eGFR Measurements Research Articles

Novel Biomarkers and Imaging Tests for AKI Diagnosis in Patients with Cancer.

The lack of non-invasive urine and blood-based biomarkers for the diagnosis of acute kidney injury (AKI) in patients with cancer is an area of significant unmet clinical need. Traditional non-invasive diagnostic tools that are currently utilized in the clinic, such as creatinine and cystatin C-based eGFR measurements, urinalysis, urine sediment exam, urine protein quantification, and urine electrolyte measurement, lack the sensitivity and specificity to distinguish between the various underlying etiologies of AKI in patients with cancer. Imaging-based diagnostics can be helpful to rule out urinary obstruction, but also lack sensitivity and specificity to diagnose the etiology of AKI. Kidney biopsy is often required for definitive diagnosis. As our scientific understanding of the biological pathways that are dysregulated in AKI has advanced, there has been considerable interest in developing new biomarkers for AKI. For example, the diagnosis of acute interstitial nephritis (AIN), which can occur in patients treated with immune checkpoint inhibitors (ICIs), promises to be revolutionized by the incorporation of urinary testing for inflammatory biomarkers such as C-X-C motif ligand 9 (CXCL9), tumor necrosis factor alpha (TNF-α), and interleukin 9 (IL-9). In the case of cisplatin administration, biomarkers such as neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule 1 (KIM-1) may improve prognostication, differentiating between persistent AKI resulting from acute tubular injury versus pre-renal azotemia. The development and validation of blood, urine and imaging biomarkers into widely utilized diagnostic tests will require a concerted effort, but could improve diagnosis, management and prognostication for a growing group of patients who are at high risk of developing AKI during the course of their illness.

Impact of arteriovenous fistula formation on trajectory of kidney function decline: a target trial emulation

Abstract Background Prior nonrandomised studies have suggested nephroprotective effects of arteriovenous fistula (AVF) formation, but these are plausibly susceptible to immortal time and selection biases. Methods We studied patients attending nephrology clinics in the West of Scotland during 2010-2022 with an eGFR ≤15mL/min/1.73m2 and no prior AVF. Using target trial emulation and a sequential trial design, we simulated a hypothetical trial that would randomise patients to either undergo AVF formation immediately or not to undergo AVF formation. The primary outcome was the difference in eGFR slope for the first six months of follow-up, estimated using a mixed-effects model. The secondary outcomes were 5-year absolute risks of dialysis and death, estimated using the Aalen-Johansen and Kaplan-Meier estimators respectively. Results 1,364 unique patients (mean age 51.1, 55.7% male) contributed 3,125 person-trials, with 561 in the AVF and 2,564 in the no AVF group. Mean eGFR was 12.6mL/min/1.73m2 and the median number of eGFR measurements per person-trial was 7 (IQR 4 – 12). Slope of eGFR decline did not differ significantly between the AVF and no AVF groups (between group difference -0.67mL/min/1.73m2/year, 95%CI -1.43, 0.10). The 5-year absolute risk of dialysis was 87% (95%CI 84, 91) in the AVF group and 75% (95%CI 73, 77) in the no AVF group and the 5-year survival probability was 77% (95%CI 70, 83) in the AVF group and 67% (95%CI 64, 69) in the no AVF group. Conclusions In this study of patients with advanced CKD, there was no evidence of a nephroprotective effect of AVF formation.

Characteristics, treatment and disease burden among stage 3-4 chronic kidney disease patients with and without type 2 diabetes in Finland during 2016-2022.

Real-world evidence on the management of chronic kidney disease (CKD) with and without type 2 diabetes (T2D) is limited. This study described the characteristics, treatment, and disease burdenin patients with stage 3-4 CKD with and without T2D in Finland. This cohort study used data from primary and hospital care in five municipalities in Finland to identify adults with stage 3-4 CKD, defined as having either one estimated glomerular filtration rate (eGFR) measurement of 15-59ml/min/1.73m2 followed by a second measurement taken≥90 days apart, or a registered CKD diagnosis. Prevalence was determined on 31 December 2022, and a cohort of incident stage 3-4 CKD patients was followed from the first date fulfilling eligibility criteria since 01 January 2016 (index) until death or 31 December 2022, and analyzed by T2D status. The prevalence of stage 3-4 CKD was 6.3%. Among the 12 474 incident stage 3-4 CKD patients, the majority were non-T2D (73%). The median age was similar for non-T2D and T2D CKD patients, respectively. Baseline albuminuria screening was 9% among non-T2D and 53% among T2D. The use of kidney-protective treatments at index was also lower in non-T2D patients (47%), compared with T2D patients (69%). The use of kidney-protective treatments remained unchanged during 12 months after index. Healthcare resource utilization was high, and CKD or heart failure contributed considerably more to the all-cause healthcare costs than atherosclerotic diseases, regardless of T2D status. In both CKD subgroups, 10% had died within one year. In Finland, CKD is highly prevalent and associated with high risks and low use of albuminuria testing and kidney-protective medications. Most CKD patients were non-T2D, which showed lower use of preventive management and similar risks compared with T2D patients. These findings call for an urgent need for improved awareness and risk management, especially in non-T2D CKD patients.

Prediction of cardiovascular events and all-cause mortality using race and race-free estimated glomerular filtration rate in African Americans: the Jackson Heart Study.

New Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations without a race adjustment were developed to estimate the glomerular filtration rate (eGFR). We aimed to compare the performance of five CKD-EPI eGFR equations, with or without race, in predicting cardiovascular disease (CVD) events and all-cause mortality in Black Americans from the Jackson Heart Study. JHS is an ongoing population-based prospective cohort study of African Americans in the Jackson, Mississippi, metropolitan area. Five CKD-EPI equations were used to estimate GFR at baseline using serum creatinine (Cr) or cystatin C (cys), including 2009 eGFRcr(ASR [age, sex, race]), 2021 eGFRcr(AS [age and sex]), 2012 eGFRcr-cys(ASR), 2021 eGFRcr-cys(AS), 2012 eGFRcys(AS). Endpoints were incident CVD events and all-cause mortality. Cox proportional hazards regression was used to assess the associations between different eGFRs and outcomes adjusting for atherosclerotic risk factors. Harrell's C-statistics and Net Reclassification Index (NRI) were used to assess the predictive utility. Among 5,129 participants (average age 54.8 ± 12.8 yrs), 1898 were male (37.0%). eGFRcr(AS) provided lower estimates and resulting in a greater proportion of participants categorized as CKD than eGFRcr(ASR), eGFRcr-cys(ASR), eGFRcr-cys(AS) and eGFRcys(AS). A median follow-up of 13.7 and 14.3 years revealed 411 (9.3%) CVD incidents and 1,207 (23.5%) deaths. Lower eGFRs were associated with CVD incidents and all-cause mortality. eGFRcr-cys(ASR), eGFRcr-cys(AS) and eGFRcys(AS) were strongly associated with incident CVD events and all-cause mortality than eGFRcr(ASR) and eGFRcr(AS). A significant discrimination improvement was found in C-statistics for predicting incident CVD events and all-cause mortality after adding each eGFR measure to the basic model including atherosclerotic risk factors. Across a 7.5% 10-year risk threshold, eGFRcys(AS) improved net classification of all-cause mortality (NRI: 2.19, 95%CI: 0.08, 4.65%). eGFR based on creatinine omit race has the lowest mean and detects more CKD patients in Black population. The eGFRs incorporating cystatin C strengthens the association between the eGFR and the risks of incident CVD and all-cause mortality. Cystatin C-based eGFR equations might be more appropriate for predicting CVD and mortality among Black population.

Prediction of subsequent CKD according to eGFR decline slope varies by the presence of hypertension

Abstract Background We reported that a declining slope in eGFR evaluated from 3-year observation could predict subsequent CKD among the relatively healthy population, even adjusted for baseline eGFR. However, its certainty may vary depending on the presence of comorbidities such as diabetes and hypertension, which are also recognized as the risk factors of CKD. Methods Annual health check-up data from a Japanese company spanning from 2009 to 2022 was used. The analyses included participants having 4 times continuous eGFR measurements for 3 years, undergoing health checkups at least once during a follow-up period, with negative for urinary protein (UP), and non-diabetic. Individual ‘eGFR slopes’ were calculated by the regression line with 4 times eGFR measurements. Participants with slopes of < -5 per year were categorized as the “decreased” group and -5 or more were categorized as the “stable” group. The cases of positive UP or less than 45mL/min/1.73m2 in eGFR during a follow-up period were defined as CKD. Cox regression analyses adjusted for sex, age, and eGFR at baseline were performed to calculate the hazard ratios and 95% CIs for CKD in the decreased group (reference; stable), stratified by hypertension. Results Out of 5598 study participants(men 36%, mean age 48.2±10.1years, mean follow-up period 4.3 years), 260 CKD cases (4.6%) were observed. CKD cases accounted for 4.5% (235/5218) in the stable group and 6.6% (25/380) in the decreased group. Multivariate-adjusted hazard ratios [95%CIs] of CKD by eGFR decline was 1.50[0.99-2.27]. The eGFR decline increased the risk of CKD only in participants with hypertension (2.09[1.09-4.04]), but not in those without hypertension (1.25[0.73-2.13]). After excluding individuals with eGFR slopes exceeding 10 per year to consider for hyperfiltration of eGFR, the results were consistent. Conclusions The eGFR decline over a 3-year observation may predict subsequent CKD only in individuals with hypertension. Key messages • With a relatively short-term evaluation period of three years, eGFR decline can predict subsequent CKD only in hypertensive individuals. • In middle-aged hypertensive patients, it would be important for the prevention of CKD to pay attention not only to low eGFR but also to the progression of eGFR decline.

Longitudinal and cross-sectional associations of NT-proBNP with kidney function and chronic kidney disease: results from KORA cohort studies

Abstract Background Chronic kidney disease (CKD) and cardiovascular disease (CVD) exhibit a bidirectional and complex relationship, and share common risk factors and mechanisms of disease development. Thus, important CVD-related biomarkers, such as N-terminal prohormone of B-type natriuretic peptide (NT-proBNP), may serve as a biomarker for CKD development. Purpose We aimed to investigate the cross-sectional and longitudinal associations of NT-proBNP with kidney function and CKD in data from two population-based cohort studies. Methods We included 5854 men and women, aged 25-74 years, from the Cooperative Health Research in the Region of Augsburg (KORA) cohort studies S3 and S4, and their 1-2 subsequent follow-up surveys, with a median follow-up time of 9.4 and 13.4 years, respectively. Kidney function was assessed by 3 estimated glomerular filtration rate (eGFR) assessments, calculated using creatinine (eGFRcr), cystatin C, and combined creatinine and cystatin C. Serum NT-proBNP was logarithmically transformed followed by Z-score standardization and categorized into 4 groups (G1-4), <48.6, 48.6-125, 125-300, and ≥300 pg/ml. In cross-sectional analysis, linear regression and logistic regression were used to estimate β/odds ratio (OR) and their 95% confidence intervals (CIs) of continuous eGFR or prevalent CKD. For longitudinal analysis of repeated eGFR measurements during follow-up (5854 participants, 11870 observations), linear mixed-effects models were used. For incident CKD associations, interval-censored Cox regression models were performed in participants free of CKD at baseline. Results In cross-sectional analyses, higher NT-proBNP levels were associated with lower eGFR and higher prevalence of CKD across all 3 eGFR assessments. For example, results based on eGFRcr showed that the fully-adjusted β (95% CIs) for per 1 SD increase in log-transformed NT-proBNP were -1.03 (-1.42, -0.64) and -7.01 (-8.93, -5.09) 60 ml/min/1.73m2 for G4 compared to G1, respectively. Corresponding OR (95% CIs) were 2.22 (1.81, 2.74) and 13.8 (5.76, 36.4), respectively. In longitudinal analyses, participants with higher baseline NT-proBNP had a faster decline in eGFR during follow-up. The fully-adjusted β (95% CIs) for 5-year eGFRcr decline were -0.67 (-0.87, -0.47) per 1 SD increase, and -0.37 (-0.79, 0.05), -1.53 (-2.18, -0.88), -4.24 (-5.57, -2.90) 60 ml/min/1.73m2/year for G2-4. Higher NT-proBNP levels were associated with higher incident CKD risks. For associations with incident creatinine-based CKD, hazard ratio (95% CIs) were 1.16 (1.00, 1.33) per 1 SD increase and 1.03 (0.77, 1.38), 1.07 (0.75, 1.52), and 1.81 (1.07, 3.04) for G2-4. Conclusions We found associations of higher NT-proBNP with lower kidney function and higher CKD prevalence. Moreover, higher baseline NT-proBNP levels were associated with faster kidney function decline and higher incident CKD risks. Our findings indicate the potential utility of NT-proBNP as a biomarker of kidney health.Figure 1.Cross-sectional associationsFigure 2.Longitudinal associations

Assessment of Kidney Function Discrepancies in Pediatric CAKUT Patients Using Bedside Schwartz Equation and Renal Scintigraphy.

This research explores the correlation between estimated glomerular filtration rates (eGFR) obtained using the bedside Schwartz equation, and renal scintigraphy in children with congenital kidney and urinary tract abnormalities (CAKUT). The objective is to enhance understanding and management of renal health in this demographic by analyzing kidney size-function relationships. A retrospective observational analysis was performed on 94 pediatric CAKUT patients at the "Louis Turcanu" Emergency Hospital for Children, Timisoara. Kidney function data, extracted from medical records, were evaluated using the Schwartz equation, renal scintigraphy, and the gold standard iohexol clearance. Ethical approval was secured for the study, which employed descriptive and inferential statistical methods, including t-tests and correlation coefficients, to compare eGFR values. Significant variances were found in eGFRs across different body surface area (BSA) percentiles. For instance, the eGFR for the right kidney in the 25th-50th BSA percentile (102.02 ± 41.52 mL/min/BSA) was notably higher than that of the left (35.60 ± 26.05 mL/min/BSA; p = 0.01). The overall sample reflected a higher eGFR in the right kidney (76.03 ± 40.91 mL/min/BSA) compared to the left (57.46 ± 35.91 mL/min/BSA; p = 0.02). Additionally, a strong positive Pearson correlation (r = 0.80, p = 0.02) was found between scintigraphy and ultrasound measures in the 50th-75th percentiles for left renal percentiles, demonstrating consistent patterns across different evaluations of kidney function. This comparison indicates a complex relationship between eGFR values and kidney size, suggesting potential inaccuracies in standard bedside eGFR measurements for pediatric CAKUT patients. The findings underscore the necessity for accurate diagnostic tools specifically designed for pediatric applications and advocate for the integration of multiple diagnostic techniques to improve clinical management.

Comparison of the correlation of creatinine- and cystatin C–Based estimated GFR and their differences with new-onset heart failure in a community-based population with type 2 diabetes

AimsThis study aimed to investigate the impact of different estimated glomerular filtration rate (eGFR) values like cystatin C-based eGFR (eGFRcys), creatinine-based eGFR (eGFRcr), and their difference (eGFRdiff; eGFRcys -eGFRcr), on the incidence of heart failure (HF) in patients with type 2 diabetes(T2D).MethodsBeing a prospective cohort study, it included 7,967 patients with T2D who underwent serum creatinine and cystatin C tests as part of the Kailuan Group’s 6th annual health examination (2016). Subsequently, eGFRcys, eGFRcr, and eGFRdiff were calculated. Patients were categorized into three groups: negative (<-15 mL/min/1.73 m2), midrange (-15 to 15 mL/min/1.73 m2), and positive (> 15 mL/min/1.73 m2) eGFRdiff groups, respectively. Furthermore, the relationship between the various eGFR measurements and new-onset HF were studied using Cox proportional hazards regression, and the potential improvement in predictive capability was evaluated by adding these eGFR metrics to established HF risk models.ResultsAmong 7967 participants with mean age of 60.51 years, there were 20.92% women and 79.08% men. At baseline, eGFRcys and eGFRcr values differed by more than 15 mL/min/1.73m2 in 41.3% of participants. During a median follow-up period of 3.76 years, there were 172 (2.16%) new HF cases and 517 (6.49%) all-cause deaths. The cumulative incidence of HF in the midrange, negative, and positive eGFRdiff groups was 1.74%, 4.10%, and 0.61%, respectively (p < 0.001). In multivariable adjusted models, participants in the negative eGFRdiff group had higher risk of HF compared with the midrange eGFRdiff group (HR, 2.15; 95% CI, 1.57–2.94). Conversely, participants in the positive eGFRdiff group had lower risk for HF (HR, 0.40; 95% CI, 0.17–0.93). And each 15 mL/min/ 1.73 m2 higher eGFRdiff was associated with 34% (HR, 0.66; 95% CI, 0.58 − 0.47)lower risk of incident HF. The predictive capacity for HF risk in diabetic individuals was enhanced by adding eGFRcys or eGFRdiff to established HF risk models, with eGFRcys showing more significant additional predictive value.ConclusionThese findings suggest that large differences between eGFRcys and eGFRcr were common in community-based population with T2D. Different eGFR metrics can independently predict HF incidence in patients with T2D. Additionally, metrics like eGFRcys and eGFRdiff provide significant predictive value for HF risks beyond traditional risk factors, with eGFRcys showing more pronounced benefits in such cases.

Longitudinal Patterns of Ankle-Brachial Index and Their Association With Progression of CKD in Patients With Type 2 Diabetes and Elevated Body Mass Index

Rationale & ObjectiveAnkle-brachial index (ABI) is used to screen for vascular complications in the setting of diabetes. This study sought to examine the relationship of longitudinal ABI data and chronic kidney disease (CKD) progression in patients with type 2 diabetes (T2D) and elevated body mass index (BMI). Study DesignA post-hoc analysis of the Look AHEAD trial. Setting & ParticipantsThis study included 3,631 participants in the Look AHEAD trial with a baseline glomerular filtration rate (eGFR) >60 ml/min/1.73 m2. ExposuresAverage ABI and average annual change in ABI were calculated based on annual ABI measurements during the first 4 years of the study. OutcomeCKD progression, defined as kidney failure requiring maintenance dialysis or the occurrence of eGFR<60 ml/min/1.73 m2 with a drop of ≥30% at a follow-up visit relative to the first eGFR measurement. Analytical ApproachRestricted cubic spline and Cox proportional hazards models were fit to estimate associations and to explore non-linearity. ResultsOver a median follow-up of 10.1 years, 1,051 participants developed CKD progression. There was a reversed J-shaped relationship of CKD progression with average ABI (when ABI <1.17: HR (per SD decrement), 1.23; 95%CI, 1.06-1.42; when ABI ≥ 1.17: HR (per SD increment), 1.10; 95%CI, 1.00-1.22) and average annual change in ABI (when change in ABI <-0.007: HR (per SD decrement), 1.37; 95%CI, 1.12-1.66; when change in ABI ≥-0.007: HR (per SD increment), 1.13; 95%CI, 1.03-1.24). LimitationsObservational study, potential unmeasured confounding. ConclusionsLow and high average ABI, even at clinically normal values, as well as decreasing and increasing average annual ABI, were associated a higher risk of CKD progression in patients with T2D and elevated BMI. Monitoring ABI and its changes over time may facilitate CKD risk stratification in patients with T2D.

O80 A HIGH 24-HOUR URINE SODIUM-TO-POTASSIUM RATIO IS ASSOCIATED WITH WORSE RENAL OUTCOME

Background and Objective: Low sodium and high potassium intake are advised to control blood pressure and may improve long term cardiorenal outcomes. The optimal potassium intake for patients with chronic kidney disease remains to be defined and. We investigated whether the 24-hour urine sodium-to-potassium ratio (Na/K-ratio), which incorporates estimates of both sodium and potassium intake, could predict long-term renal outcome. Methods: We selected adult outpatients of a Dutch tertiary hospital who collected at least one 24-hour urine collection between 1998-2023. Patients with a history of dialysis or kidney transplantation were excluded. We examined the need for persistent renal replacement therapy (RRT), defined as dialysis or kidney transplantation, using Cox-regression. The association between the 24-hour urine Na/K-ratio and the estimated glomerular filtration rate (eGFR) slope was assessed using linear regression in patients who had ≥3 eGFR measurements available in ≥3 years, adjusted for age, sex, baseline eGFR, diabetes mellitus and hypertension. In the Cox-regression analysis, we additionally adjusted for the interaction between the 24-hour urine Na/K-ratio and baseline eGFR. Hypertension was defined as a clinical diagnosis or an office blood pressure ≥140/90 mmHg. Results: We included 720 patients aged 50±15 years, of whom 52% were male, 58% had hypertension and 31% diabetes mellitus. The baseline eGFR was 64±34 ml/min/1.73m2. The 24-hour urine Na/K ratio was 2.5±1.2 in a median number of 1 (IQR=1-2) urine collection. During a median follow-up of 11.2±14.0 years, 29% of patients needed RRT. The median annual eGFR decline was 1.51 (IQR=0.49-3.98) ml/min/1.73m2. Every unit increase in 24-hour urine Na/K-ratio was associated with a 19% higher risk for RRT (HR 1.19, 95% CI 1.03-1.39; p=0.02) and an additional 0.44 ml/min/1.73m2 (95% CI -0.83, -0.04; p=0.03) annual eGFR decline. Conclusions: This study suggests that higher 24-hour urine Na/K-ratio is associated with faster kidney function decline and the need for RRT, independent of hypertension, in a selected group of outpatients with available 24-hour urine measurements.

O40 TELOMERE LENGTH AS A BIOMARKER FOR KIDNEY HEALTH: EVIDENCE FROM A MENDELIAN RANDOMISATION STUDY

Background and Objective: Chronic kidney disease (CKD) is a significant public health challenge, often progressing undetected until advanced stages. Early detection through biomarkers can enhance CKD management and improve patient outcomes. Previous studies suggested a link between telomeres and kidney health, but these results were inconsistent. This study aims to clarify the association between telomere length, kidney function and disease, and assess its causality using Mendelian randomisation (MR). Methods: Using the UK Biobank data, we examined the relationship between leukocyte telomere length (LTL) and kidney health. We performed multiple linear and logistic regression analyses using estimated glomerular filtration rate (eGFR) measures and reported kidney disease diagnoses, adjusting for age, sex, white blood cell count, body mass index, and hypertension. The causality of associations was tested using MR with established genetic instruments. Results: 338,143 participants were included in our analysis. The cohort had an average age of 56.52 years, with 54.41% being females. LTL was associated with eGFR from serum creatinine (eGFRcrea, beta = 0.001, p &lt;0.01), serum cystatin C (eGFRcys, beta = 0.004, p &lt;0.0001), and their combination (eGFRcreacys, beta = 0.003, p &lt;0.0001). Additionally, longer LTL was associated with reduced odds of CKD (OR = 0.94 [95% CI 0.93-0.96], p &lt;0.0001). Significant associations were also observed between LTL and acute renal failure (OR = 0.95 [95% CI 0.93-0.97], p &lt;0.0001), and hypertensive kidney disease (OR = 0.91 [95% CI 0.86-0.96], p &lt;0.001). MR analysis supported a causal effect of LTL on eGFRcrea (Effect size = 0.006, Bonferroni corrected p = 0.04). However, no causal effect was observed between LTL and CKD or other kidney diseases. Bi-directional MR analysis revealed that the relationship between LTL and kidney function is unidirectional. Conclusions: Longer LTL correlates with better kidney function and reduced kidney disease risk. MR findings suggest a potential causal relationship between LTL and kidney function, highlighting telomeres as promising biomarkers for early detection of CKD.

Screening and diagnosis of chronic kidney disease among patients living with diabetes: A retrospective cohort study using the Canadian Primary Care Sentinel Surveillance Network

IntroductionIn Canada, regional evaluations of screening practices for chronic kidney disease (CKD) among people with diabetes highlight areas for improvement; however, national estimates are notably absent. Estimates of CKD incidence often discount the expected decline in eGFR associated with age; age-adaptive thresholds may help account for this. We describe the frequency of screening and diagnosis of CKD among adults with diabetes among a nationally representative primary care cohort. MethodsIn this retrospective cohort study, we used electronic medical record data from the Canadian Primary Care Sentinel Surveillance Network (CPCSSN). We followed adult patients (18+) with diabetes without CKD at baseline for 5 years starting in 2014. We determined the frequency of ACR and/or eGFR testing over time. We identified incident CKD diagnoses based on eGFR measurements using fixed-threshold and age-adaptive definitions and quantified the incidence proportion and rate. ResultsWe analysed records from 37,604 patients with diabetes. Only 13% of patients had yearly eGFR and ACR testing for CKD, though roughly 60% had non-yearly use of both tests in 5 years. eGFR testing was performed more frequently than ACR testing (94.1% vs. 76.6% having testing over follow-up). We found increased incidence proportions (14.6 % vs. 6.0%) and rates (33.1 vs. 13.4 diagnoses/1000 person-years) of CKD using the fixed-threshold compared to age-adaptive definitions. ConclusionsOur study presents the first national understanding of screening practices for CKD among people with diabetes in Canada. In particular, increased use of ACR testing should be encouraged for early detection of changes in kidney function.

Estimated glomerular filtration rate slope and risk of primary and secondary major adverse cardiovascular events and heart failure hospitalization in people with type 2 diabetes: An analysis of the EXSCEL trial.

The decline in estimated glomerular filtration rate (eGFR), a significant predictor of cardiovascular disease (CVD), occurs heterogeneously in people with diabetes because of various risk factors. We investigated the role of eGFR decline in predicting CVD events in people with type 2 diabetes in both primary and secondary CVD prevention settings. Bayesian joint modelling of repeated measures of eGFR and time to CVD event was applied to the Exenatide Study of Cardiovascular Event Lowering (EXSCEL) trial to examine the association between the eGFR slope and the incidence of major adverse CV event/hospitalization for heart failure (MACE/hHF) (non-fatal myocardial infarction, non-fatal stroke, CV death, or hospitalization for heart failure). The analysis was adjusted for age, sex, smoking, systolic blood pressure, baseline eGFR, antihypertensive and lipid-lowering medication, diabetes duration, atrial fibrillation, high-density cholesterol, total cholesterol, HbA1c and treatment allocation (once-weekly exenatide or placebo). Data from 11 101 trial participants with (n = 7942) and without (n = 3159) previous history of CVD were analysed. The mean ± SD eGFR slope per year in participants without and with previous CVD was -0.68 ± 1.67 and -1.03 ± 2.13 mL/min/1.73 m2, respectively. The 5-year MACE/hHF incidences were 7.5% (95% CI 6.2, 8.8) and 20% (95% CI 19, 22), respectively. The 1-SD decrease in the eGFR slope was associated with increased MACE/hHF risks of 48% (HR 1.48, 95% CI 1.12, 1.98, p = 0.007) and 33% (HR 1.33, 95% CI 1.18,1.51, p < 0.001) in participants without and with previous CVD, respectively. eGFR trajectories over time significantly predict incident MACE/hHF events in people with type 2 diabetes with and without existing CVD, with a higher hazard ratio for MACE/hHF in the latter group.

Prevalence and predictors of long-term progression of chronic kidney disease in people with HIV in Ghana from 2003–2018

BackgroundHIV is associated with an increased risk of progression to chronic kidney disease (CKD), and this risk is higher in people of West African descent than many other ethnicities. Our study assessed the rates of eGFR change and predictors of rapid eGFR progression in patients receiving antiretroviral therapy (ART), including tenofovir disoproxil fumarate (TDF), in central Ghana between 2003 and 2018.MethodsThis single-centre retrospective study enrolled people with HIV (PWH) initiating ART in Ghana between 2003–2018. Demographics, hepatitis B (HBsAg) status, ART regimens and estimated glomerular filtration rate (eGFR) measurements were recorded, and analyses including multi-level model linear regression were performed to determine predictors of greater levels of eGFR decline and risk of rapid eGFR decline.ResultsSix hundred and fifty-nine adult participants were included in the study with a median follow-up time of 6 years (IQR 3.6–8.9). 149 participants (22.6%) also had confirmed HBV co-infection. eGFR mean values were lowest at the point of diagnosis and highest on the second measurement taken; mean eGFR slowly decreased over subsequent measures thereafter. TDF use was associated with the highest mean rate of eGFR decline of all nucleoside or nucleotide reverse transcriptase inhibitors (NRTIs) with a statistically significant greater annual decline of -1.08 mL/min/1.73m2/year (CI: -1.92, -0.24) compared with zidovudine. Nevirapine (-0.78mL /min/173m2/year; CI: -1.39, -0.17) and protease inhibitors (-1.55mL/mil/173m2/year; CI: -2.68, -0.41) were associated with greater eGFR declines compared with efavirenz. Negative HBsAg status was associated with greater eGFR decline compared with positive HBsAg status (-1.25mL/mil/173m2/year; CI 0.29. -2.20).ConclusionsIncreased rates of eGFR decline amongst PWH in Ghana were associated with TDF, nevirapine, and protease inhibitor use as well as negative HBsAg status. Additional research using mortality outcome data is needed to closely assess long-term predictors of eGFR decline in African populations.

Associations of Cerebral Small Vessel Disease and Chronic Kidney Disease in Patients With Acute Intracerebral Hemorrhage: A Cross-Sectional Study.

Chronic kidney disease (CKD) may be associated with the pathogenesis and phenotype of cerebral small vessel disease (SVD), which is the commonest cause of intracerebral hemorrhage (ICH). The purpose of this study was to investigate the associations of CKD with ICH neuroimaging phenotype, volume, and location, total burden of small vessel disease, and its individual components. In 2 cohorts of consecutive patients with ICH evaluated with MRI, we investigated the frequency and severity of CKD based on established Kidney Disease Improving Global Outcomes criteria, requiring estimated glomerular filtration rate (eGFR) measurements <60 mL/min/1.732 ≥ 3 months apart to define CKD. MRI scans were rated for ICH neuroimaging phenotype (arteriolosclerosis, cerebral amyloid angiopathy, mixed location SVD, or cryptogenic ICH) and the presence of markers of SVD (white matter hyperintensities [WMHs], cerebral microbleeds [CMBs], lacunes, and enlarged perivascular spaces, defined according to the STandards for ReportIng Vascular changes on nEuroimaging criteria). We used multinomial, binomial logistic, and ordinal logistic regression models adjusted for age, sex, hypertension, and diabetes to account for possible confounding caused by shared risk factors of CKD and SVD. Of 875 patients (mean age 66 years, 42% female), 146 (16.7%) had CKD. After adjusting for age, sex, and comorbidities, patients with CKD had higher rates of mixed SVD than those with eGFR >60 (relative risk ratio 2.39, 95% CI 1.16-4.94, p = 0.019). Severe WMHs, deep microbleeds, and lacunes were more frequent in patients with CKD, as was a higher overall SVD burden score (odds ratio 1.83 for each point on the ordinal scale, 95% CI 1.31-2.56, p < 0.001). Patients with eGFR ≤30 had more CMBs (median 7 [interquartile range 1-23] vs 2 [0-8] for those with eGFR >30, p = 0.007). In patients with ICH, CKD was associated with SVD burden, a mixed SVD phenotype, and markers of arteriolosclerosis. Our findings indicate that CKD might independently contribute to the pathogenesis of arteriolosclerosis and mixed SVD, although we could not definitively account for the severity of shared risk factors. Longitudinal and experimental studies are, therefore, needed to investigate causal associations. Nevertheless, stroke clinicians should be aware of CKD as a potentially independent and modifiable risk factor of SVD.

Suboptimal monitoring and management in patients with unrecorded stage 3 chronic kidney disease in real-world settings: Insights from REVEAL-CKD.

Clinical practice guidelines for patients with chronic kidney disease (CKD) recommend regular monitoring and management of kidney function and CKD risk factors. However, the majority of patients with stage 3 CKD lack a diagnosis code, and data on the implementation of these recommendations in the real world are limited. To assess the implementation of guideline-directed monitoring and management practices in the real world in patients with stage 3 CKD without a recorded diagnosis code. REVEAL-CKD (NCT04847531) is a multinational, observational study of patients with stage 3 CKD. Eligible patients had ≥2 consecutive estimated glomerular filtration rate (eGFR) measurements indicative of stage 3 CKD recorded >90 and ≤730 days apart, lacked an International Classification of Diseases 9/10 diagnosis code corresponding to CKD any time before and up to 6 months after the second eGFR measurement. Testing of key measures of care quality were assessed. The study included 435,971 patients from 9 countries. In all countries, the prevalence of urinary albumin-creatinine ratio and albuminuria testing was low. Angiotensin-converting enzyme inhibitor, angiotensin receptor blocker and statin prescriptions were highly variable, and sodium-glucose cotransporter-2 inhibitor prescriptions remained below 21%. Blood pressure measurements were recorded in 20.2%-89.9% of patients. Overall, a large proportion of patients with evidence of stage 3 CKD did not receive recommended, guideline-directed monitoring and management. The variability in standard of care among countries demonstrates a clear opportunity to improve monitoring and management of these patients, most likely improving long-term outcomes.

Population-wide eGFR percentiles in younger adults and clinical outcomes.

Identifying meaningful estimated glomerular filtration rate (eGFR) reductions in younger adults (<65 years) could guide prevention efforts. To aid in interpretation and identification of young adults at risk, we examined the association of population-level eGFR percentiles relative to the median by age and clinical outcomes. We conducted a retrospective cohort study of 8.7 million adults from Ontario, Canada from age 18 to 65 from 2008 to 2021 with an eGFR measure (both single outpatient value and repeat measures). We calculated median eGFR values by age and examined the association of reduced eGFR percentiles (≤10th, 5th, 2.5th and 1st) with outcomes using time to event models. Outcomes were a composite of all-cause mortality, major adverse cardiac outcomes (MACE) with/without heart failure (MACE+) and kidney failure as well as each component individually. From age 18 to 65, the median eGFR declined with age (range 128 to 90) and across percentiles [eGFR ranges 102 to 68 for ≤10th, 96 to 63 for ≤5th, 90 to 58 for ≤2.5th and 83 to 54 for 1st]. The adjusted rate for any adverse outcome was elevated at ≤ 10th percentile (HR 1.14 95%CI 1.10-1.18) and was consistent for all-cause mortality, MACE, MACE+ and predominant for kidney failure (HR 5.57 95%CI 3.79-8.19) compared to the median eGFR for age. Young adults with an eGFR in the lower percentiles were less likely to be referred to a specialist, have a repeat eGFR or albumin to creatinine ratio measure. eGFR values at the 10th percentile or lower based on a population-level distribution are associated with adverse clinical outcomes and in younger adults (18 to 39) this corresponds to a higher level of eGFR that may be underrecognized. Application of population-based eGFR percentiles may aid interpretation and improve identification of younger adults at risk.

Clinical Outcomes in Patients with CKD and Rapid or Non-rapid eGFR Decline: A Report from the DISCOVER CKD Retrospective Cohort.

This analysis examined the baseline characteristics and clinical outcomes of patients with chronic kidney disease (CKD) and rapid or non-rapid estimated glomerular filtration rate (eGFR) decline, using retrospective data from DISCOVER CKD (ClinicalTrials.gov, NCT04034992). Data (2008-2020) were extracted from UK Clinical Practice Research Datalink, US TriNetX, US Limited Claims and Electronic Health Record Dataset, and Japan Medical Data Vision. Patients with CKD (two consecutive eGFR measures < 75mL/min/1.73m2 recorded 90-730days apart) were included. Rapid eGFR decline was defined as an annual decline of > 4mL/min/1.73m2 at 2years post-index; non-rapid eGFR decline was defined as an annual decline of ≤ 4mL/min/1.73m2. Clinical outcomes assessed included all-cause mortality, kidney outcomes (composite risk of kidney failure [progression to CKD stage5] or > 50% eGFR decline, and kidney failure alone), cardiovascular events-including major adverse cardiovascular events (MACE; non-fatal myocardial infarction/stroke and cardiovascular death)-and all-cause hospitalization. Across databases, rapid eGFR decline occurred in 13.7% of 804,237 eligible patients. Mean annual eGFR decline ranged between - 6.21 and - 6.86mL/min/1.73m2 in patients with rapid eGFR decline versus between - 0.11 and - 0.77mL/min/1.73m2 in patients with non-rapid eGFR decline. Rapid eGFR decline was associated with increased comorbidity burden and medication prescriptions. Across databases, the composite risk of kidney failure or > 50% decline in eGFR was significantly greater in patients with rapid versus non-rapid eGFR decline (P < 0.01); all-cause mortality, kidney failure alone, MACE, and all-cause hospitalization each significantly increased in two databases (P < 0.01-0.05). Understanding patient factors associated with rapid eGFR decline in patients with CKD may help identify individuals who would benefit from proactive management to minimize the risk of adverse outcomes. ClinicalTrials.gov identifier, NCT04034992.

Effect of Pravastatin on Kidney Function in Patients with Dyslipidemia and Type2 Diabetes Mellitus: A Multicenter Prospective Observational Study.

Several studies have reported that pravastatin can mitigate the progression of kidney disease, but limited evidence exists regarding its effects on kidney function in Asian patients. This multicenter prospective observational study aimed to assess the effect of pravastatin on kidney function in Korean patients with dyslipidemia and type2 diabetes mellitus (T2DM) in clinical practice. This 48-week prospective multicenter study included 2604 of 2997 eligible patients with dyslipidemia and T2DM who had available estimated glomerular filtration rate (eGFR) measurements. The primary endpoint was eGFR percent change at week24 from baseline. We also assessed secondary endpoints, which included percent changes in eGFR at weeks12 and 48 from baseline, as well as changes in eGFR, metabolic profiles (lipid and glycemic levels) at 12, 24, and 48weeks from baseline, and safety. We noted a significant improvement in eGFR, with mean percent changes of 2.5%, 2.5%, and 3.0% at 12, 24, and 48weeks, respectively (all adjusted p < 0.05). The eGFR percent changes significantly increased in subgroups with baseline eGFR 30-90mL/min/1.73m2, glycated hemoglobin (HbA1c) ≥ 7 at baseline, no hypertension history, T2DM duration > 5years, or previous statin therapy. Lipid profiles were improved and remained stable throughout the study, and interestingly, fasting glucose and HbA1c were improved at 24weeks. Our findings suggest that pravastatin may have potential benefits for improving eGFR in Korean patients with dyslipidemia and T2DM. This could make it a preferable treatment option for patients with reduced kidney function. NCT05107063 submitted October 27, 2021.

Comparison of Glomerular Filtration Rate Equations in a Rural New Mexico Cohort: Results from the COMPASS Study.

The NKF-ASN Task Force recommends accurate kidney function estimation avoiding biases through racial adjustments. We explored the use of multiple kidney function biomarkers and hence estimated glomerular filtration rate (eGFR) equations to improve kidney function calculations in an ethnically diverse patient population. Prospective community cohort study. rural New Mexico clinic with patients > 18 yo. Markers of kidney function, IDMS-Creatinine (SCr), chemiluminescence Beta-2 Microglobulin (B2M), Nephelometry-calibrated ELISA Cystatin C (CysC), inflammation, glucose tolerance, demographics, BUN/UACR from the baseline visit of the COMPASS cohort, were analyzed by Kernel-based Virtual Machine learning methods. Among 205 participants, the mean age was 50.1, 62% were female, 54.1% Hispanic American and 30.2% Native American. Average kidney function biomarkers were: SCr 0.9 mg/dl, B2M 1.8 mg/L, and CysC 0.7 mg/dl. The highest agreement was observed between SCr and B2M-based eGFR equations [mean difference in eGFRs: (4.48 ml/min/1.73m2], and the lowest agreement between B2M and CysC-based eGFR equations (-24.75 ml/min/1.73m2). There was no pattern of association between the differences in eGFR measures and gender. In the continuous analyses, the absolute eGFR value (p<2 x 10-16) and serum albumin (p =6.4 x 10-5) predicted the difference between B2M- and SCr-based e-GFR. The absolute eGFR value (p<2 x 10-16) and age (p =7.6 x 10-5) predicted the difference between CysC- and SCr-based e-GFR. Relatively small sample size, elevated inflammatory state in majority of study participants and no inulin excretion rate measurements. B2M should be strongly considered as a kidney function biomarker fulfilling the criteria for the NKF-ASN. B2M's eGFR equation does not need adjustment for gender or race and showed the highest agreement with SCr-based eGFR equations.