American Society Of Nephrology Research Articles

1216-P: Prevalence of SGLT2i and GLP1RA Use among U.S. Adults with Type 2 Diabetes

Objective: To determine the prevalence of sodium-glucose contransporter-2 inhibitor (SGLT2i) and glucagon-like peptide-1 receptor agonist (GLP1RA) use among adults with type 2 diabetes (T2D) in the United States. Methods: We studied adults with T2D and eGFR ≥30mL/min/1.73m2 who participated in the National Health and Nutrition Examination Survey (NHANES) , focusing on the 2017-2020 examination cycle. We tested prevalence of SGLT2i and GLP1RA use among subgroups based on demographic variables and relevant comorbidities, including chronic kidney disease (CKD) , congestive heart failure (CHF) , and atherosclerotic cardiovascular disease (ASCVD) . We compared use of SGLT2i and GLP1RA to other glucose-lowering medications and assessed trends from prior NHANES cycles. Results: Among 1,375 participants studied in 2017-2020, mean age was 60 years, 46% were women, 13% self-identified as non-Hispanic Black, 10% self-identified as Mexican American, 37% had CKD, 8.5% had CHF, and 23% had ASCVD. The prevalence of SGLT2i and GLP1RA use was 5.8% and 4.4%, respectively. SGLT2i were used by 7.2% of adults with CKD or CHF, and GLP1RA were used by 3.5% of adults with ASCVD. Differences in SGLT2i or GLP1RA use were observed by age, race, ethnicity, and health insurance status. Biguanides, sulfonylureas, DPP-4 inhibitors, and insulin were used more frequently than SGLT2i or GLP1RA. Overall, prevalence of SGLT2i but not GLP1RA use increased significantly from 2013-2014 to 2017-2020. Conclusions: SGLT2i and GLP1RA use is low among adults with T2D, including among those with strong indications. Enhanced implementation of these agents is crucial to improving kidney and cardiovascular outcomes and mitigating health disparities in T2D. Disclosure C.Limonte: None. Y.Hall: None. S.Trikudanathan: Research Support; Bionic pancreas, Bionic pancreas , Insulet Corporation, Insulet Corporation. K.R.Tuttle: Advisory Panel; Boehringer Ingelheim International GmbH, Gilead Sciences, Inc., Consultant; AstraZeneca, Eli Lilly and Company, Research Support; Bayer AG, Goldfinch Bio, Inc., Novo Nordisk, Travere. I.B.Hirsch: Consultant; Abbott Diabetes, Bigfoot Biomedical, Inc., GWave, Roche Diabetes Care, Research Support; Beta Bionics, Inc., Insulet Corporation, Medtronic. I.De boer: Advisory Panel; AstraZeneca, Bayer AG, Cyclerion Therapeutics, Inc., George Clinical, Goldfinch Bio, Inc., Other Relationship; American Society of Nephrology, Research Support; Dexcom, Inc. L.Zelnick: None. Funding This work was supported by an unrestricted fund from the Northwest Kidney Centers. CPL was funded by NIDDK grant T32DK007467 and the American Kidney Fund Clinical Scientist in Nephrology grant program. Additional funding was provided by R01DK126373, R01DK125084, R01DK088762.

395-P: BeAM Value and Glycemia Assessed by Continuous Glucose Monitoring among Participants with Type 2 Diabetes and Chronic Kidney Disease

Introduction: The difference between bedtime and morning glucose levels (BeAM value) is a clinically relevant measure that can guide clinicians regarding insulin titrations. As chronic kidney disease (CKD) develops, changes in insulin sensitivity and kinetics and limitations to available medications may contribute to over-basalization, insufficient prandial control, and large BeAM. We hypothesized that CKD and less time in range (TIR) derived from continuous glucose monitoring (CGM) are associated with large BeAM in T2DM. Methods: This was a prospective observational cohort study of 1people with T2DM treated with insulin or sulfonylurea, 81 participants with CKD (eGFR <60 mL/min/1.73 m2) , and 24 controls with eGFR ≥60 frequency matched on age, duration of diabetes, HbA1c, and glucose-lowering medications. Each participant wore a CGM for two 6-day periods. BeAM was calculated as the difference between mean bedtime sensor glucose values and mean morning sensor values, with large BeAM defined as ≥30 mg/dL glucose drop from bedtime to morning. Results: Participants had a mean age of 68 years, diabetes duration years and HbA1c 7.7%. CKD and controls had a mean eGFR 38 and 83 mL/min/1.73 m2 respectively. Median (IQR) BeAM was 29 (9-52) mg/dL for participants with CKD and (-4-31) mg/dL for controls (p = 0.11) . Forty participants with CKD (49%) and 7 controls (29%) had a large BeAM. Those with a large BeAM had less TIR (58 v 68%) , higher HbA1c (8.0 vs. 7.5%) , and higher glucose management indicator (GMI, 7.5 vs. 7.2%) compared to those with BeAM <30 mg/dL (each p<0.05, adjusting for age, sex, and race) . Coefficient of variation, diabetes duration, and insulin dose (total or basal) did not correlate with BeAM. Conclusions: Large BeAM was common among participants with long-standing T2DM and CKD and was associated with less TIR and higher GMI. These data suggest that there is opportunity for improvement in daytime and prandial diabetes management among patients with CKD. Disclosure L.Mayeda: None. L.Zelnick: None. S.Trikudanathan: Research Support; Bionic pancreas, Bionic pancreas , Insulet Corporation, Insulet Corporation. I.B.Hirsch: Consultant; Abbott Diabetes, Bigfoot Biomedical, Inc., GWave, Roche Diabetes Care, Research Support; Beta Bionics, Inc., Insulet Corporation, Medtronic. I.De boer: Advisory Panel; AstraZeneca, Bayer AG, Cyclerion Therapeutics, Inc., George Clinical, Goldfinch Bio, Inc., Other Relationship; American Society of Nephrology, Research Support; Dexcom, Inc. Funding American Diabetes Association (4-15-CKD-20) ; National Institute of Diabetes and Digestive and Kidney Diseases (R01DK088762, R01087726)

394-P: Baseline Risk Markers and Visit-to-Visit Variability in Relation to Kidney Outcomes: A Post Hoc Analysis of the PERL Study

Background: Baseline risk variables and visit-to-visit variability (VV) of systolic blood pressure (SBP) , HbA1c, serum creatinine, and uric acid (UA) are potential risk markers of kidney function decline in type 1 diabetes. Methods: Post-hoc analysis of the PERL study (NCT02017171) - a double-blind randomized placebo-controlled clinical trial investigating allopurinol’s effect on iohexol-derived glomerular filtration rate (iGFR) in type 1 diabetes with elevated UA. Primary outcome was iGFR change over three years. Linear regression with backwards selection of baseline clinical variables was performed to identify an optimized model forecasting iGFR change. VV of SBP, HbA1c, serum creatinine, and UA were calculated as standard deviations of the residuals in individual linear regression models (LV) and coefficients of variation (CV) using all available measurements in the run-in period; thereafter assessed by linear regression, with iGFR change as the dependent variable. Adjustment included sex, baseline age, diabetes duration, BMI, HbA1c, SBP, kidney function (iGFR or eGFR, as appropriate) , urine albumin excretion rate (UAER) , smoking, and renin-angiotensin system inhibitor use. Results: 422 participants completed the trial, 4were included in this analysis. In the optimized baseline risk marker model, race other (including but not limited to Hawaiian/Pacific Islander) than White, Black, or Asian, higher HbA1c, UAER, and heart rate, and lower iGFR were associated with faster iGFR decline; Hispanic/Latino ethnicity was not. Assessing VV, higher LV and CV of SBP was associated with faster iGFR decline (adjusted LV β: -0.79, p=0.01; CV β: -0.79, p=0.04) ; VVs of HbA1c, creatinine, and UA were not. Conclusions: We identified several risk markers of faster iGFR decline in a high-risk population of individuals with type 1 diabetes. In addition to previously described associations, higher SBP VV was a risk marker for faster kidney function decline. Disclosure V.Rotbain curovic: None. S.Polsky: Advisory Panel; Medtronic, Other Relationship; diaTribe, Research Support; Dexcom, Inc., Eli Lilly and Company, Leona M. and Harry B. Helmsley Charitable Trust, Medtronic, National Institute of Diabetes and Digestive and Kidney Diseases, Sanofi-Aventis U.S. R.Pop-busui: Advisory Panel; Averitas Pharma, Inc., Boehringer Ingelheim International GmbH, Nevro Corp., Novo Nordisk, Reata Pharmaceuticals, Inc., Regenacy Pharmaceuticals, Inc. R.J.Sigal: Advisory Panel; Novo Nordisk Canada Inc., Research Support; Novo Nordisk Canada Inc. K.R.Tuttle: Advisory Panel; Boehringer Ingelheim International GmbH, Gilead Sciences, Inc., Consultant; AstraZeneca, Eli Lilly and Company, Research Support; Bayer AG, Goldfinch Bio, Inc., Novo Nordisk, Travere. G.E.Umpierrez: Research Support; AstraZeneca, Dexcom, Inc., Novo Nordisk. A.Wallia: Advisory Panel; Eli Lilly and Company, Research Support; Novo Nordisk, UnitedHealth Group. S.Rosas: Advisory Panel; AstraZeneca, Teladoc Health, Other Relationship; Bayer AG, Research Support; AstraZeneca, Bayer AG. P.Rossing: Consultant; Astellas Pharma Inc., AstraZeneca, Bayer AG, Gilead Sciences, Inc., Merck Sharp & Dohme Corp., Novo Nordisk A/S, Sanofi, Speaker's Bureau; Eli Lilly and Company. The perl study group: n/a. N.Roy: None. T.W.Hansen: Stock/Shareholder; Novo Nordisk A/S. L.Caramori: Advisory Panel; Bayer AG, Consultant; AstraZeneca, Boehringer Ingelheim International GmbH, Novo Nordisk, Research Support; Bayer AG, Novartis AG. D.Cherney: Other Relationship; AbbVie Inc., AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Janssen Research & Development, LLC, Lilly, Maze, BMS, CSL-Behring, Merck, Otsuka, Novartis and Novo-Nordisk , Mitsubishi Tanabe Pharma Corporation, Sanofi, Research Support; Boehringer Ingelheim-Lilly, Merck, Janssen, Sanofi, AstraZeneca and Novo-Nordisk. I.De boer: Advisory Panel; AstraZeneca, Bayer AG, Cyclerion Therapeutics, Inc., George Clinical, Goldfinch Bio, Inc., Other Relationship; American Society of Nephrology, Research Support; Dexcom, Inc. I.B.Hirsch: Consultant; Abbott Diabetes, Bigfoot Biomedical, Inc., GWave, Roche Diabetes Care, Research Support; Beta Bionics, Inc., Insulet Corporation, Medtronic. I.Lingvay: Advisory Panel; AstraZeneca, Boehringer Ingelheim International GmbH, Lilly, Mannkind, TARGET PharmaSolutions; Valeritas;; Altimmune; DataRevive; Click; Medscape Duke CRI; Janssen Pharma; Bayer; Intercept, Novo Nordisk, Sanofi, Zealand Pharma A/S, Consultant; Novo Nordisk, Research Support; NovoNordisk; Mylan; Merck, Sanofi. J.B.Mcgill: Advisory Panel; Gilead Sciences, Inc., Lilly Diabetes, MannKind Corporation, Novo Nordisk A/S, Provention Bio, Inc., Salix Pharmaceuticals, Consultant; Bayer AG, Boehringer Ingelheim International GmbH, Research Support; Dexcom, Inc., Novo Nordisk. Funding Supported by grants from the NIDDK (R03-DK-094484, R34-DK-097808, UC4-DK-101108, P30-DK-036836, and P30-DK-020572) , the JDRF (17-2012-377) , the National Center for Advancing Translational Sciences (UL1-TR-002494, UL1-TR- 001422, UL1-TR-002556, UL1-TR-002319, and UL1-TR- 001105) , and the National Institute on Aging (Claude Pepper Center grant number, P30-AG-024824)

MO891: Poor Tolerability of the Standard, Extended, 48h Ambulatory Blood Pressure Monitoring in Haemodialysis Patients

Abstract BACKGROUND AND AIMS Ambulatory blood pressure monitoring (ABPM), extended to 44h or 48h for the diagnosis of hypertension in end-stage kidney disease (ESKD) patients, is recommended by Consensus Documents of the American Society of Nephrology and the European Renal Association. About 10%–20% of individuals in the general population report sleeping problems and other symptoms during 24 h ABPM. Because the longer recording period (44 or 48 h versus 24 h), the notorious sleeping disturbances and the high symptom burden of the ESKD population, the feasibility of the technique may be limited in this population. However, the large-scale tolerability of ABPM in the haemodialysis population, has never been investigated. METHOD We performed an international survey of feasibility and tolerability of 48 h ABPM in six centres in three European countries. These centres are led by motivated clinical nephrologists, all members of the EURECA-m working group. 48 h ABPM recording was proposed to a large, representative sample of the whole dialysis population of these centres. Well validated instruments (AAMI/ESH/ISO) were applied in all centres. As recommended by the European Society of Hypertension guidelines, recordings were made at 15-min intervals during the day and 30 min during the night. Reasons for refusal to undergo the test were accurately registered. A tolerability (symptoms) questionnaire and a specific questionnaire for sleep evaluation were administered to all participants who underwent 48h ABPM. Reasons for not completing of the ABPM monitoring were systematically recorded. RESULTS In the whole haemodialysis population of participating centres including 735 patients, 440 (60%) were invited to participate in the study. Among these patients, 119 (27%) refused to undergo ABPM recording. Reasons for refusal were fear of discomfort (n = 30, 25%), measurement too long (n = 22, 18%), logistic problems (n = 17, 14%), previous negative experience (n = 13, 11%), clinical reasons (n = 12, 10%), other reasons (n = 25). Among the 321 patients who performed the 48h ABPM recording, 29 (9%) did not complete it and the main reason for interrupting the recording were discomfort [12 patients (41%)], followed by device failure [10 patients (34%)]. Among symptoms developed during the ABPM study, frequent interruption of sleeping because of noise or discomfort was reported by 32% of patients, followed by itching (24%) and pain during the measurements (20%). The detailed list of symptoms, is reported in the Table 1. CONCLUSION Overall, about 25% of haemodialysis patients consider 48h ABPM a laborious and discomforting test and prejudicially refuse to undergo it. Among patients who undergo 48h ABPM, itching and interruption of sleeping are complained by about 1/3 of patients. These figures are substantially higher than those reported in studies in the general population and in hypertensive patients and point to peculiar barriers at applying extended ABPM recordings in the haemodialysis population. Studies applying more tolerable instruments and a minimum set of measurements over a shorter time, with a reduced number of measurements overnight, are clinical research priority for extending the use of ABPM in the haemodialysis population.

Changing the Trajectory of Heart Failure and Kidney Disease: A Call for Action.

Changing the Trajectory of Heart Failure and Kidney Disease: A Call for Action.

Editorial introductions.

Current Opinion in Nephrology and Hypertension was launched in 1992. It is part of a successful series of review journals whose unique format is designed to provide a systematic and critical assessment of the literature as presented in the many primary journals. The field of nephrology and hypertension is divided into 12 sections that are each reviewed once a year. Each section is assigned a Section Editor, a leading authority in the area, who identifies the most important topics at that time. Here we are pleased to introduce the Section Editors for this issue. SECTION EDITORS Agnes B. FogoAgnes B. FogoProfessor Agnes B. Fogo completed her medical training at Vanderbilt University Medical School, USA. She has remained at Vanderbilt for residency in pathology and fellowship in renal pathology and experimental kidney disease models. Her main research interests are focused on potential regression of chronic kidney disease and tubular-glomerular crosstalk in this process, pursued with funding from the National Institutes of Health and other sources. She is also dedicated to diagnostic renal pathology and has created an online Atlas of Renal Pathology with the American Journal of Kidney Disease and the National Kidney Foundation. She has also authored two books on renal pathology. Prof. Fogo enjoys teaching renal pathology and received the Robert G. Narins award from the American Society of Nephrology in 2011 as well as the Roscoe R. Robinson award from the International Society of Nephrology in 2019, for her contributions in teaching. She is currently President of the ISN and the John L. Shapiro Professor of Pathology, Microbiology and Immunology, Professor of Medicine and Paediatrics and Director of the Renal/Electron Microscopy Laboratory at Vanderbilt University Medical Center, Nashville, Tennessee, USA. Navdeep TangriNavdeep TangriDr Tangri is an attending physician and Associate Professor in the Division of Nephrology, Department of Medicine and the Department of Community Health Sciences at the University of Manitoba, Canada. Dr Tangri's research program is clinical and translational and focused on improving clinical decision making for patients with advanced chronic kidney disease. He developed and validated the Kidney Failure Risk Equation (KFRE) to predict the need for dialysis in patients with Chronic Kidney Disease (CKD), and is presently engaged in multiple validation and implementation exercises to increase the uptake of the KFRE. In addition, Dr Tangri is conducting a large prospective study on frailty, physical and cognitive function in advanced CKD, as well as leading a multinational randomized trial on the safety and efficacy of a new therapy in this population. He has published over 250 manuscripts and presented at multiple national and international scientific meetings. He is also a recipient of the CIHR New Investigator Award and a CIHR Foundation grant.

Breaking the Barriers to Innovation in Kidney Care: The Time is Now.

Breaking the Barriers to Innovation in Kidney Care: The Time is Now.

Risks and burdens of incident diabetes in long COVID: a cohort study

BackgroundThere is growing evidence suggesting that beyond the acute phase of SARS-CoV-2 infection, people with COVID-19 could experience a wide range of post-acute sequelae, including diabetes. However, the risks and burdens of diabetes in the post-acute phase of the disease have not yet been comprehensively characterised. To address this knowledge gap, we aimed to examine the post-acute risk and burden of incident diabetes in people who survived the first 30 days of SARS-CoV-2 infection.MethodsIn this cohort study, we used the national databases of the US Department of Veterans Affairs to build a cohort of 181 280 participants who had a positive COVID-19 test between March 1, 2020, and Sept 30, 2021, and survived the first 30 days of COVID-19; a contemporary control (n=4 118 441) that enrolled participants between March 1, 2020, and Sept 30, 2021; and a historical control (n=4 286 911) that enrolled participants between March 1, 2018, and Sept 30, 2019. Both control groups had no evidence of SARS-CoV-2 infection. Participants in all three comparison groups were free of diabetes before cohort entry and were followed up for a median of 352 days (IQR 245–406). We used inverse probability weighted survival analyses, including predefined and algorithmically selected high dimensional variables, to estimate post-acute COVID-19 risks of incident diabetes, antihyperglycaemic use, and a composite of the two outcomes. We reported two measures of risk: hazard ratio (HR) and burden per 1000 people at 12 months.FindingsIn the post-acute phase of the disease, compared with the contemporary control group, people with COVID-19 exhibited an increased risk (HR 1·40, 95% CI 1·36–1·44) and excess burden (13·46, 95% CI 12·11–14·84, per 1000 people at 12 months) of incident diabetes; and an increased risk (1·85, 1·78–1·92) and excess burden (12·35, 11·36–13·38) of incident antihyperglycaemic use. Additionally, analyses to estimate the risk of a composite endpoint of incident diabetes or antihyperglycaemic use yielded a HR of 1·46 (95% CI 1·43–1·50) and an excess burden of 18·03 (95% CI 16·59–19·51) per 1000 people at 12 months. Risks and burdens of post-acute outcomes increased in a graded fashion according to the severity of the acute phase of COVID-19 (whether patients were non-hospitalised, hospitalised, or admitted to intensive care). All the results were consistent in analyses using the historical control as the reference category.InterpretationIn the post-acute phase, we report increased risks and 12-month burdens of incident diabetes and antihyperglycaemic use in people with COVID-19 compared with a contemporary control group of people who were enrolled during the same period and had not contracted SARS-CoV-2, and a historical control group from a pre-pandemic era. Post-acute COVID-19 care should involve identification and management of diabetes.FundingUS Department of Veterans Affairs and the American Society of Nephrology.

Етіологія, патогенез та інтенсивна терапія метаболічного ацидозу

У статті надані дані щодо етіології, патогенезу, клінічних проявів, принципів діагностики та лікування метаболічних ацидозів: діабетичного і недіабетичного кетоацидозу, лактатацидозу в дорослих і дітей. Викладено сучасні напрямки інфузійної терапії кетоацидозу і лактатацидозу із застосуванням новітніх вітчизняних інфузійних засобів. У своїй статті автори зіставили алгоритми лікування кетоацидозу і лактатацидозу з рекомендаціями Британського товариства клінічної діабетології і Американської асоціації нефрологів, роблячи поправку на можливості вітчизняних лабораторних досліджень. Характерною особливістю деяких форм кислотно-основного дисбалансу, що часто зустрічаються, є тісне переплетення ушкоджуючих або пристосувальних елементів, чіткої межі між якими не існує. Багатофакторність і патогенетична неоднозначність порушень кислотно-основного гомео­стазу зумовлюють значні розбіжності в оцінці прогностичної значимості і стратегії лікування його складних форм. У клінічній практиці це часто призводить до невиправданої схематизації, «знеособлення» терапії, або, що ще гірше, до прагнення враховувати параметри кислотно-основного стану тільки при зміщенні рН в області загрожуючих життю значень.

Women in Nephrology: The Journey, Barriers, Challenges and the Future

Women in Nephrology: The Journey, Barriers, Challenges and the Future

A Unifying Approach for GFR Estimation: Recommendations of the NKF-ASN Task Force on Reassessing the Inclusion of Race in Diagnosing Kidney Disease.

In response to a national call for re-evaluation of the use of race in clinical algorithms, the National Kidney Foundation (NKF) and the American Society of Nephrology (ASN) established a Task Force to reassess inclusion of race in the estimation of GFR in the United States and its implications for diagnosis and management of patients with, or at risk for, kidney diseases. The Task Force organized its activities over 10 months in phases to ( 1 ) clarify the problem and evidence regarding eGFR equations in the United States (described previously in an interim report), and, in this final report, ( 2 ) evaluate approaches to address use of race in GFR estimation, and ( 3 ) provide recommendations. We identified 26 approaches for the estimation of GFR that did or did not consider race and narrowed our focus, by consensus, to five of those approaches. We holistically evaluated each approach considering six attributes: assay availability and standardization; implementation; population diversity in equation development; performance compared with measured GFR; consequences to clinical care, population tracking, and research; and patient centeredness. To arrive at a unifying approach to estimate GFR, we integrated information and evidence from many sources in assessing strengths and weaknesses in attributes for each approach, recognizing the number of Black and non-Black adults affected. ( 1 ) For US adults (>85% of whom have normal kidney function), we recommend immediate implementation of the CKD-EPI creatinine equation refit without the race variable in all laboratories in the United States because it does not include race in the calculation and reporting, included diversity in its development, is immediately available to all laboratories in the United States, and has acceptable performance characteristics and potential consequences that do not disproportionately affect any one group of individuals. ( 2 ) We recommend national efforts to facilitate increased, routine, and timely use of cystatin C, especially to confirm eGFR in adults who are at risk for or have CKD, because combining filtration markers (creatinine and cystatin C) is more accurate and would support better clinical decisions than either marker alone. If ongoing evidence supports acceptable performance, the CKD-EPI eGFR-cystatin C (eGFRcys) and eGFR creatinine-cystatin C (eGFRcr-cys_R) refit without the race variables should be adopted to provide another first-line test, in addition to confirmatory testing. ( 3 ) Research on GFR estimation with new endogenous filtration markers and on interventions to eliminate race and ethnic disparities should be encouraged and funded. An investment in science is needed for newer approaches that generate accurate, unbiased, and precise GFR measurement and estimation without the inclusion of race, and that promote health equity and do not generate disparate care. This unified approach, without specification of race, should be adopted across the United States. High-priority and multistakeholder efforts should implement this solution.

Reevaluating race and the glomerular filtration rate calculator.

Estimated glomerular filtration rate (eGFR) calculators have included a race adjustment to help approximate measured GFR. Over the past several years, as more attention has been directed toward uncovering racial bias, the appropriateness of including race in these calculators has been called into question. The American Society of Nephrology and the National Kidney Foundation convened an expert task force to review the inclusion of race in eGFR. The deliberative review showed that race can be removed from eGFR calculators without causing adverse reactions in any group of patients. This new, refitted CKD-EPI equation can be used immediately by all laboratories in the United States. The task force also recommended greater use of cystatin C nationally in eGFR calculations. This would enable the new CKD-EPI equation to incorporate both creatinine and cystatin C without race and would yield better accuracy than a calculator that uses creatinine alone.

Kynurenine induces T cell fat catabolism and has limited suppressive effects in vivo.

BackgroundL-kynurenine is a tryptophan-derived immunosuppressive metabolite and precursor to neurotoxic anthranilate and quinolinate. We evaluated the stereoisomer D-kynurenine as an immunosuppressive therapeutic which is hypothesized to produce less neurotoxic metabolites than L-kynurenine.MethodsL-/D-kynurenine effects on human and murine T cell function were examined in vitro and in vivo (homeostatic proliferation, colitis, cardiac transplant). Kynurenine effects on T cell metabolism were interrogated using [13C] glucose, glutamine and palmitate tracing. Kynurenine was measured in tissues from human and murine tumours and kynurenine-fed mice.FindingsWe observed that 1 mM D-kynurenine inhibits T cell proliferation through apoptosis similar to L-kynurenine. Mechanistically, [13C]-tracing revealed that co-stimulated CD4+ T cells exposed to L-/D-kynurenine undergo increased β-oxidation depleting fatty acids. Replenishing oleate/palmitate restored effector T cell viability. We administered dietary D-kynurenine reaching tissue kynurenine concentrations of 19 μM, which is close to human kidney (6 μM) and head and neck cancer (14 μM) but well below the 1 mM required for apoptosis. D-kynurenine protected Rag1–/– mice from autoimmune colitis in an aryl-hydrocarbon receptor dependent manner but did not attenuate more stringent immunological challenges such as antigen mismatched cardiac allograft rejection.InterpretationOur dietary kynurenine model achieved tissue concentrations at or above human cancer kynurenine and exhibited only limited immunosuppression. Sub-suppressive kynurenine concentrations in human cancers may limit the responsiveness to indoleamine 2,3-dioxygenase inhibition evaluated in clinical trials.FundingThe study was supported by the NIH, the Else Kröner-Fresenius-Foundation, Laffey McHugh foundation, and American Society of Nephrology.

The Future Nephrology Workforce: There Will Be One.

In 2011, the introduction of the American Society of Nephrology (ASN) Workforce Committee was heralded by a Public Policy Series article titled, “The Future Nephrology Workforce: Will There Be One?” ([1][1]). The title was intended to evoke concern over a precipitous drop in nephrology

Value-Based Care in Nephrology: The Kidney Care Choices Model and Other Reforms.

The Advancing American Kidney Health (AAKH) initiative has reinvigorated the focus on improving the care of patients with advanced CKD. Multiple interventions have been planned, focusing on education campaigns for both clinicians and patients, delaying the progression of kidney disease and improving utilization of home dialysis modalities and kidney transplantation. Value-based care models for patients with advanced kidney disease are being rolled out, with the ESKD treatment choices model starting in January 2021, and the Kidney Care Choices model planned to start in January 2022. There is increasing emphasis on the role of the nephrologist as the "captain of the ship," leading efforts in care coordination as physician leaders. The transplant reforms have focused on changes to organ procurement organizations aiming to increase availability of organs, and transplants performed, both deceased and living donor, and removing financial disincentives from live organ donation. The American Society of Nephrology (ASN) and the National Kidney Foundation (NKF) are partnering with the Department of Health and Human Services to develop educational material for clinicians and patients. In this review, we discuss these reforms, potential challenges that have arisen, and potential solutions, with emphasis on the Kidney Care Choices model.

Transforming the Care of Patients with Diabetic Kidney Disease.

Diabetes and its associated complications pose an immediate threat to humankind. Diabetic kidney disease is one of the most devastating complications, increasing the risk of death more than ten-fold over the general population. Until very recently, the only drugs proven and recommended to slow the progression of diabetic kidney disease were angiotensin-converting enzyme inhibitors and angiotensin II type 1 receptor blockers, which act by inhibiting the renin-angiotensin system. Despite their efficacy as kidney and cardiovascular protective therapies and as antihypertensive agents, renin-angiotensin system inhibitors have been grossly underutilized. Moreover, even when renin-angiotensin system inhibitors are used, patients still have a high residual risk of diabetic kidney disease progression. Finally, the kidney-protective effect of renin-angiotensin system inhibitors has been categorically demonstrated only in patients with macroalbuminuria included in the Irbesartan Diabetic Nephropathy Trial (IDNT) and Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan (RENAAL) trials, not in other individuals. The lack of new therapies to treat diabetic kidney disease over the past 2 decades has therefore represented a tremendous challenge for patients and health care providers alike. In recent years, a number of powerful new therapies have emerged that promise to transform care of patients with diabetes and kidney disease. The challenge to the community is to ensure rapid implementation of these treatments. This white paper highlights advances in treatment, opportunities for patients, challenges, and possible solutions to advance kidney health, and introduces the launch of the Diabetic Kidney Disease Collaborative at the American Society of Nephrology, to aid in accomplishing these goals.

Dialysis and Total Health Care Costs in the United States and Worldwide: The Financial Impact of a Single-Payer Dominant System in the US.

Significance Statement In the United States, dialysis provision is an example of a robust, single-payer dominant system with cost containment. When compared with the cost of dialysis in other countries, Medicare dialysis costs in the United States as a function of overall health care expenditures are approximately $60,000 per patient less than expected, likely due to substantial cost containment imposed by Medicare as the dominant payer.

Understanding and Overcoming the Challenges Related to Cardiovascular Trials Involving Patients with Kidney Disease.

Cardiovascular disease is a prevalent and prognostically important comorbidity among patients with kidney disease, and individuals with kidney disease make up a sizeable proportion (30%-60%) of patients with cardiovascular disease. However, several systematic reviews of cardiovascular trials have observed that patients with kidney disease, particularly those with advanced kidney disease, are often excluded from trial participation. Thus, currently available trial data for cardiovascular interventions in patients with kidney disease may be insufficient to make recommendations on the optimal approach for many therapies. The Kidney Health Initiative, a public-private partnership between the American Society of Nephrology and the US Food and Drug Administration, convened a multidisciplinary, international work group and hosted a stakeholder workshop intended to understand and develop strategies for overcoming the challenges with involving patients with kidney disease in cardiovascular clinical trials, with a particular focus on those with advanced disease. These efforts considered perspectives from stakeholders, including academia, industry, contract research organizations, regulatory agencies, patients, and care partners. This article outlines the key challenges and potential solutions discussed during the workshop centered on the following areas for improvement: building the business case, re-examining study design and implementation, and changing the clinical trial culture in nephrology. Regulatory and financial incentives could serve to mitigate financial concerns with involving patients with kidney disease in cardiovascular trials. Concerns that their inclusion could affect efficacy or safety results could be addressed through thoughtful approaches to study design and risk mitigation strategies. Finally, there is a need for closer collaboration between nephrologists and cardiologists and systemic change within the nephrology community such that participation of patients with kidney disease in clinical trials is prioritized. Ultimately, greater participation of patients with kidney disease in cardiovascular trials will help build the evidence base to guide optimal management of cardiovascular disease for this population.

EGFR and chemotherapy: will removing race create disparities?

Assessment of glomerular filtration rate (GFR) is necessary for determining eligibility and dosing of chemotherapeutic agents that are excreted by the kidney. Measured GFR (mGFR), determined from filtration marker clearance, is infrequent in clinical practice; instead, current guidelines recommend estimated GFR (eGFR) from serum creatinine (eGFRCr) in adults using the Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) 2009 equation, which includes age, sex, and race. 1 Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work GroupKDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int Suppl. 2012; 3: 1-150 Google Scholar As part of a broader movement to avoid potential racial bias in clinical algorithms, the US National Kidney Foundation and American Society of Nephrology have established a task force to consider removing race from GFR-estimating equations. 2 Delgado C Baweja M Burrows NR et al. Reassessing the inclusion of race in diagnosing kidney diseases: an interim report from the NKF-ASN task force. Am J Kidney Dis. 2021; 1: 103-115 Summary Full Text Full Text PDF Scopus (15) Google Scholar Several methods could be used; one commonly used method is to assign the non-Black eGFR value to Black patients. 3 Powe NR Black kidney function matters: use or misuse of race?. JAMA. 2020; 324: 737-738 Crossref PubMed Scopus (46) Google Scholar The effects on eGFR are easy to compute, but the effects on clinical practice have not yet been carefully studied. In The Lancet Oncology, Morgan Casal and colleagues 4 Casal MA Ivy SP Beumer JH Nolin TD Effect of removing race from glomerular filtration rate-estimating equations on anticancer drug dosing and eligibility: a retrospective analysis of National Cancer Institute phase 1 clinical trial participants. Lancet Oncol. 2021; (published online Aug 13.)https://doi.org/10.1016/S1470-2045(21)00377-6 Summary Full Text Full Text PDF PubMed Scopus (3) Google Scholar report the simulated effects of removing race from the CKD-EPI equation on eligibility and recommended dosage adjustments for ten chemotherapeutic agents for Black patients with cancer. Effect of removing race from glomerular filtration rate-estimating equations on anticancer drug dosing and eligibility: a retrospective analysis of National Cancer Institute phase 1 clinical trial participantsRemoving race from the CKD-EPI equation will calculate a lower eGFR for Black patients and exclude more patients from receiving anticancer therapy, which could lead to undertreatment of Black patients with cancer and adversely affect their outcomes. Full-Text PDF

Editorial introductions.

Current Opinion in Nephrology and Hypertension was launched in 1992. It is part of a successful series of review journals whose unique format is designed to provide a systematic and critical assessment of the literature as presented in the many primary journals. The field of nephrology and hypertension are divided into 11 sections that are reviewed once a year. Each section is assigned a Section Editor, a leading authority in the area, who identifies the most important topics at that time. Here we are pleased to introduce the Journal's Section Editors for this issue. SECTION EDITORS Aline MartinAline MartinDr Aline Martin, PhD, MSc, is Associate Professor of Medicine in the Division of Nephrology and Hypertension at the Northwestern University Feinberg School of Medicine, Chicago, USA. She is a graduate of the University Jean Monnet, Saint-Etienne, France, and completed her postdoctoral training at the Jared Grantham Kidney Institute, Kansas University Medical Center, Kansas City, USA. Dr Martin conducts basic and translational science research in the area of bone and mineral metabolism disorders and actively mentors undergraduate, graduate and postdoctoral trainees. Dr Martin's research involves multiple national and international collaborations. She has received research support from the National Institute of Health and is a current member of the American Society for Bone and Mineral Research, American Society of Nephrology and American Heart Association. Tamara IsakovaTamara IsakovaDr Tamara Isakova, MD, MMSc, is Associate Professor of Medicine in the Division of Nephrology and Hypertension at the Northwestern University Feinberg School of Medicine, Chicago, USA. She is also Director of the Center for Translational Metabolism and Health within the Institute for Public Health and Medicine at Northwestern. She is a graduate of the State University of New York Downstate College of Medicine, USA, and she completed internal medicine training at the Massachusetts General Hospital, Boston, USA. She also received nephrology training in the combined Massachusetts General Hospital and Brigham & Women's Hospital nephrology fellowship program. Dr Isakova conducts clinical research in the area of disordered mineral metabolism in chronic kidney disease. She has received research support from the American Kidney Fund, the American Heart Association, the American Society of Nephrology, and the National Institute of Health. Dr Isakova provides clinical care for patients with chronic kidney disease, bone and mineral metabolism disorders, and kidney stones. Orson W. MoeOrson W. MoeDr Orson W. Moe received his medical degree from the University of Toronto, Canada and is currently Professor of Internal Medicine and Physiology at the University of Texas Southwestern Medical Center, Dallas, USA. He serves administratively as the Director of the Charles and Jane Pak Center of Mineral Metabolism and Clinical Research and Chief of the Division of Nephrology. He is an active clinician, researcher, and educator holding the Charles and Jane Pak Distinguished Chair in Mineral Metabolism Research and the Donald Seldin Professorship in Clinical Investigation. Dr Moe conducts both basic science and patient-oriented research on renal physiology and metabolism, as well as epithelial biology. His research strives to cross from the level of the whole patient, to animal and cell culture models, and down to single molecules. He is active in teaching at the undergraduate and post-graduate levels, nationally and internationally. In addition to editing Current Opinion in Nephrology and Hypertension, Dr Moe also edits the textbook, The Kidney: Physiology and Pathophysiology by Seldin and Giebisch. He is currently a member of the American Society of Clinical Research, American Association of Physicians, American Society of Nephrology, International Society of Nephrology, and the American Physiologic Society. Susan E. QuagginSusan E. QuagginSusan E. Quaggin, MD, FRCP(C), FASN, is a graduate of the University of Toronto, Canada, where she completed her residency and served as chief medical resident for the University's St. Michael's Hospital. She completed her nephrology fellowship at the University of Toronto and Yale University, USA, where she also completed research and post-doctoral training. Dr Quaggin's research focuses on fundamental processes needed to establish and maintain the integrity of the specialized vascular beds in the kidney and other organs. To understand and identify new therapeutic targets, she has worked to develop genetic mouse models that allow cell and time-specific manipulation of functional genes. Translation of her group's findings regarding the vasculature reveals pathogenic mechanisms and new therapeutic targets for a number of diseases, including diabetic kidney and eye disease, nephrotic syndrome, and glaucoma. She is currently the Charles Horace Mayo Professor of Medicine at Northwestern University, USA, where she serves as the Chief of the Division of Nephrology and Hypertension and the Director of the Feinberg Cardiovascular and Renal Research Institute, USA. Dr Quaggin was elected to the American Society for Clinical Investigation in 2006, the Association of American Physicians in 2013, and the National Academy of Medicine in 2019. She is also President of the American Society of Nephrology.