111/ajt.16441DOI Listing
December 2020

Reflections and Next Stages for .

Kidney Int Rep 2021 Jan 28;6(1):1-2. Epub 2020 Nov 28.

Vagelos College of Physicians and Surgeons, Columbia University, New York, New York, USA.

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http://dx.doi.org/10.1016/j.ekir.2020.11.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7698824PMC
January 2021

A Newly Recognized Endemic Region of CKD of Undetermined Etiology (CKDu) in South India-"Tondaimandalam Nephropathy".

Kidney Int Rep 2020 Nov 15;5(11):2066-2073. Epub 2020 Sep 15.

Division of Nephrology, Columbia University Medical Centre, New York, USA.

Introduction: Chronic kidney disease (CKD) is being increasingly recognized as a public health problem in India. The entity of CKD of undetermined etiology (CKDu) is increasingly being reported globally. Here we describe the burden of CKDu in a heretofore undescribed population in South India.

Methods: We prospectively enrolled all patients with CKD referred to the nephrology department in an observational registry. We analyzed their sociodemographic and clinical features over 4 years. The diagnosis of CKD and its etiology was determined using predefined criteria. Geolocalization of CKD patients was performed. Subsequently, CKD screening was conducted in a village located in an area of CKDu clustering.

Results: A total of 2424 patients were analyzed; the median age was 52 years and 75.3% were male. Seventy-five percent had advanced CKD. CKDu was the most common (51.7%) etiologic category. This is the highest proportion of CKDu reported among all published CKD studies to date from India. The clinical and demographic profile of this patient population match that of CKDu patients reported from Sri Lanka and Central America, where CKDu is endemic. A clustering of cases of CKDu was noted in specific districts using a geographic information system software. Screening of 447 people in an outreach program at a village located in an area identified to have clustering of CKDu showed a CKD prevalence of 19%.

Conclusion: We report a previously unrecognized endemic area of CKDu among the underprivileged population engaged in agricultural labor in coastal southeastern India in the states of Tamil Nadu and Puducherry (Tondaimandalam) in India.
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http://dx.doi.org/10.1016/j.ekir.2020.08.032DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7609951PMC
November 2020

Rule Out Acute Kidney Injury in the Emergency Department With a Urinary Dipstick.

Kidney Int Rep 2020 Nov 18;5(11):1982-1992. Epub 2020 Sep 18.

Division of Nephrology, Columbia University Irving Medical Center, New York, New York, USA.

Introduction: The identification of acute injury of the kidney relies on serum creatinine (SCr), a functional marker with poor temporal resolution as well as limited sensitivity and specificity for cellular injury. In contrast, urinary biomarkers of kidney injury have the potential to detect cellular stress and damage in real time.

Methods: To detect the response of the kidney to injury, we have tested a lateral flow dipstick that measures a urinary protein called neutrophil gelatinase-associated lipocalin (NGAL). Analysis of urine was performed in a prospective cohort of 479 patients (final cohort  = 426) entering an emergency department in New York City and subsequently admitted for inpatient care.

Results: Colorimetric development had high interrater reliability (88% concordance rate) and correlated with traditional enzyme-linked immunosorbent assay (ELISA) measurements (ρ = 0.732,  < .0001). Of the 14% of the cohort who met Acute Kidney Injury Network (AKIN) SCr criteria for acute kidney injury (AKI), 67% demonstrated transient (<2 days) and 33% demonstrated sustained (>2 days) elevation of SCr. Comparing the outcomes of patients with sustained versus transient or undetectable changes in SCr revealed that the urinary NGAL (uNGAL) dipstick had high specificity and negative predictive value (NPV) (high- vs. low-intermediate readings, sensitivity = 0.55, specificity = 0.91, positive predictive value = 0.24, NPV = 0.97, χ = 20.39,  < 0.001).

Conclusion: We show that the introduction of a bedside uNGAL dipstick permits accurate triage by identifying individuals who do not have tubular injury. In an era of shortening length of stay and rapid decisions based on isolated SCr measurements, real-time exclusion of kidney injury by a dipstick will be particularly useful to overcome the retrospective, insensitive, and nonspecific attributes of SCr.
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http://dx.doi.org/10.1016/j.ekir.2020.09.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7609964PMC
November 2020

Impact of Deceased Donor Kidney Procurement Biopsy Technique on Histologic Accuracy.

Kidney Int Rep 2020 Nov 14;5(11):1906-1913. Epub 2020 Aug 14.

Department of Medicine, Division of Nephrology, Columbia University College of Physicians and Surgeons and New York Presbyterian Hospital, New York, New York, USA.

Introduction: The factors that influence deceased donor kidney procurement biopsy reliability are not well established. We examined the impact of biopsy technique and pathologist training on procurement biopsy accuracy.

Methods: We retrospectively identified all deceased donor kidney-only transplants at our center from 2006 to 2016 with both procurement and reperfusion biopsies performed and information available on procurement biopsy technique and pathologist (n = 392). Biopsies were scored using a previously validated system, classifying "suboptimal" histology as the presence of at least 1 of the following: glomerulosclerosis ≥11%, moderate/severe interstitial fibrosis/tubular atrophy, or moderate/severe vascular disease. We calculated relative risk ratios (RRR) to determine the influence of technique (core vs. wedge) and pathologist (renal vs. nonrenal) on concordance between procurement and reperfusion biopsy histologic classification.

Results: A total of 171 (44%) procurement biopsies used wedge technique, and 221 (56%) used core technique. Results of only 36 biopsies (9%) were interpreted by renal pathologists. Correlation between procurement and reperfusion glomerulosclerosis was poor for both wedge ( = 0.11) and core ( = 0.14) biopsies. Overall, 34% of kidneys had discordant classification on procurement versus reperfusion biopsy. Neither biopsy technique nor pathologist training was associated with concordance between procurement and reperfusion histology, but a larger number of sampled glomeruli was associated with a higher likelihood of concordance (adjusted RRR = 1.12 per 10 glomeruli, 95% confidence interval = 1.04-1.22).

Conclusions: Biopsy technique and pathologist training were not associated with procurement biopsy histologic accuracy in this retrospective study. Prospective trials are needed to determine how to optimize procurement biopsy practices.
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http://dx.doi.org/10.1016/j.ekir.2020.08.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7609887PMC
November 2020

Racial disparities in preemptive waitlisting and deceased donor kidney transplantation: Ethics and solutions.

Am J Transplant 2021 03 3;21(3):958-967. Epub 2020 Dec 3.

Department of Medicine, Renal-Electrolyte and Hypertension Division, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.

Kidney transplantation prior to dialysis, known as "preemptive transplant," enables patients to live longer and avoid the substantial quality of life burdens due to chronic dialysis. Deceased donor kidneys are a public resource that ought to provide health benefits equitably. Unfortunately, White, better educated, and privately insured patients enjoy disproportionate access to preemptive transplantation using deceased donor kidneys. This problem has persisted for decades and is exacerbated by the first-come, first-served approach to kidney allocation for predialysis patients. In this Personal Viewpoint, we describe the diverse barriers to preemptive waitlisting and kidney transplant. The analysis focuses on healthcare system features that particularly disadvantage Black patients, such as the waitlisting eligibility criterion of a single glomerular filtration rate or creatinine clearance ≤20 ml/min, and neglect of wide variation in the rate of progression to end-stage kidney disease (ESKD) in allocating preemptive transplants. We propose initiatives to improve equity including: (1) standardization of waitlisting eligibility criteria related to kidney function; (2) aggressive education for clinicians about early transplant referral; (3) innovations in electronic medical record capabilities; and (4) rapid status 7 listing by centers. If those initiatives fail, the transplant field should consider eliminating preemptive waitlisting and transplantation with deceased donor kidneys.
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http://dx.doi.org/10.1111/ajt.16392DOI Listing
March 2021

COVID-19-associated acute kidney injury: consensus report of the 25th Acute Disease Quality Initiative (ADQI) Workgroup.

Nat Rev Nephrol 2020 12 15;16(12):747-764. Epub 2020 Oct 15.

Department of Critical Care Medicine, Center for Critical Care Nephrology, University of Pittsburgh, Pittsburgh, PA, USA.

Kidney involvement in patients with coronavirus disease 2019 (COVID-19) is common, and can range from the presence of proteinuria and haematuria to acute kidney injury (AKI) requiring renal replacement therapy (RRT; also known as kidney replacement therapy). COVID-19-associated AKI (COVID-19 AKI) is associated with high mortality and serves as an independent risk factor for all-cause in-hospital death in patients with COVID-19. The pathophysiology and mechanisms of AKI in patients with COVID-19 have not been fully elucidated and seem to be multifactorial, in keeping with the pathophysiology of AKI in other patients who are critically ill. Little is known about the prevention and management of COVID-19 AKI. The emergence of regional 'surges' in COVID-19 cases can limit hospital resources, including dialysis availability and supplies; thus, careful daily assessment of available resources is needed. In this Consensus Statement, the Acute Disease Quality Initiative provides recommendations for the diagnosis, prevention and management of COVID-19 AKI based on current literature. We also make recommendations for areas of future research, which are aimed at improving understanding of the underlying processes and improving outcomes for patients with COVID-19 AKI.
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http://dx.doi.org/10.1038/s41581-020-00356-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7561246PMC
December 2020

Major Variation across Local Transplant Centers in Probability of Kidney Transplant for Wait-Listed Patients.

J Am Soc Nephrol 2020 12 9;31(12):2900-2911. Epub 2020 Oct 9.

Division of Nephrology, Department of Medicine, Columbia University Vagelos College of Physicians and Surgeons, New York, New York

Background: Geographic disparities in access to deceased donor kidney transplantation persist in the United States under the Kidney Allocation System (KAS) introduced in 2014, and the effect of transplant center practices on the probability of transplantation for wait-listed patients remains unclear.

Methods: To compare probability of transplantation across centers nationally and within donation service areas (DSAs), we conducted a registry study that included all United States incident adult kidney transplant candidates wait listed in 2011 and 2015 (pre-KAS and post-KAS cohorts comprising 32,745 and 34,728 individuals, respectively). For each center, we calculated the probability of deceased donor kidney transplantation within 3 years of wait listing using competing risk regression, with living donor transplantation, death, and waiting list removal as competing events. We examined associations between center-level and DSA-level characteristics and the adjusted probability of transplant.

Results: Candidates received deceased donor kidney transplants within 3 years of wait listing more frequently post-KAS (22%) than pre-KAS (19%). Nationally, the probability of transplant varied 16-fold between centers, ranging from 4.0% to 64.2% in the post-KAS era. Within DSAs, we observed a median 2.3-fold variation between centers, with up to ten-fold and 57.4 percentage point differences. Probability of transplantation was correlated in the post-KAS cohort with center willingness to accept hard-to-place kidneys (=0.55, <0.001) and local organ supply (=0.44, <0.001).

Conclusions: Large differences in the adjusted probability of deceased donor kidney transplantation persist under KAS, even between centers working with the same local organ supply. Probability of transplantation is significantly associated with organ offer acceptance patterns at transplant centers, underscoring the need for greater understanding of how centers make decisions about organs offered to wait-listed patients and how they relate to disparities in access to transplantation.
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http://dx.doi.org/10.1681/ASN.2020030335DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7790218PMC
December 2020

Content Coverage Evaluation of the OMOP Vocabulary on the Transplant Domain Focusing on Concepts Relevant for Kidney Transplant Outcomes Analysis.

Appl Clin Inform 2020 08 7;11(4):650-658. Epub 2020 Oct 7.

Department of Biomedical Informatics, Columbia University, New York, New York, United States.

Background: Improving outcomes of transplant recipients within and across transplant centers is important with the increasing number of organ transplantations being performed. The current practice is to analyze the outcomes based on patient level data submitted to the United Network for Organ Sharing (UNOS). Augmenting the UNOS data with other sources such as the electronic health record will enrich the outcomes analysis, for which a common data model (CDM) can be a helpful tool for transforming heterogeneous source data into a uniform format.

Objectives: In this study, we evaluated the feasibility of representing concepts from the UNOS transplant registry forms with the Observational Medical Outcomes Partnership (OMOP) CDM vocabulary to understand the content coverage of OMOP vocabulary on transplant-specific concepts.

Methods: Two annotators manually mapped a total of 3,571 unique concepts extracted from the UNOS registry forms to concepts in the OMOP vocabulary. Concept mappings were evaluated by (1) examining the agreement among the initial two annotators and (2) investigating the number of UNOS concepts not mapped to a concept in the OMOP vocabulary and then classifying them. A subset of mappings was validated by clinicians.

Results: There was a substantial agreement between annotators with a kappa score of 0.71. We found that 55.5% of UNOS concepts could not be represented with OMOP standard concepts. The majority of unmapped UNOS concepts were categorized into transplant, measurement, condition, and procedure concepts.

Conclusion: We identified categories of unmapped concepts and found that some transplant-specific concepts do not exist in the OMOP vocabulary. We suggest that adding these missing concepts to OMOP would facilitate further research in the transplant domain.
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http://dx.doi.org/10.1055/s-0040-1716528DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7557323PMC
August 2020

Effect of the ASCENT Intervention to Increase Knowledge of Kidney Allocation Policy Changes Among Dialysis Providers.

Kidney Int Rep 2020 Sep 2;5(9):1422-1431. Epub 2020 Jul 2.

Department of Surgery, Division of Transplantation, Emory University School of Medicine, Atlanta, Georgia, USA.

Introduction: The Allocation System Changes for Equity in Kidney Transplantation (ASCENT) trial was a cluster-randomized pragmatic, effectiveness-implementation study designed to test whether a multicomponent educational intervention targeting leadership, clinic staff, and patients in dialysis facilities improved knowledge and awareness of the 2014 Kidney Allocation System (KAS) change.

Methods: Participants included 690 dialysis facility medical directors, nephrologists, social workers, and other staff within 655 US dialysis facilities, with 51% ( = 334) in the intervention group and 49% ( = 321) in the control group. Intervention activities included a webinar targeting medical directors and facility staff, an approximately 10-minute educational video targeting dialysis staff, an approximately 10-minute educational video targeting patients, and a facility-specific audit and feedback report of transplant performance. The control group received a standard United Network for Organ Sharing brochure. Provider knowledge was a secondary outcome of the ASCENT trial and the primary outcome of this study; knowledge was assessed as a cumulative score on a 5-point Likert scale (higher score = greater knowledge). Intention-to-treat analysis was used.

Results: At baseline, nonintervention providers had a higher mean knowledge score (mean ± SD, 2.45 ± 1.43) than intervention providers (mean ± SD, 2.31 ± 1.46). After 3 months, the average knowledge score was slightly higher in the intervention (mean ± SD, 3.14 ± 1.28) versus nonintervention providers (mean ± SD, 3.07 ± 1.24), and the estimated mean difference in knowledge scores between the groups at follow-up minus the mean difference at baseline was 0.25 (95% confidence interval [CI], 0.11-0.48;  = 0.039). The effect size (0.41) was low to moderate.

Conclusion: Dialysis facility provider education could help extend the impact of a national policy change in organ allocation.
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http://dx.doi.org/10.1016/j.ekir.2020.06.027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7486341PMC
September 2020

Tocilizumab for severe COVID-19 in solid organ transplant recipients: a matched cohort study.

Am J Transplant 2020 11 15;20(11):3198-3205. Epub 2020 Oct 15.

Department of Medicine, Division of Digestive & Liver Diseases, Columbia University College of Physicians & Surgeons, New York, NY.

The safety and efficacy of tocilizumab for the treatment of severe respiratory symptoms due to COVID-19 remain uncertain, in particular among solid organ transplant (SOT) recipients. Thus, we evaluated the clinical characteristics and outcomes of 29 hospitalized SOT recipients who received tocilizumab for severe COVID-19, compared to a matched control group who did not. Among a total of 117 total SOT recipients hospitalized with COVID-19, 29 (24.8%) received tocilizumab. The 90-day mortality was significantly higher among patients who received tocilizumab (41%) compared to those who did not (20%, P = .03). When compared to control patients matched by age, hypertension, chronic kidney disease, and administration of high dose corticosteroids, there was no significant difference in mortality (41% vs 28%, P = .27), hospital discharge (52% vs 72%, P = .26), or secondary infections (34% vs 24%, P = .55). Among patients who received tocilizumab, there was also no difference in mortality based on the level of oxygen support (intubated vs not intubated) at the time of tocilizumab initiation. In this matched cohort study, tocilizumab appeared to be safe but was not associated with decreased 90-day mortality. Larger randomized studies are needed to identify whether there are subsets of SOT recipients who may benefit from tocilizumab for treatment of COVID-19.
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http://dx.doi.org/10.1111/ajt.16314DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7537322PMC
November 2020