eGFR Categories Research Articles

Chronic Kidney Disease Stage and Cardiovascular and Mortality Events Among Older Adults: The SPRINT Trial

Rationale & ObjectiveThe risk implications of the Kidney Disease: Improving Global Outcomes (KDIGO) CKD classification in older adults are controversial. We evaluated the risk of adverse outcomes in this population across categories of estimated glomerular filtration rate (eGFR) and urine albumin to creatinine ratio (UACR). Study DesignProspective cohort. Settings & Participants2509 participants aged ≥75 years in the Systolic Blood Pressure Intervention Trial (SPRINT). ExposuresKDIGO eGFR and UACR categories. We combined KDIGO categories G1 and G2, G3b and G4, as well as A2 and A3. OutcomesPrimary SPRINT outcome (composite of myocardial infarction, other acute coronary syndromes, stroke, heart failure, or death from cardiovascular causes), and all-cause death. Analytical ApproachMultivariable Cox proportional hazard models. ResultsMean age was 79.8 years, 37.4% were female, mean eGFR was 64.0 ml/min/1.73 m2, and median UACR 13.1 mg/g. In multivariable Cox proportional hazard analysis, compared with participants with eGFR ≥60 ml/min/1.73 m2 and UACR <30 mg/g, there was no statistically significant difference in the risk of the primary outcome among participants with eGFR 45-59 or 15-44 ml/min/1.73 m2 and UACR <30 mg/g. However, those with eGFR 45-59 or 15-44 ml/min/1.73 m2 and UACR ≥30 mg/g had higher risk of the primary outcome (HR [95% CI], 1.97 [1.27, 3.04] and 3.32 [2.23, 4.93], respectively). The risk for all-cause death was higher for each category of abnormal eGFR and UACR, with the highest risk observed among those with eGFR 15-44 ml/min/1.73 m2 and UACR ≥30 mg/g (3.34 [2.05, 5.44]). LimitationsIndividuals with diabetes and urine protein >1 g/day were excluded from SPRINT. ConclusionAmong older adults SPRINT participants, low eGFR without albuminuria was associated with higher mortality but not with increased risk of cardiovascular events. Additional studies are needed to evaluate an adapted CKD stage-based risk stratification for older adults.

Sex differences in chronic kidney disease-related complications and mortality across levels of glomerular filtration rate.

Chronic kidney disease (CKD) is a growing global health concern. Recent research has indicated sex disparities in CKD-related complications, yet the impact of sex differences on critical kidney function levels that trigger these complications and mortality remains inadequately documented. We investigated sex-specific disparities in CKD-related complications and mortality according to eGFR levels. We analyzed NHANES data spanning from 1999 to 2018, including adult participants with an eGFR of 15-150ml/min per 1.73m². The outcomes were CKD-related complications (hypertension, anaemia, CV diseases, acidosis, hyperphosphatemia, hyperparathyroidism) and all-cause and cause-specific mortality (CV mortality and non-CV mortality). Sex-stratified multivariable logistic and Cox regression models yielded odds ratios (ORs) and hazard ratios (HRs) for the relationship between eGFR categories and outcomes. Sex-stratified natural splines were used to explore the relationship between continuous eGFR and outcomes and identified eGFR thresholds of statistical significance. The study included 49558 participants (50.3% women, 49.7% men). Multivariable logistic regression demonstrated a significant eGFR association with all CKD-related complications, exhibiting a linear trend across eGFR categories. Modelling eGFR as a natural spline revealed varied significance thresholds between sexes for anaemia and hyperparathyroidism. Additionally, the eGFR-hyperphosphatemia association was more pronounced in men. We observed substantial but not statistically significant differences between men and women in the thresholds of statistical significance for CV (significance appeared at a higher eGFR in men) and non-CV mortality (significance appeared at a higher eGFR in women). Research shows sex disparities in most CKD-related complications. Men develop anaemia and hyperparathyroidism earlier, women show steeper anaemia increase. Men have higher CV mortality risk. As eGFR decreased, men faced a higher risk of CV mortality at a higher eGFR threshold than women.

Impact of CT-determined low kidney volume on renal function decline: a propensity score-matched analysis

ObjectivesTo investigate the relationship between low kidney volume and subsequent estimated glomerular filtration rate (eGFR) decline in eGFR category G2 (60–89 mL/min/1.73 m2) population.MethodsIn this retrospective study, we evaluated 5531 individuals with eGFR category G2 who underwent medical checkups at our institution between November 2006 and October 2017. Exclusion criteria were absent for follow-up visit, missing data, prior renal surgery, current renal disease under treatment, large renal masses, and horseshoe kidney. We developed a 3D U-net-based automated system for renal volumetry on CT images. Participants were grouped by sex-specific kidney volume deviations set at mean minus one standard deviation. After 1:1 propensity score matching, we obtained 397 pairs of individuals in the low kidney volume (LKV) and control groups. The primary endpoint was progression of eGFR categories within 5 years, assessed using Cox regression analysis.ResultsThis study included 3220 individuals (mean age, 60.0 ± 9.7 years; men, n = 2209). The kidney volume was 404.6 ± 67.1 and 376.8 ± 68.0 cm3 in men and women, respectively. The low kidney volume (LKV) cutoff was 337.5 and 308.8 cm3 for men and women, respectively. LKV was a significant risk factor for the endpoint with an adjusted hazard ratio of 1.64 (95% confidence interval: 1.09–2.45; p = 0.02).ConclusionLow kidney volume may adversely affect subsequent eGFR maintenance; hence, the use of imaging metrics may help predict eGFR decline.Critical relevance statementLow kidney volume is a significant predictor of reduced kidney function over time; thus, kidney volume measurements could aid in early identification of individuals at risk for declining kidney health.Key points• This study explores how kidney volume affects subsequent kidney function maintenance.• Low kidney volume was associated with estimated glomerular filtration rate decreases.• Low kidney volume is a prognostic indicator of estimated glomerular filtration rate decline.Graphical

Community pharmacist-led point-of-care eGFR screening: early detection of chronic kidney disease in high-risk patients

Adherence to scheduled physician screenings for renal function monitoring in patients with chronic kidney disease (CKD) or those at high risk remains suboptimal despite the endorsement of regular screenings by several clinical practice guidelines. Our study aims to assess the effectiveness of a point-of-care CKD screening program led by these pharmacists using the PICCOLO device while recognizing the unique position of community pharmacists in primary care. We conducted an 11-month prospective point-of-care interventional research study in the United Arab Emirates to evaluate the performance of a community pharmacist-led CKD screening program for high-risk patients. Six diverse community pharmacies were selected based on staff availability, patient volume, and their offered range of services. Eligible individuals with risk factors for CKD were identified during medication evaluations. The PICCOLO Comprehensive Metabolic Panel facilitated on-site blood analysis, delivering estimated Glomerular Filtration Rate (eGFR) results within 10 to 15 min. Data also included eGFR categories, demographic information, and insights into lifestyle and health habits collected through a questionnaire. Pharmacists conducted comprehensive medication reviews and offered referrals and lifestyle guidance as part of the program. The study encompassed a total of 400 patients, with an average age of 69 ± 13.4 years within the study cohort. Notably, 38.8% (155 individuals) of the 400 patients were found to have undiagnosed CKD stages 3–5. Univariate logistic regression analysis revealed a significant association between a higher incidence of CKD stages 3–5 and factors such as older age, a history of hypertension, vascular disease, and diabetes mellitus. In the multivariate regression model, age and a history of diabetes mellitus emerged as significant predictors of an elevated risk of CKD. This study sheds light on the viability and impact of CKD screening programs conducted by community pharmacists, particularly in detecting CKD stages 3–5. The findings have implications for healthcare policies, as they can influence the enhancement of early detection and management of CKD. Moreover, these insights may catalyze focused screening initiatives and strengthen collaboration between community pharmacies and healthcare systems to benefit patients at high risk of CKD.

Association of decreased estimated glomerular filtration rate with lung cancer risk in the Korean population.

Inconsistent results are available regarding the association between low estimated glomerular filtration rate (eGFR) and lung cancer risk. We aimed to explore the risk of lung cancer according to eGFR category in the Korean population. We included 358,293 adults who underwent health checkups between 2009 and 2010, utilizing data from the National Health Insurance Service-National Sample Cohort. Participants were categorized into 3 groups based on their baseline eGFR, as determined using the Chronic Kidney Disease Epidemiology Collaboration equation: group 1 (eGFR ≥90 mL/min/1.73 m2), group 2 (eGFR ≥60 to <90 mL/min/1.73 m2), and group 3 (eGFR <60 mL/min/1.73 m2). Incidences of lung cancer were identified using the corresponding codes from the International Classification of Diseases, 10th revision. Multivariate Cox proportional hazard models were employed to calculate the adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for lung cancer incidence up to 2019. In multivariate analysis, group 2 exhibited a 26% higher risk of developing lung cancer than group 1 (HR, 1.26; 95% CI, 1.19 to 1.35). Furthermore, group 3 demonstrated a 72% elevated risk of lung cancer relative to group 1 (HR, 1.72; 95% CI, 1.58 to 1.89). Among participants with dipstick proteinuria of 2+ or greater, group 3 faced a significantly higher risk of lung cancer than group 1 (HR, 2.93; 95% CI, 1.37 to 6.24). Low eGFR was significantly associated with increased lung cancer risk within the Korean population. A particularly robust association was observed in individuals with severe proteinuria, emphasizing the need for further investigation.

Association between soft drinks intake and low glomerular filtration rate in Mexican adults: Results from RenMex

To evaluate the association between soft drinks (SDs) consumption and estimated glomerular filtration rate (eGFR) in a Mexican adult population. We used data from the RenMex consortium (n=2095) that included the Mexican Teachers Cohort Study (34-65 years), the Health Workers Cohort Study (18-90 years), and the Comitán Study (19-91 years). In this cross-sectional study, we assessed SDs consumption (cola and flavored soda) using a food frequency questionnaire (FFQ) and estimated eGFR using the CKD Epidemiology Collaboration equation. Quantile regression was used to assess the association between SDs consumption and eGFR with eGFR as a continuous variable. Multinomial logistic regression models were used for eGFR categories derived from quantile regression (mildly decreased eGFR, ≥72.9-87.9mL/min/1.73m2 and moderately decreased eGFR, <72.9mL/min/1.73m2). Mean age of study participants was 47.2 years, 67.5% were women, and 12.2% had diabetes. eGFR was <60mL/min/1.73m2 in 3.7% of study participants. Mildly decreased eGFR was present in 14.8%, and moderately decreased eGFR was present in 10.1% of study participants. Quantile regression results showed that SDs consumption was associated with lower eGFR at the 10th, 25th, 50th and 75th percentile. Based on the final adjusted multinomial model, ≥7 servings/week was positively associated with moderately decreased eGFR relative to <1 serving/week (Relative Risk Ratio=1.95; 95% CI: 1.07-3.57). Our results suggest that higher SDs consumption is associated with lower eGFR. Encouraging healthy dietary choices should be part of the management and prevention of CKD.

Associations of metabolic variabilities and cardiovascular outcomes according to estimated glomerular filtration rate in chronic kidney disease: a nationwide observational cohort study.

The impact of baseline estimated glomerular filtration rate (eGFR) on the risk of adverse outcomes according to metabolic parameter variabilities in chronic kidney disease has rarely been investigated. We conducted a retrospective nationwide cohort study using the National Health Insurance System data in Korea from 2007 to 2013 to identify individuals with three or more health screenings. The metabolic components variability was defined as intraindividual variability between measurements using the variability independent of the mean. The metabolic variability score was defined as the total number of high-variability metabolic components. Multivariable-adjusted Cox regression analysis was conducted to evaluate the risks of all-cause mortality, myocardial infarction, and ischemic stroke. During a mean follow-up of 6.0 ± 0.7 years, 223,531 deaths, 107,140 myocardial infarctions, and 116,182 ischemic strokes were identified in 9,971,562 patients. Low eGFR categories and higher metabolic variability scores were associated with a higher risk of adverse outcomes. The degree of association between metabolic variability and adverse outcomes was significantly larger in those with low eGFR categories than in those with preserved eGFR (p for interaction < 0.001). Representatively, those with high metabolic variability in the eGFR of <15 mL/min/1.73 m2 group showed a prominently higher risk for all-cause mortality (adjusted hazard ratio [aHR], 5.28; 95% confidence interval [CI], 4.02-6.94) when the degree was compared to the findings in those with preserved (eGFR of ≥60 mL/min/1.73 m2) kidney function (aHR, 2.55; 95% CI, 2.41-2.69). The degree of adverse association between metabolic variability and poor prognosis is accentuated in patients with impaired kidney function.

Association of Renal Impairment with Clinical Outcomes Following Endovascular Therapy in Acute Basilar Artery Occlusion.

Renal impairment (RI) is associated with unfavourable outcome after acute ischaemic stroke with anterior circulation large vessel occlusion. We assessed the association of RI with clinical outcomes in patients with acute basilar artery occlusion (ABAO), and the impact of RI on the effects of endovascular therapy (EVT) versus standard medical treatment (SMT). We used data from the BASILAR registry, an observational, prospective, nationwide study of patients with ABAO in routine clinical practice in China. Baseline estimated glomerular filtration rate (eGFR) was recorded at admission. The primary outcome was the modified Rankin Scale (mRS) score at 90 days. Secondary outcomes included favourable outcome (mRS score 0-3), mortality, and symptomatic intracranial haemorrhage (sICH). Multivariate logistic regression was used to assess the association of RI with mortality and functional improvement at 90 days. Among 829 patients enrolled, 747 patients were analysed. The median baseline eGFR was 89 mL/min/1.73m2 (IQR, 71-100), and 350 (46.8%), 297 (39.8%), and 100 (13.4%) patients had baseline eGFR values of ≥90, 60-89, and <60 mL/min/1.73m2, respectively. RI was associated with increased mortality (adjusted odds ratio [aOR], 1.97; 95% CI, 1.15-3.67) at 90 days and decreased survival probability (aOR 1.74; 95% CI, 1.30-2.33) within 1 year. EVT was associated with better functional improvement (common aOR, 2.50; 95% CI, 1.43-4.35), favourable outcome (aOR 5.42; 95% CI, 1.92-15.29) and lower mortality (aOR 0.47; 95% CI, 0.25-0.88) in ABAO patients with eGFR ≥90 mL/min/1.73m2. However, RI was not modified the relationship of EVT with functional improvement (common aOR, 3.03; 95% CI, 0.81-11.11), favourable outcome (aOR 2.10; 95% CI, 0.45-9.79), and mortality (aOR 0.56; 95% CI, 0.15-2.06) by eGFR categories. RI is associated with reduced efficacy of EVT and worse functional outcome and higher mortality at 3 months and lower survival probability at 1 year in patients with ABAO.

High-Throughput Computing to Automate Population-Based Studies to Detect the 30-Day Risk of Adverse Outcomes After New Outpatient Medication Use in Older Adults with Chronic Kidney Disease: A Clinical Research Protocol.

Safety issues are detected in about one third of prescription drugs in the years following regulatory agency approval. Older adults, especially those with chronic kidney disease, are at particular risk of adverse reactions to prescription drugs. This protocol describes a new approach that may identify credible drug-safety signals more efficiently using administrative health care data. To use high-throughput computing and automation to conduct 700+ drug-safety cohort studies in older adults in Ontario, Canada. Each study will compare 74 acute (30-day) outcomes in patients who start a new prescription drug (new users) to a group of nonusers with similar baseline health characteristics. Risks will be assessed within strata of baseline kidney function. The studies will be population-based, new-user cohort studies conducted using linked administrative health care databases in Ontario, Canada (January 1, 2008, to March 1, 2020). The source population for these studies will be residents of Ontario aged 66 years or older who filled at least one outpatient prescription through the Ontario Drug Benefit (ODB) program during the study period (all residents have universal health care, and those aged 65+ have universal prescription drug coverage through the ODB). We identified 3.2 million older adults in the source population during the study period and built 700+ initial medication cohorts, each containing mutually exclusive groups of new users and nonusers. Nonusers were randomly assigned cohort entry dates that followed the same distribution of prescription start dates as new users. Eligibility criteria included a baseline estimated glomerular filtration rate (eGFR) measurement within 12 months before the cohort entry date (median time was 71 days before cohort entry in the new user group), no prior receipt of maintenance dialysis or a kidney transplant, and no prior prescriptions for drugs in the same subclass as the study drug. New users and nonusers will be balanced on ~400 baseline health characteristics using inverse probability of treatment weighting on propensity scores within 3 strata of baseline eGFR: ≥60, 45 to <60, <45 mL/min per 1.73 m2. We will compare new user and nonuser groups on 74 clinically relevant outcomes (17 composites and 57 individual outcomes) in the 30 days after cohort entry. We used a prespecified approach to identify these 74 outcomes. In each cohort, we will obtain eGFR-stratum-specific weighted risk ratios and risk differences using modified Poisson regression and binomial regression, respectively. Additive and multiplicative interaction by eGFR category will be examined. Drug-outcome associations that meet prespecified criteria (identified signals) will be further examined in additional analyses (including survival, negative-control exposure, and E-value analyses) and visualizations. The initial medication cohorts had a median of 6120 new users per cohort (interquartile range: 1469-38 839) and a median of 1 088 301 nonusers (interquartile range: 751 697-1 267 009). Medications with the largest number of new users were amoxicillin trihydrate (n = 1 000 032), cephalexin (n = 571 566), prescription acetaminophen (n = 571 563), and ciprofloxacin (n = 504,374); 19% to 29% of new users in these cohorts had an eGFR <60 mL/min per 1.73 m2. Despite our use of robust techniques to balance baseline indicators and to control for confounding by indication, residual confounding will remain a possibility. Only acute (30-day) outcomes will be examined. Our data sources do not include nonprescription (over-the-counter) drugs or drugs prescribed in hospitals and do not include outpatient prescription drug use in children or adults <65 years. This accelerated approach to conducting postmarket drug-safety studies has the potential to more efficiently detect drug-safety signals in a vulnerable population. The results of this protocol may ultimately help improve medication safety.

Decreasing lifetime prevalence of diabetes-related foot ulcers in Norway: repeated cross-sectional population-based surveys from the HUNT study (1995-2019).

Diabetes-related foot ulcers (DFU) are a persistent healthcare challenge, impacting both patients and healthcare systems, with adverse effects on quality of life and productivity. Our primary aim was to examine the trends in lifetime prevalence of DFU, as well as other micro- and macrovascular complications in the Trøndelag Health Study (HUNT) in Norway. This study consists of individuals ≥20 years with diabetes participating in the population-based cross-sectional HUNT surveys (1995-2019). Prevalence ratios, comparing the lifetime prevalence of DFU and other relevant micro- and macrovascular complications between the HUNT surveys, were calculated using Poisson regression. The lifetime prevalence (95% confidence interval (CI)) of a DFU requiring three or more weeks to heal was 11.0% (9.5-12.7) in HUNT2, 7.5% (6.3-8.8) in HUNT3 and 5.3% (4.4-6.3) in HUNT4. The decrease in DFU prevalence from 1995 to 2019 was observed in both men and women, for all age groups, and for both type 1 and type 2 diabetes. The highest lifetime prevalence of DFU was found among those with type 1 diabetes. The decrease in HbA1c from HUNT2 to HUNT4 did not differ between those with and without a DFU. The prevalence of chronic kidney disease (eGFR <60 mL/min/1.73 m2 (eGFR categories G3-G5)) increased in both individuals with and without a DFU. Results from the HUNT surveys show a substantial decline in the lifetime prevalence of DFU from 1995 to 2019.

Obesity and Albuminuria in Patients with Chronic Renal Disease and Hypertension as a Comorbidity: The Optimum Body Mass Index

Background: Obesity was associated with a greater risk for development of Chronic Kidney Disease (CKD) among subjects with and without hypertension, diabetes or cardiovascular disease. We aimed to consider the association between obesity and albuminuria in patients with CKD according to Estimated Glomerular Filtration Rate (e-GFR) and demonstrated hypertension. We also aimed to observe the optimum Body Mass Index (BMI) in this population. Methods: One hundred-thirty-three overweight and/or obese subjects with manifested hypertension were participated and they were matched to forty-three hypertensive control subjects with a normal body weight. Our participants were classified in both eGFR and albuminuria categories according to the Kidney Disease Improving Global Outcomes (KDIGO) 2012 criteria. The obesity was defined as a high BMI (≥25 Kg/m2 as overweight and/or ≥30 Kg/m2 as obese) and the central obesity as a high waist circumference (WC) (≥94 cm in males and ≥80 cm in females). Results: The most of subjects with a lean/normal BMI did not have albuminuria (x2=24.2, p=0.001) and the most of those with a high BMI, but with a normal WC did not have albuminuria (x2=39.7, p=0.001). The high WC was found to be a main risk factor for albuminuria adjusting to confounders. Conclusions: The central obesity was shown to be the most important factor for albuminuria in patients with classified CKD rather than a high BMI independently on hypertension. The optimum BMI seems to be in the normal range for these patients similarly to the general population.

Cardiovascular and renal outcomes with varying degrees of kidney disease in high-risk people with type 2 diabetes: An epidemiological analysis of data from the AMPLITUDE-O trial.

To estimate the incidence of a major adverse cardiovascular event (MACE) and a composite kidney outcome across estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (UACR) levels, and to determine whether efpeglenatide's effect varies with these indices. AMPLITUDE-O trial data were used to estimate the relationship of eGFR, UACR, and Kidney Disease Improving Global Outcomes (KDIGO) category to the hazard of MACE and the kidney composite. Interactions on these outcomes between eGFR and the UACR, and between each of these variables and efpeglenatide were also assessed. Baseline eGFR and UACR were available for 3983 participants (mean age 64.5 years). During a median follow-up of 1.8 years, the hazards of MACE and the kidney composite for the lowest versus highest eGFR third were 1.6 (95% confidence interval [CI] 1.2, 2.2) and 2.3 (95% CI 1.9, 2.8), respectively. The hazards for the highest versus the lowest UACR third were 2.3 (95% CI 1.8, 3.1) and 18.0 (95% CI 12.7, 25.5), respectively, and for the high- versus low-risk KDIGO categories the hazards were 2.4 (95% CI 1.8, 3.1) and 16.0 (95% CI 11.6, 22.0), respectively. eGFR and UACR were independent determinants of both outcomes, but negatively interacted with each other for the kidney outcome. Efpeglenatide's effect on both outcomes did not vary with any kidney disease measure (all interaction p values ≥0.26). In high-risk people with diabetes, eGFR, UACR, and KDIGO category have different relationships to incident cardiovascular and kidney outcomes. The beneficial effect of efpeglenatide on these outcomes is independent of kidney-related risk category.

Association between cumulative uric acid to high-density lipoprotein cholesterol ratio and the incidence and progression of chronic kidney disease.

The ratio of uric acid to high-density lipoprotein cholesterol (UHR) was related to the risk of chronic kidney disease (CKD), we aimed to investigate the association of cumulative UHR (cumUHR) with incidence and progression of CKD. Our study included a total of 49,913 participants (mean age 52.57 years, 77% males) from the Kailuan Study conducted between 2006 and 2018. Participants who completed three consecutive physical examinations were included. Cumulative UHR (cumUHR) was computed as the summed average UHR between two consecutive physical examinations, multiplied by the time between the two examinations. Participants were then categorized into four groups based on cumUHR quartiles. Subsequently, participants were further divided into a CKD group and a non-CKD group. The associations between cumUHR and CKD and it's progression were assessed by Cox proportional hazards regression models. The cumulative incidence of endpoint events was compared between the cumUHR groups using the log-rank test. The C-index, net reclassification improvement (NRI) and integrated discrimination improvement (IDI) were calculated to assess the predictive performance of cumUHR. After a mean follow-up of 8.0 ± 1.7 years, there were 4843 cases of new-onset CKD, 2504 of low eGFR, and 2617 of proteinuria in the non-CKD group. Within the CKD group, there were 1952 cases of decline in eGFR category, 1465 of >30% decline in eGFR, and 2100 of increased proteinuria. In the non-CKD group, the adjusted hazard ratios (HRs) and confidence intervals (CIs) in the fourth quartile were 1.484 (1.362-1.617), 1.643 (1.457-1.852), and 1.324 (1.179-1.486) for new-onset CKD, low eGFR, and proteinuria, respectively. In the CKD group, the adjusted HRs in the fourth quartile were 1.337 (1.164-1.534), 1.428 (1.216-1.677), and 1.446 (1.267-1.651) for decline in eGFR category, >30% decline in eGFR, and increase in proteinuria, respectively. In addition, we separately added a single UHR measurement and cumUHR to the CKD base prediction model and the CKD progression base prediction model, and found that the models added cumUHR had the highest predictive value. High cumUHR exposure was an independent risk factor for the incidence and progression of CKD, and it was a better predictor than a single UHR measurement.

The association between trypsin-like protease activity in the oral cavity and kidney function in Japanese workers.

To evaluate the association between trypsin-like protease (TLP) activity in the oral cavity as an indicator of periodontal health status and kidney function in Japanese workers. This cross-sectional study included 1117 Japanese workers (mean age = 43.8 years). Tongue-swab TLP activity was quantified as a* value (the redness intensity of the matrix disc of the TLP activity assessment kit; a larger value indicates more intense enzymatic activity in the samples and poorer periodontal health status). Kidney function was assessed using the estimated glomerular filtration rate (eGFR; a lower value indicates poorer kidney function). We performed ordinal logistic regression analyses to assess the association of the a* value with three eGFR categories: ≥90, 60-89 and <60 mL/min/1.73 m2 . The prevalence for each eGFR category was as follows: ≥90 (31.6%), 60-89 (63.8%) and <60 mL/min/1.73 m2 (4.6%). After adjusting for potential confounders, the a* value was found to be significantly associated with reduced kidney function. The multivariable-adjusted odds ratio (95% confidence interval) for reduced kidney function was 1.12 (1.02-1.22) per unit increase in the a* value. Higher TLP activity was associated with reduced kidney function in Japanese workers.

Low-Dose Methotrexate and Serious Adverse Events Among Older Adults With Chronic Kidney Disease

Low-dose methotrexate is used to treat rheumatoid arthritis and psoriasis. Due to its kidney elimination, better evidence is needed to inform its safety in adults with chronic kidney disease (CKD). To compare the 90-day risk of serious adverse events among adults with CKD who started low-dose methotrexate vs those who started hydroxychloroquine and to compare the risk of serious adverse events among adults with CKD starting 2 distinct doses of methotrexate vs those starting hydroxychloroquine. This retrospective, population-based, new-user cohort study was conducted in Ontario, Canada (2008-2021) using linked administrative health care data. Adults aged 66 years or older with CKD (defined as an estimated glomerular filtration rate [eGFR] <60 mL/min/1.73 m2 but not receiving dialysis) who started low-dose methotrexate (n = 2309) were matched 1:1 with those who started hydroxychloroquine. Low-dose methotrexate (5-35 mg/wk) vs hydroxychloroquine (200-400 mg/d). The primary outcome was a composite of serious adverse events: a hospital visit with myelosuppression, sepsis, pneumotoxic effects, or hepatotoxic effects within 90 days of starting the study drug. Prespecified subgroup analyses were conducted by eGFR category. Propensity score matching was used to balance comparison groups on indicators of baseline health. Risk ratios (RRs) were obtained using modified Poisson regression, and risk differences (RDs) using binomial regression. In a propensity score-matched cohort of 4618 adults with CKD (3192 [69%] women; median [IQR] age, 76 [71-82] years), the primary outcome was higher in patients who started low-dose methotrexate vs those who started hydroxychloroquine (82 of 2309 [3.55%] vs 40 of 2309 [1.73%]; RR, 2.05 (95% CI, 1.42-2.96); RD, 1.82% [95% CI, 0.91%-2.73%]). In subgroup analysis, the risks increased progressively at lower eGFR (eg, eGFR <45 mL/min/1.73 m2: RR, 2.79 [95% CI, 1.51-5.13]). In the secondary comparison with hydroxychloroquine, methotrexate users at 15 to 35 mg/wk had a higher risk of the primary outcome. In this cohort of 4618 older patients with CKD, the 90-day risk of serious adverse events was higher among those who started low-dose methotrexate than those who started hydroxychloroquine. If verified, these risks should be balanced against the benefits of low-dose methotrexate use.

Evaluation of the CKD-EPI 2021 creatinine equation using laboratory data: Considerations for practice changes among clinical laboratories in British Columbia, Canada

IntroductionClinical laboratories in British Columbia, Canada implemented the CKD-EPI 2009 equation without the race variable for estimated glomerular filtration rate (eGFR) reporting since 2014. As more clinical laboratories adopt the new CKD-EPI 2021 equation, the study aims to compare these two race-free CKD-EPI eGFR equations using the laboratory data from a large tertiary hospital in BC and evaluate the impact on reclassification of eGFR category. MethodsSerum/plasma creatinine results and demographic data were collected from Vancouver General Hospital laboratory. The CKD-EPI 2009 without the race variable and CKD-EPI 2021 equations were computed. eGFR and its distributions were compared and reclassification of eGFR category was assessed across the full cohort and in specific patient populations. ResultsThe analysis included 58,763 patients. The median age was 57 years, with women comprising 51 % of the population. The median of eGFR changed from 85 to 90 mL/min/1.73 m2 using the CKD-EPI 2009 equation without the race variable and the CKD-EPI 2021 equation, respectively. The CKD-EPI 2021 equation reclassified 11.86 % of patients, mainly from G3a (45–59 mL/min/1.73 m2) to G2 (60–89 mL/min/1.73 m2). There was statistical significance between the non-renal and the renal population reclassified from G5 (<15 mL/min/1.73 m2) to G4 (15–29 mL/min/1.73 m2). ConclusionsUsing laboratory data representative of local populations, we observed an overall positive shift to higher eGFR, with 11.86 % of individuals having improved eGFR categories based on the CKD-EPI 2021 equation. This study provides insights into clinical implications at both the individual and population levels. The data-based approach is the first step towards adopting the CKD-EPI 2021 equation within the province.

Association of eGFR and Albuminuria with Venous Thromboembolism.

CKD has been implicated as a risk factor of venous thromboembolism, but the evidence is limited to relatively healthy populations. The objective of this study was to discern whether parameters of kidney function and damage are associated with the occurrence of venous thromboembolism after hospitalization. We conducted a retrospective study including 23,899 and 11,552 adult individuals hospitalized within Geisinger Health System and New York University (NYU) Langone Health from 2004 to 2019 and 2012 to 2022, respectively. A Poisson model was used to evaluate adjusted incidence rates of venous thromboembolism according to eGFR and albuminuria categories in each cohort. Cox proportional hazards models were used to analyze associations of eGFR and urinary albumin-to-creatinine ratio (UACR) with venous thromboembolism, and hazard ratios (HRs) were meta-analyzed across cohorts. Both lower eGFR and higher UACR were associated with higher risks of venous thromboembolism. In the Geisinger cohort, the incidence of venous thromboembolism after hospital discharge ranged from 10.7 (95% confidence interval [CI], 9.2 to 12.6) events per 1000 person-years in individuals in G1A1 (eGFR >90 ml/min per 1.73 m 2 and UACR <30 mg/g) to 27.7 (95% CI, 20.6 to 37.2) events per 1000 person-years in individuals with G4-5A3 (eGFR <30 ml/min per 1.73 m 2 and UACR >300 mg/g). A similar pattern was observed in the NYU cohort. Meta-analyses of the two cohorts showed that every 10 ml/min per 1.73 m 2 reduction in eGFR below 60 ml/min per 1.73 m 2 was associated with a 6% higher risk of venous thromboembolism (HR 1.06 [95% CI, 1.02 to 1.11], P = 0.01), and each two-fold higher UACR was associated with a 5% higher risk of venous thromboembolism (HR 1.05 [95% CI, 1.03 to 1.07], P < 0.001). Both eGFR and UACR were independently associated with higher risk of venous thromboembolism after hospitalization. The incidence rate was higher with greater severity of CKD. This article contains a podcast at https://dts.podtrac.com/redirect.mp3/www.asn-online.org/media/podcast/CJASN/2023_12_14_CJN0000000000000352.mp3.

Impact of worsening renal function in patients with incident heart failure across the spectrum of ejection fraction: a population-based longitudinal study

Abstract Background Renal dysfunction is a common occurrence in patients with heart failure (HF) and may impact on HF treatment and outcomes. HF clinical trial data suggest that worsening renal function (WRF) is associated with worse prognosis, however many of the medications used in HF cause a short-term decline in renal function that may improve in the longer-term. The real-world incidence and implications of WRF following an initial diagnosis of HF across the spectrum of ejection have not been well-characterised. Purpose The present study was designed to establish the incidence and outcomes associated with WRF in patients with incident HF on the risk of mortality and HF hospitalisation (hHF) in a real-world setting. Methods Electronic health records were linked to echocardiography data between 2016 to 2021 to define incident HF with reduced/mildly reduced/preserved EF (HFrEF/HFmrEF/HFpEF). Incidence of WRF at 6 months was determined as a composite endpoint of (i) having two consecutive eGFR declined by 40% or greater; (ii) having an eGFR &amp;lt;15 mL/min/1.73m^2; (iii) on sustained dialysis; or (iv) receiving kidney transplantation. Incidence of hHF and all-cause mortality were compared in HF patients with versus without WRF. We performed a stratified analysis according to baseline renal function (eGFR: &amp;gt;60, 45-59, 30-44, 15-29, or &amp;lt;15 mL/min/1.73m2). Results 4254 individuals were identified, 1100 HFrEF, 650 HFmrEF, 1252 HFpEF, and 1252 HF with unknown EF. Within 6 months of HF diagnosis, 592 patients died and 349 had WRF. Baseline eGFR &amp;lt;60 was present in 32% of individuals with HFrEF, 32% in HFpEF, 27% in HFmrEF, and 37% in HF with unknown EF. The incidence of WRF was similar in HFrEF (20.7 [95% CI: 16.9 – 25.1] per 100 person-years) and in HF with unknown EF (20.9 [17.1 – 25.3]), but was significantly lower in HFmrEF (13.6 [9.8 – 18.4]) and HFpEF (16.8 [13.7 – 20.5]). Patients with WRF were more likely to be female (adjusted hazard ratio [aHR]: 1.32 [1.06 – 1.64], p=0.014), having diabetes (1.34 [1.07 – 1.69], p = 0.012), and with lower baseline renal function (eGFR categories 45-59, 30-44, 15-29, or &amp;lt;15 compared with &amp;gt;60: aHR 1.75 [1.29 – 2.38], p&amp;lt;0.001; 1.64 [1.12 – 2.42], p=0.012; 5.65 [4.06 – 7.87], p&amp;lt;0.001; 90.74 [63.2 – 130.28], p&amp;lt;0.001). Individuals with WRF had significantly higher incidence of subsequent hHF (HR adjusted for age, sex, baseline renal function, and diabetes: 1.79 [1.35 – 2.39], p&amp;lt;0.001) and all-cause death (2.18 [1.66 – 2.88], p&amp;lt;0.001), compared to those without WRF. This was driven by patients diagnosed with HFrEF (2.46 [1.45 – 4.18], p&amp;lt;0.001) or HFpEF (3.45 [2.21 – 5.40], p&amp;lt;0.001), but was not seen in HFmrEF (1.91 [0.91 – 3.99], p=0.086) or HF within unknown EF (1.28 [0.65 – 2.52], p=0.484). Conclusion WRF is an important and common consequence following initial diagnosis of HF across the spectrum of EF with associated severe clinical outcomes in HF. Priority should be given to prevention of WRF in patients with incident HF.Impact of WRF on Clinical Outcomes

Decreased estimated glomerular filtration rate increase the risk of pancreatic cancer: A nationwide retrospective cohort study.

Decreased kidney function is a putative risk factor for various cancers. However, few studies have investigated the association between a decreased estimated glomerular filtration rate (eGFR) and incident pancreatic cancer. We aimed to investigate the risk of incident pancreatic cancer according to eGFR categories. In this retrospective cohort study, we included 359721 adults who underwent health checkups in 2009 or 2010 by using the Korean National Health Insurance Database. The study population was categorized into four groups by eGFR (mL/min/1.73m2 ) using the Chronic Kidney Disease Epidemiology Collaboration equation: group 1 (eGFR<45), group 2 (eGFR ≥45 to <60), group 3 (eGFR ≥60 to <90), and group 4 (eGFR≥90). Multivariate Cox proportional hazards models were used to determine the adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for the incidence of pancreatic cancer until 2019 by comparing the eGFR groups. During the 3493589.05 person-years of follow-up, 1702 pancreatic cancer cases were identified. Compared with group 4 (eGFR≥90), HRs and 95% CIs for the incidence of pancreatic cancer were 1.39 (1.24-1.56) for group 3 (eGFR ≥60 to <90), 1.79 (1.47-2.16) for group 2 (eGFR ≥45 to <60), and 2.05 (1.62-2.60) for group 1 (eGFR<45) in the multivariate adjusted model. Decreased eGFR was significantly associated with an increased risk of pancreatic cancer in Korean population. Further studies are needed to investigate the relationship between a decreased eGFR and the risk of pancreatic cancer in other ethnic groups.

Abstract 15660: Mitral Regurgitation in Patients With Chronic Kidney Disease: Results From the Chronic Renal Insufficiency Cohort Study

Background: Mitral regurgitation (MR) is more common in patients with chronic kidney disease (CKD) compared to the general population, However, longitudinal associations of MR and adverse outcomes in CKD, such as mortality and heart failure (HF), have not been well studied yet. Hypothesis/Aim: We aim to investigate the prevalence of MR and its association with mortality, incidence of HF, and atrial fibrillation (AF) in patients with CKD. Methods: We studied patients with CKD who had an echocardiography exam (2008-2013) in the Chronic Renal Insufficiency Cohort (CRIC) study. Independent t-tests and Chi-square tests were used to compare clinical and echocardiographic characteristics in patients with vs. without MR. The degree of MR was quantified using effective regurgitant orifice area (EROA) from apical-four chamber view and further categorized as trace, mild and moderate/severe. Kaplan-Meier (KM) Curves and Cox hazard models were used to estimate the association of MR degree and EROA with mortality, incidence of HF and AF. Results: Among a total of 2951 patients with CKD, 2167 (73.4%) patients had MR (EROA, 0.14±0.19 cm 2 ) with degrees of trace, mild, and moderate /severe MR comprising 54.3%, 12.5%, and 6.6%, respectively. Patients with MR were more likely to be female (47.39 vs. 42.73%), non-White race (51.8 vs. 46.8%), and have worse B-type Natriuretic Peptide (NTproBNP; 524.86 vs. 271.66 pg/ml) and left ventricular ejection fraction (53.7 vs. 55.8%) compared to those without MR. When stratified by estimated glomerular filtration rate (eGFR; 60-45, 45-30, &lt;30 ml/min/1.73 m 2 ), the group in the lowest eGFR category (n=703) had the highest prevalence of moderate/severe MR (9.2%, p &lt;0.05). KM Curves showed patients with CKD and moderate/sever MR had higher incidence of HF and AF than those with CKD and absent, trace, or mild MR ( p &lt;0.01). EROA was associated with the incidence of AF (hazard ratio [HR] = 1.08, p &lt;0.01) and HF (HR=1.06, p &lt;0.01), independent of age, sex, race, traditional cardiovascular risk factors, urine albumin-to-creatinine ratio, eGFR and NTproBNP, but not mortality. Conclusion: In patients with CKD, MR is independently associated with HF and AF, highlighting the importance of MR-specific interventions to improve cardiovascular outcomes.