eGFR Categories Research Articles

Removing race from the CKD-EPI equation and its impact on prognosis in a predominantly White European population.

While American nephrology societies recommend using the 2021 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) estimated glomerular filtration rate (eGFR) equation without a Black race coefficient, it is unknown how this would impact disease distribution, prognosis and kidney failure risk prediction in predominantly White non-US populations. We studied 1.6 million Stockholm adults with serum/plasma creatinine measurements between 2007 and 2019. We calculated changes in eGFR and reclassification across KDIGO GFR categories when changing from the 2009 to 2021 CKD-EPI equation; estimated associations between eGFR and the clinical outcomes kidney failure with replacement therapy (KFRT), (cardiovascular) mortality and major adverse cardiovascular events using Cox regression; and investigated prognostic accuracy (discrimination and calibration) of both equations within the Kidney Failure Risk Equation. Compared with the 2009 equation, the 2021 equation yielded a higher eGFR by a median [interquartile range (IQR)] of 3.9 (2.9-4.8) mL/min/1.73 m2, which was larger at older age and for men. Consequently, 9.9% of the total population and 36.2% of the population with CKD G3a-G5 was reclassified to a higher eGFR category. Reclassified individuals exhibited a lower risk of KFRT, but higher risks of all-cause/cardiovascular death and major adverse cardiovascular events, compared with non-reclassified participants of similar eGFR. eGFR by both equations strongly predicted study outcomes, with equal discrimination and calibration for the Kidney Failure Risk Equation. Implementing the 2021 CKD-EPI equation in predominantly White European populations would raise eGFR by a modest amount (larger at older age and in men) and shift a major proportion of CKD patients to a higher eGFR category. eGFR by both equations strongly predicted outcomes.

Fracture Risk of Sodium-Glucose Cotransporter-2 Inhibitors in Chronic Kidney Disease.

Sodium-glucose cotransporter-2 (SGLT2) inhibitors have been associated with a higher risk of skeletal fractures in some randomized, placebo-controlled trials. Secondary hyperparathyroidism and increased bone turnover (also common in CKD) may contribute to the observed fracture risk. We aimed to determine if SGLT2 inhibitor use associates with a higher risk of fractures compared with dipeptidyl peptidase-4 (DPP-4) inhibitors, which have no known association with fracture risk. We hypothesized that this risk, if present, would be greatest in patients with lower eGFR. We conducted a population-based cohort study in Ontario, Canada between 2015 and 2019 using linked provincial administrative data to compare the incidence of fracture between new users of SGLT2 inhibitors and DPP-4 inhibitors. We used inverse probability of treatment weighting on the basis of propensity scores to balance the two groups of older adults (≥66 years of age) on indicators of baseline health. We compared the 180- and 365-day cumulative incidence rates of fracture between groups. Prespecified subgroup analyses were conducted by eGFR category (≥90, 60 to <90, 45 to <60, and 30 to <45 ml/min per 1.73 m2). Weighted hazard ratios were obtained using Cox proportional hazard regression. After weighting, we identified a total of 38,994 new users of a SGLT2 inhibitor and 37,449 new users of a DPP-4 inhibitor and observed a total of 342 fractures at 180 days and 689 fractures at 365 days. The weighted 180- and 365-day risks of a fragility fracture did not significantly differ between new users of a SGLT2 inhibitor versus a DPP-4 inhibitor: weighted hazard ratio, 0.95 (95% confidence interval, 0.79 to 1.13) and weighted hazard ratio, 0.88 (95% confidence interval, 0.88 to 1.00), respectively. There was no observed interaction between fracture risk and eGFR category (P=0.53). In this cohort study of older adults, starting a SGLT2 inhibitor versus DPP-4 inhibitor was not associated with a higher risk of skeletal fracture, regardless of eGFR.

529-P: Impact of Medication Adherence (MA) to Oral Glycemic Agents (OHAs) on Initiation of Dialysis in Patients with Moderately Impaired Renal Function

Although we showed a significant association of poor adherence to OHAs with start of dialysis, this relationship according to the estimated glomerular filtration rate (eGFR) was not clarified. Patients with eGFR &amp;lt;60 mL/min/1.73m2 are at high risk for dialysis. To identify the impact of MA by eGFR categories, we analyzed a nationwide claims-based database of 7,862 people with DM and without prior dialysis from 2008-16 aged 18-72 y with available records for OHAs for at least 1 year (mean age 54 y, HbA1c 7.2%) . MA was evaluated by the proportion of days covered (PDC) , and PDC &amp;lt;80% indicated poor adherence. Other factors were also analyzed (Table) . Median follow-up was 5.1 years. Incidence of dialysis per 1000 person-years was 10.7 in the eGFR&amp;lt;60 group and 0.62 in the eGFR ≥60 group. By Cox regression analysis (Table) an increased risk of dialysis was associated with poor MA (HR 2.98[95% CI 1.69-5.23]) , high systolic blood pressure (SBP) (1.27[1.11-1.44]) ], or current smoking (1.98[1.11-3.51]) in the eGFR&amp;lt;60 group and with high SBP (1.41[1.10-1.80]) and high HbA1c (1.45[1.13-1.87]) in the eGFR ≥60 group. Other factors in addition to MA might lead to dialysis, but poor MA was a strong risk factor for dialysis in this short observation period, especially in patients with impaired renal function. Clinicians should pay special attention to MA in these patients to prevent dialysis. Disclosure Y.Yaguchi: None. H.Sone: Research Support; Astellas Pharma Inc., Eisai Co., Ltd., Kyowa Kirin Co., Ltd., Novo Nordisk, Ono Pharmaceutical Co., Ltd., Taisho Pharmaceutical Holdings Co., Ltd., Takeda Pharmaceutical Company Limited. K.Fujihara: None. M.H.Yamada: None. Y.Matsubayashi: None. T.Yamada: None. M.Iwanaga: None. M.Kitazawa: None. M.Yamamoto: None. S.Kodama: None.

864-P: Glycemic Control across eGFR Categories with the Dual SGLT1 and 2 Inhibitor Sotagliflozin in SCORED

In cardiovascular (CV) outcome trials (OT) of glucose-lowering medications (GLM) , glycated hemoglobin (A1c) is typically treated according to local standard of care, with aim of glycemic equipoise between the randomized groups. However, in SGLT inhibitor CVOTs, larger A1c reductions are consistently seen in the active therapy vs. placebo (PBO) groups, since the former has access to an additional class of GLM. SCORED was a multicenter, double-blind, placebo-controlled CVOT of the dual SGLT1 and 2 inhibitor sotagliflozin (SOTA) , which may have preserved antihyperglycemic effects even in those with advanced chronic kidney disease (CKD.) We assessed the association between A1c lowering and assignment to SOTA vs. PBO in the overall trial population and across various pre-specified subgroups, including CKD categories. 10,584 type 2 diabetes (T2D) (A1c ≥7%) patients with CKD (eGFR 25-60 mL/min/1.73 m2) and increased CV risk were randomized to SOTA vs. PBO and followed for a median of 15.9 months. We previously reported that the risk for the primary composite outcome of total CV deaths and hospitalizations or urgent visits for heart failure was reduced by 26% in the SOTA group (p&amp;lt;0.001) . In the overall population, from a baseline A1c of 8.7%, the least-squares mean change in A1c was -0.60% with SOTA and -0.17% with placebo (mean difference [95% CI] = -0.42% [-0.47, -0.38]; p&amp;lt;0.0001) . Differences were larger with increasing baseline A1C: &amp;lt;8%: -0.31%; 8-&amp;lt;9%: -0.40%; and ≥9%: -0.57% (all p&amp;lt;0.0001) . The association between SOTA use and A1c lowering vs. placebo was consistent across strata of baseline eGFR, including those with CKD stage 4 (eGFR&amp;gt;45, 30-&amp;lt;45, and &amp;lt;30: -0.47%. -0.38%, and -0.31%, respectively [all p&amp;lt;0.001]) . These results were similarly consistent across age, sex, race/ethnicity, age, and BMI subgroups. In SCORED, SOTA consistently reduced A1c across all pre-specified subgroups, including patients with the lowest baseline eGFR, possibly reflecting SOTA’s dual mechanism of action. Disclosure S.E.Inzucchi: Advisory Panel; Abbott Diagnostics, ESPERION Therapeutics, Inc., vTv Therapeutics, Consultant; Merck &amp; Co., Inc., Pfizer Inc., Other Relationship; AstraZeneca, Boehringer Ingelheim International GmbH, Lexicon Pharmaceuticals, Inc., Novo Nordisk. J.P.Dwyer: Consultant; Akebia Therapeutics, Inc., AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Cincor, Inc, CSL Behring, FibroGen, Inc., Reata Pharmaceuticals, Inc., Sanofi, Tricida, Inc. B.M.Scirica: Consultant; Allergan, Boehringer Ingelheim International GmbH, ESPERION Therapeutics, Inc., Hanmi Pharm. Co., Ltd., Novo Nordisk, Research Support; Better Therapeutics, Eisai Co., Ltd., Merck &amp; Co., Inc., Novo Nordisk, Pfizer Inc., Stock/Shareholder; Heath At Scale. C.J.Bailey: None. P.L.Banks: Employee; Lexicon Pharmaceuticals, Inc. R.Diaz: None. K.K.Ray: Consultant; Abbott, AstraZeneca, Cargene, CSL Behring, Daiichi Sankyo, Eli Lilly and Company, ESPERION Therapeutics, Inc., GlaxoSmithKline plc., Kaleido, Kowa Company, Ltd., New Amsterdam Pharma, Novartis Pharmaceuticals Corporation, Pfizer Inc., Regeneron Pharmaceuticals Inc., Roche Diagnostics, The Medicines Company, Research Support; Amgen Inc., Daiichi Sankyo, Regeneron Pharmaceuticals Inc., Sanofi, Speaker's Bureau; Amgen Inc., AstraZeneca, Boehringer Ingelheim International GmbH, Daiichi Sankyo, Medscape, Novartis Pharmaceuticals Corporation, Novo Nordisk, Sanofi, Viatris Inc., Stock/Shareholder; Cargene, PEMI31. J.A.Udell: Consultant; Boehringer Ingelheim International GmbH, Novartis AG, Sanofi, Other Relationship; GlaxoSmithKline plc., Sanofi, Research Support; Amgen Inc., Bayer AG, Boehringer Ingelheim International GmbH, Janssen Research &amp; Development, LLC. R.D.Lopes: Consultant; Bayer AG, Boehringer Ingelheim International GmbH, Daiichi Sankyo, GlaxoSmithKline plc., Medtronic, Pfizer Inc., Portola Pharmaceuticals, Inc., Other Relationship; Bristol-Myers Squibb Company, Sanofi, Research Support; Medtronic, Pfizer Inc. L.A.Leiter: Advisory Panel; AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck &amp; Co., Inc., Novo Nordisk, Pfizer Inc., Sanofi, Research Support; AstraZeneca, Bayer AG, Lexicon Pharmaceuticals, Inc., Speaker's Bureau; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Novo Nordisk, Servier Laboratories. P.G.Steg: Advisory Panel; AstraZeneca, Bristol-Myers Squibb Company, Board Member; Novartis AG, Consultant; Amarin Corporation, Amgen Inc., Bayer AG, Idorsia Pharmaceuticals Ltd., Lexicon Pharmaceuticals, Inc., PhaseBio Pharmaceuticals, Inc., Sanofi. D.L.Bhatt: Research Support; Afimmune Limited, Amarin Corporation, Amgen Inc., AstraZeneca, Boehringer Ingelheim International GmbH, Chiesi USA, Inc., Lexicon Pharmaceuticals, Inc., Lilly, Novartis AG, Sanofi. Scored investigators: n/a. B.Pitt: Advisory Panel; Merck &amp; Co., Inc., Consultant; AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Lexicon Pharmaceuticals, Inc., Vifor Pharma Funding Sanofi/Lexicon

Initiation Dose of Allopurinol and the Risk of Severe Cutaneous Reactions in Older Adults With CKD: A Population-Based Cohort Study

Allopurinol should be started at lower doses in patients with chronic kidney disease (CKD) to avoid adverse effects. We examined the risk of severe cutaneous reactions in older adults with CKD who were newly prescribed allopurinol at varied doses. Population-based cohort study using linked health care databases. Patients in Ontario, Canada (2008-2019) aged≥66 years, with an estimated glomerular filtration rate (eGFR) of<60 mL/min/1.73 m2, and who were new users of allopurinol. A new prescription for allopurinol >100 mg/d versus a dose≤100 mg/d. The primary outcome was a hospital visit with a severe cutaneous reaction within 180 days of starting allopurinol. Secondary outcomes included all-cause hospitalization and all-cause mortality. The exposure and referent groups were balanced on indicators of baseline health using inverse probability of treatment weighting on the propensity score. Weighted risk ratios (RR) were obtained using modified Poisson regression and weighted risk differences (RD) using binomial regression. Of 47,315 patients (median age, 76 years; median eGFR, 45 mL/min/1.73 m2), 55% started allopurinol at >100 mg/d. Starting allopurinol at >100 versus≤100 mg/d was associated with an increased risk of a severe cutaneous reaction: number of events (weighted), 103 of 25,802 (0.40%) versus 46 of 25,816 (0.18%), respectively (weighted RR, 2.25 [95% CI, 1.50-3.37]; weighted RD, 0.22% [95% CI, 0.12%-0.32%]. Starting allopurinol at >100 versus≤100 mg/d was associated with an increased risk of all-cause hospitalization but not with all-cause mortality. This study was underpowered to detect risk differences in the association of allopurinol dose with outcomes across eGFR categories (ie, 45-59, 30-44, and<30 mL/min/1.73 m2). Older patients with CKD who started allopurinol at >100 mg/d versus≤100 mg/d were twice as likely to visit a hospital with a severe cutaneous reaction in the next 180 days.

MO516: Clusters of Chronic Conditions Across the Spectrum of Kidney Function: A Nationwide Cohort Study

Abstract BACKGROUND AND AIMS Multimorbidity is the presence of two or more chronic conditions. Patients with multimorbidity suffer from a high treatment burden as they have to cope with numerous medications and attend multiple specialists. Some chronic conditions co-exist in predictable ways, such as ischaemic heart disease and heart failure, but others may not. Multimorbidity is common in people with chronic kidney disease (CKD) and is associated with adverse outcomes. We aimed to explore: (1) what different clusters of conditions are associated with CKD and how these change as kidney function declines and (2) associations between clusters of conditions and adverse outcomes. METHOD We studied the Secure Anonymised Information Linkage Databank (SAIL): an electronic health records repository for 79% of the population of Wales (UK). We estimated the date at which patients crossed estimated glomerular filtration rate (eGFR) thresholds: 90, 75, 60, 45, 30 and 15 mL/min/1.73 m2. We used eGFRs recorded between 2006 and 2021 and estimated the dates of eGFR decline using mixed effects models. We identified 27 chronic conditions using ICD-10 codes and prescription data. We applied a k-modes clustering algorithm within each eGFR category, at the dates patients crossed eGFR thresholds. We chose the number of clusters via the elbow method. To help describe each cluster, we identified `key conditions’ that were common in the cluster and more common than in the overall eGFR category (prevalence &amp;gt;20% and more than double the prevalence in the overall eGFR category). To help determine whether these clusters were clinically meaningful, we studied the association between clusters and adverse outcomes risk using Cox proportional hazards models (all-cause mortality and major adverse cardiovascular events: MACE), with clusters having no key conditions as the reference group. RESULTS Overall, 533 362 patients were included in the analysis. The median age was lowest in the eGFR 90 category (56 years, IQI: 47–64) and the highest in the eGFR 30 category (81 years, IQI: 73–87). Patients in the low eGFR categories had the highest number of conditions (Fig. 1). The most frequently recorded condition was hypertension, which ranged from 34.4% for eGFR 90%–86.1% for eGFR 15. Diabetes ranged from 17.5% for eGFR 90%–53.4% for eGFR 15. Chronic pain ranged from 21.5% for eGFR 90%–41.6% for eGFR 30. The models with six clusters/eGFR category were chosen as they provided the best fit. In most eGFR categories, the majority of patients were included in one cluster with no key conditions (Fig. 2). Various conditions were clustered together, with cardiovascular conditions often co-existing at eGFR 30. Chronic pain featured prominently, either as the sole key condition or in combination with mental or physical conditions. The relative rates of each outcome were highest in the clusters with cardiovascular key conditions; for example, at eGFR 15, the hazard ratio for MACE in the `Pulmonary disease, asthma &amp; heart failure’ cluster was 2.3 [95% confidence interval (95% CI) 1.9–2.9; adjusted for age and sex). CONCLUSION We have described the prevalence of chronic conditions at different levels of kidney function, and we have identified clusters of conditions. Multimorbidity became extremely common at lower eGFR, clustering in unexpected ways: at lower eGFR, combinations of cardiovascular diseases and depression became prominent, as well as chronic pain. Patients in clusters with cardiovascular key conditions were at the greatest risk of adverse outcomes. Identification of disease clusters with refinement by eGFR may allow targeted approaches to therapy.

FC078: Impact of Removing Race from the CKD-EPI Equation: Analysis of 1.6 Million Swedish Adults

Abstract BACKGROUND AND AIMS The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) recently developed a novel creatinine-based eGFR equation without a race coefficient. While American nephrology societies recommend using this novel equation, its implications are unknown. METHOD We included 1.6 million adult individuals with routine outpatient serum creatinine testing during 2007–2018 in Stockholm, Sweden. First, we calculated reclassification across KDIGO eGFR categories when changing from the 2009 to 2021 CKD-EPI equation. Second, for both equations, the association between eGFR and (1) kidney failure with replacement therapy (KFRT), (2) all-cause mortality, (3) cardiovascular mortality and (4) major adverse cardiovascular events was estimated with Cox regression. Third, prognostic accuracy of both eGFR equations within the Kidney Failure Risk Equation was assessed with discrimination and calibration. RESULTS Compared with the 2009 equation, the 2021 equation yielded a higher eGFR by a median (IQR) of 3.9 (2.9–4.8) mL/min/1.73 m2, decreasing prevalence of CKD G3–G5 from 5.1 to 3.8%. The 2021 equation reclassified 9.9% of the total population and 36.2% of the CKD G3–G5 population to a less severe eGFR category. Individuals who were reclassified to less severe eGFR categories were older and therefore exhibited higher crude risks of all-cause/cardiovascular death and major adverse cardiovascular events, and lower risk of kidney replacement therapy compared with nonreclassified participants of similar eGFR. eGFR by both equations strongly predicted study outcomes, with similar discrimination and calibration for the Kidney Failure Risk Equation. CONCLUSION Implementing the 2021 CKD-EPI equation in predominantly white European populations raises eGFR by a modest amount (larger at older age and men) and shifts a major proportion of CKD patients to a higher eGFR category, with eGFR by both equations strongly predicting outcomes.

FC078: Impact of Removing Race from the CKD-EPI Equation: Analysis of 1.6 Million Swedish Adults

Abstract BACKGROUND AND AIMS The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) recently developed a novel creatinine-based eGFR equation without a race coefficient. While American nephrology societies recommend using this novel equation, its implications are unknown. METHOD We included 1.6 million adult individuals with routine outpatient serum creatinine testing during 2007–2018 in Stockholm, Sweden. First, we calculated reclassification across KDIGO eGFR categories when changing from the 2009 to 2021 CKD-EPI equation. Second, for both equations, the association between eGFR and (1) kidney failure with replacement therapy (KFRT), (2) all-cause mortality, (3) cardiovascular mortality and (4) major adverse cardiovascular events was estimated with Cox regression. Third, prognostic accuracy of both eGFR equations within the Kidney Failure Risk Equation was assessed with discrimination and calibration. RESULTS Compared with the 2009 equation, the 2021 equation yielded a higher eGFR by a median (IQR) of 3.9 (2.9–4.8) mL/min/1.73 m2, decreasing prevalence of CKD G3–G5 from 5.1 to 3.8%. The 2021 equation reclassified 9.9% of the total population and 36.2% of the CKD G3–G5 population to a less severe eGFR category. Individuals who were reclassified to less severe eGFR categories were older and therefore exhibited higher crude risks of all-cause/cardiovascular death and major adverse cardiovascular events, and lower risk of kidney replacement therapy compared with nonreclassified participants of similar eGFR. eGFR by both equations strongly predicted study outcomes, with similar discrimination and calibration for the Kidney Failure Risk Equation. CONCLUSION Implementing the 2021 CKD-EPI equation in predominantly white European populations raises eGFR by a modest amount (larger at older age and men) and shifts a major proportion of CKD patients to a higher eGFR category, with eGFR by both equations strongly predicting outcomes.

MO515: Mortality Differences Between Men and Women With Chronic Kidney Disease in the Irish Health System: The National Kidney Disease Surveillance Programme

Abstract BACKGROUND AND AIMS Chronic kidney disease is associated with higher mortality compared with the general population, but mortality differences between men and women with CKD are poorly understood. Although the prevalence of CKD is consistently higher in women than in men, emerging studies suggest that men experience poorer survival. The primary goal of this study was to compare mortality rates between men and women in the Irish health system and determine whether kidney function influenced these sex-specific risks. METHOD We created a cohort of 125 890 patients from the National Kidney Disease Surveillance System (NKDSS) to compare mortality rates between men and women. Patients were recruited from 1 January 2005 to 31 December 2010 and followed until 31 December 2013. Kidney function was determined using the CKD-EPI equation, generating estimated glomerular filtration rate (mL/min/1.73 m2) (eGFR). The primary outcome was all-cause mortality from national records provided by the Central Statistics Office (CSO). The principal exposure was participant sex, classified as men or women. Patients were censored at the date of initiation of dialysis or kidney transplantation, death, loss to follow-up or end of follow-up 31 December 2013. Mortality risks were compared using the Fine-Gray approach, which accounted for the competing risks of renal replacement therapy. Adjustments were made for baseline age, kidney function and blood biomarkers, which indicated the presence and severity of clinical disease. RESULTS Of the 125 890 participants, 55.1% were women, with a mean age of 54.1 (SD: 17.7) years. The median follow-up was 7.75 years (IQR: 6.33–8.55), 243 patients (0.19%) patients progressed to RRT and 14 179 patients (11.26%) died. Overall, mortality rates were significantly higher in men than in women (18.4 versus 16.6 deaths/1000 pyrs, respectively). Compared with women, men with CKD experienced significantly higher rates of death and RRT, P &amp;lt; .001 (Figure 1a). With each worsening GFR category, crude mortality rates increased by 18-fold in women compared with 9-fold in men. The P-value for the interaction of sex and GFR with mortality was &amp;lt;0.001. In stratified analyses, the magnitude of the sHR for men versus women decreased with each descending eGFR category from a peak of 2.17 (1.88–2.49) for eGFR &amp;gt;90 mL/min down to 1.21 (0.98–1.49) for eGFR &amp;lt;29 mL/min/1.72 m2 (Table 1) and was no longer significant in the eGFR &amp;lt;29 mL/min/1.72 m² category. CONCLUSION Although women have a higher burden of CKD than men in the Irish health system, the overall risks of death and RRT were far greater in men than in women. However, the excess risk in men diminished with increasing severity of kidney disease such that mortality risks for women approached those of men with advanced kidney disease. While these findings may have a biologic basis, fundamental disparities in care delivery, quality or accessibility between men and women is a far more likely explanation.

Kidney disease parameters, metabolic goal achievement, and arterial stiffness risk in Chinese adult people with type 2 diabetes.

BackgroundTo investigate the arterial stiffness (AS) risk within urinary albumin‐to‐creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR) categories and the joint effect between kidney disease parameters and metabolic goal achievement on AS risk in adult people with type 2 diabetes (T2D).MethodsA total of 27 439 Chinese participants with T2D from 10 National Metabolic Management Centers (MMC) were categorized into four albuminuria/decreased eGFR groups. The criteria for decreased eGFR and AS were eGFR <90 ml/min/1.73 m2 and brachial‐ankle pulse wave velocity value >the 75th percentile (1770.0 cm/s). Three metabolic goals were defined as glycated hemoglobin <7%, BP <130/80 mmHg, andlow‐density lipoprotein cholesterol <2.6 mmol/L.ResultsAfter full adjustment, odds ratios (ORs) for AS were highest for albuminuria and decreased eGFR (2.23 [1.98–2.52]) and were higher for albuminuria and normal eGFR (1.52 [1.39–1.67]) than for those with nonalbuminuria and decreased eGFR (1.17 [1.04–1.32]). Both UACR and eGFR in the subgroup or overall population independently correlated with AS risk. The achievement of ≥2 metabolic goals counteracted the association between albuminuria and AS risk (OR: 0.93; 95% CI: 0.80–1.07; p = .311). When the metabolic goals added up to ≥2 for patients with decreased eGFR, they showed significantly lower AS risk (OR: 0.65; 95% CI: 0.56–0.74; p < .001).ConclusionsBoth higher UACR and lower eGFR are determinants of AS risk, with UACR more strongly related to AS than eGFR in adults with T2D. The correlation between albuminuria/decreased eGFR and AS was modified by the achievement of multiple metabolic elements.

MP52-14 ESTIMATED GLOMERULAR FILTRATION RATE PREDICTS ADVERSE OUTCOMES AMONG MEN UNDERGOING ARTIFICIAL URINARY SPHINCTER SURGERY

You have accessJournal of UrologyCME1 May 2022MP52-14 ESTIMATED GLOMERULAR FILTRATION RATE PREDICTS ADVERSE OUTCOMES AMONG MEN UNDERGOING ARTIFICIAL URINARY SPHINCTER SURGERY Carlos Riveros, Victor Chalfant, Ahmed Elshafei, and K.C. Balaji Carlos RiverosCarlos Riveros More articles by this author , Victor ChalfantVictor Chalfant More articles by this author , Ahmed ElshafeiAhmed Elshafei More articles by this author , and K.C. BalajiK.C. Balaji More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002627.14AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: More than 15% of the adult population in the US is estimated to have chronic kidney disease (CKD) defined as a glomerular filtration rate (GFR) below 60 ml/min/1.73 m2 for three months or longer. For men with moderate to severe urinary incontinence after prostatectomy, artificial urinary sphincter (AUS) is considered the gold standard treatment. The impact of CKD staging on postoperative complications after AUS surgery is not well defined. The goal of this study was to assess whether male patients with an estimated glomerular filtration rate (eGFR) that is higher or lower than population-based standards have an increased risk of 30-day complications after AUS surgery. METHODS: Using the American College of Surgeons National Improvement Quality Improvement Program (NSQIP) database, we identified adult males who underwent AUS surgery between 2006-2019. To calculate eGFR, the Modification of Diet in Renal Disease (MDRD) equation was utilized: eGFR (ml/min/1.73 m2) = 186 x serum Cr-1.154 x age-0.203 x 1.210 (if African American). Based on eGFR, patients were divided into five different groups: 0-29 (advanced CKD), 30-59 (Stage III CKD), 60-89 (Stage II CKD), 90-119 (Stage I CKD), and >120 (hyperfiltration). We investigated 30-day outcomes including readmission, reoperation, complications (both minor and major), and non-home discharge in all groups. A multivariate logistic regression analysis was performed to control for confounding variables and to identify eGFR categories as an independent risk factor for each outcome. RESULTS: A total of 2,410 cases met inclusion criteria. Overall, most patients were elderly, overweight, and had hypertension. Patients with advanced CKD had high rates of hypertension (84.4%) and diabetes (43.8%). Patients with advanced CKD had 9.9x higher odds of non-home discharge, 7.1x higher odds of minor complications, and 6.7x higher odds of major complications (p-value <0.05). CONCLUSIONS: Patients with non-advanced CKD had complication rates comparable to patients with better renal function. Patients with advanced CKD (eGFR<30) should be carefully selected prior to AUS surgery due to higher complication rates compared to patients with higher eGFR. Low eGFR may be used to counsel patients about risk for 30-day surgical complications. Source of Funding: None © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e892 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Carlos Riveros More articles by this author Victor Chalfant More articles by this author Ahmed Elshafei More articles by this author K.C. Balaji More articles by this author Expand All Advertisement PDF DownloadLoading ...

Hyperkalemia and Metabolic Acidosis Occur at a Higher eGFR in Sickle Cell Disease.

People with sickle cell disease (SCD) have an elevated estimated glomerular filtration rate (eGFR) compared with the general population, and this may alter the usual creatinine-based eGFR cutoffs for which physiologic evidence of kidney dysfunction is apparent. This study aimed to identify eGFR thresholds for hyperkalemia and metabolic acidosis in patients with SCD. This was a cross-sectional analysis of 733 patients with severe (hemoglobin SS or Sβ0-thalassemia) SCD genotype, 238 patients with moderate (hemoglobin SC or Sβ+-thalassemia) SCD genotype, and 1333 age- and sex-matched African Americans from the National Health and Nutrition Examination Survey (NHANES). The prevalence rates of hyperkalemia and metabolic acidosis were compared by eGFR category. Cutoffs for hyperkalemia and metabolic acidosis were determined using generalized additive models. Hyperkalemia and metabolic acidosis were more common in those with severe SCD genotype (13% and 21%, respectively) compared with the NHANES (0.3% and 5%, respectively); the prevalence rates in the moderate SCD genotype were intermediate for hyperkalemia (3%) and metabolic acidosis (11%). The proportion of patients with hyperkalemia and metabolic acidosis progressively increased with lower eGFR category in both SCD genotype groups. The eGFR thresholds for hyperkalemia and metabolic acidosis were higher in the severe (85 and 91 ml/min per 1.73 m2, respectively) and moderate (52 and 102 ml/min per 1.73 m2, respectively) SCD genotypes compared with the NHANES (34 and 46 ml/min per 1.73 m2). We demonstrate that hyperkalemia and metabolic acidosis are more common and occur at higher eGFR values in patients with SCD compared with age- and sex-matched African Americans, including in eGFR ranges considered to be normal. Future studies using redefined creatinine-based eGFR thresholds for abnormal kidney function may identify high-risk patients for earlier intervention strategies and referral for specialized renal care in SCD.

Assessing the Risk of Decrease in Kidney Function in Patients Prescribed Direct-Acting Antivirals for Hepatitis C Utilizing the MID-NET® Medical Information Database Network in Japan

An association between kidney disease and direct-acting antivirals against hepatitis C (DAAs) has been suggested, however the warning on the package insert (PI) of the drug varies among DAAs. In this study, the risk of decreased kidney function associated with DAAs marketed in Japan was investigated to determine whether the risk of kidney disease is a common adverse event and class effect of DAAs. Data for patients who were new users of DAAs marketed in Japan, with eGFR ≥ 45 mL/min/1.73 m2 and without specific risk factors, were extracted from the MID-NET® medical information database network in Japan. Changes from the baseline on estimated glomerular filtration rate (eGFR) categories (eGFR ≥ 90, 90 > eGFR ≥ 60, 60 > eGFR ≥ 45, 45 > eGFR ≥ 30, 30 > eGFR ≥ 15, 15 > eGFR; unit: mL/min/1.73 m2) were used for evaluating the risk of decreased kidney function. Exposure groups for DAAs and relevant concomitant drugs were categorized into 10 patterns based on the PI. Among the 10 patterns, a significant increase in the incidence rate ratio (P < 0.01) was observed in the prescription patterns of concomitant use of telaprevir with peginterferon alpha and ribavirin, concomitant use of daclatasvir hydrochloride with asunaprevir, and ombitasvir hydrate combined with paritaprevir hydrate and ritonavir, which were concomitantly used with ribavirin; such an increase was not observed in the other prescription patterns. The effects of DAAs on kidney function may differ among drugs, suggesting the possibility that the risk of kidney disease is not a class effect of DAAs and should be evaluated individually for each DAA.

Association of impaired kidney function with mortality in rural Uganda: results of a general population cohort study

ObjectiveTo determine the association between baseline kidney function and subsequent all-cause mortality.Design and settingA general population-based cohort study from rural Uganda.ParticipantsPeople aged 18 years and above with measured baseline estimated...

Eligibility for pharmacological therapies in heart failure with reduced ejection fraction: implications of the new Chronic Kidney Disease Epidemiology Collaboration creatinine equation for estimating glomerular filtration rate.

AimsThe new Chronic Kidney Disease Epidemiology Collaboration (CKD‐EPI) equation for estimating glomerular filtration rate (eGFR), based on serum creatinine, that does not incorporate race may reclassify individuals, irrespective of race, from one eGFR category to another, with implications for eligibility for treatments in patients with heart failure and reduced ejection fraction (HFrEF).Methods and resultsA total of 43 138 ambulatory patients with HFrEF from 12 clinical trials were included (mean age 64.3 years; 9580 [22.2%] women). Mean eGFR was 67 (standard deviation [SD] 21) ml/min/1.73 m2 and 70 (SD 21) ml/min/1.73 m2 using the original and new CKD‐EPI equations, respectively (mean difference 3.20 ml/min/1.73 m2, 95% confidence interval [CI] 3.17–3.23, p < 0.001). Of the 935 patients with chronic kidney disease (CKD) stages 4 or 5, identified using the original equation, 309 (33.0%) were reclassified to CKD stages 1–3 (eGFR ≥30 ml/min/1.73 m2) with the new equation. However, the opposite was observed among the 2521 Black patients (5.8%) included, with a reduction in mean eGFR from 75 to 68 ml/min/1.73 m2 using the original and new equations, respectively (mean difference 6.94 ml/min/1.73 m2, [95% CI 6.82–7.06], p < 0.001). The number of Black patients with an eGFR <30 ml/min/1.73 m2 increased from 49 (1.9%) using the original equation to 71 (2.8%) with the new equation.ConclusionsThe new CKD‐EPI creatinine equation reclassified CKD stage in a large proportion of patients with HFrEF enrolled in clinical trials. As eGFR is an essential determinant of eligibility for several key pharmacological therapies in HFrEF, this reclassification could result in a substantial change in the proportion of patients considered eligible for such therapies and reduce the proportion of eligible Black patients.

Increased Cerebral Small Vessel Disease Burden With Renal Dysfunction and Albuminuria in Patients Taking Antithrombotic Agents: The Bleeding With Antithrombotic Therapy 2.

BackgroundThe aim of this study was to determine the associations of cerebral small vessel disease (SVD) burden with renal dysfunction and albuminuria in patients taking oral antithrombotic agents.Methods and ResultsPatients who newly started or continued taking oral antiplatelets or anticoagulants were enrolled in a prospective, multicenter, observational study. Obligatorily acquired multimodal magnetic resonance imaging at registration with prespecified imaging conditions was assessed for cerebral microbleeds, white matter hyperintensities, enlarged basal ganglia perivascular spaces, or lacunes, and an ordinal SVD score was calculated (range, 0–4). Multivariable adjusting covariates were age, sex, hypertension, diabetes, dyslipidemia, current smoking, drinking, and estimated glomerular filtration rate (eGFR). Of 5324 patients (1762 women; median age, 73 years), 4797 (90.1%) patients were taking oral antithrombotic agents for secondary stroke prevention. Cerebral microbleeds were present in 32.7%, confluent white matter hyperintensities in 51.8%, extensive basal ganglia perivascular spaces in 38.9%, and lacunes in 59.4%. Median SVD score was 2. Compared with eGFR category G1 (eGFR ≥90 mL/min per 1.73 m2), adjusted odds ratios for SVD score increment were 1.63 (95% CI, 1.11–2.39) at category G4 (eGFR 15–<30 mL/min per 1.73 m2) and 2.05 (95% CI, 1.33–3.16) at G5 (eGFR <15 mL/min per 1.73 m2). Corresponding odds ratios relative to urinary albumin‐to‐creatinine ratio (ACR) category A1 (ACR <30 mg/g) were 1.29 (95% CI, 1.12–1.49) for category A2 (ACR 30–<300 mg/g) and 1.37 (95% CI, 1.05–1.77) for A3 (ACR ≥300 mg/g). When combined eGFR and ACR categories were assessed, risks for SVD score increment generally increased as eGFR decreased and ACR increased.ConclusionsBoth reduced eGFR and albuminuria were independently associated with increased cerebral SVD burden in patients requiring oral antithrombotic medication mainly for secondary stroke prevention.RegistrationURL: https://www.clinicaltrials.gov; Unique identifier: NCT01581502; URL: https://www.umin.ac.jp/ctr; Unique identifier: UMIN000023669.

Potential Effects of Elimination of the Black Race Coefficient in eGFR Calculations in the CREDENCE Trial.

The effect of including race in the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation on screening, recruitment, and outcomes of clinical trials is unclear. The inclusion and outcomes of participants in the Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) trial, which randomized individuals with type 2 diabetes and CKD to canagliflozin or placebo, were evaluated after calculating eGFR using the 2009 CKD-EPI creatinine equation with and without a race-specific coefficient or the 2021 CKD-EPI creatinine equation. Treatment effects were estimated using proportional hazards models and piecewise linear mixed effects models for eGFR slope. Of 4401 randomized participants, 2931 (67%) were White participants, 224 (5%) were Black participants, 877 (20%) were Asian participants, and 369 (8%) participants were other race. Among randomized participants, recalculation of screening eGFR using the 2009 equation without a race-specific coefficient had no effect on the likelihood of non-Black participants meeting inclusion criteria but would have excluded 22 (10%) randomized Black participants for eGFR<30 ml/min per 1.73 m2. Recalculation with the 2021 equation would have excluded eight (4%) Black participants for low eGFR and one (0.4%) Black participant for eGFR≥90 ml/min per 1.73 m2, whereas 30 (0.7%) and 300 (7%) non-Black participants would have been excluded for low and high eGFR, respectively. A high proportion (eight of 22; 36%) of end points in Black participants occurred in individuals who would have been excluded following recalculation using the race-free 2009 equation but not when recalculated with the 2021 equation (one of eight; 13%). Cardiovascular and kidney treatment effects remained consistent across eGFR categories following recalculation with either equation. Changes in estimated treatment effects on eGFR slope were modest but were qualitatively larger following recalculation using the 2021 equation. However, the effect of canagliflozin on chronic change in eGFR was attenuated by 7% among Black participants and increased 6% in non-Black participants. In the CREDENCE trial, eGFR recalculation without the race-specific coefficient had small but potentially important effects on event rates and the relative proportion of Black participants without substantially changing efficacy estimates. Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE), NCT02065791.

A real-world study on SGLT2 inhibitors and diabetic kidney disease progression.

ABSTRACTBackgroundRandomized controlled trials have demonstrated the benefits of sodium–glucose cotransporter 2 inhibitors (SGLT2is) in people with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD). However, real-world data on CKD progression and the development of end-stage kidney disease (ESKD) remains scarce. Our aim was to study renal outcomes of people with diabetic kidney disease (DKD) using SGLT2is in a highly prevalent DKD population.MethodsBetween 2016 and 2019 we recruited T2DM patients in the renal and diabetic clinics in a regional hospital in Singapore. Patients prescribed SGLT2is were compared with those on standard anti-diabetic and renoprotective treatment. The outcome measures were CKD progression [a ≥25% decrease from baseline and worsening of estimated glomerular filtration rate (eGFR) categories according to the Kidney Disease: Improving Global Outcomes guidelines] and ESKD (eGFR <15 mL/min/1.73 m2).ResultsWe analysed a total of 4446 subjects; 1598 were on SGLT2is. There was a significant reduction in CKD progression {hazard ratio [HR] 0.60 [95% confidence interval (CI) 0.49–0.74]} with SGLT2is. The HR for eGFR ≥45 mL/min/1.73 m2 and 15–44 mL/min/1.73 m2 was 0.60 (95% CI 0.47–0.76) and 0.43 (95% CI 0.23–0.66), respectively. There was also a reduction in risk for developing ESKD for the entire cohort [HR 0.33 (95% CI 0.17–0.65)] and eGFR 15–44 mL/min/1.73 m2 [HR 0.24 (95% CI 0.09–0.66)]. Compared with canagliflozin and dapagliflozin, empagliflozin showed a sustained risk reduction of renal outcomes across CKD stages 1–4.ConclusionsThis real-world study demonstrates the benefits of SGLT2is on CKD progression and ESKD. The effect is more pronounced in moderate to advanced CKD patients.

Angiotensin-neprilysin inhibition and renal outcomes across the spectrum of ejection fraction in heart failure.

Patients with heart failure are at higher risk of progression to end-stage renal disease (ESRD), regardless of ejection fraction (EF). We assessed the renal effects of angiotensin-neprilysin inhibition in a pooled analysis of 13 195 patients with heart failure with reduced and preserved EF. We combined data from PARADIGM-HF (EF ≤40%; n=8399) and PARAGON-HF (EF ≥45%; n=4796) in a pre-specified pooled analysis. We assessed the effect of treatment (sacubitril/valsartan vs. enalapril or valsartan) on a composite of either ≥50% reduction in estimated glomerular filtration rate (eGFR), ESRD, or death from renal causes, in addition to changes in eGFR slope. We assessed whether baseline renal function or EF modified the effect of therapy on renal outcomes. At randomization, eGFR was 68 ± 20 ml/min/1.73 m2 in PARADIGM-HF and 63 ± 19 ml/min/1.73 m2 in PARAGON-HF. The composite renal outcome occurred in 70 of 6594 patients (1.1%) in the sacubitril/valsartan group and in 123 of 6601 patients (1.9%) in the valsartan or enalapril group (hazard ratio 0.56, 95% confidence interval [CI] 0.42-0.75; p < 0.001). The mean eGFR change was -1.8 (95% CI -1.9 to -1.7) ml/min/1.73 m2 /year for the sacubitril/valsartan group, compared with -2.4 (95% CI -2.5 to -2.2) ml/min/1.73 m2 /year for the valsartan or enalapril group. The treatment effect on the composite renal endpoint was not modified by categories of baseline eGFR (p-interaction=0.64), but was most pronounced in those with baseline EF between 30% and 60% (p-interaction=0.001). In patients with heart failure, sacubitril/valsartan reduced the risk of serious adverse renal outcomes and slowed decline in eGFR, compared with valsartan or enalapril, independent of baseline renal function.

Long-Term Prognostic Impact of Estimated Glomerular Filtration Rate on Admission in Patients Hospitalized for Acute Heart Failure

Introduction: Although small-sample size studies have shown that basal alterations of estimated glomerular filtration rate (eGFR) are related to short- and mid-term higher mortality in acute heart failure (AHF), there is scarce information on the influence of an altered eGFR on long-term mortality and readmissions. Therefore, this multicenter study sought to investigate the relationship between eGFR on admission for AHF and both long-term mortality and readmissions in a large sample of patients. Methods: We retrospectively evaluated 4,595 patients consecutively discharged after admission for AHF at three tertiary-care hospitals from January 1, 2008, to January 1, 2020. To investigate the effect of eGFR on admission with long-term morbimortality, we stratified the patients according to four eGFR categories: <30 mL·min⁻¹·1.73 m⁻² (G4 and G5 patients, n = 534), 30–44 mL·min⁻¹·1.73 m⁻² (G3b patients, n = 882), 45–59 mL·min⁻¹·1.73 m⁻² (G3a patients, n = 1,080), and ≥60 mL·min⁻¹·1.73 m⁻² (G1 and G2 patients, n = 2,099). eGFR was calculated by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation within the first 24 h following admission. Results: At a median follow-up of 2.20 years, multivariate analyses revealed that compared to G1 and G2 patients, G4 and G5 patients exhibited a higher risk of all-cause (HR = 1.15, 95% CI: 01.02–1.30, p = 0.020) and cardiovascular (CV) (HR = 1.20, 95% CI: 1.04–1.39, p = 0.013) mortality. Similarly, multivariate analyses also showed that the lower the eGFR, the higher the risk of readmissions. In fact, compared to G1 and G2 patients, G4 and G5 patients displayed significantly increased incident rate ratios of total all-cause (28%), CV (26%), and HF-related (30%) readmissions. Conclusion: Data from this large study provide evidence that an eGFR below 30 mL·min⁻¹·1.73 m⁻² on admission could be an independent predictor for long-term mortality and readmissions in patients with AHF.