Creatinine-based eGFR Research Articles

Structural equation modeling (SEM) of kidney function markers and longitudinal CVD risk assessment.

Lower kidney function is known to enhance cardiovascular disease (CVD) risk. It is unclear which estimated glomerular filtration rate (eGFR) equation best predict an increased CVD risk and if prediction can be improved by integration of multiple kidney function markers. We performed structural equation modeling (SEM) of kidney markers and compared the performance of the resulting pooled indexes with established eGFR equations to predict CVD risk in a 10-year longitudinal population-based design. We split the study sample into a set of participants with only baseline data (n = 647; model-building set) and a set with longitudinal data (n = 670; longitudinal set). In the model-building set, we fitted five SEM models based on serum creatinine or creatinine-based eGFR (eGFRcre), cystatin C or cystatin-based eGFR (eGFRcys), uric acid (UA), and blood urea nitrogen (BUN). In the longitudinal set, 10-year incident CVD risk was defined as a Framingham risk score (FRS)>5% and a pooled cohort equation (PCE)>5%. Predictive performances of the different kidney function indexes were compared using the C-statistic and the DeLong test. In the longitudinal set, a SEM-based estimate of latent kidney function based on eGFRcre, eGFRcys, UA, and BUN showed better prediction performance for both FRS>5% (C-statistic: 0.70; 95% CI: 0.65-0.74) and PCE>5% (C-statistic: 0.75; 95%CI: 0.71-0.79) than other SEM models and different eGFR formulas (DeLong test p-values<3.21×10-6 for FRS>5% and <1.49×10-9 for PCE>5%, respectively). However, the new derived marker could not outperform eGFRcys (DeLong test p-values = 0.88 for FRS>5% and 0.20 for PCE>5%, respectively). SEM is a promising approach to identify latent kidney function signatures. However, for incident CVD risk prediction, eGFRcys could still be preferrable given its simpler derivation.

Concordance and Discrepancies Among 5 Creatinine-Based Equations for Assessing Estimated Glomerular Filtration Rate in Older Adults

There is uncertainty as to which estimated glomerular filtration rate (eGFR) equation should be used among older adults. To compare the 5 most commonly used creatinine-based eGFR equations in older adults, quantifying the concordance among the equations, comparing their discriminative capacity in regards to 15-year mortality, and identifying sources of potential discrepancies. This cohort study used data from the Swedish National Study on Aging and Care in Kungsholmen (SNAC-K), a longitudinal study of adults aged 60 years or older in Sweden. Participants were recruited between 2001 and 2004 and followed up for mortality until December 2016. Participants missing creatinine values were excluded. Data were originally analyzed March through July 2022, and were rerun in January 2023. Five creatinine-based equations were considered: Modification of Diet in Renal Disease (MDRD), 2009 Chronic Kidney Disease Epidemiological Collaboration (CKD-EPI), Revised Lund-Malmö (RLM), Berlin Initiative Study (BIS), and European Kidney Function Consortium (EKFC). Concordance between equations was quantified using Cohen κ. Discriminative capacity for mortality was quantified using area under the receiver operating characteristic curve (AUC) and the Harrel C statistic. Calf circumference, body mass index (BMI), and age were explored as correlates of discrepancies. The study sample consisted of 3094 older adults (1972 [63.7%] female; median [IQR] age, 72 [66-81] years). Cohen κ between dyads of equations ranged from 0.42 to 0.91, with poorest concordance between MDRD and BIS, and best between RLM and EKFC. MDRD and CKD-EPI provided higher estimates of GFR compared with the other equations. The best mix of AUC and Harrel C statistic was observed for BIS (0.80 and 0.73, respectively); however, the prognostic accuracy for death decreased among those aged over 78 years and those with low calf circumference. Differences between equations were inconsistent across levels of calf circumference, BMI, and age. In this cohort study, we found that eGFR equations were not interchangeable when assessing kidney function. BIS outperformed other equations in predicting mortality; however, its discriminative capacity was reduced in subgroup analyses. Clinicians should consider these discrepancies when monitoring kidney function in old age.

A Comparative Study on the Efficacy Between Cystatin C and Creatinine-Based Equations for Early Detection of Renal Damage in Patients of Eastern India.

Chronic kidney disease (CKD) is one of the leading causes of mortality across the globe. Early diagnosis of the disease is important in order to prevent the adverse outcome related to CKD. Many laboratories adopt creatinine-based e-GFR equations which yields imprecise results leading to misdiagnosis of CKD. Emerging studies indicated cystatin C as a better renal marker than creatinine. The aim of the study is to compare the efficacy of CKD epidemiology collaboration (CKD-EPI) creatinine e-GFR equations with (CKD EPI) cystatin-based e-GFR equations alone and in combination with creatinine for early detection of CKD. A cross-sectional study employing 473 patients was conducted. Three estimating GFR equations were calculated based on creatinine and cystatin C. Pearson Correlation study was done to assess the correlation of creatinine and cystatin C with their respective GFRs. A predictive model was developed, and ROC curve was constructed to compare efficacy, sensitivity and specificity of the creatinine and cystatin C based equations. Cystatin C exhibited better negative correlation with GFR than creatinine in correlation studyperformed with three commonly employed eGFRequations including CKD EPICreatine cystatin C combinedequation (2021),cys C alone and CKD EPI creatinine(2021) equations respectively[r=(-) 0.801 vs. r=(-)0.786 vs. r=(-)0.773]. Predictive model demonstrated highest efficiency, sensitivity and specificity for creatinine-cystatin C combined equation(88%, 81% and 93%) followed by cystatin C alone equation(73%,63% and 82%) and creatinine-based equation(61%, 56% and 66% respectively). The study showed better performance of cystatin C based equations for early detection of advance stages in chronic kidney disease as compared to creatinine-based e-GFR equation.

Biomarkers of alloimmune events in pediatric kidney transplantation.

Alloimmune events such as the development of de novo donor-specific antibody (dnDSA), T cell-mediated rejection (TCMR), and antibody-mediated rejection (ABMR) are the primary contributors to kidney transplant failure in children. For decades, a creatinine-based estimated glomerular filtration rate (eGFR) has been the non-invasive gold standard biomarker for detecting clinically significant alloimmune events, but it suffers from low sensitivity and specificity, especially in smaller children and older allografts. Many clinically "stable" children (based on creatinine) will have alloimmune events known as "subclinical acute rejection" (based on biopsy) that merely reflect the inadequacy of creatinine-based estimates for alloimmune injury rather than a distinct phenotype from clinical rejection with allograft dysfunction. The poor biomarker performance of creatinine leads to many unnecessary surveillance and for-cause biopsies that could be avoided by integrating non-invasive biomarkers with superior sensitivity and specificity into current clinical paradigms. In this review article, we will present and appraise the current state-of-the-art in monitoring for alloimmune events in pediatric kidney transplantation. We will first discuss the current clinical standards for assessing the presence of alloimmune injury and predicting long-term outcomes. We will review principles of biomarker medicine and the application of comprehensive metrics to assess the performance of a given biomarker against the current gold standard. We will then highlight novel blood- and urine-based biomarkers (with special emphasis on pediatric biomarker studies) that have shown superior diagnostic and prognostic performance to the current clinical standards including creatinine-based eGFR. Finally, we will review some of the barriers to translating this research and implementing emerging biomarkers into common clinical practice, and present a transformative approach to using multiple biomarker platforms at different times to optimize the detection and management of critical alloimmune events in pediatric kidney transplant recipients.

Estimated GFR With Cystatin C and Creatinine in Clinical Practice: A Retrospective Cohort Study

Estimation of glomerular filtration rate (eGFR) and staging of chronic kidney disease (CKD) are essential to guide management. Although creatinine is routinely used, a recent national task force recommended the use of cystatin C for confirmation. The objective of this study was to examine the following parameters: (1) how cystatin C correlates with creatinine eGFR; (2) how it indicates differences in CKD staging; and (3) how it may affect kidney care delivery. Retrospective observational cohort study. 1,783 inpatients and outpatients who had cystatin C and creatinine levels drawn within 24 hours at Brigham Health-affiliated clinical laboratories. Serum creatinine levels, basic clinical/sociodemographic variables, and reasons for ordering cystatin C from a structured partial chart review. Univariate and multivariable linear and logistic regression. Cystatin C-based eGFR was very strongly correlated with creatinine-based eGFR (Spearman correlation ρ=0.83). Cystatin C eGFR resulted in a change to a later CKD stage in 27%, an earlier stage in 7%, and no change in 66% of patients. Black race was associated with a lower likelihood of change to a later stage (OR, 0.53; 95% CI [0.36, 0.75]; P<0.001), whereas age (OR per year OR, 1.03; 95% CI [1.02, 1.04]; P<0.001) and Elixhauser score (OR per point OR, 1.22; 95% CI [1.10, 1.36]; P<0.001) were associated with a higher likelihood of change to a later stage. Single center, no direct measurement of clearance for comparison, and inconsistent self-identification of race/ethnicity. Cystatin C eGFR correlates strongly with creatinine eGFR but can have a substantial effect on CKD staging. As cystatin C is adopted, clinicians must be informed on this impact.

GFR estimated with creatinine rather than cystatin C is more reflective of the true risk of adverse outcomes with low GFR in kidney transplant recipients.

Serum cystatin C-based estimated glomerular filtration rate (eGFRcys) generally associates with clinical outcomes better than serum creatinine-based eGFR (eGFRcr) despite similar precision in estimating measured GFR (mGFR). We sought to determine whether the risk of adverse outcomes with eGFRcr or eGFRcys was via GFR alone or also via non-GFR determinants among kidney transplant recipients. Consecutive adult kidney transplant recipients underwent a standardized GFR assessment during a routine follow-up clinic visit between 2011 and 2013. Patients were followed for graft failure or the composite outcome of cardiovascular (CV) events or mortality through 2020. The risk of these events by baseline mGFR, eGFRcr and eGFRcys was assessed unadjusted, adjusted for mGFR and adjusted for CV risk factors. There were 1135 recipients with a mean baseline mGFR of 55.6, eGFRcr of 54.8 and eGFRcys of 46.8ml/min/1.73m2 and a median follow-up of 6years. Each 10ml/min/1.73m2 decrease in mGFR, eGFRcr or eGFRcys associated with graft failure [hazard ratio (HR) 1.79, 1.68 and 2.07, respectively; P<.001 for all) and CV events or mortality outcome (HR 1.28, 1.19 and 1.43, respectively; P<.001 for all). After adjusting for mGFR, eGFRcys associated with graft failure (HR 1.57, P<.001) and CV events or mortality (HR 1.49, P<.001), but eGFRcr did not associate with either. After further adjusting for CV risk factors, risk of these outcomes with lower eGFRcys was attenuated. eGFRcr better represents the true relationship between GFR and outcomes after kidney transplantation because it has less non-GFR residual association. Cystatin C is better interpreted as a nonspecific prognostic biomarker than is eGFR in the kidney transplant setting.

Estimated glomerular filtration rates are higher when creatinine-based equations are compared with a cystatin C-based equation in coronavirus disease 2019.

Estimations of glomerular filtration rate (eGFR) are based on analyses of creatinine and cystatin C, respectively. Coronavirus disease 2019 (COVID-19) patients in the intensive care unit (ICU) often have acute kidney injury (AKI) and are at increased risk of drug-induced kidney injury. The aim of this study was to compare creatinine-based eGFR equations to cystatin C-based eGFR in ICU patients with COVID-19. After informed consent, we included 370 adult ICU patients with COVID-19. Creatinine and cystatin C were analyzed at admission to the ICU as part of the routine care. Creatinine-based eGFR (ml/min) was calculated using the following equations, developed in chronological order; the Cockcroft-Gault (C-G), Modified Diet in Renal Disease (MDRD)1999, MDRD 2006, Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), and Lund-Malmö revised (LMR) equations, which were compared with eGFR calculated using the cystatin C-based Caucasian Asian Pediatric Adult (CAPA) equation. The median eGFR when determined by C-G was 99 ml/min and interquartile range (IQR: 67 ml/min). Corresponding estimations for MDRD1999 were 90 ml/min (IQR: 54); MDRD2006: 85 ml/min (IQR: 51); CKD-EPI: 91 ml/min (IQR: 47); and for LMR 83 ml/min (IQR: 41). eGFR was calculated using cystatin C and the CAPA equation value was 70 ml/min (IQR: 38). All differences between creatinine-based eGFR versus cystatin C-based eGFR were significant (p < .00001). Estimation of GFR based on various analyses of creatinine are higher when compared with a cystatin C-based equation. The C-G equation had the worst performance and should not be used in combination with modern creatinine analysis methods for determination of drug dosage in COVID-19 patients.

Relation between obesity-related comorbidities and kidney function estimation in children

BackgroundThe current childhood obesity pandemic is likely to result in an increased risk of chronic kidney disease (CKD) later in life. Correlations between obesity-related comorbidities and kidney function can be found, but it is unclear to what extent this is caused by bias due to different mathematical forms of the estimated glomerular filtration rate (eGFR) equations. The present study aimed to analyze correlations between obesity-related comorbidities and different eGFR equations and to investigate whether rescaled serum creatinine (SCr/Q) for sex and age or height might be an alternative biomarker for kidney function estimation.MethodsThis cross-sectional cohort study included 600 children with overweight and obesity. Mean age was 12.20 ± 3.28 years, 53.5% were female, and mean BMI z-score was 3.31 ± 0.75. All children underwent a comprehensive assessment that included anthropometrical and blood pressure measurements, laboratory examination, air displacement plethysmography, and polysomnography. Qage and Qheight polynomials were used to rescale SCr and multiple creatinine-based eGFR equations were compared.ResultsSCr/Q and almost all GFR estimations significantly correlated with a waist-to-hip ratio, fat mass, homeostasis model assessment for insulin resistance, and triacylglyceride, HDL cholesterol, alanine transaminase, and serum uric acid concentrations. Multiple correlations, however, were not confirmed by all equations, which suggests dependency on the mathematical form of the different eGFR equations.ConclusionsCorrelations between obesity-related comorbidities and creatinine-based eGFR are present in children with overweight and obesity, but depend to a large extent on the eGFR equation of choice. SCr/Q might be an alternative biomarker for assessing correlations between obesity-related comorbidities and kidney function in children with overweight and obesity.Graphical A higher resolution version of the Graphical abstract is available as Supplementary information

Performance of Glomerular Filtration Rate Estimating Equations in Cancer Patients Evaluated for Chimeric Antigen Receptor T-Cell Therapy

Background: An accurate assessment of kidney function is necessary to evaluate candidates seeking chimeric antigen receptor T-cell (CAR-T) therapy.(Jain, et al, 2019, Yakoub-Agha, et al, 2019) Additionally, kidney function quantification is essential to selecting the appropriate dose for fludarabine-based lymphodepleting chemotherapy prior to CAR-T cell infusion in order to optimize outcomes.(Hirayama, et al, 2019) Treatment decisions are currently guided by a glomerular filtration rate (GFR) that is estimated using serum creatinine. However, estimated GFR (eGFR) utilizing cystatin C-based equations has been suggested to overcome the known limitations of creatinine-based eGFR in patients with cancer.(Kellum, et al, 2012, Hersh, et al, 1986) The accuracy and precision of these eGFR assessment strategies in potential CAR-T therapy recipients has not been explored, and the preferred method for quantifying GFR in this patient population remains unknown. Methods: This IRB-approved, single-center, observational study evaluated the performance of contemporary eGFR equations in any adult patient being evaluated for CAR-T therapy with a measured GFR (mGFR) by iothalamate clearance. Excluded individuals were those without a serum creatinine (SCr) and serum cystatin C (cysC) concentration performed within 14 days of the mGFR. Baseline characteristics and pertinent laboratory values were abstracted from the medical record. eGFR was calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations, including the most recent iterations that were developed without the race parameter.(Levey, et al, 2009, Inker, et al, 2012, Inker, et al, 2021) Bias, accuracy (percentage of estimates within 10% and 30% of mGFR), and precision (SD of the difference between the eGFR and the mGFR) were assessed. The prediction of mGFR by each eGFR equation was assessed with scatterplots. Results: The 135 patients that were included had a median age of 63 (IQR: 56, 69) years and 77 (57%) were male. Two patients (1%) were African American and 123 (91%) were White. Relapsed lymphoma was the most common cancer diagnosis (n=94, 70%), followed by multiple myeloma (n=38, 28%) and acute lymphoblastic leukemia (n=3, 2%). Median mGFR was 73 ml/min/1.73m2 (IQR: 57, 92) with mGFR >60 ml/ml/1.73m2 in 95 (70%) patients. Table 1 summarizes baseline characteristics, laboratory values, and eGFR. The average absolute bias ranged from -10.1 to -0.1 ml/min/1.73m2 indicating that all equations underestimated mGFR to some degree. CKD-EPI 2021 SCr and CKD-EPI 2021 cysC+SCr had the least bias at -0.1 ml/min/1.73m2 and -4.0 ml/min/1.73m2, respectively. CKD-EPI 2021 cysC+SCr had the greatest accuracy within 10% of GFR and within 30% of mGFR. Additional bias, precision, and accuracy details of each estimating equation are summarized in table 1. The CKD-EPI 2012 cysC+SCr and the CKD-EPI 2021 cysC+SCr equations most closely correlated with mGFR in all patients (r=0.82 and 0.81, respectively). Correlation of measured glomerular filtration rate (GFR) with each of the GFR estimating equations is depicted in figure 1. Conclusion: CKD-EPI 2021 SCr and CKD-EPI 2021 cysC+SCr were the equations with the least bias. Contemporary eGFR equations had the greatest correlation with mGFR and seem acceptable when evaluating CAR-T therapy candidacy. Accuracy when dosing medications with a narrow therapeutic index, such as chemotherapy, is paramount, and all eGFR methods had limited accuracy within 10% of mGFR. Though the CKD-EPI 2021 cysC+SCr demonstrated the highest degree of accuracy within 10% of mGFR and within 30% of mGFR, iothalamate clearance should be the preferred method for kidney function assessment in patients seeking and receiving CAR-T therapy. Future research should investigate the impact of fludarabine dose selection on clinical outcomes of CAR-T recipients. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

National Projections for Clinical Implications of Race-Free Creatinine-Based GFR Estimating Equations.

The National Kidney Foundation and American Society of Nephrology Task Force on Reassessing the Inclusion of Race in Diagnosing Kidney Disease recently recommended a new race-free creatinine-based equation for eGFR. The effect on recommended clinical care across race and ethnicity groups is unknown. We analyzed nationally representative cross-sectional questionnaires and medical examinations from 44,360 participants collected between 2001 and 2018 by the National Health and Nutrition Examination Survey. We quantified the number and proportion of Black, White, Hispanic, and Asian/Other adults with guideline-recommended changes in care. The new equation, if applied nationally, could assign new CKD diagnoses to 434,000 (95% confidence interval [CI], 350,000 to 517,000) Black adults, reclassify 584,000 (95% CI, 508,000 to 667,000) to more advanced stages of CKD, restrict kidney donation eligibility for 246,000 (95% CI, 189,000 to 303,000), expand nephrologist referrals for 41,800 (95% CI, 19,800 to 63,800), and reduce medication dosing for 222,000 (95% CI, 169,000 to 275,000). Among non-Black adults, these changes may undo CKD diagnoses for 5.51 million (95% CI, 4.86 million to 6.16 million), reclassify 4.59 million (95% CI, 4.28 million to 4.92 million) to less advanced stages of CKD, expand kidney donation eligibility for 3.96 million (95% CI, 3.46 million to 4.46 million), reverse nephrologist referral for 75,800 (95% CI, 35,400 to 116,000), and reverse medication dose reductions for 1.47 million (95% CI, 1.22 million to 1.73 million). The racial and ethnic mix of the populations used to develop eGFR equations has a substantial effect on potential care changes. The newly recommended 2021 CKD-EPI creatinine-based eGFR equation may result in substantial changes to recommended care for US patients of all racial and ethnic groups.

Cystatin C-based eGFR predicts cardiovascular disease in patients with overweight/obesity and hyperglycemia.

Although many clinical parameters have been identified as predictors for cardiovascular disease (CVD) development in the general population, the accurate predictor for CVD in patients with obesity is still unknown. The study aimed to explore an additional risk factor and predictor for CVD in patients with overweight/obesity considering the interaction of obesity-related pathophysiology. The Japan Obesity and Metabolic Syndrome study, a multicenter prospective study, enrolled 787 outpatients, of which 318 eligible patients were analyzed. Patients with fasting plasma glucose (FPG) levels ≥6.11 and<6.11mmol/L were considered to have high FPG (HFPG) and normal FPG (NFPG), respectively. Thirty-six patients who developed CVD during the 5years follow-up were assigned to the CVD group. Cox's proportional hazards model revealed no significant association between CVD and cystatin C-based estimated glomerular filtration rate (eGFRcys) or creatinine-based eGFR (eGFRcr) in the NFPG group. In the HFPG group, lower eGFRcys, but not eGFRcr, was significantly associated with CVD development. A generalized linear mixed model demonstrated greater reduction in eGFRcys levels over time with HFPG than with NFPG. Although the CVD group showed gradual reduction in eGFRcys levels, the non-CVD group-matched using propensity scores-did not show a decline in eGFRcys levels. Lower eGFRcys levels may be more accurate than eGFRcr in predicting CVD development in patients with overweight/obesity and hyperglycemia. Furthermore, eGFRcys reduction over time is associated with CVD development. UMIN000000559.

Kidney function in patients with bipolar disorder with and without lithium treatment compared with the general population in northern Sweden: results from the LiSIE and MONICA cohorts

The clinical relevance of lithium nephropathy is subject to debate. Kidney function decreases with age and comorbidities, and this decline might lead to attribution bias when erroneously ascribed to lithium. We aimed to investigate whether patients with bipolar or schizoaffective disorder had faster decline in estimated glomerular filtration rate (eGFR) compared with the general population, whether observed differences in the steepness of the decline were attributable to lithium, and whether such changes depended on the length of lithium exposure. In this cross-sectional cohort study, we used clinical data from the Lithium-Study into Effects and Side-effects (LiSIE) retrospective cohort study, which included patients with bipolar disorder or schizoaffective disorder whose medical records were reviewed up to Dec 31, 2017, and the WHO Monitoring of Trends and Determinants in Cardiovascular Disease (MONICA) study, covering a representative sample of the general population in northern Sweden aged 25-74 years. The primary outcome was the age-associated decline of creatinine-based eGFR, assessed using linear regression. We adjusted for sex and grouped for different lengths of lithium exposure (never or <1 year, 1-5 years, >5-10 years, and >10 years). For patients with moderate-to-severe kidney disease we identified the underlying nephropathy in the case records. From LiSIE, we included 785 patients (498 [63%] female and 287 [37%] male), with a mean age of 49·8 years (SD 13·2; range 25-74). From MONICA, we included 1549 individuals (800 [52%] female and 749 [48%] male), with a mean age of 51·9 years (13·8; 25-74). No ethnicity data were collected. Adjusted for duration of lithium exposure, eGFR declined by 0·57 mL/min/1·73 m2/year (95% CI 0·50-0·63) in patients with bipolar disorder or schizoaffective disorder and by 0·57 mL/min/1·73 m2/year (0·53-0·61) in the reference population. Lithium added 0·54 mL/min/1·73 m2 (0·43-0·64) per year of treatment (p<0·0001). After more than 10 years on lithium, decline was significantly steeper than in all other groups including the reference population (p<0·0001). Lithium nephropathy was judged to be the commonest cause of moderate-to-severe chronic kidney disease, but comorbidities played a role. The effect of lithium on eGFR showed a high degree of inter-individual variation. Steeper eGFR decline in patients with bipolar disorder or schizoaffective disorder can be attributed to lithium, but the trajectory of kidney function decline varies widely. Comorbidities affecting kidneys should be treated assertively as one possible means to affect the trajectory. In patients with a fast trajectory, a trade-off is required between continuing lithium to treat mental health problems and discontinuing lithium for the sake of renal health. Norrbotten County Research and Learning Fund Sweden, Visare Norr (Northern County Councils Regional Federation Fund), Swedish Kidney Foundation (Njurfonden), Swedish Kidney Association (Njurförbundet), Norrbotten section. For the Swedish translation of the Summary see Supplementary Materials section.

Kidney Function in Factory Workers Exposed to Heat Stress: A 2-Year Follow-up Study.

The aims of the study are to re-evaluate kidney function in workers exposed and not exposed to heat stress after 2 years and to compare kidney function cross-shift using creatinine and cystatin C. Participants were workers from a metallurgical industry. The clinical and biochemical markers of hydration and kidney function were evaluated before and after a single shift in work. We included 14 workers (6 in the heat group and 8 in the control group). The serum creatinine levels did not change during the follow-up period. Cross-shift, creatinine-based eGFR (estimated glomerular filtration rate) decreased, and cystatin C-based eGFR was maintained in the heat and control groups. Workers exposed to heat stress maintained their kidney function after a 2-year follow-up. Cystatin C is a better kidney function marker than creatinine for cross-shift assessments in this setting.

Impact of Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) GFR Estimating Equations on CKD Prevalence and Classification Among Asians

BackgroundIn 2021, the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) validated a new equation for estimated glomerular filtration rate (eGFR). However, this new equation is not ethnic-specific, and prevalence of CKD in Asians is known to differ from other ethnicities. This study evaluates the impact of the 2009 and 2021 creatinine-based eGFR equations on the prevalence of CKD in multiple Asian cohorts.MethodsEight population-based studies from China, India, Russia (Asian), Singapore and South Korea provided individual-level data (n = 67,233). GFR was estimated using both the 2009 CKD-EPI equation developed using creatinine, age, sex, and race (eGFRcr [2009, ASR]) and the 2021 CKD-EPI equation developed without race (eGFRcr [2021, AS]). CKD was defined as an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73m2 (G3-G5). Prevalence of eGFR categories was compared within each study and within subgroups of age, sex, body mass index (BMI), diabetes, and hypertension status. The extent of reclassification was examined using net reclassification improvement (NRI).FindingsOf 67,233 adults, CKD prevalence was 8.6% (n = 5800/67,233) using eGFRcr (2009, ASR) and 6.4% (n = 4307/67,233) using eGFRcr (2021, AS). With the latter, CKD prevalence was reduced across all eight studies, ranging from −7.0% (95% CI −8.5% to −5.4%) to −0.4% (−1.3% to 0.5%), and across all subgroups except those in the BMI < 18.5% subgroup. Net reclassification index (NRI) was significant at −2.33% (p < 0.001). No individuals were reclassified as a higher (more severe) eGFR category, while 1.7%−4.2% of individuals with CKD were reclassified as one eGFR category lower when eGFRcr (2021, AS) rather than eGFRcr (2009, ASR) was used.InterpretationeGFRcr (2021, AS) consistently provided reduced CKD prevalence and higher estimation of GFR among Asian cohorts than eGFRcr (2009, ASR). Based on current risk-stratified approaches to CKD management, more patients reclassified to lower-risk GFR categories could help reduce inappropriate care and its associated adverse effects among Asian renal patients. Comparison of both equations to predict progression to renal failure or adverse outcomes using prospective studies are warranted.FundingNational Medical Research Council, Singapore.

Measuring kidney function: the voice of Africa

Measuring kidney function: the voice of Africa

Shrunken Pore Syndrome Is Associated with Renal Function Decline in Female Patients with Kidney Diseases.

Background Shrunken pore syndrome (SPS) represents selective impairment of kidney filtration of low-molecular-weight molecules between 1 and 30 kDa and has been related to outcomes including morbidity, mortality, and cardiovascular events. However, the prevalence and kidney outcomes of SPS have not been investigated in patients with IgA nephropathy (IgAN) and membranous nephropathy (MN). Methods We retrospectively collected information of 536 patients including 414 with IgAN and 122 with MN. SPS was mainly defined by cystatin C-based eGFR < 70% of creatinine-based eGFR using the CAPA-LM equation pairs, while CKD-EPI equations were also employed in sensitivity analyses. Prevalence rate of SPS and its association with end-stage renal disease (ESRD) or severe eGFR decline (≥50% eGFR reduction or doubling of baseline creatinine) were investigated. Results 44% (8%) patients were identified as possessing SPS using the CAPA-LM definition. ESRD happened in 24 patients during the average follow-up period of 27.7 months. Despite dramatic increase of incidence rate of ESRD for SPS, significant hazard ratio (HR) only existed in IgAN patients after multivariable adjustment (HR: 8.35, 95% CI: 2.10~33.26), but lost significance in sensitivity analyses. 36 patients were determined as having experienced severe eGFR decline after excluding transient creatinine fluctuation. SPS was associated with severe eGFR decline by Kaplan-Meier survival analyses in the overall population as well as the IgAN, MN, male, and female subpopulations, which remained significant in multivariable adjustments in all groups except IgAN. However, only in female patients the association between SPS and eGFR decline remained significant in all the sensitivity analyses. Conclusions SPS was independently associated with eGFR decline in female patients with IgAN and MN.

Cystatin C in risk prediction after transcatheter aortic valve replacement: a retrospective analysis.

AimsNo study has evaluated the prognostic value of the chronic kidney disease (CKD) classification by cystatin C‐based estimated glomerular filtration rate (eGFR) (CKDCys classification) in patients undergoing transcatheter aortic valve replacement (TAVR). This study aimed to compare the prognostic value of CKDCys classification and CKD classification by creatinine‐based eGFR (CKDCr classification) in risk prediction after TAVR.Methods and resultsWe retrospectively analysed consecutive 219 patients with symptomatic severe aortic stenosis who underwent TAVR at our institute between December 2016 and June 2019. Pre‐operative CKDCr and CKDCys classifications were evaluated for their prognostic value of 2‐year major adverse cardiovascular and cerebrovascular events (MACCE) after TAVR. MACCE was defined as the composite of all‐cause mortality, non‐fatal myocardial infarction, stroke, and rehospitalization for worsening congestive heart failure. Participants had a median age of 86.0 years and were predominantly female (76.9%). In 96.6% of the cases, TAVR was performed using transfemoral access. The median creatinine‐based eGFR (52.85 mL/min/1.73 m2) was higher than the cystatin C‐based eGFR (41.50 mL/min/1.73 m2). Downward reclassification in CKD stages based on eGFRCys was observed in 49.0% of patients. During a median follow‐up period of 575.5 (interquartile range: 367.0–730.0) days, 58 patients presented with MACCE. CKDCys classification, but not CKDCr classification, significantly stratified the risk of 2‐year MACCE in patients after TAVR by log‐rank test (P = 0.003). In multivariate Cox regression analysis, only CKDCys stage 3b [hazard ratio (HR) = 4.37; 95% confidence interval (CI): 1.28–14.91; P = 0.019] and CKDCys stage 4 + 5 (HR = 3.72; 95% CI: 1.06–12.99; P = 0.040) were significant predictors of MACCE after adjustment for potential confounders.ConclusionsThe CKDCys classification could better assess the risk than the CKDCr classification in patients undergoing TAVR. CKDCys stage 3b and stage 4 + 5 correlated with adverse outcomes.

Kidney function at 3 months after acute kidney injury is an unreliable indicator of subsequent kidney dysfunction: the NARA-AKI Cohort Study.

The relationship between kidney function at 3 months after acute kidney injury (AKI) and kidney function prognosis has not been characterized. This retrospective cohort study included adults who underwent noncardiac surgery under general anesthesia. Exclusion criteria included obstetric or urological surgery, missing data and preoperative dialysis. Linear mixed-effects models were used to compare estimated glomerular filtration rate (eGFR) slopes in patients with and without AKI. Multivariable Cox proportional hazard models were used to examine the associations of AKI with incident chronic kidney disease (CKD) and decline in eGFR≥30%. Among 5272 patients, 316 (6.0%) developed AKI. Among 1194 patients with follow-up creatinine values, eGFR was stable or increased in patients with and without AKI at 3 months postoperatively and declined thereafter. eGFR decline after 3 months postoperatively was faster among patients with AKI than among patients without AKI (P=.09). Among 938 patients without CKD-both at baseline and at 3 months postoperatively-226 and 161 developed incident CKD and a decline in eGFR≥30%, respectively. Despite adjustment for eGFR at 3 months, AKI was associated with incident CKD {hazard ratio [HR] 1.73 [95% confidence interval (CI) 1.06-2.84]} and a decline in eGFR≥30% [HR 2.41 (95% CI 1.51-3.84)]. AKI was associated with worse kidney outcomes, regardless of eGFR at 3 months after surgery. Creatinine-based eGFR values at 3 months after AKI might be affected by acute illness-induced loss of muscle mass. Kidney function might be more accurately evaluated much later after surgery or using cystatin C values.

Relationship of iothalamate clearance and NRM in patients receiving fludarabine and melphalan reduced-intensity conditioning

AbstractThe reduced-intensity conditioning regimen, fludarabine and melphalan, is frequently used in allogeneic hematopoietic stem cell transplantation (HSCT). Melphalan and the active metabolite of fludarabine, F-ara-A, are excreted via the kidneys. Existing methods to assess clearance in this setting are based on serum creatinine, which has known limitations for glomerular filtration rate (GFR) estimation in patients with malignancy. Measured GFR (mGFR) may better predict drug dosing to mitigate toxicity and increase the chances of successful engraftment. The primary objective of this study was to assess the association between mGFR and risk for nonrelapse mortality (NRM) in patients who have undergone allogeneic HSCT receiving conditioning with fludarabine and melphalan. In the 109 included patients, mGFR <65 mL/min/1.73 m2 predicted a significantly higher rate of overall NRM (hazard ratio [HR], 2.13; 95% confidence interval [CI], 1.03-4.35; P = 04) and 1-year incidence of infection (HR, 2.63; 95% CI, 1.54-4.55; P < .001) in addition to a significantly lower 2-year survival (P = .019). Kidney function estimated via estimated GFR (eGFR) and estimated creatinine clearance did not correlate with posttransplant outcomes. These results suggest that mGFR is a promising approach for assessing clearance in patients who have undergone allogeneic HSCT and may be preferred to standard creatinine-based eGFR strategies.

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

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