Chronic Kidney Disease Epidemiology Research Articles

Using eGFR and Albumin Creatinine Ratio as an Initial Screening Tool in Trinidadian Primary Care to Identify High-risk Population for CKD: A Cross-Sectional Study

Background: Chronic kidney disease (CKD) is a major public health burden and is often undiagnosed in the primary care setting. Untested and untreated, this often leads to renal failure and dialysis. Materials and Methods: This was a cross-sectional study of adults aged 20 years and over, diagnosed with type 2 diabetes mellitus and/or hypertension, with no previous history or record of CKD, and attending three chronic disease clinics in the Eastern Regional Health Authority (ERHA). Patients were screened for risk of CKD by using the albumin creatinine ratio. The eGFR was calculated based on serum creatinine by using the CKD Epidemiology Collaboration (EPI) 2009 equation. Results: In total, 430 patients agreed to participate with 61.2% of response rate. Of the 385 with complete data, 357 (92%) were detected as having a high risk for CKD; older patients (>66 years) and those with both diabetes and hypertension had high proportions of risk for CKD. There were significant associations between age, systolic hypertension, and the severity of risk for CKD. Conclusion: CKD is common at the primary care level among adults with NCDs in Trinidad, with many patients having been left out without being tested for CKD. Primary care physicians must take this into consideration in caring for NCD patients.

Abstract 6381: Long-term kidney function after treatment for unilateral, non-metastatic, non-syndromic Wilms tumor. A report from the St. Jude Lifetime Cohort Study

Abstract Background: We previously reported that the estimated glomerular filtration rate (eGFR) was decreased among survivors of unilateral, non-metastatic, non-syndromic Wilms tumor (WT) treated with whole abdomen radiation therapy (WART) compared to controls, but not compared to unirradiated WT survivors (Pediatr Blood Cancer 2020;67:e28271). The impact of sex on estimates of kidney function among adult survivors of WT has not been well-documented. Methods: We clinically evaluated male and female WT survivors with creatinine and cystatin C, calculated eGFR using the Chronic Kidney Disease - Epidemiology (CKD-EPI) equations with and without cystatin C and measured 99mTc diethylenetriamine pentaacetic acid (DTPA) plasma clearance. WT survivors consisted of 20 treated with unilateral nephrectomy (UN), non-nephrotoxic chemotherapy (NNC) and whole abdomen radiation therapy (WART) (mean - 20.2 Gray (Gy); standard deviation (SD) - 9.12 Gy), and 20 treated with UN, no radiation therapy, and NNC. Correlations between 99mTc DTPA clearance and eGFR were calculated. Results: Among female WT survivors, none of the eGFR calculations was statistically significantly correlated with 99mTc DTPA clearance. Among male WT survivors, 99mTc DTPA clearance correlated well with eGFR calculations that included creatinine. Results are shown in the Table. Conclusions: Among female survivors of unilateral, non-metastatic, non-syndromic WT who have undergone UN, eGFR is poorly correlated with 99mTc DTPA clearance. Evaluation of treatment-related changes in body composition may provide insight into these results. Correlation between eGFR and 99mTc DTPA clearance Females eGFR(CKD-EPI) 99mTc DTPA clearance No radiation therapy (n=13) Whole abdomen radiation therapy(n=12) Pearson correlation coefficient p-value Pearson correlation coefficient p-value Creatinine only 0.109 0.723 -0.295 0.352 Cystatin C only 0.311 0.301 0.094 0.782 Creatinine and cystatin C 0.348 0.244 -0.028 0.935 Males No radiation therapy (n=6) Whole abdomen radiation therapy(n=6) Pearson correlation coefficient p-value Pearson correlation coefficient p-value Creatinine only 0.827 0.043 0.859 0.028 Cystatin C only 0.811 0.050 0.592 0.216 Creatinine and cystatin C 0.878 0.021 0.866 0.026 Citation Format: Daniel M. Green, Mingjuan Wang, Matthew J. Krasin, Andrew M. Davidoff, DeoKumar Srivastava, Dennis W. Jay, Kirsten K. Ness, Barry L. Shulkin, Jennifer Q. Lanctot, Kyla C. Shelton, Rachel C. Brennan, Matthew J. Ehrhardt, Stephanie Dixon, Beth A. Kurt, Leslie L. Robison, Melissa M. Hudson, Sheri L. Spunt. Long-term kidney function after treatment for unilateral, non-metastatic, non-syndromic Wilms tumor. A report from the St. Jude Lifetime Cohort Study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6381.

Estimated glomerular filtration rate as a tool for early identification of patients with insufficient exposure to beta-lactam antibiotics in intensive care units

Background Only about 50% of intensive care unit (ICU) patients reach a free trough concentration above MIC (100% fT > MIC) of beta-lactam antibiotics. Although dose adjustments based on therapeutic drug monitoring (TDM) could be beneficial, TDM is not widely available. We investigated serum creatinine-based estimated GFR (eGFR) as a rapid screening tool to identify ICU patients at risk of insufficient exposure. Method Ninety-three adult patients admitted to four ICUs in southeast Sweden treated with piperacillin/tazobactam, meropenem, or cefotaxime were included. Beta-lactam trough concentrations were measured. The concentration target was set to 100% fT > MICECOFF (2, 4, and 16 mg/L based on calculated free levels for meropenem, cefotaxime, and piperacillin, respectively). eGFR was primarily determined via Chronic Kidney Disease–Epidemiology Collaboration (CKD-EPI) and compared to three other eGFR equations. Data was analysed using logistic regression and receiver operative characteristic (ROC) curves. Results With intermittent standard dosing, insufficient exposure was common in patients with a relative eGFR ≥48mL/min/1.73m2 [85%, (45/53)], particularly when treated with cefotaxime [96%, (24/25)]. This eGFR cut-off had a sensitivity of 92% and specificity of 82% (AUC 0.871, p < 0.001) in identifying insufficient exposure. In contrast, patients with eGFR <48mL/min/1.73m2 had high target attainment [90%, (36/40)] with a wide variability in drug exposure. There was no difference between the four eGFR equations (AUC 0.866–0.872, cut-offs 44–51 ml/min/1.73m2). Conclusion Serum creatinine-based eGFR is a simple and widely available surrogate marker with potential for early identification of ICU patients at risk of insufficient exposure to piperacillin, meropenem, and cefotaxime.

Assessment of renal and cardiovascular risks in patients with type 2 diabetes when using non-steroidal mineralocorticoid receptor antagonists

Background. Given the proven excessive activation of the renin-angiotensin-aldosterone system and the clinical manifestations of hypertension, mostly of renal origin, there is a need to optimize antihypertensive therapy aimed at an active nephroprotection. The purpose of the study is to carry out a comprehensive assessment of kidney and heart risk factors in patients with type 2 diabetes mellitus and chronic kidney disease (CKD) and to justify the administration of non-steroidal mineralocorticoid receptor antagonists to these patients. Materials and methods. In a prospective cohort study, 88 patients with type 2 diabetes were examined: group 1 — estimated glomerular filtration rate (eGFR) &lt; 60 ml/min/m2, group 2 — eGFR ≥ 60 ml/min/m2. eGFR was evaluated according to the CKD-EPI (Chronic Kidney Disease Epidemiology Colla­boration) formula based on serum creatinine. GFR category was defined according to the KDIGO (Kidney Disease: Improving Global Outcomes) criteria. The albumin-creatinine ratio was calcula­ted. The level of glycated hemoglobin (HbA1c) was assessed by the method of high-performance liquid chromatography. Aldosterone was evaluated by immunoenzymatic method. Results. In patients with eGFR &lt; 60 ml/min/m2, the albumin-creatinine ratio in daily urine is statistically significantly higher compared to group 2. Patients with eGFR &lt; 60 ml/min/m2 had an average uric acid level of 410.3 ± 98.8 μmol/l, which is statistically significantly higher than in those with eGFR ≥ 60 ml/min/m2 — 321.10 ± 74.54 μmol/l. A statistically significant correlation between the level of uric acid and markers of renal dysfunction was found only in patients with eGFR &lt; 60 ml/min/m2. Aldosterone levels were higher in the first group. No statistical difference was found between the average value of HbA1c in the studied groups. Conclusions. Numerous factors of unfavorable prognosis regarding kidney and heart risks have been identified: hypertension, increased albumin-creatinine ratio and cholesterol, unsatisfactory compensation of diabetes, obesity. There is an increase in the frequency of resistant hypertension, hyperuricemia, and hyperaldosteronism in patients with decreased eGFR. In patients with diabetic kidney damage on the background of type 2 diabetes, the administration of finerenone, a non-steroidal mine­ralocorticoid receptor antagonist, at a dose of 10–20 mg/day is pathogenetically justified.

Predictors of metabolic syndrome and its components in patients with type 2 diabetes: A cross-sectional study in the Ho municipality, Ghana

BackgroundMetabolic syndrome refers to a group of risk factors that individually or synergistically increase the risk of cardiovascular disease. The predictors of metabolic syndrome are thought to vary between populations and ethnicities. Hence, this study aimed to investigate the factors predicting metabolic syndrome and its components among patients with type 2 diabetes in the Ho municipality. MethodsA hospital-based cross-sectional study was designed to include 197 patients with type 2 diabetes at the Ho Municipal Hospital. A semi-structured questionnaire was used to obtain data on demography and lifestyle variables. Anthropometric, haemodynamic, and biochemical parameters were measured. Metabolic syndrome was defined according to the harmonised criteria. Renal function was evaluated based on the Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI)] and the evidence of proteinuria. Chi-square test and logistic regression analyses were performed to determine the predictors of metabolic syndrome and its components. ResultsOverall, the prevalence of metabolic syndrome was 59.90 %. Females had higher odds of metabolic syndrome [OR: 2.64, 95 % CI: 1.48–4.71; p = 0.001], abdominal obesity [OR: 11.49, 95 % CI: 5.18–25.49, p < 0.001], and low HDL-C levels [OR: 17.67, 95 % CI: 4.73–65.99, p < 0.001]. Having a family history of diabetes increased the risk of metabolic syndrome [OR: 1.94, 95 % CI: 1.09–3.54, p = 0.023] and abdominal obesity [OR: 2.60, 95 % CI: 1.25–5.42, p = 0.011]. Having diabetes for 5 years or more was associated with uncontrolled FBG [OR: 4.75, 95 % CI: 1.25–17.98, p = 0.022] and low HDL-C levels [OR: 4.52, 95 % CI: 1.64–12.45, p = 0.004]. Attainment of secondary education increased the risk of abdominal obesity [OR: 5.73, 95 % CI: 1.46 – 22.49, p = 0.012], while the attainment of tertiary education increased the risk of low HDL-C [OR: 4.20, 95 % CI: 1.09 – 16.24, p = 0.038]. Physical inactivity was associated with metabolic syndrome [OR: 2.19, 95 % CI: 1.12 – 4.28, p = 0.022]. Being older than 50 years had a two-fold increased risk of elevated BP [OR: 2.53, 95 % CI: 1.36–4.69, p = 0.003]. However, females were about 56 % unlikely to be associated with elevated BP [OR: 0.44, 95 % CI: 0.23–0.84, p = 0.013]. ConclusionThe female gender, family history of diabetes, and longer duration of diabetes as well as attainment of secondary and tertiary level education and physical inactivity were significant predictors of metabolic syndrome and its components in patients with type 2 diabetes.

Questionable Validity of Creatinine-Based eGFR in Elderly Patients but Cystatin C Is Helpful in First-Line Diagnostics.

The recommended chronic kidney disease (CKD) first-line diagnostic test is based on the creatinine-derived (estimated) glomerular filtration rate (eGFR). Cystatin C use may provide a better assessment. We compared creatinine- and cystatin C-derived eGFR determination as the first-line diagnostic test for 112 hospital patients aged > 60 years (median = 76 years). The patients were judged to not have CKD (no-CKD group) according to the first-line diagnostic recommendations (n = 61, eGFR (CKD Epidemiology Collaboration (CKD-EPI)) ≥ 60 mL/min/1.73 m2, total urine protein < 150 mg/g creatinine, urinary red/white blood cells not increased) or classified to be at risk for kidney insufficiency due to aortic valve dysfunction (at-risk group; n = 51). The accuracy of the eGFR values was evaluated retrospectively with the final case diagnoses. The eGFR (Caucasian, Asian, pediatric, and adult formula (CAPA)) was found to be linearly correlated to the eGFR (CKD-EPI) (R2 = 0.5, slope = 0.69, p < 0.0001). In 93/112 (>80%) cases, the eGFR (CAPA) yielded lower values (on average ≈-20%). In 55/112 (49%) cases, the cystatin C-derived CKD stage was lower. CKD reclassification from no-CKD to a kidney-insufficient state (i.e., CKD1/2 to CKD3a/b or 4) or reclassification to a more severe kidney insufficiency (i.e., CKD3a → 3b/4 or 3b → 4) was found in 41/112 (37%) cases. A worse CKD classification (no-CKD → kidney-insufficient) based on the eGFR (CAPA) was plausible in 30% of cases in light of the final case diagnoses. In elderly patients (>60 years), renal function appears to be systematically overestimated by the creatinine-based eGFR (CKD-EPI), indicating that, for this group, the cystatin C-based eGFR (CAPA) should be used as the first-line diagnostic test.

Methods of Estimating Renal Function for Use in Clinical Trial Eligibility Criteria Widely Vary in Phase II and III Clinical Trials in Acute Myeloid Leukemia

Background Renal function is an important parameter to inform drug-dosing in oncology. In acute myeloid leukemia (AML), commonly used therapies or their metabolites are renally cleared. Several equations are commonly used to estimate renal function, such as Cockcroft-Gault (CG) to estimate creatinine clearance (CrCl) and the Modification of Diet in Renal Disease (MDRD) or Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) equations to calculate estimated glomerular filtration rates (eGFR). These equations frequently use endogenous serum markers, such as creatinine (Cr) and cystatin-C due to their ready availability but can have limitations. For example, Cr can be affected by muscle mass, diet, and age. Current ADDIKD international consensus guidelines recommend using the CKD-EPI creatinine formula to calculate eGFR to guide anti-cancer drug dosing unless direct GFR measurement is indicated. Renal function criteria are commonly used in clinical trial eligibility. In this study, we analyzed the types of reported renal eligibility criteria in phase II and III trials in AML and the methodology specified for renal function estimation, which can significantly impact treatment options for patients and potentially confound toxicity evaluation. Methods We examined the clinicaltrials.gov database to review publicly reported renal eligibility criteria for interventional phase II and III clinical trials recruiting adults with AML between 2021 to 2023. Trials including pediatric patients and exclusive phase I studies were excluded. Chi-square tests were used to evaluate for potential associations between eGFR cutoff criteria and disease variables. Results A total of 134 trials met criteria for review, including 84 (63%) trials specifically for AML and 50 (37%) allowing additional diagnoses. Of the total study cohort, 107 trials (80%) were evaluating chemotherapy, small molecule inhibitors, immunotherapy and/or combinations of these whereas 27 (20%) were evaluating primarily cell therapy and/or transplant-based regimens. Among the 134 trials, 21 (16%) did not mention renal or general organ function in eligibility criteria; 16 (12%) mentioned renal or organ function in inclusion/exclusion criteria but did not specify an eGFR cutoff value; and 15 (11%) specified a serum Cr cutoff value without a specific eGFR cutoff value. Among 82 (61%) studies specifying eGFR cutoffs: 18 required eGFR ≥60 ml/min and 64 specified cutoffs between 30 ml/min to 50 ml/min or greater (table 1). We found an association between studies requiring an eGFR of 60 ml/min or greater and studies investigating cell therapy or transplant-based regimens (p&amp;lt;0.01). We did not find associations between eGFR cutoff requirements and trials based on disease status (relapsed/refractory AML versus other AML states, p=0.24). We next evaluated methodologies reported in eligibility criteria to estimate renal function. Among the 113 trials commenting on renal function criteria: 15 (13%) did not report either an eGFR cutoff or methodology of determination; 67 (59%) specified eGFR cutoffs without specifying the methodology of determination and/or provided serum Cr-based cutoffs; and 31 (27%) specified either a method of direct measurement or equations to estimate eGFR (including CG-based in 25, CKD-EPI in 1, MDRD-based in 3 and radioisotope methodology in 1) (table 1). No trials mentioned cystatin-C as part of renal function determination. Conclusion In contemporary phase II/III clinical trials for adult patients with AML, we identified that while most trials include renal function in inclusion/exclusion criteria, there was tremendous heterogeneity in methodologies specified for determination of renal function which may make efficacy and toxicity comparisons challenging and impact patient eligibility across institutions. Several trials specified serum Cr cutoffs which can be impacted by factors besides renal function such as age or muscle mass. This study was limited by what trial criteria were publicly available and additional information specifying methodologies to calculate renal function may be available in full trial protocols. Further research is needed to determine the most suitable method for assessing eGFR in patients with AML to optimize treatment exposures for patients and to help reduce confounding of trial results or trial eligibility by institutional practice variation.

Diagnostic standard: assessing glomerular filtration rate

ABSTRACT Creatinine-based estimated glomerular filtration rate (eGFR) is imprecise at individual level, due to non-GFR-related serum creatinine determinants, including atypical muscle mass. Cystatin C has the advantage of being independent of muscle mass, a feature that led to the development of race- and sex-free equations. Yet, cystatin C–based equations do not perform better than creatinine-based equations for estimating GFR unless both variables are included together. The new race-free Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation had slight opposite biases between Black and non-Black subjects in the USA, but has poorer performance than that the previous version in European populations. The European Kidney Function Consortium (EKFC) equation developed in 2021 can be used in both children and adults, is more accurate in young and old adults, and is applicable to non-white European populations, by rescaling the Q factor, i.e. population median creatinine, in a potentially universal way. A sex- and race-free cystatin C–based EKFC, with the same mathematical design, has also be defined. New developments in the field of GFR estimation would be standardization of cystatin C assays, development of creatinine-based eGFR equations that incorporate muscle mass data, implementation of new endogenous biomarkers and the use of artificial intelligence. Standardization of different GFR measurement methods would also be a future challenge, as well as new technologies for measuring GFR. Future research is also needed into discrepancies between cystatin C and creatinine, which is associated with high risk of adverse events: we need to standardize the definition of discrepancy and understand its determinants.

Changes in renal blood flow after surgically induced weight loss: can bariatric surgery halt the progression of chronic kidney disease?

BackgroundWe previously demonstrated how kidney injury in patients with morbid obesity can be reversed by bariatric surgery (BaS). Objective(s)Based on previous experience, we hypothesize patients’ potentially reversible kidney injury might be secondary to reduction in renal blood flow (RBF), which improves following BaS. SettingAcademic Hospital. MethodsWe conducted a retrospective analysis of patients who underwent BaS at our institution from 2002 to 2019. We identified patients with chronic kidney disease (CKD) using the estimated glomerular filtration rate (eGFR) from the CKD Epidemiology Collaboration Study (CKD-EPI) classification system. We used the BUN/Creatinine (Cr) ratio pre- and postoperatively to determine a prerenal (decreased RBF) versus intrinsic component as the responsible cause of CKD in this patient population. Decreased RBF was defined as BUN/Cr > 20 preoperatively. ResultsOur analysis included n = 2924 patients, of which 11% (n = 325) presented decreased RBF. From our original sample, only n = 228 patients had the complete data necessary to assess both eGFR and RBF (BUN/Cr). Patients with baseline CKD stage 2 demonstrated preoperative BUN/Cr 20.85 ± 10.23 decreasing to 14.99 ± 9.10 at 12-month follow-up (P < .01). Patients with baseline CKD stage 3 presented with preoperative BUN/Cr 23.88 ± 8.75; after 12-month follow-up, BUN/Cr ratio decreased to 16.38 ± 9.27 (P < .01). Patients with CKD stage 4 and ESRD (eGFR < 30) did not demonstrate a difference for pre- and postoperative BUN/Cr 21.71 ± 9.28 and 19.21 ± 14.58, respectively. Conclusion(s)According to our findings, patients with CKD stages 1–3 present improvement of their kidney function after BaS. This amelioration could be secondary to improvement of the RBF, an unstudied reversible mechanism of kidney injury in the bariatric population.

Smokeless tobacco consumption and its association with risk factors of chronic kidney disease in rural and peri-urban Bangladesh.

Compared to smoking, which has major consequences in chronic kidney disease (CKD) initiation and progression, smokeless tobacco (SLT) consumption is considered to have fewer health consequences. We investigated the prevalence of SLT consumption and its association with risk factors of CKD in a rural and peri-urban Bangladeshi population. Using random sampling we recruited 872 adults in 2020, from the Mirzapur Demographic Surveillance System of Bangladesh, who had resided in the area for at least five years. Interviews using a semi-structured questionnaire, physical examination and anthropometric measurements were done, followed by blood and urine testing. The blood and urine tests were repeated in selected participants after three months as per the CKD Epidemiology Collaboration equation. The prevalence of SLT consumption was 29%. Being aged ≥46 years (OR=7.10; 95% CI: 4.79-10.94), female (OR=1.64; 95% CI: 1.21-2.22), housewife (OR=1.82; 95% CI: 1.35-2.45), farmer (OR=1.71; 95% CI: 1.06-2.76), widow (OR=3.40; 95% CI: 2.24-5.17), and having no formal schooling (OR=4.91; 95% CI: 3.59-6.72), family income of <$100/month (OR=1.66; 95% CI: 1.13-2.43), sleeping duration <7 hours per day (OR=2.33; 95% CI: 1.70-3.19), were associated with a significantly higher odds of SLT consumption. However, being aged 31-45 years (OR=0.25; 95% CI: 0.16-0.38) had significantly lower odds of being an SLT consumer. Among the diseases investigated, undernutrition (OR=1.63; 95% CI: 1.15-2.33), hypertension (OR=1.52; 95% CI: 1.13-2.05), anemia (OR=1.94; 95% CI: 1.39-2.71) and CKD (OR=1.62; 95% CI: 1.15-2.27) were significantly associated with SLT consumption. In the multivariable analysis, being aged 31-45 years (AOR=3.06; 95% CI: 1.91-4.90), ≥46 years (AOR=15.69; 95% CI: 4.64-53.09) and having no formal schooling (AOR=2.47; 95% CI: 1.72-3.55) were found to have a significant association with being an SLT consumer. SLT consumption is associated with most of the established risk factors of CKD within the studied population.

Performance of Future Glomerular Filtration Rate Equation by Race in a Large, Racially Diverse Patient Cohort Undergoing Nephrectomy for Renal Cell Carcinoma

ObjectiveTo examine the performance of the Palacios et al. (2021) post-nephrectomy future glomerular function rate (fGFR) equation in a diverse cohort using both the Chronic Kidney Disease Epidemiology (CKD-EPI) 2009 equation with race, used in the creation of the formula, as well as the CKD-EPI 2021 equation without race. MethodsPatients that underwent partial or radical nephrectomy for renal cell carcinoma from 2005-2021 were identified in our institutional database. Patients with creatinine values preoperatively and 3-12 months postoperatively were included. Correlation/bias/accuracy/precision of the fGFR equation (fGFR=35+ [preoperative eGFR x 0.65]- 18 [if radical] - [age x 0.25]+ 3 [if tumor >7cm]-2 [if diabetes]) with observed postoperative eGFR was determined by both the CKD-EPI-2021 and CKD-EPI 2009 equations. Results1,443 patients were analyzed. 71% (1,024) were white and 22.9% (331) were black. Most underwent radical nephrectomy (60.3%). 40% T3-T4 RCC, with 14.8% of patients having M1 disease. Median observed vs predicted fGFR was 58.0 vs 58.7 ml/min/1.73m2 for CKD-EPI 2021 and 56.0 vs 57.5 for CKD-EPI 2009. For the total cohort, the correlation/bias/accuracy/precision of the fGFR equation was 0.805/-0.5/81.7/7.9-9.0 for CKD-EPI 2021 and 0.809/-0.8/81.3/-8.1-8 for CKD-EPI 2009. In black patients, fGFR equation demonstrated >75% accuracy with both CKD-EPI equations; however, accuracy was lower in black patients with the CKD-EPI2021 equation (76.1% vs. 83.4%, p=0.003). ConclusionsThe fGFR equation performed well in our large, diverse cohort, though accuracy was relatively lower when using CKD-EPI 2021 compared to CKD-EPI 2009.

Abstract P374: Greater Burden Of Chronic Kidney Disease Is Associated With Hypertension Prevalence And Management In South Africa

Introduction: Complications e.g., chronic kidney disease (CKD) are frequent with longstanding hypertension, particularly if poorly managed. Hypothesis: We assessed the hypothesis that prevalence and associations of CKD differed by hypertension prevalence, awareness, treatment and control in South Africa using five CKD estimates. Methods: In this randomly selected cross-sectional study, glomerular filtration rate (GFR) was estimated by CKD Epidemiology Collaboration (CKD-EPI) equations [CKD-EPI creatinine (CKD-EPIcr), CKD-EPI cystatin C, CKD-EPI creatinine-cystatin C], Modification of Diet in Renal Disease (MDRD) and Cockcroft-Gault formula (CGF). Blood pressures were measured, and history of hypertension management collected. Results: Among 1092 participants, mean age 43.5 years, 64% women, the prevalence of hypertension was 42% with similar rates in men (41%) and women (43%). In participants with hypertension (n=460), awareness, treatment and control were 61.5% (283/460), 47.2% (217/460) and 27.0% (124/460), with better rates in women compared with men (p&lt;0.001). CKD prevalence (GFR&lt;60 mL/min/1.73m 2 ) was 2.0-5.9% overall using 5 formulae, and significantly higher in participants with (3.9-10.2%) compared to without hypertension (0.6-2.7%) (p&lt;0.001). In participants with hypertension, CKD was higher in those aware (5.7-13.8%) vs unaware (1.1-4.5%) of their diagnosis (p≤0.015), on treatment (6.9-14.3%) vs none (1.2-6.6%) (p≤0.016), and those with controlled (BP&lt;140/90 mmHg) vs uncontrolled hypertension (6.5-15.1% vs. 3-8%, p≤0.096). In models adjusted for age, sex and obesity, higher hypertension prevalence and awareness were significantly (p&lt;0.05) associated with CKD by CKD-EPIcr and MDRD equations; hypertension treatment was significantly associated with CKD by CKD-EPIcr, MDRD and CGF formulae, while hypertension control was not associated with CKD. Conclusions: This study highlights the higher prevalence and greater likelihood of CKD in participants with hypertension and those who were diagnosed and receiving treatment, likely due to the longer duration of their hypertension compared with their counterparts. Higher CKD in the diagnosed and treated reinforces the need for optimal control, which was low in this cohort.

Why do we keep ignoring sex in kidney disease?

Throughout the history of nephrology, little attention has been paid to the sex and gender differences in kidney disease. This lack of awareness prevents optimal diagnosis and management of kidney disease. In today's world of precision medicine, it is imperative to appreciate the differential factors regarding gender and kidney disease. This editorial summarizes the up-to-date literature regarding sex and gender differences in kidney disease and considers areas where knowledge is incomplete and where further research is needed. We address sex-specific effects on chronic kidney disease epidemiology; risks of dialysis underdosing and medication overdosing in women; unexplained loss of female sex advantage in life expectancy during dialysis, and impact of sex on diagnosis and management of genetic kidney disease. We also aim to highlight the impact of gender on kidney health and raise awareness of disparities that may be faced by women, and transgender and gender-diverse persons when a male-model approach is used by healthcare systems. By understanding the link between sex and kidney disease, kidney specialists can improve the care and outcomes of their patients. In addition, research on this topic can inform the development of targeted prevention and intervention strategies that address the specific needs and risk factors of different populations.

Comparison of the performance of currently used estimated glomerular filtration rate equations with 24-hour urine creatinine clearance: sample analysis of randomised controlled trial participants

ObjectiveThere are several equations for estimating the glomerular filtration rate (GFR), and each method has its limitations. We compared various estimated GFR (eGFR) equations with 24 hours urine creatinine clearance...

THE POTENTIAL ROLE OF EGFR IN DIFFERENTIATING BETWEEN TRUE AND PSEUDOHYPERKALEMIA AT A TERTIARY CARE HOSPITAL

Objective: To determine the potential role of eGFR in differentiating between true and pseudohyperkalemia at a tertiary care hospital. Material and Methods: Cross-sectional study conducted in department of Chemical Pathology, Sheikh Zayed Hospital, Rahim Yar khan from January 1, 2022 to August 31, 2022. A total of 101 study subjects satisfying the inclusion criteria were included in study. Included specimen were analysed for serum creatinine level and estimated glomerular filtration rate (eGFR) was calculated by using chronic kidney disease-Epidemiology Collaboration (CKD-EPI) creatinine equation. Results: Of the total 101 study subjects, 59(58.4%) were male and 42(41.65%) were females. Mean age of study subjects was 45.28±12.265 years. Of the total 101 study samples, 75(74.3%) were classified as true hyperkalemia while 26(25.7%) were classified as pseudohyperkalemia with statistically significant difference of eGFR between two groups (P value: 0.00). Conclusion: Serum electrolytes are one of the most frequently requested diagnostic tests; thus, errors in these readings may alter the course of treatment for patients. As shown in our study that true hyperkalemia is very rare in patients with normal kidney function. So, estimated GFR can be taken as useful tool to differentiate between true and pseudohyperkalemia. Key Words: Pseudohyperkalemia, True hyperkalemia, Estimated GFR, CKD

#5817 EPIDEMIOLOGY OF CHRONIC KIDNEY DISEASE AND COMORBID ILLNESS IN OLDER HOSPITALIZED PATIENTS

Abstract Background and Aims The number of older people in Europe is expanding. Although chronic kidney disease (CKD) becomes more common with increasing age, data concerning epidemiology of CKD in older people are scarce, especially in Eastern Europe countries. These patients have multiple chronic conditions that must be correctly quantified for guiding risk stratification and subsequent management. Previously, European Renal Best Practice (ERBP) guidelines shed some light on managing older patients with advanced CKD, by stimulating the implementation of validated tools for predicting the most critical risks (death and progression to end-stage renal disease). Risk stratification can further inform decisions about the intensity of care (dialysis versus conservative treatment). In the current analysis, we aimed to fill the gap in CKD epidemiology in older people from Romania by describing a large population of hospitalized geriatric patients. Method In this retrospective cohort study, we included all patients aged ≥ 65 years hospitalized in the Geriatric Department of “Dr. C. I. Parhon” Hospital from Iași, Romania, between 2012 – 2022. This Geriatric Unit covers the entire North-East region of the country, so patients are representative of a population of almost 4 million people. CKD was identified as decreased estimated glomerular filtration rate (&amp;lt;60 ml/min/1.73 m2) according to CKD-EPI equation. We investigated comorbid conditions including diabetes mellitus, hypertension/hypertensive heart disease, coronary artery disease, congestive heart failure, atrial fibrillation, chronic respiratory failure and anemia. Results 3563 geriatric patients (59,2% females) were hospitalized between 2012–2022, totalling 5124 hospital admissions. The most common diagnosis was congestive heart failure (1958 cases, 38,2%) frequently due to hypertensive heart disease (877 patients, 44.8% of CHF cases). 3116 patients (87,4% of the total population) had a serum creatinine assay. Among these patients, the prevalence of CKD using the CKD-EPI equation was 32%. The mean age of CKD patients was 79 years, gender distribution was unequal (63,4% females) and almost half of them (49,1%) had stage 3a CKD. The most frequent comorbidities in patients with CKD were congestive heart failure (33%), diabetes (19%) and hypertension (17%), followed by atrial fibrillation (11%), chronic respiratory failure (9%), coronary artery disease (6%) and anemia (3%). The distribution of CKD patients stratified by the number of comorbidities showed that 86,7% had ≥ 2 comorbidities. The largest CKD subgroup was the one that associated three comorbidities (315 patients, 31.5%), followed by two subgroups that had two comorbidities (249 patients, 24,9%), respectively four comorbidities (189 patients, 18.9%). Only a minority of CKD patients (24 adults, 2,4%) had no other chronic condition. Conclusion With the ageing of the population, cardiovascular disease is becoming more common. In our population of geriatric patients, heart failure was the leading cause of hospitalization and the most frequent comorbid condition in CKD patients. One in three adults ≥ 65 years had CKD, a finding similar to other literature data. We emphasized that in older adults, CKD is not an isolated entity, which makes caring for these patients challenging, especially if we add the negative impact of other superimposed geriatric syndromes like frailty and cognitive decline.

#3901 PROGRESSION OF INCIDENT CHRONIC KIDNEY DISEASE: A DANISH NATIONWIDE POPULATION-BASED COHORT STUDY

Abstract Background and Aims The increasing global burden of kidney failure calls for targeted interventions to slow progression of chronic kidney disease (CKD). However, the understanding of progression from CKD stage G3 is limited. We aimed to characterise individuals with incident CKD stage G3 in Denmark and to examine CKD progression defined by three different measures. Method We conducted a nationwide, population-based cohort study using routinely collected individual-level data from national health and administrative databases in Denmark (population ∼5.9 million). Using creatinine tests performed in general practice and the outpatient hospital setting from 1 January 2017 to 31 December 2020, we included all adults in Denmark with incident CKD stage G3, based on the Kidney Disease: Improving Global Outcomes (KDIGO) criteria (≥2 creatinine measurements corresponding to an estimated glomerular filtration rate (eGFR) between 30-59 ml/min/1.73 m2 separated by ≥90 days). We used the 2009 CKD Epidemiology Collaboration Creatinine Equation for calculating eGFR. The three years leading up to the study period comprised a washout period to minimise inclusion of individuals with prevalent CKD. We explored CKD progression based on three outcome measures of different sensitivity, including 1) rapid CKD progression (decline in eGFR of ≥5 ml/min/1.73 m2/year, that is, for each eGFR measurement taken during follow-up, we considered this and the measurements taken in the prior year (requiring ≥3 eGFR measurements separated by ≥90 days)); 2) drop in GFR category (drop between GFR categories, 45–59 [G3a], 30–44 [G3b], 15–29 [G4], &amp;lt;15 [G5] ml/min/1.73 m2, accompanied by ≥25% drop in eGFR from baseline); and 3) kidney failure (≥2 eGFR measurements &amp;lt;15 ml/min/1.73 m2 separated by ≥90 days and/or kidney replacement therapy). The 1- and 3-year risks of CKD progression according to the three definitions and all-cause mortality were examined as cumulative incidences using the Aalen-Johansen method. Results We included 133,443 individuals with incident CKD stage G3. The median age at inclusion was 75 years (interquartile range (IQR): 69-82) and 55% were females with 59% having hypertension, 18% having diabetes and 10% having heart failure. The median eGFR at inclusion was 56 ml/min/1.73 m2 (IQR: 51-58) and the median number of eGFR measurements was 3 (IQR: 2-5) in the prior year. Among the 133,443 individuals with incident CKD stage G3, 48,997 (37%) fulfilled the criteria for rapid CKD progression at inclusion. Among the 84,446 individuals without rapid progression on the day of inclusion, the 1- and 3-year risks of rapid CKD progression were 25.0% (95% confidence interval (CI): 24.7-25.3) and 46.0% (95% CI: 45.6-46.4), respectively. The risk of a drop in GFR category was 6.9% (95% CI: 6.8-7.1) after 1 year and 16.6% (95% CI: 16.4-16.8) after 3 years. The risks of kidney failure/renal replacement therapy were 0.1% (95% CI: 0.1-0.1) and 0.3% (95% CI: 0.3-0.4) after 1 and 3 years, respectively. All-cause mortality was 6.8% (95% CI: 6.7-6.9) in the first year and the 3-year mortality was 18.1% (95% CI: 17.9-18.4) (Table 1). Conclusion This nationwide, population-based cohort study showed that a substantial proportion of individuals experienced rapid CKD progression in the 3 years following incident CKD stage G3, whereas the risk of drop in GFR category was considerably lower. Kidney failure within 3 years was rare, while all-cause mortality was relatively modest, taking the high average age into account. This highlights the potential for preventive interventions in patients at risk of rapidly deteriorating kidney function, who might benefit from regular monitoring and targeted treatment.

#2850 EFFICIENCY OF THE GENETIC STUDY IN THE DIAGNOSIS OF AUTOSOMAL DOMINANT TUBULOINTERSTITIAL NEPHROPATHY

Abstract Background and Aims Autosomal dominant tubulointerstitial nephropathy (ADTKD) is a rare underdiagnosed cause of chronic kidney disease (CKD). ADTKD is a renal disease with a non-specific phenotypic expression that cause a slow progression over time. Given the great variability in its inter-familial presentation and among the same family members carrying the same mutation, its diagnosis is a challenge. Five genes have been identified to date such as Uromodulin (UMOD), Renin (REN), Hepatocyte Nuclear Factor 1b (HNF1β), Mucin-1 (MUC1) and, more recently, new genes, SEC61A1(encoding protein transport protein Sec61 subunit α and atypical (DNAJB11). Our main objective is to analyze the diagnostic yield of the genetic study in cases of clinical suspicion of ADTKD in patients with CKD of unknown etiology. We present a case series of patients from our center with CKD of unknown etiology and clinical suspicion of ADTKD. Genetic analysis of the gene SEC61A1 and DNAJB11 was not available at that time. Method This is a descriptive observational retrospective study from 2016 to 2021 at the Virgen del Rocio University Hospital in Seville, Spain. A total of 26 cases had phenotypic presentation of ADTKD. We collected clinical, laboratory, radiologic, and pathologic data. We performed in all the cases genetic testing for UMOD, MUC1, REN and HNF1β mutations. We collected data in a database, including age of presentation of kidney disease, sex, family history of kidney disease, the presence of hypertension at early age (defined as under 40 years of age), hyperuricemia (defined as uric acid &amp;gt;7.5 mg/dl) at early age (&amp;lt;40 years), hemoglobin at the time of diagnosis, age at last follow up with renal function and estimated glomerular filtration rate (eGFR) using the CKD-EPI (CKD Epidemiology Collaboration), urine elemental, renal ultrasound and renal biopsy if it had been performed. Descriptive results of quantitative variables are expressed as median. For categorical data, frequency and percentage are reported. Results Of the 26 cases with suspected ADTKD, 4 cases presented a genetic study that confirmed the diagnosis, that is, 15% of the cases. The median age at the time of the diagnosis was 41 years (IQR 32.7–48). 84% of the cases were male; 34% of cases had a family history of CKD of unknown etiology. 65% percent of the cases had a history of hyperuricemia at early age (&amp;lt;40 years), with a personal history of hypertension &amp;lt;40 years in 30% of the cases; 44% of the cases had renal lithiasis. The median glomerular filtration rate (CKD-EPI) at the time of diagnosis was 70 ml/min/1.73 m2 (46.4–70.7). In most of the patients, the urine elemental was normal. Renal cysts were found on ultrasound in 46% of patients. In 5 of the twenty-six patients a renal biopsy was performed, in which 60% presented data compatible with ADTKD with interstitial fibrosis and tubular atrophy. 4 of the patients with clinical suspicion of ADTKD obtained a genetic study that confirmed the diagnosis. The most frequently identified gene was HNF1β, being present in two of the four patients. The other genes identified were UMOD and MUC. The results are summarized in Table 1. Conclusion Adequate selection of patients based on clinical suspicion is essential to give greater profitability to the genetic study of this entity. The negativity of the study cannot exclude the diagnosis, since at the moment not all the causative genes of this pathology have been identified and it is necessary to use massive sequencing techniques or even the analysis of the complete exome to see the possibility of other variants of the disease.

Prediction of worsening postoperative renal function in older candidates to elective cardiac surgery: Choosing the best eGFR formula may not be enough

BackgroundThough renal impairment is highly prevalent in older patients and influence post-operative outcomes in cardiac surgery; its prognostic relevance is debated and not fully assessed by surgical risk scores. ObjectiveWe investigated the predictive role of estimated glomerular filtration rate formulas for in-hospital worsening renal function (WRF) after cardiac surgery. MethodsWe prospectively enrolled in single-center cohort study, patients aged ≥ 75 years candidate to elective cardiac surgery. Four creatinine-based equations were used to calculate estimated glomerular filtration rate (eGFR) formulas: Cockroft-Gault, Modification of Diet in Renal Disease, Chronic Kidney Disease Epidemiology, and Berlin Initiative Study 1 formulas. Each patient underwent geriatric and clinical evaluation before surgery with calculation of the Society of Thoracic Surgeons scores. In-hospital WRF was defined as a composite of an increase in SCr ≥0.5 mg/dl or the occurrence of grade III KDIGO acute kidney injury. The association between each eGFR equation, alone and in models including clinical variables, and WRF was analyzed using logistic regressions and ROC analysis. ResultsWRF occurred in 69 patients (19.8%), and the predictors of WRF were previous acute myocardial infarction, hypertension, 4-mt gait speed performance, and preoperative eGFR, irrespective of the equation used. With all equations, inclusion of these additional variables in the logistic regression models improved the prediction of WRF (AUCs 0.798–0.810). ConclusionsAn accurate assessment of renal function and of physical performance should be incorporated into cardiac surgery risk scores to improve prediction of in-hospital WRF and, hence, risk stratification in older adults undergoing elective cardiac surgery.

Dairy products and kidney function decline after myocardial infarction: A prospective analysis in the Alpha Omega Cohort

Population-based studies have shown both beneficial and neutral associations between dairy consumption and kidney function outcomes. We investigated the association between dairy products and kidney function decline in drug-treated post-myocardial infarction (MI) patients. We analysed data of 2169 post-MI patients (aged 60-80 years, 81% male) of the Alpha Omega Cohort. Dietary data were collected at baseline (2002-2006) using a validated 203-item food frequency questionnaire. The 2021 Chronic Kidney Disease Epidemiology (CKD-EPI) equation was used to estimate 40-months change in creatinine-cystatin C based glomerular filtration rate (eGFRcr-cysC, mL/min per 1.73m2). Beta coefficients and 95% confidence intervals (CIs) for dairy products in relation to annual eGFRcr-cysC change were obtained from multivariable linear regression, adjusted for age, sex, energy intake, and other lifestyle and dietary factors. Baseline energy-adjusted median intakes were 64g/day for total milk, 20g/day for hard cheeses, 18g/day for plain yogurt, and 70g/day for dairy desserts. Mean±SD eGFRcr-cysC was 84±20 (13% with CKD), and annual eGFRcr-cysC change was-1.71±3.85. In multivariable models, high vs. low intakes of total milk, cheese, and dairy desserts were not associated with annual eGFRcr-cysC change (βtotal milk:-0.21 [-0.60; 0.19], βcheese:-0.08 [-0.52; 0.36], βdairy desserts:-0.24 [-0.72; 0.24]). High vs. low intake of yogurt was adversely associated with annual eGFRcr-cysC change (βtotal yogurt:-0.50 [-0.91;-0.09]), but subsequent spline analyses showed no clear dose-response association. Intakes of milk, cheese or dairy desserts were not associated with a delayed kidney function decline after MI. The observed adverse association for yogurt should be interpreted with caution. Our findings require confirmation in other cohorts of coronary heart disease patients.