Glomerular Filtration Rate Categories Research Articles

#2856 Sleep disturbances in non-dialysis dependent chronic kidney disease—The CKD-REIN cohort study

Abstract Background and Aims Sleep disturbances are common in patients on dialysis, but little is known about their prevalence and determinants in earlier chronic kidney disease (CKD) stages. We assessed the prevalence of insomnia, excessive daytime sleepiness (EDS), and sleep apnea, and studied their relation with kidney function, before and after accounting for various other potential determinants in patients with moderate or severe CKD. Method This study included 2657 nephrology outpatients with non-dialysis dependent CKD (mean age, 67 ± 12 years; 66% men; mean eGFR, 33 ± 12 mL/min/1.73 m2) from the French CKD-REIN (CKD-Renal Epidemiology and Information Network) cohort study who completed the Basic Nordic Sleep Questionnaire at baseline. Insomnia was defined as having badly or rather badly been sleeping, or having had difficulties falling asleep or awakened too early without being able to fall asleep again at least 3 times per week, over the past 3 months. And EDS, as feeling excessively sleepy during daytime at least 3 times per week over the past 3 months. Sleep apnea with or without continuous positive airway pressure use were identified from medical records. For each sleep disturbance, we assessed the crude prevalence by sex and by estimated glomerular filtration rate (eGFR) categories. We estimated adjusted odds ratios (OR) with 95% confidence interval (95% CI) associated with eGFR decrease (per 10 mL/min/1.73 m2) and urinary albumin-to-creatinine ratio (ACR) categories (A1-A3), as well as with age, sex, education (years), smoking, alcohol consumption, physical activity (estimated by the Global Physical Activity Questionnaire), performance score in Instrumental Activities of Daily Living [IADL], obesity, diabetes, cardiovascular disease, depression, patient-reported cramps, itching and stress or worry about CKD, and relevant drug use. Results Overall prevalence of insomnia, EDS, and sleep apnea were 23%, 15%, and 14%, respectively, with differences between women and men for insomnia, 30% vs 19%, EDS, 17% vs 13%, and sleep apnea, 10% vs 17%, respectively (all P-values <.001). Crude prevalence of EDS significantly increased with decreasing eGFR category (without interaction with sex), but not those for insomnia and sleep apnea (Figure). ACR categories were not associated with either sleep disturbances. In multivariable analyses, factors significantly associated with higher prevalence of insomnia included female sex, smoking, low physical activity, depression, and thyroid hormone use. There were also strong dose-response relations between insomnia prevalence and to what extend patients reported being bothered by cramps or itching, or stressed/worried about CKD. The crude relation of eGFR with EDS tended to weaken (ORs [95% CI], 1.10 [0.99-1.22] per 10 mL/min decrease, p-value 0.09) in multivariable analysis, which showed higher ORs associated with past smoking, depression, lower IADL score, insomnia, and betablocker use, as well as dose-response relations with itching, and stress/worry about CKD. Factors significantly associated with increased prevalence of sleep apnea included male sex, alcohol consumption, lower IADL score, obesity, depression, and cardiovascular disease. Conclusion This analysis of baseline data from the CKD-REIN cohort shows that, in patients with non-dialysis dependent CKD, EDS alone appeared to be related to kidney function level. The study, however, suggests the potential role of modifiable CKD-related symptoms, cramps and itching, and of being stressed or worried about CKD, in addition to that well-documented for behavioral and clinical risk factors, and drugs in the risk of insomnia and EDS.

Association of kidney function with physical performance: the Maastricht study.

Kidney failure has been associated with decreased physical capacity, although evidence regarding the physical performance of individuals with earlier stages of chronic kidney disease (CKD)remains limited. Cross-sectional data were derived from the prospective, population-based Maastricht Study. Multivariate linear regression models were fitted to assess the association of estimated glomerular filtration rate (eGFR) and albuminuria categories with physical performance test outcomes. Overall, 7396 participants were included. Compared to eGFR 60-90ml/min/1.73m2, values < 60ml/min/1.73m2 were associated with significantly shorter 6-min walk distance (β: - 13.04m, 95% confidence intervals-CI - 19.95; - 6.13), worse timed chair rise stand test time (β: 0.91s, 95% CI 0.36; 1.47), lower maximal grip (β: - 0.83kg, 95% CI - 1.50; - 0.15) and elbow flexion (β: - 3.64 Nm, 95% CI - 7.11; - 0.16) strength. Additionally, eGFR > 90ml/min/1.73m2 was linked to significantly shorter 6-min walk distance (β: - 6.13m, 95% CI - 9.44; - 2.82). Urinary albumin excretion > 30mg/24h was associated with shorter 6-min walk distance (β: - 12.48m, 95% CI - 18.28; - 6.68), worse timed chair rise stand test time (β: 0.51s, 95% CI 0.11; 1.06), lower maximal grip (β: - 1.34kg, 95% CI - 1.91; - 0.76) and elbow flexion strength (β: - 3.31Nm, 95% CI - 5.80; - 0.82). Reduced eGFR and higher albuminuria levels were associated with worse physical performance, especially shorter 6-min walk distance and lower muscle strength. The relationship between eGFR and physical function was non-linear, with also high eGFR values being associated with worse performance, especially in the six-minute walk test.

Data mining of reference intervals for serum creatinine: an improvement in glomerular filtration rate estimating equations based on Q-values.

Glomerular filtration rate (GFR) estimating equations based on rescaled serum creatinine (SCr/Q) have shown better performance, where Q represents the median SCr for age- and sex-specific healthy populations. However, there remains a scarcity of investigations in China to determine this value. We aimed to develop Chinese age- and sex-specific reference intervals (RIs) and Q-values for SCr and to validate the equations incorporating new Q-values. We included 117,345 adults from five centers for establishing RIs and Q-values, and 3,692 participants with reference GFR (rGFR, 99mTc-DTPA renal dynamic imaging measurement) for validation. Appropriate age partitioning was determined using the decision tree method. Lower and upper reference limits and medians were calculated using the refineR algorithm, and Q-values were determined accordingly. We evaluated the full age spectrum (FAS) and European Kidney Function Consortium (EKFC) equations incorporating different Q-values considering bias, precision (interquartile range, IQR), and accuracy (percentage of estimates within ±20 % [P20] and ±30 % [P30] of rGFR). RIs for males were: 18-79 years, 55.53-92.50 μmol/L;≥80 years, 54.41-96.43 μmol/L. RIs for females were: 18-59 years, 40.42-69.73 μmol/L; 60-79 years, 41.16-73.69 μmol/L;≥80 years, 46.50-73.20 μmol/L. Q-values were set at 73.82 μmol/L (0.84 mg/dL) for males and 53.80 μmol/L (0.61 mg/dL) for females. After validation, we found that the adjusted equations exhibit less bias, improved precision and accuracy, and increased agreement of GFR categories. We determined Chinese age- and sex-specific RIs and Q-values for SCr. The adjustable Q-values provide an effective alternative to obtain valid equations for estimating GFR.

Elimination and penetration of amikacin into urine in patients with decreased glomerular filtration rate.

Amikacin monotherapy is recommended for urinary tract infection (UTI) treatment with multi-resistant pathogens. Even though amikacin efficacy in the treatment of UTIs is dependent on its urinary concentration, there are no robust data proving that sufficiently high urinary concentration is reached in patients with reduced glomerular filtration rate (GFR). A prospective study to monitor amikacin penetration into urine of 70 patients [40 males, median (interquartile range) age 70 (65-79) years] with different levels of glomerular filtration decline, including patients treated by dialysis, was conducted. The bactericidal efficacy of amikacin in urine samples has been evaluated. Patients with estimated GFR (eGFR) <30mL/min had significantly lower median amikacin urinary concentration than patients with eGFR >30mL/min (89.75 vs 186.0mg/L, P<.0001; 200.5 vs 830.0mg/L, P<.0001; and 126.0 vs 408.0mg/L, P<.0001 for minimal, maximal and minimal together with maximal concentrations, respectively). The amount of amikacin eliminated in the first 10-13h after dose administration was dependent on eGFR (r2=0.6144, P<.0001). The urinary concentration of amikacin in patients treated by dialysis was indirectly proportional to pH of urine. The plasma concentrations of amikacin did not correlate with urinary levels in patients in either of the GFR categories. Microbiological evaluation showed that the critical urinary concentration for efficacy of amikacin during UTI monotherapy in patients treated by dialysis is 100mg/L. We found that 4 out of 11 patients treated by dialysis did not reach this level during the treatment. Systemic administration of amikacin monotherapy in patients treated by dialysis is questionable as the concentrations of amikacin in their urine are often below the threshold of effectivity. Amikacin plasma concentrations are not a major determinant of amikacin concentration in urine, therefore pulse dosing is neither necessary nor safe in patients treated by dialysis, and may cause undesirable toxicity.

Kidney damage in hypertension disease

Essential hypertension (EH) is the most common cardiovascular disease and the leading cause of chronic kidney disease (CKD) worldwide. The aim of the study was to investigate the frequency and nature of kidney damage in hypertension. 189 patients (69 men and 120 women) with hypertension (stages I, II, and III) aged 43 years and older were examined. The average age of the patients was 61.2 ± 8.7 years. Clinical and biochemical tests were conducted on all patients, including red blood cell indices, C-reactive protein (CRP), lipid profile, fibrinogen, electrolytes, glucose, uric acid, creatinine, and cystatin C. The duration of hypertension was also recorded for each patient. Kidney function was assessed using serum creatinine (CKD-EPI) and cystatin C (F. Houcke). Patients were categorized according to the degree of decrease in glomerular filtration rate (GFR) based on the recommendations of the Russian Nephrology Society. Patients with kidney damage were divided into two groups: Group 1 consisted of patients with hypertension without signs of CKD (GFR calculated by cystatin C ≥ 60 ml/min), while Group 2 consisted of patients with hypertension complicated by CKD. The results showed that hypertension was accompanied by target organ damage in 70.8% of cases. The prevalence of CKD among patients with hypertension was 28.5%. Proteinuria was mainly detected in patients with renal insufficiency. The frequency of GFR categories according to CKD-EPI and F. Houcke formulas was as follows: G1 — 54.4% and 13.7% (p &lt; 0.05); G2 — 35.9% and 57.6% (p &lt; 0.05); G3a — 5.2% and 19.5% (p &lt; 0.05); G3b — 3.1% and 5.2% (p &lt; 0.05); G4 — 0.5% and 3.1% (p &lt; 0.05) and G5 — 0.5% and 0.5%, respectively. There was a strong correlation between GFR and serum creatinine (r = –0.439; p &lt; 0.05) and cystatin C (r = –0.866; p &lt; 0.0001). Patients in Group 2 (hypertension with kidney damage) had significantly higher levels of CRP, low-density lipoprotein cholesterol, cystatin C, and longer duration of hypertension, but lower levels of total calcium than patients in Group 1. In conclusion, CKD was present in 28.5% of patients with hypertension, and proteinuria was mainly detected in patients with renal insufficiency. Serum cystatin C levels most accurately reflect kidney filtration function.

Prevention, Diagnosis, Evaluation, and Treatment of Hepatitis C in Chronic Kidney Disease: Synopsis of the Kidney Disease: Improving Global Outcomes 2022 Clinical Practice Guideline.

The Kidney Disease: Improving Global Outcomes (KDIGO) 2022 clinical practice guideline on prevention, diagnosis, evaluation, and treatment of hepatitis C in chronic kidney disease (CKD) is an update of the 2018 guideline from KDIGO. The KDIGO Work Group (WG) updated the guideline, which included reviewing and grading new evidence that was identified and summarized. As in the previous guideline, the WG used the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach to appraise evidence and rate the strength of recommendations and used expert judgment to develop recommendations. New evidence led to updating of recommendations in the chapters on treatment of hepatitis C virus (HCV) infection in patients with CKD (Chapter 2), management of HCV infection before and after kidney transplant (Chapter 4), and diagnosis and management of kidney disease associated with HCV infection (Chapter 5). Recommendations in chapters on detection and evaluation of hepatitis C in CKD (Chapter 1) and prevention of HCV transmission in hemodialysis units (Chapter 3) were not updated because of an absence of significant new evidence. The 2022 updated guideline includes 43 graded recommendations and 20 ungraded recommendations, 7 of which are new or modified on the basis of the most recent evidence and consensus among the WG members. The updated guidelines recommend expanding treatment of hepatitis C with sofosbuvir-based regimens to patients with CKD glomerular filtration rate categories G4 and G5, including those receiving dialysis; expanding the donor pool for kidney transplant recipients by accepting HCV-positive kidneys regardless of the recipient's HCV status; and initiating direct-acting antiviral treatment of HCV-infected patients with clinical evidence of glomerulonephritis without requiring kidney biopsy. The update also addresses the use of immunosuppressive regimens in such patients.

Association between serum complements and kidney function in patients with diabetic kidney disease.

We aimed to explore the association between serum complements and kidney function of diabetic kidney disease (DKD) in Chinese patients. This is a retrospective study involving 2,441 participants. DKD was diagnosed according to the Kidney Disease: Improving Global Outcomes (KDIGO) categories. Participants were classified as stages G1-G5 by KDIGO glomerular filtration rate (GFR) categories. Effect sizes are expressed as odds ratio (OR) with 95% confidence interval (CI). After balancing age, gender, systolic blood pressure (SBP), hemoglobin A1c (HbA1C), serum triglyceride (TG), and urinary albumin-to-creatinine ratio (UACR) between the G2-G5 and control groups, per 0.1 g/L increment in serum complement C3 was significantly associated with a 27.8% reduced risk of DKD at G5 stage (OR, 95% CI, P: 0.722, 0.616-0.847, <0.001) relative to the G1 stage. Conversely, per 0.1 g/L increment in serum complement C4 was associated with an 83.0-177.6% increased risk of G2-G5 stage (P<0.001). Serum complement C1q was not statistically significant compared to controls at all stages prior to or after propensity score matching. Our results indicate that high concentrations of serum C4 were associated with the significantly elevated risk of kidney function deterioration across all stages, and reduced serum C3 levels with an increased risk of DKD stage G5.

Management and outcomes of myocardial infarction in people with impaired kidney function in England

BackgroundAcute myocardial infarction (AMI) causes significant mortality and morbidity in people with impaired kidney function. Previous observational research has demonstrated reduced use of invasive management strategies and inferior outcomes in this population. Studies from the USA have suggested that disparities in care have reduced over time. It is unclear whether these findings extend to Europe and the UK.MethodsLinked data from four national healthcare datasets were used to investigate management and outcomes of AMI by estimated glomerular filtration rate (eGFR) category in England. Multivariable logistic and Cox regression models compared management strategies and outcomes by eGFR category among people with kidney impairment hospitalised for AMI between 2015–2017.ResultsIn a cohort of 5 835 people, we found reduced odds of invasive management in people with eGFR < 60mls/min/1.73m2 compared with people with eGFR ≥ 60 when hospitalised for non-ST segment elevation MI (NSTEMI). The association between eGFR and odds of invasive management for ST-elevation MI (STEMI) varied depending on the availability of percutaneous coronary intervention. A graded association between mortality and eGFR category was demonstrated both in-hospital and after discharge for all people.ConclusionsIn England, patients with reduced eGFR are less likely to receive invasive management compared to those with preserved eGFR. Disparities in care may however be decreasing over time, with the least difference seen in patients with STEMI managed via the primary percutaneous coronary intervention pathway. Reduced eGFR continues to be associated with worse outcomes after AMI.

Renal stiffness measured by shear wave elastography and its relationship with perirenal fat in patients with chronic kidney disease.

This study aimed to utilize shear wave elastography (SWE) to assess changes in renal stiffness and its influencing factors in patients with chronic kidney disease (CKD) across different estimated glomerular filtration rate (eGFR) categories. It also sought to determine the correlation between perirenal fat (PF) and renal stiffness at various stages of CKD. A total of 190 CKD patients and 50 healthy controls were evaluated. Clinical parameters, conventional renal ultrasound measurements, PF, and renal stiffness trends were assessed separately. Factors independently associated with renal stiffness and PF were further analyzed. Renal parenchymal stiffness was significantly higher in the Albumin-CKD G1-2 (ALB-CKD G1-2) and CKD G3 groups than in the control group (p < 0.05). The parenchymal stiffness of the CKD G3 group was higher than that of the ALB-CKD G1-2 group (p < 0.05). The independent factors of renal parenchymal stiffness varied at different stages of disease development, with eGFR and PF being significant factors in the CKD G3 group. PF was elevated in the ALB-CKD G1-2 and CKD G3 groups compared to the control group, and the independent factors of PF varied across different stages, although waist circumference remained a common factor. Using SWE to detect renal elastic moduli can effectively assess changes in renal stiffness in patients with CKD with varying eGFRs. PF is an independent factor of renal stiffness in patients with CKD G3, providing a foundation for early diagnosis and clinical treatment.

A-107 Estimating Glomerular Filtration Rate by the Serum Creatinine and Cystatin C-plus-Creatinine Equations: Concordance and Effect on GFR Categorization

Abstract Background Estimating the glomerular filtration rate (GFR) is essential for evaluating kidney function, which is part of routine medical care. Most clinical laboratories report an estimated glomerular filtration rate (eGFR) based on serum creatinine, but cystatin C is a potential alternative marker. Evidence suggests that using the creatinine-plus-cystatin C (the 2021 CKD-EPI creatinine-cystatin C equation) eGFR gives more accurate results than the eGFR based on creatinine alone. Here we compared two 2021 CKD-EPI equations for estimating GFR—one using standardized creatinine alone (Cre) and the other using cystatin C combined with standardized creatinine (Cre-Cys). We also explored the effect of the equations on the GFR category. Methods: We retrospectively analyzed 777 simultaneous values for eGFR calculated by the two 2021 CKD-EPI equations over a period of nine months, from the time our laboratory initiated the Cre-Cys equation to the present.Cystatin C was measured turbidometrically on the Optilite (Binding Site, Birmingham, UK) and the creatinine was measured by the DxC method (Beckman Coulter, California, USA). We excluded any patient with Cre eGFR &amp;gt;90 mL/min/1.73 m2 because we do not result any value above 90 for that parameter. Results Out of 777 patients (52% female and 48% male), we excluded 82 results with Cre GFR &amp;gt; 90. The mean ± SD for Cre-Cys eGFR and Cre eGFR were 37.3 ± 23.8 and 37.1 ± 23.1, respectively, with a non-statistical difference between both groups using the paired T-Test (t = −0.8249, P-value = 0.4097). The mean difference (Cre-Cys eGFR minus Cre eGFR) was 0.28, with a standard deviation of 9.027. The correlation coefficient between Cre eGFR and Cre-Cys eGFR was r = 0.93. Two hundred and seventy-four (35%) samples had a difference between the numerical value of the two eGFR equations significant enough to change the GFR classification. 128 (34.5%) of the males had different categories when both equations calculated the eGFR vs 146 (36%) females. 36.3% of the white and 34% of the black patients had a discrepancy. The calculations matched for the other 502 patients. Of the 274 samples with discordant category classifications, the Cre-Cys equation gave a lower result and a higher (worse) category in 144 (53%), and a higher result and lower (better) category in 130 (47%). Conclusion The use of Cystatin C is growing and has moved beyond the nephrology community. Furthermore, the 2012 KDIGO guidelines suggest using additional tests (such as cystatin C or a clearance measurement) for confirmatory testing in specific circumstances when eGFR based on serum creatinine is less accurate. Currently, cystatin C testing is only available M-F, 8 AM–4 PM at our institute, but increasing availability and decreasing cost will likely expand Cre-Cys eGFR testing in the future. However, understanding the relationships between eGFR values from the different equations and how they will affect patient management can help clinicians optimize their use for kidney function evaluation.

Association between serum phosphate levels and anemia in non-dialysis patients with chronic kidney disease: a retrospective cross-sectional study from the Fuji City CKD Network

BackgroundPatients with chronic kidney disease (CKD) present high mortality and morbidity rates despite the availability of various therapies. Although CKD-mineral and bone disorder (MBD) and renal anemia are important factors in patients with CKD, only few studies have analyzed the relationship between them. Therefore, this study aimed to evaluate the relationship between CKD-MBD and anemia in patients with CKD who did not receive erythropoiesis-stimulating agent or iron therapies.MethodsThis retrospective cross-sectional study included patients with CKD aged ≥ 20 years with estimated glomerular filtration rate (eGFR) categories G2a to G5 who were referred to the Fuji City General Hospital between April 2018 and July 2019. The exclusion criterion was ongoing treatment for CKD-MBD and/or anemia.ResultsThe data of 300 patients with CKD were analyzed in this study. The median age of patients was 71 (range, 56.5–79) years. The median eGFR was 34 (range, 20–48) mL/min/1.73 m2, and the mean hemoglobin (Hb) level was 12.7 g/dL (standard deviation, 2.3), which decreased as the CKD stage increased. In a multivariate linear regression analysis of anemia-related factors, including age, renal function (eGFR), nutritional status, inflammation, and iron dynamics (serum iron level, total iron-binding capacity, ferritin levels), the serum phosphate levels were significantly associated with the Hb levels (coefficient [95% confidence interval], -0.73 [-1.1, -0.35]; P < 0.001). Subgroup analysis revealed a robust association between serum phosphate levels and Hb levels in the low-ferritin (coefficient [95% confidence interval], -0.94 [-1.53, -0.35]; P = 0.002) and advanced CKD groups (coefficient [95% confidence interval], -0.89 [-1.37, -0.41]; P < 0.001).ConclusionsWe found an association between high serum phosphate levels and low Hb levels in patients with CKD not receiving treatment for anemia. These results underscore the possibility of a mechanistic overlap between CKD-MBD and anemia.

Primary graft dysfunction grade correlates with acute kidney injury stage after lung transplantation.

Primary graft dysfunction (PGD) and acute kidney injury (AKI) are major early complications of lung transplantation and are associated with increased mortality. Lung injury after PGD can contribute to renal dysfunction; however, the association between PGD and AKI severity has not been thoroughly investigated. We analyzed the association between PGD grading and AKI staging, and the impact of AKI on subsequent changes to chronic kidney disease (CKD), including glomerular filtration rate (GFR), over time. This was a retrospective review of a single-center lung transplantation database between January 2018 and June 2022. AKI and GFR categories were classified according to the Kidney Disease: Improving Global Outcomes criteria. Spearman's and Kaplan-Meier tests were used to compare disease severity and assess survival. In a total of 206 patients: 119 (57.8%), 25 (12.1%), 34 (16.5%), and 28 (13.6%) had PGD grades 0, 1, 2, and 3, respectively; 96 (46.6%), 47 (22.8%), 27 (13.1%), and 36 (17.5%) had AKI stages 0, 1, 2, and 3, respectively. Twenty-one of the 28 patients (75.0%) with PGD grade 3 had AKI stage 3. There was a significant correlation between PGD grade and AKI stage (P<0.001). There was also a significant correlation between AKI stage and GFR category of CKD at 3, 6, 9, and 12 months after lung transplantation (all P<0.001). For all AKI stages, GFR categories worsened with postoperative time. PGD grade was significantly correlated with AKI stage, and AKI stage was correlated with GFR categories of CKD.

Modifiability of Composite Cardiovascular Risk Associated With Chronic Kidney Disease in Type 2 Diabetes With Finerenone

It is currently unclear whether chronic kidney disease (CKD)-associated cardiovascular risk in type 2 diabetes (T2D) is modifiable. To examine whether cardiovascular risk can be modified with finerenone in patients with T2D and CKD. Incidence rates from Finerenone in Chronic Kidney Disease and Type 2 Diabetes: Combined FIDELIO-DKD and FIGARO-DKD Trial Programme Analysis (FIDELITY), a pooled analysis of 2 phase 3 trials (including patients with CKD and T2D randomly assigned to receive finerenone or placebo) were combined with National Health and Nutrition Examination Survey data to simulate the number of composite cardiovascular events that may be prevented per year with finerenone at a population level. Data were analyzed over 4 years of consecutive National Health and Nutrition Examination Survey data cycles (2015-2016 and 2017-2018). Incidence rates of cardiovascular events (composite of cardiovascular death, nonfatal stroke, nonfatal myocardial infarction, or hospitalization for heart failure) were estimated over a median of 3.0 years by estimated glomerular filtration rate (eGFR) and albuminuria categories. The outcome was analyzed using Cox proportional hazards models stratified by study, region, eGFR and albuminuria categories at screening, and cardiovascular disease history. This subanalysis included a total of 13 026 participants (mean [SD] age, 64.8 [9.5] years; 9088 male [69.8%]). Lower eGFR and higher albuminuria were associated with higher incidences of cardiovascular events. For recipients in the placebo group with an eGFR of 90 or greater, incidence rates per 100 patient-years were 2.38 (95% CI, 1.03-4.29) in those with a urine albumin to creatinine ratio (UACR) less than 300 mg/g and 3.78 (95% CI, 2.91-4.75) in those with UACR of 300 mg/g or greater. In those with eGFR less than 30, incidence rates increased to 6.54 (95% CI, 4.19-9.40) vs 8.74 (95% CI, 6.78-10.93), respectively. In both continuous and categorical models, finerenone was associated with a reduction in composite cardiovascular risk (hazard ratio, 0.86; 95% CI, 0.78-0.95; P = .002) irrespective of eGFR and UACR (P value for interaction = .66). In 6.4 million treatment-eligible individuals (95% CI, 5.4-7.4 million), 1 year of finerenone treatment was simulated to prevent 38 359 cardiovascular events (95% CI, 31 741-44 852), including approximately 14 000 hospitalizations for heart failure, with 66% (25 357 of 38 360) prevented in patients with eGFR of 60 or greater. Results of this subanalysis of the FIDELITY analysis suggest that CKD-associated composite cardiovascular risk may be modifiable with finerenone treatment in patients with T2D, those with eGFR of 25 or higher, and those with UACR of 30 mg/g or greater. UACR screening to identify patients with T2D and albuminuria with eGFR of 60 or greater may provide significant opportunities for population benefits.

#4771 PROGNOSTIC RELEVANCE OF ELECTROCARDIOGRAPHIC ABNORMALITIES ACCORDING TO EGFR CATEGORIES

Abstract Background and Aims Electrocardiogram (ECG) abnormalities are associated with adverse cardiovascular outcomes in patients with chronic kidney disease (CKD), but their prognostic relevance according to estimated glomerular filtration rate (eGFR) categories remains unexplored. This study investigated the associations between no, minor, and major ECG abnormalities and fatal cardiovascular disease (CVD) according to different strata of renal function. Method This was a retrospective cohort study including 310.060 individuals aged ≥16 years from the Copenhagen General Practitioners' Laboratory that had an available digital ECG and creatinine measurement within 7 days from 2001–2015. eGFR was calculated using The Chronic Kidney Disease Epidemiology Collaboration equation, and data were cross-linked with Danish nation-wide healthcare registries to gain information on medication, comorbidity, and fatal CVD. ECG abnormalities were categorized as either no abnormalities, minor (first-degree atrioventricular block, incomplete bundle branch block or corrected QT prolongation) or major (left ventricular hypertrophy, atrial fibrillation/flutter, bundle branch block, Q waves, or ST-T deviations), as done previously [1]. Patients with both minor and major ECG abnormalities were assigned as major ECG abnormalities. ECG abnormalities and their association with fatal CVD were compared across strata of renal function [eGFR (ml/min/1.73m2) &amp;gt;90, 61–90, 46–60, 31–45, 16–30 and ≤15] based on multivariable Cox-regression analysis adjusted for age, sex, and comorbidities. Counterfactual G-estimation of Hazard Ratios (HRs) standardized to age and sex was performed to estimate 5-year absolute risk of fatal CVD. Results The median age was 55 [IQR, 41-69] years and 46% were male. Median study follow-up time was 10.3 [IQR, 6.7-14.4] years. A total of 47,249 (17.9%) of the included patients had an eGFR &amp;lt;60. The rate of fatal CVD according to ECG abnormalities and their adjusted HRs is shown in Fig. 1, while 5-year standardized risk of fatal CVD is depicted in Fig. 2. Generally, having minor or major ECG abnormalities, conferred a worse prognosis across all eGFR strata, with the highest 5-year absolute risk of fatal CVD being observed among patients with major ECG abnormalities and an eGFR between 31–45 [19% (95% CI, 18–20%)], eGFR 16–30 [25% (95% CI, 24–26%)] or an eGFR ≤15 [27.5% (95% CI, 24–31%)], Fig. 1–2. Conclusion In a population-based setting, having minor or major ECG abnormalities were associated with an increased risk of fatal CVD across all strata of renal function. Patients with an eGFR ≤45 and major ECG abnormalities represent a high-risk population, that might benefit from careful monitoring and cardiovascular risk management.

Kidney protection with canagliflozin: A combined analysis of the randomized CANVAS program and CREDENCE trials.

In the CANVAS Program and CREDENCE trials, the sodium glucose co-transporter 2 inhibitor canagliflozin reduced the risk of cardiovascular and kidney events in patients with type 2 diabetes. The current study analysed a pooled population to ascertain the kidney protection provided by canagliflozin across the full spectrum of kidney parameters. This post-hoc pooled analysis of the CANVAS Program (N = 10 142) and CREDENCE trial (N = 4401), assessed the risk of the primary kidney composite (doubling of serum creatinine, end-stage kidney disease, renal death), in all patients and subgroups defined by baseline estimated glomerular filtration rate (<30, 30 to <45, 45 to <60 and ≥60 ml/min/1.73 m2 ), albuminuria [<30, 30-300, >300 mg/g (<3.39, 3.39-33.9, >33.9 mg/mmol)] and 2012 Kidney Disease: Improving Global Outcomes (KDIGO) classification of chronic kidney disease (low/moderate, high and very high risk). In the overall population, the risk for the primary kidney composite outcome was 37% lower in the canagliflozin group versus placebo (HR: 0.63; 95% CI: 0.53, 0.77; p < .001). There was no evidence of heterogeneity in the kidney protective effects of canagliflozin across a range of kidney risks when stratified by baseline estimated glomerular filtration rate, albuminuria or KDIGO risk category (all pinteraction > .05). A statistically significant risk reduction of the primary kidney composite outcome was sustained by approximately 18 months after randomization. These results emphasize a critical role of canagliflozin in kidney protection across a broad spectrum of participants with type 2 diabetes with varying levels of kidney function.

PD40-12 FUNCTIONAL OUTCOMES PREDICTION AFTER ROBOTIC PARTIAL NEPHRECTOMY USING PADUA SCORE ASSESSED WITH 3D VIRTUAL MODELS: PRELIMINARY RESULTS OF A COLLABORATIVE ERUS STUDY

PD40-12 FUNCTIONAL OUTCOMES PREDICTION AFTER ROBOTIC PARTIAL NEPHRECTOMY USING PADUA SCORE ASSESSED WITH 3D VIRTUAL MODELS: PRELIMINARY RESULTS OF A COLLABORATIVE ERUS STUDY

Incident Atrial Fibrillation and Risk of Dementia in a Diverse, Community‐Based Population

Background Atrial fibrillation (AF) is the most common, clinically relevant arrhythmia in adults and associated with ischemic stroke and premature death. However, data are conflicting on whether AF is independently associated with risk of dementia, particularly in diverse populations. Methods and Results We identified all adults from 2 large integrated health care delivery systems between 2010 and 2017 and performed a 1:1 match of incident AF: no AF by age at index date, sex, estimated glomerular filtration rate category, and study site. Subsequent dementia was identified through previously validated diagnosis codes. Fine-Gray subdistribution hazard models were used to examine the association of incident AF (versus no AF) with risk of incident dementia, adjusting for sociodemographics and comorbidity and accounting for competing risk of death. Subgroup analyses by age, sex, race, ethnicity, and chronic kidney disease status were also performed. Among 196 968 matched adults, mean (SD) age was 73.6 (11.3) years, with 44.8% women, and 72.3% White. Incidence rates (per 100 person-years) for dementia over a median follow-up of 3.3 (interquartile range, 1.7-5.4) years were 2.79 (95% CI, 2.72-2.85) and 2.04 (95% CI, 1.99-2.08) per 100 person-years in persons with versus without incident AF, respectively. In adjusted models, incident AF was associated with a significantly greater risk of diagnosed dementia (subdistribution hazard ratio [sHR], 1.13 [95% CI, 1.09-1.16]). With additional adjustment for interim stroke events, the association of incident AF with dementia remained statistically significant (sHR, 1.10 [95% CI, 1.07-1.15]). Associations were stronger for age<65 (sHR, 1.65 [95% CI, 1.29-2.12]) versus ≥65 (sHR, 1.07 [95% CI, 1.03-1.10]) years (interaction P<0.001); and those without (sHR, 1.20 [95% CI, 1.14-1.26]) versus with chronic kidney disease (sHR, 1.06 [95% CI, 1.01-1.11]; interaction P<0.001). No meaningful differences were seen by sex, race, or ethnicity. Conclusions In a large, diverse community-based cohort, incident AF was associated with a modestly increased risk of dementia that was more prominent in younger patients and those without chronic kidney disease but did not substantially vary across sex, race, or ethnicity. Further studies should delineate mechanisms underpinning these findings, which may inform use of AF therapies.

Impact of baseline kidney function on the effects of sodium-glucose co-transporter-2 inhibitors on kidney and heart failure outcomes: A systematic review and meta-analysis of randomized controlled trials.

To determine whether the magnitude of the cardiorenal benefits of sodium-glucose co-transporter-2 inhibitors (SGLT2is) varies with baseline kidney function. We searched randomized, placebo-controlled trials testing the effects of SGLT2is on renal and cardiovascular outcomes. Efficacy outcomes, stratified by baseline estimated glomerular filtration rate (eGFR) categories, included renal disease progression, a composite heart failure (HF) outcome and mortality. Thirteen trials testing SGLT2is in 90 402 participants with available eGFR data were included. The risk of bias was judged as low for all trials. SGLT2is reduced the relative risks of renal disease progression by 27% to 57% and of HF outcomes by 13% to 32% across different eGFR categories, with an overall low heterogeneity. Meta-regression analyses showed a significant direct relationship between baseline eGFR and the magnitude of SGLT2is' renal protection (P = .003). The greatest risk reduction was in participants with an eGFR of 90 ml/min/1.73m2 or higher (HR 0.43, 95% CI: 0.32-0.58) and the smallest was in those with an eGFR of less than 30 ml/min/1.73m2 (HR 0.73, 95% CI: 0.62-0.86, P < .001). Conversely, for HF, the greatest risk reduction was in those with an eGFR of less than 30 ml/min/1.73m2 (HR 0.68, 95% CI: 0.48-0.96) and the smallest was in those with an eGFR of 90 ml/min/1.73m2 or higher (HR 0.87, 95% CI: 0.56-1.34). SGLT2is reduce the risk of renal and HF outcomes for all eGFR categories. The greatest benefits in terms of kidney protection may be achieved by early initiation of SGLT2is in people with preserved eGFR. The greatest risk reduction for HF outcomes is observed in people with lower eGFR values.

Prevalence of anemia and its predictors among patients with chronic kidney disease admitted to a teaching hospital in Ethiopia: A hospital-based cross-sectional study.

Anemia is a common complication of chronic kidney disease (CKD) and is associated with adverse patient outcomes. However, data on the prevalence of anemia in CKD patients is sparse, particularly in resource-limited settings. Therefore, this study aimed to assess the prevalence of anemia and its predictors among patients with CKD admitted to the Jimma medical center, southwest Ethiopia. A hospital-based prospective cross-sectional study was conducted from September 1 to November 30, 2020. All adult patients with CKD aged ≥18 years who fulfilled the inclusion criteria were consecutively recruited into the study. Data were entered into the Epi data manager version 4.4.1 and then exported to SPSS version 22 (IBM Corp., Armonk, NY) for analysis. The predictors of anemia were determined using multivariable logistic regression analysis. Statistical significance was set at P < .05. A total of 150 patients were included in this study. Of these, 64.67% were male, 56.67% had stage 5 CKD, 78% had a CKD duration of less than 1 year, and 74% had proteinuria. Hypertension (40.7%) and diabetes (14.7%) were the common causes of CKD. The prevalence of anemia was 85.33%. Of the patients, 28.67%, 40.67%, and 16% had mild, moderate, and severe anemia, respectively. On multivariate logistic regression, stage 4 CKD (adjusted odds ratio [AOR] 3.2, confidence interval [CI]: 1.78-12.91, P = .025), stage 5 CKD (AOR 4.03, CI: 1.17-13.73, P = .016), and CKD duration of less than 1 year (AOR 3, CI: 1.19-9.11, P = .007) were significantly associated with anemia. The prevalence of anemia among stage 3 to 5 CKD patients was very high. Anemia was significantly associated with the severity and duration of CKD. Therefore, serial follow-up of patients with a long duration and advanced stages of CKD may help prevent anemia and its adverse consequences.

Differential Associations of Cystatin C Versus Creatinine-Based Kidney Function With Risks of Cardiovascular Event and Mortality Among South Asian Individuals in the UK Biobank.

Background South Asian individuals have increased cardiovascular disease and mortality risks. Reliance on creatinine- rather than cystatin C-based estimated glomerular filtration rate (eGFRcys) may underestimate the cardiovascular disease risk associated with chronic kidney disease. Methods and Results Among 7738 South Asian UK BioBank participants without prevalent heart failure (HF) or atherosclerotic cardiovascular disease, we investigated associations of 4 eGFRcys and creatinine-based estimated glomerular filtration rate categories (<45, 45-59, 60-89, and ≥90 mL/min per 1.73 m2) with risks of all-cause mortality, incident HF, and incident atherosclerotic cardiovascular disease. The mean age was 53±8 years; 4085 (53%) were women. Compared with creatinine, cystatin C identified triple the number of participants with estimated glomerular filtration <45 (n=35 versus n=113) and 6 times the number with estimated glomerular filtration 45 to 59 (n=80 versus n=481). After multivariable adjustment, the eGFRcys 45 to 59 category was associated with higher risks of mortality (hazard ratio [HR], 2.38 [95% CI, 1.55-3.65]) and incident HF (sub-HR [sHR], 1.87 [95% CI, 1.09-3.22]) versus the eGFRcys ≥90 category; the creatinine-based estimated glomerular filtration rate 45 to 59 category had no significant associations with outcomes. Of the 7623 participants with creatinine-based estimated glomerular filtration rate ≥60, 498 (6.5%) were reclassified into eGFRcys <60 categories. Participants who were reclassified as having eGFRcys <45 had higher risks of mortality (HR, 4.88 [95% CI, 2.56-9.31]), incident HF (sHR, 4.96 [95% CI, 2.21-11.16]), and incident atherosclerotic cardiovascular disease (sHR, 2.29 [95% CI, 1.14-4.61]) versus those with eGFRcys ≥90; those reclassified as having eGFRcys 45 to 59 had double the mortality risk (HR, 2.25 [95% CI, 1.45-3.51]). Conclusions Among South Asian individuals, cystatin C identified a high-risk chronic kidney disease population that was not detected by creatinine and enhanced estimated glomerular filtration rate-based risk stratification for mortality, incident HF, and incident atherosclerotic cardiovascular disease.