Creatinine-based Chronic Kidney Disease Epidemiology Collaboration Research Articles

The New Creatinine-Based Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) 2021 Equation: Potential Impact on Screening for Chronic Kidney Disease in an Asymptomatic Black African Population.

In 2021, a new Chronic Kidney Disease Epidemiology (CKD-EPI) Collaboration equation was introduced that excluded race correction. We set out to compare estimated glomerular filtration rate (eGFR) determined using the creatinine-based CKD-EPI 2009 and 2021 equations and the reclassification of chronic kidney disease (CKD) eGFR staging to explore the potential ramifications of adopting the 2021 equation on reported eGFR and CKD staging. We analyzed secondary data previously utilized to determine reference intervals among Black African individuals residing in urban towns in Kenya. Serum creatinine was measured using a standardized modified Jaffé kinetic method on a Beckman AU5800 analyzer. Glomerular filtration rate (GFR) was estimated using both the 2009 and 2021 CKD-EPI creatinine equations. Classification of CKD based on eGFR was performed using the Kidney Disease: Improving Global Outcomes (KDIGO) practice guidelines. Using 533 study samples, the median eGFR was highest when determined using the race-corrected CKD-EPI 2009 equation. The CKD-EPI 2021 equation yielded a median eGFR that was similar to the non-race-corrected CKD-EPI 2009 equation. The race-corrected CKD-EPI 2009 equation classified 93.6% of participants into CKD stage G1 compared with 85.6% by the CKD-EPI 2021 equation. The CKD-EPI 2021 equation classified 14.3% of participants into CKD stage G2 compared to 6.4% by the race-corrected CKD-EPI 2009 equation. The CKD-EPI 2021 equation gave a comparable eGFR to the non-race-corrected CKD-EPI 2009 equation and its implementation in laboratories reporting eGFR in Kenya will help in identifying patients with an appropriate decrease in renal function.

OR31-06 Gender-Affirming Hormone Therapy Affects Serum Cystatin C-based eGFR In Transgender Individuals

Abstract Disclosure: S.A. van Eeghen: None. C. Wiepjes: None. N. Nokoff: None. P. Bjornstad: None. M. Den Heijer: None. D. van Raalte: None. Background: Previous studies in transgender individuals have shown that masculinizing (testosterone) hormone therapy increases and feminizing (estradiol combined with anti-androgen) hormone therapy decreases serum creatinine. Translating this into estimated glomerular filtration rate (eGFR) according to the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation, eGFR increases in transwomen and decreases in transmen during gender-affirming hormone therapy (GAHT). However, serum creatinine is significantly correlated with lean body mass (LBM), which also changes during GAHT, with transmen gaining and transwomen loosing muscle mass. Thus changes in creatinine-derived eGFR during hormone therapy may not reflect true changes in GFR. Another manner to estimate GFR, which is not affected by body composition, is by measuring plasma cystatin C concentrations. Therefore, we studied the effects of GAHT on serum cystatin C, a sex-independent marker for GFR. Methods: In this prospective, observational sub study of the European Network for the Investigation of Gender Incongruence (ENIGI), serum cystatin C was measured in 266 transwomen and 285 transmen before and at 12 months of GAHT. Transwomen received feminizing hormone therapy, consisting of oral (n= 122) or transdermal administration (n= 144) of estrogen in combination with the oral anti-androgen cyproteroneacetate. Transmen received masculinizing hormone therapy, which consisted of intramuscular (n= 144) or transdermal (n= 141) administration of testosterone. Serum cystatin C-based eGFR was calculated according to the full-age-spectrum equation (FAScysC; mL/min/1.73m2). Linear regression was used to assess the means. Results: In transwomen (baseline characteristics; median age 29 (IQR 23-43) years; median BMI 22.9 (IQR 20.8-26.4) kg/m2; creatinine 78.6 ± 9.9 μmol/L; creatinine-based CKD-EPI eGFR 110 ± 14 mL/min/1.73m2), cystatin C decreased by 0.07 (95% CI, 0.05 to 0.09) mg/L; from 0.94 ± 0.17 mg/L before GAHT to 0.87 ± 0.15 mg/L during GAHT. This corresponds with an increase in FAScysC of 7 (95% CI, 5 to 9) mL/min/1.73m2; from 93 ± 17 to 100 ± 18 mL/min/1.73m2. On the contrary, in transmen (baseline characteristics; median age 22 (IQR 20-28) years; median BMI 24.7 (IQR 21.4-30.1) kg/m2; creatinine 66.8 ± 9.3 μmol/L; creatinine-based CKD-EPI eGFR 110 ± 15 mL/min/1.73m2) cystatin C increased by 0.05 (95% CI, 0.03 to 0.07) mg/L; from 0.89 ± 0.17 mg/L before GAHT to 0.95 ± 0.16 mg/L during 12 months of GAHT. This is consistent with a decrease in FASCysC of 6 (95% CI, 4 to 8) mL/min/1.73m2; from 101 ± 19 to 94 ± 15 mL/min/1.73m2. Conclusions: In this large-sized cohort of transgender individuals, cystatin C-based eGFR increased with feminizing hormone therapy and decreased with masculinizing hormone therapy, indicating true biological effects of sex hormones on kidney physiology, which warrants further investigation. Presentation: Sunday, June 18, 2023

Renal hyperfiltration revisited—Role of the individual body surface area on mortality

BackgroundHigher than normal estimated glomerular filtration rate (eGFR), i.e. renal hyperfiltration (RHF), has been associated with mortality. MethodsA population-based screening program in Finland identified 1747 apparently healthy middle-aged cardiovascular risk subjects in 2005–2007. GFR was estimated with the creatinine-based Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation indexed for 1.73 m2 and for the actual body surface area (BSA) of the subjects. This individually corrected eGFR was calculated as eGFR (ml/min/BSA m2) = eGFR (ml/min/1.73 m2) x (BSA/1.73). BSA was calculated by the Mosteller formula. RHF was defined as eGFR of more than 1.96 SD above the mean eGFR of healthy individuals. All-cause mortality was obtained from the national registry. ResultsThe higher the eGFR, the greater was the discrepancy between the two GFR estimating equations. During the 14 years of follow-up, 230 subjects died. There were no differences in mortality rates between the categories of individually corrected eGFR (p = 0.86) when adjusted for age, sex, body mass index, systolic BP, total cholesterol, new diabetes, current smoking, and alcohol use. The highest eGFR category was associated with increased standardized mortality rate (SMR) when CKD-EPI formula indexed for 1.73 m2 was used, but SMR was at the population level when individually corrected eGFR was applied. ConclusionsHigher than normal eGFR calculated by the creatinine-based CKD-EPI equation is associated with all-cause mortality when indexed to 1.73 m2, but not when indexed to actual BSA of a person. This challenges the current perception of the harmfulness of RHF in apparently healthy individuals.

New developments and future prospects in the field of glomerular filtration rate estimation

Glomerular filtration rate (GFR) is estimated from equations based on serum or plasma concentrations of endogenous markers (creatinine and/or cystatin C), and demographic data (age, sex, ± ethnicity). These equations are accurate at the population level, but often inaccurate at the individual level. The creatinine-based Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) equation published in 2009 (CKD-EPIcr-2009), and the CKD-EPI equation published in 2012 based on creatinine and cystatin C, were recalibrated in 2021 to remove their dedicated race correction factors for black American subjects. All creatinine-based CKD-EPI equations overestimate true GFR in subjects younger than 30 years. The Full Age Spectrum (FAS) equation, applicable across the entire age spectrum (pediatrics to old age), solved this problem, but remained suboptimal at low GFR values. The European Kidney Function Consortium (EKFC) equation published in 2021 was an improvement of the FAS equation, which also includes the Q factor (median creatinine in the general population). EKFC is applicable across the age spectrum and is efficient at low and normal GFR values. The new creatinine-based CKD-EPI equation (CKD-EPIcr-2021) underestimates GFR in Black Americans and overestimates it in non-Black Americans. In European and African subjects, CKD-EPIcr-2021 overestimates true GFR and should not be adopted. The EKFC equation, which performs well in this population, also performs well in European Black subjects and in African subjects, provided dedicated Q factors are used.

The Relationship of Kidney Function, Cardiovascular Morbidity, and All-Cause Mortality: a Prospective Primary Care Cohort Study

BackgroundLower-than-normal estimated glomerular filtration rate (eGFR) is associated with the risk for all-cause mortality and adverse cardiovascular events. In this regard, the role of higher-than-normal eGFR is still controversial.ObjectiveInvestigate long-term clinical consequences across the levels of eGFR calculated by the creatinine-based Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation among apparently healthy cardiovascular risk subjects.DesignProspective study.ParticipantsParticipants (n=1747) of a population-based screening and intervention program for cardiovascular risk factors in Finland during the years 2005–2007.Main MeasuresCardiovascular morbidity and all-cause mortality.Key ResultsOver the 14-year follow-up, subjects with eGFR ≥105 ml/min/1.73 m2 (n=97) had an increased risk for all-cause mortality [HR 2.15 (95% CI: 1.24–3.73)], incident peripheral artery disease [HR 2.62 (95% CI: 1.00–6.94)], and atrial fibrillation/flutter [HR 2.10 (95% CI: 1.21–3.65)] when compared to eGFR category 90–104 ml/min after adjustment for cardiovascular and lifestyle-related risk factors. The eGFR category ≥105 ml/min was also associated with a two-fold increased mortality rate compared to the Finnish general population.ConclusionsRenal hyperfiltration defined as eGFR ≥105 ml/min/1.73 m2 is a frequent and important finding in patients commonly treated in primary care. These patients should be followed closely for timely interventions, such as strict BP and blood glucose regulation.

Uremic Metabolites Are Associated with Albuminuria and Estimated Glomerular Filtration Rate (eGFR) in Sickle Cell Disease

Introduction: Chronic kidney disease (CKD) is common in patients with sickle cell disease (SCD) and is associated with increased morbidity and mortality. As albuminuria and changes in estimated glomerular filtration rate (eGFR) occur well after substantial functional and structural damage have occurred, identification of novel biomarkers which could predict the development of CKD is necessary. Previous studies have shown an increase in the level of the uremic metabolite indoxyl-sulfate (IS) in urine in patients with SCD. IS and other uremic metabolites are cleared by active secretion in kidney tubule cells and their accumulation in these cells leads to increased oxidative stress, and apoptotic and necrotic cell death. In this single center, cross-sectional study, we investigated the associations between both urinary levels of uremic toxins and biomarkers of kidney tubular injury with persistent albuminuria and eGFR in patients with SCD. Methods: The participants represent a subset of patients with HbSS or HbSβ0 thalassemia enrolled in a prospective cohort study to assess the natural history of kidney disease in SCD. We excluded patients with diabetic nephropathy, cancer, connective tissue disease, other glomerular diseases, known infection with hepatitis (B or C) or HIV, end-stage kidney disease on dialysis and who had undergone bone marrow transplantation. Participants were enrolled during routine clinic visits. Urine levels of uremic toxins, indoxyl sulfate (IS) and trimethylamine-n-oxide (TMAO), and tubular injury biomarkers, monocyte chemoattractant protein-1 (MCP-1; also called CC-chemokine ligand 2 [CCL2]) and neutrophil gelatinase-associated lipocalin (NGAL) were measured using quantitative ELISA assay. All values obtained for urine biomarkers were normalized to urine creatinine. Persistent albuminuria was defined based on at least 2 of 3 spot urine albumin/creatinine ratio (ACR) values ≥30 mg/g of creatinine or a single value ≥100 mg/g. Glomerular filtration rate was estimated using the 2009 creatinine-based Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula. As the distribution of the biomarkers were skewed, the data were log-transformed. Associations between both ACR and eGFR with each of the urine biomarkers were assessed using linear regression. Results: One hundred and sixteen subjects, 26 (22.4%; ACR - median 276.5 mg/g [IQR: 156, 802]) with persistent albuminuria (PA), and 90 (77.6%; ACR - median 13 mg/g [IQR: 6.5, 25.5]) without persistent albuminuria (non-PA) were evaluated. Subjects with PA appeared to be older and had lower hemoglobin and fetal hemoglobin levels, but higher reticulocyte counts, lactate dehydrogenase levels and systolic and diastolic blood pressures than subjects with non-PA (Table 1). Log-transformed urine levels of IS (β=0.52, 95% confidence interval [CI]: 0.08, 0.96, p=0.02), MCP-1 (β=0.65, 95% CI: 0.29, 1.01, p=0.0006) and NGAL (β=0.25, 95% CI: 0.02, 0.49, p=0.03) were positively associated with log-transformed ACR (Table 2). Log-transformed urine levels of IS (β=-8.0, 95% CI: -14.7, -1.3, p=0.02), MCP-1 (β=-11.6, 95% CI: -16.9, -6.3, p<0.0001) and NGAL (β=-6.0, 95% CI: -9.4, -2.6, p=0.0008) were inversely associated with eGFR. Log-transformed urine level of TMAO was not associated with either ACR or eGFR. Conclusion: This study demonstrates a novel association of IS with albuminuria and eGFR in patients with SCD. In addition, we confirm the association of biomarkers of tubular injury, MCP-1 and NGAL, with persistent albuminuria and eGFR in SCD. Future studies will determine whether uremic metabolites may predict the development of albuminuria in patients with SCD. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Association of Novel Urinary Protein Biomarkers with Persistent Albuminuria in Patients with Sickle Cell Disease

Introduction: Standard assessments for kidney disease, albuminuria and decline in estimated glomerular filtration rate (eGFR), occur well after substantial functional and structural damage have ensued. Chronic kidney disease (CKD) is common in patients with sickle cell disease (SCD). With its association with increased morbidity and mortality, identification of novel biomarkers that could predict early development of CKD offers opportunities to modify risk factors in hopes of attenuating kidney function loss and decreasing mortality risk. Methods: The participants of this exploratory study represent a subset of patients with HbSS or HbSβ0 thalassemia enrolled in a prospective cohort study to assess the natural history of kidney disease in SCD. We excluded patients with diabetic nephropathy, cancer, connective tissue disease, other glomerular diseases, known infection with hepatitis (B or C) or HIV, end-stage kidney disease on dialysis and those who had undergone bone marrow transplantation. Participants were enrolled during routine clinic visits. Urine levels of clusterin [CLU; also referred to as apolipoprotein J], retinol-binding protein 4 [RBP4], alpha-1-microglobulin [A1M], interleukin-18 [IL-18], beta-2 microglobulin [B1M], insulin-like growth factor-binding protein 7 [IGFBP7], tissue inhibitor of metalloproteinases-2 [TIMP2], angiotensinogen [AGT], podocalyxin, and cysteine-rich with EGF-like domains 2 [CRELD2] were measured using quantitative ELISA assay. All values of urine biomarkers were normalized to urine creatinine. Persistent albuminuria (PA) was defined based on presence of at least 2 of 3 spot urine albumin/creatinine ratio (ACR) values ≥30 mg/g of creatinine or a single value ≥100 mg/g. Glomerular filtration rate was estimated using the 2009 creatinine-based Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula. Medians are presented with the interquartile range [IQR]. Associations between ACR and eGFR with each urine biomarker were assessed using linear regression. Levels of urinary biomarkers were compared using the Wilcoxon-Mann-Whitney test. Results: Thirty-seven subjects, 13 (35.2%) with PA (ACR - 147mg/g [IQR: 136.4, 223]), and 24 (64.9%) without PA (non-PA) (ACR - 12 mg/g [IQR: [6, 20]) were evaluated. Subjects with PA were older, had higher blood urea nitrogen (BUN), blood aspartate transaminase, and lower eGFR (Table 1). Urinary levels of CLU, RBP4, A1M, and AGT normalized to urine creatinine were significantly higher in subjects with PA vs. those with non-PA (Table 2). In univariate analysis, significant associations were identified between A1M and ACR (p=0.035) as well as between AGT and ACR (p<0.0001) (Table 2). In multivariable analyses, only AGT remained significantly associated with ACR (p=0.0003). Conclusion: The higher urinary levels of RBP4 and A1M, both low molecular weight proteins freely filtered in the glomerulus and reabsorbed by kidney proximal tubule cells, in subjects with PA suggests the presence of tubular injury. Higher levels of clusterin, a ubiquitously expressed glycoprotein that is rapidly upregulated upon acute kidney damage and present in de-differentiated kidney tubule cells, also indicates tubular injury in subjects with PA. Urinary AGT, the only precursor of all angiotensin peptides, is independently associated with ACR in this cohort. Higher levels of AGT indicates increased intrarenal renin-angiotensin system activity in subjects with PA. More studies are required to evaluate the association of these biomarkers with persistent albuminuria in SCD. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Evaluating Equations for Estimated Glomerular Filtration Rate (eGFR) in Patients with Sickle Cell Disease (SCD)

Background: Assessment of kidney function in sickle cell disease poses a unique dilemma, both due to the presence of hyperfiltration and the increased tubular secretion of creatinine, the metabolite most often used in eGFR assessment. In the general population, formulae utilizing serum creatinine have been developed to estimate GFR. The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) have developed the most recent formulae. Until recently, the CKD-EPI-2009 creatinine-based formula has been the standard for estimating eGFR and included black race as a variable in the formula. This formula has been noted to overestimate eGFR in SCD patients, but its bias is improved when the black race variable is excluded. Among available formulae, the CKD-EPI-2012 cystatin C-based formula was shown to have the least bias in SCD patients compared to radionucleotide measured GFR but loses its accuracy when combined with creatinine. The recently developed CKD-EPI-2021 formula which excludes race as a variable is becoming the standard formula in most clinical laboratories. In this multicenter study, we sought to evaluate the agreement of various CKD-EPI formulae in SCD patents. Methods: Patients with HbSS or HbSb0 thalassemia between ages 18 and 65 years were enrolled in a prospective cohort study to assess the natural history of kidney disease in SCD. We excluded patients with bone marrow transplantation, diabetic nephropathy, cancer, connective tissue disease, other glomerular diseases, known infection with hepatitis (B or C) or HIV, and end-stage kidney disease on dialysis. Participants were enrolled during routine clinical visits at four centers. At baseline, blood samples and urine were obtained, and kidney function was assessed using each sites clinical laboratory to measure serum creatinine. Serum cystatin C was also measured at baseline using a commercially available ELISA kit. We calculated eGFR using each of the CKD-EPI formula, excluding the race variable in the CKD-EPI-2009 formula. Spearman's rank correlation coefficients were calculated for each formula compared to the others. Prevalence of CKD was assessed using the CKD-EPI-2009, CKD-EPI-2012 (cystatin C) and CKD-EPI-2021 formulae and defined as the presence of albuminuria or an eGFR ≤ 90 ml/min/1.73m2. Prevalence of CKD derived from the CKD-EPI-2012 was compared to the other two formulae using McNemar's Chi-squared test with 95% confidence intervals determined using bootstrap replications. Results: Our cohort enrolled 284 subjects with HbSS or HbSb0 thalassemia. For these analyses, 277 patients with baseline serum creatinine were included. The mean age of included subjects was 32.9 (SD ±11.5) years and 57% were female (N=158). The median eGFR of these subjects using the creatinine-based CKD-EPI-2009 formula was 123.9 (IQR 105.9, 134.0) ml/min/1.73m2. Cystatin C was available in 270 patients and had median value of 0.72 (IQR 0.59, 0.92) mg/L. Correlation between the several eGFR formulae are presented in Table 1. CKD-EPI-2009 and CKD-EPI-2021 creatinine-based formulae were very highly correlated with each other; both had similar but less correlation with the CKD-EPI-2012 cystatin C-based formula, which has been shown previously to have the least bias when compared to measured GFR. The prevalence of CKD using the creatinine-based CKD-EPI-2009 formula was 51.3% and 50.5% using the creatinine-based CKD-EPI-2021 formula. When assessed with the cystatin C-based CKD-EPI-2012 formula, CKD prevalence was higher at 55.7% (p<0.0001) than that seen with both of creatinine-based CKD-EPI formulae. Conclusions: When comparing the new CKD-EPI-2021 creatinine-based formula to the CKD-EPI-2009 formula (excluding the black race variable), eGFR calculation remains very similar in SCD patients. The CKD-EPI-2009 formula is well recognized to overestimate eGFR in SCD patients. Our data would suggest the newer formula would have similar bias. Using the cystatin C-based CKD-EPI-2012 formula, the prevalence of CKD is higher in this SCD cohort than using creatinine-based CKD-EPI formulae, although our data are limited by lack of directly measured GFR. We anticipate the newer CKD-EPI-2021 creatinine-based formula would similarly underestimate prevalence of CKD in SCD. Use of cystatin C for assessing kidney function in SCD patients should be considered, and resources should be utilized to make this measure more widely and readily available. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Comparison of 2021 CKD-EPI Equations for Estimating Racial Differences in Preemptive Waitlisting for Kidney Transplantation.

Wait time for kidney transplantation can accrue when GFR is ≤20 ml/min. We examined whether using the race-free 2021 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations to guide preemptive waitlisting could attenuate racial differences in accruable preemptive wait time. Our retrospective cohort study included Black or White Chronic Renal Insufficiency Cohort (CRIC) participants who were theoretically eligible for waitlist registration. We used Weibull accelerated failure time models to determine the association between race (Black or White) and time to kidney failure from the qualifying visit when the eGFR by creatinine or creatinine-cystatin C 2021 CKD-EPI equations fell to ≤20 ml/min per 1.73 m2. We then tested for differences in the time ratios from models using the 2021 creatinine- or creatinine-cystatin C-based CKD-EPI equation through a bootstrapping approach. By the creatinine equation, 472 CRIC participants were theoretically eligible for waitlist registration, and potential preemptive wait time was similar for Black versus White participants (time ratio, 1.05; 95% confidence interval, 0.81 to 1.35). The median wait time by the creatinine equation that could be accrued for Black participants was 23 versus 22 months in White participants. By the creatinine-cystatin C equation, 441 CRIC participants were eligible, and potential wait time was 20% shorter (95% confidence interval, 0.62 to 1.02) for Black than White participants. The median wait time that could be accrued for Black participants was 21 versus 26 months for White participants when using the creatinine-cystatin C equation. Using bootstrapping, the ratio of the time ratio of the models using the creatinine versus creatinine-cystatin C equation was statistically significantly different (ratio of the time ratios = 1.31 with 95% confidence interval, 1.06 to 1.62). Use of the 2021 creatinine-based CKD-EPI equation to determine preemptive waitlist eligibility reduced racial differences in preemptive wait time accrual more than use of the creatinine-cystatin C 2021 CKD-EPI equation within a theoretical context.

Twenty-year Follow-up of Patients With Epidemic Glomerulonephritis due to Streptococcus zooepidemicus in Brazil

IntroductionPost-streptococcal glomerulonephritis (PSGN) has a good prognosis in children, but few studies have evaluated the long-term renal outcomes in adults with PSGN.MethodsIn a follow-up study, 47 predominantly adult patients with PSGN due to group C Streptococcus zooepidemicus were reassessed 20 years after an outbreak in Nova Serrana, Brazil. We evaluated clinical characteristics, renal outcomes, and the trajectory of the estimated glomerular filtration rate (eGFR) by the creatinine-based chronic kidney disease-epidemiology collaboration equation from 5 follow-up assessments. Logistic regression and mixed-effects regression were used in the analysis.ResultsAfter 20 years, the participants’ mean age was 56.6±15.1 years. Thirty-four (72%) patients had hypertension, 21 (44.7%) had eGFR <60 ml/min per 1.73 m2, 8 of 43 (18.6%) had urine protein-to-creatinine ratio >150 mg/g, and 25 (53%) had CKD (low eGFR and/or increased proteinuria). Increasing age was associated with CKD (odds ratio: 1.07; 95% confidence interval [CI]: 1.02–1.13; P = 0.011) in multivariate analysis. The mean eGFR decline in the last 11 years of follow-up was −3.2 ml/min per 1.73 m2 per year (95% CI: −3.7 to −2.7). Older age at baseline (coefficient −1.05 ml/min per 1.73 m2 per year; 95% CI −1.28 to −0.81; P < 0.001), and hypertension 5 years after the outbreak (coefficient −7.78 ml/min/1.73 m2; 95% CI −14.67 to −0.78; P = 0.027) were associated with lower eGFR during the whole study period.ConclusionThere was a marked worsening of renal function and a high prevalence of CKD and hypertension after 20 years of PSGN outbreak. Long-term follow-up is warranted after PSGN, especially among older patients.

The Use of Serum Endothelin1and Myoglobin in the Evaluation of Renal Injury in Methamphetamine Abusers

Methamphetamine is a type of psychoactive drug. It is a widely abused synthetic stimulant. Long-termexposure to methamphetamine leads to kidney damage and subsequently a gradual reduction in its function.Methamphetamine toxicity is the trigger of creatinine increase. Myoglobin is released to the blood circulationfrom injured muscle tissues after its long-term use and forms deposits in the renal tubules. Endothelin-1 isknown as the most powerful recognized renal vasoconstrictor. Estimated glomerular filtration rate (eGFR) isthe most sensitive index to determine kidney function, and it is an important indicator of early diagnosis ofrenal injury. The study was conducted on 48 patients (study group) and 36 control group; their age range wasbetween 18-40 years. Those with history of chronic kidney disease, cardiovascular diseases, hypertension,and alcohol addiction were excluded from the study. Fasting venous plasma samples were used to measurecreatinine, urea, eGFR, myoglobin and ET-1. The estimated glomerular filtration rate (eGFR) was calculatedusing the creatinine-based chronic kidney disease epidemiology collaboration (CKD-EPI) formula. Themean (±SD) values of serum urea and creatinine levels of abuser subjects were significantly higher thanthose of control subjects. The mean (±SD) value of eGFR of abuser individuals was significantly lowerwhen compared with that of the control group (p &lt; 0.0001). In addition, inabuser subjects we observed asignificant increase in mean values of serum levels of endothelin1 (p&lt; 0.015) and myoglobin (p&lt; 0.0001)in comparison with those of control group. Significant negative correlations between eGFR and duration ofmethamphetamine abuse (p&lt; 0.0002) as well as a significant positive correlation between serum creatininelevels and duration of methamphetamine abuse (p&lt; 0.0004) were noted in the patient’s group. Moreover,there was a significant positive correlation between serum myoglobin concentrations and endothelin1 levels(p&lt;0.00001). This study concluded that abusers of methamphetamine need to be screened periodically forkidney function and measurements of their serum creatinine level as well as eGFR value. Both endothelin 1and myoglobin are important indicators of methamphetamine-induced kidney damage.

Serum creatinine as a predictor of mortality in patients readmitted to the intensive care unit after cardiac surgery: a retrospective cohort study in China.

BackgroundPatients readmitted to the intensive care unit (ICU) after cardiac surgery have a high mortality rate. The relationship between renal function and in-hospital mortality in readmitted patients has not been well demonstrated.MethodsWe retrospectively evaluated cardiac surgery patients who were readmitted to the ICU at least once. Data on serum creatinine levels before surgery and on the day of ICU readmission were collected. The estimated glomerular filtration rate (eGFR) was calculated according to the creatinine-based Chronic Kidney Disease-Epidemiology Collaboration equation. We used logistic regression models and restricted cubic spline curves with four knots (5%, 35%, 65%, 95%) to investigate the relationship between renal function indicators and mortality.ResultsOf the 184 patients evaluated, 30 patients died during hospitalization, yielding a mortality rate of 16.30%. Cardiac dysfunction (n=84, 45.65%) and respiration disorder (n=51, 27.72%) were the most common reasons for ICU readmission. Creatinine [odds ratio (OR): 1.14, 95% confidence interval (CI): 1.07–1.25] and eGFR (OR: 0.95, 95% CI: 0.93–0.98) were independently associated with in-hospital mortality after adjusting for various confounders. Both creatinine level and eGFR had a linear association with in-hospital mortality (P for non-linearity ˃0.05).ConclusionRenal function is significantly associated with the in-hospital mortality of patients readmitted to the ICU after cardiac surgery, as evidenced by the independent correlation of both creatinine and eGFR with in-hospital mortality.

Performance and Determinants of Serum Creatinine and Cystatin C–Based GFR Estimating Equations in South Asians

IntroductionThe creatinine-based Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) estimated glomerular filtration rate (eGFR) equation was calibrated for the general Pakistan population (eGFRcr-PK) to eliminate bias and improve accuracy. Cystatin C–based CKD-EPI equations (eGFRcys and eGFRcr-cys) have not been assessed in this population, and non-GFR determinants of cystatin C are unknown.MethodsWe assessed eGFRcys, eGFRcr-cys, and non-GFR determinants of cystatin C in a cross-sectional study of 557 participants (≥40 years of age) from Pakistan. We compared bias (median difference in measured GFR [mGFR] and eGFR), precision (interquartile range [IQR] of differences), accuracy (percentage of eGFR within 30% of mGFR), root mean square error (RMSE), and classification of mGFR <60 ml/min/1.73 m2 (area under the receiver operating characteristic curve [AUC] and net reclassification index [NRI]) among eGFR equations.ResultsWe found that eGFRcys underestimated mGFR (bias, 12.7 ml/min/1.73 m2 [95% confidence interval {CI} 10.7–15.2]). eGFRcr-cys did not improve performance over eGFRcr-PK in precision (P = 0.52), accuracy (P = 0.58), or RMSE (P = 0.49). Results were consistent among subgroups by age, sex, smoking, body mass index (BMI), and eGFR. NRI was 7.31% (95% CI 1.52%–13.1%; P < 0.001) for eGFRcr-cys versus eGFRcr-PK, but AUC was not improved (0.92 [95% CI 0.87–0.96] vs. 0.90 [95% CI 0.86–0.95]; P = 0.056). Non-GFR determinants of higher cystatin C included male sex, smoking, higher BMI and total body fat, and lower lean body mass.ConclusioneGFRcys underestimated mGFR in South Asians and eGFRcr-cys did not offer substantial advantage compared with eGFRcr-PK. Future studies are warranted to better understand the large bias in eGFRcys and non-GFR determinants of cystatin C in South Asians.

Evaluation of the diagnostic performance of the creatinine-based Chronic Kidney Disease Epidemiology Collaboration equation in people with diabetes: A systematic review.

GFR estimated with the creatinine-based Chronic Kidney Disease Epidemiology Collaboration (CKD-EPICr ) equation is used to screen for diabetic kidney disease and assess its severity. We systematically reviewed the process and outcome of evaluating CKD-EPICr in estimating point GFR or GFR decline over time in adults with type 1 or type 2 diabetes. In this systematic review, MEDLINE, Embase and Cochrane Central Register of Controlled Trials were searched up to August 2019. Observational studies comparing CKD-EPICr with measured GFR (mGFR) in adults with diabetes were included. Studies on people with kidney transplant, non-diabetes related kidney disease, pregnancy, potential kidney donors, and those with critical or other systematic illnesses were excluded. Two independent reviewers extracted data from published papers and disagreements were resolved by consensus. Risk-of-bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 tool. (PROSPERO registration number: CRD42018108776). From the 2820 records identified, 29 studies (14704 participants) were included. All studies were at risk of bias. Bias (eight different forms) ranged from -26 to 35mlmin-1 1.73m-2 ; precision (five different forms) ranged between 9 and 63mlmin-1 1.73m-2 ; accuracy (five different forms) ranged between 16% and 96%; the correlation coefficient between CKD-EPICr and mGFR (four different forms) ranged between 0.38 and 0.86; and the reduced major axis regression slope ranged between 0.8 and 1.8. Qualitative synthesis of data suggested CKD-EPICr was inaccurate in estimating point GFR or GFR decline over time. Furthermore, a lack of consistency in the methods and processes of evaluating the diagnostic performance of CKD-EPICr limits reliable quantitative assessment. The equation needs to be improved in adults with diabetes.

Diagnostic performance of the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation at estimating glomerular filtration rate in adults with diabetes mellitus: a systematic review and meta-analysis protocol

IntroductionTimely detection leading to the implementation of reno-protective measures reduces the progression of diabetic kidney disease. Estimated glomerular filtration rate (eGFR) is a major surrogate of kidney function. The Chronic...

Identification of young adults at risk of an accelerated loss of kidney function in an area affected by Mesoamerican nephropathy

BackgroundAfter two-years of follow-up of 263 apparently healthy 18- to 30-year-old men in communities affected by Mesoamerican nephropathy (MeN), we identified three distinct case groups: a subgroup with (i) established renal dysfunction (case-group 1); individuals with (ii) a rapid decline in kidney function (case-group 2); and individuals with (iii) stable kidney function (non-cases). This paper investigates whether local tests are potentially useful for the timely identification of these case groups.MethodsCreatinine levels were measured in local laboratories every six months for two years. Aliquots were sent to a centralized laboratory for measurements of cystatin C and creatinine levels. We investigated agreement between the locally and centrally measured creatinine-based Chronic Kidney disease Epidemiology Collaboration (CKD-EPI) equation for estimating the Glomerular Filtration Rate (eGFR). A logistic regression analysis was used to assess predictive factors for case groups 1 and 2 compared to non-cases. Predictive variables were locally measured eGFR, and urinary neutrophil gelatinase-associated lipocalin (uNGAL) levels. The discrimination performance of the model was assessed using the area under the receiver operating characteristic curve (AUC).ResultsConsiderable variation in local eGFR measurements was observed. The prediction model for case-group 1 included baseline kidney function and with or without uNGAL (AUC = 0.98, 95% confidence interval (CI), 0.91–1.00). The prediction model for case-group 2 also required eGFRScr at six and twelve months after baseline, with or without uNGAL levels (AUC = 0.88; 95% CI 0.80–0.99).ConclusionsEstablished renal dysfunction was detected at a single time point using local measurements and uNGAL. For the detection of a rapid decline in kidney function over time, at least 2 more measurements at six and twelve months are needed.

Estimated Glomerular Filtration Rates Show Minor but Significant Differences Between the Single and Subgroup Creatinine-Based Chronic Kidney Disease Epidemiology Collaboration Equations.

The creatinine-based Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation can be calculated according to race, sex, and creatinine concentration (subgroup equation) or in the form expressed by one equation (single equation). Minor differences in the constants used in the CKD-EPI equations (subgroup vs single equations) could result in a significant difference in the estimated glomerular filtration rate (eGFR). We evaluated the impact of this difference in 79,709 Korean patients. The eGFR was calculated as an integer using the single and subgroup CKD-EPI equations. The differences in eGFR and GFR categories between the equations were analyzed. eGFR was higher in the subgroup equation than the single equation by 1 mL/min/1.73 m2 for 12,476 (27.4%) Korean females. The GFR category based on the subgroup equation was reclassified using the single equation for 352 (0.77%) females. Based on the results, the constant of the single equation was optimized. There was no difference in eGFR values between equations using a multiplier of 1.0213 instead of 1.018 for the “white or other” females constant in the single CKD-EPI equation. Clinicians should carefully apply the CKD-EPI equation because eGFR values may differ by 1 mL/min/1.73 m2 depending on the manner of calculation. To minimize these differences, the constants of the single equation should be revised.

Combined creatinine-cystatin C CKD-EPI equation significantly underestimates measured glomerular filtration rate in people with type 2 diabetes mellitus

AimTo evaluate the accuracy of creatinine and cystatin C (cysC) equations to estimate glomerular filtration rate (GFR) in type 2 diabetes mellitus (DM) patients and healthy adults. MethodsCase-control study including 84 patients with type 2 DM and 100 healthy adults with measured GFR (mGFR)≥60mL/min/1.73m2. GFR was measured by 51Cr-EDTA and estimated (eGFR) by the following equations using creatinine, cysC or both markers: Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), Caucasian Asian Pediatrics and Adults (CAPA), CKD-EPI creatinine-cystatin C (CKDEPI-CC), and CKD-EPI cystatin C (CKDEPIcysC). Agreement was evaluated by Bland & Altman analysis. ResultsHealthy individuals were 66% females, aged 38±14years; they presented mGFR 112±19mL/min/1.73m2 and eGFR by CKD-EPI, CKDEPI-CC, CKDEPIcysC and CAPA equations, respectively, 108±17, 102±15, 97±16 and 93±16mL/min/1.73m2. DM group were 50% females, aged 59±19years and presented mGFR 104±27 and eGFR 87±19, 80±18, 74±20 and 73±18mL/min/1.73m2, respectively. All equations significantly underestimated mGFR, excepting creatinine-based CKD-EPI in the healthy group. The performance was considerably worse for GFRs above 120mL/min/1.73m2. ConclusionIn both healthy and type 2 DM patients, cystatin C-based equations, including the combined CKD-EPI creatinine-cystatin equation, failed to improve the accuracy of GFR estimation, especially for normal and high normal GFR values.

Accuracy Assessment of Five Equations Used for Estimating the Glomerular Filtration Rate in Korean Adults.

BackgroundWe aimed to assess the performance of the five creatinine-based equations commonly used for estimates of the glomerular filtration rate (eGFR), namely, the creatinine-based Chronic Kidney Disease Epidemiology Collaboration (CKD-EPIcr), Asian CKD-EPI, revised Lund–Malmö (revised LM), full age spectrum (FAS), and Korean FAS equations, in the Korean population.MethodsA total of 1,312 patients, aged 20 yr and above who underwent 51Cr-EDTA GFR measurements (mGFR), were enrolled. The bias (eGFR–mGFR) and precision (root mean square error [RMSE]) were calculated. The accuracy (P30) of four eGFR equations was compared to that of the CKD-EPIcr equation. P30 was defined as the percentage of patients whose eGFR was within±30% of the mGFR.ResultsThe mean bias (mL·min-1·1.73 m-2) of the five eGFR equation was as follows: CKD-EPIcr, -0.6; Asian CKD-EPI, 2.7; revised LM, -6.5; FAS, -2.5; and Korean FAS, -0.2. The bias of the Asian CKD-EPI, revised LM, and FAS equations showed a significant difference from zero (P<0.001). The RMSE values were as follows: CKD-EPIcr, 15.6; Asian CKD-EPI, 15.6; revised LM, 17.9; FAS, 16.3; and Korean FAS, 15.8. There were no significant differences in the P30 except for the Asian CKD-EPI equation: CKD-EPIcr, 76.6%; Asian CKD-EPI, 74.7%; revised LM, 75.8%; FAS, 76.0%; and Korean FAS, 75.8%.ConclusionsThe CKD-EPIcr and Korean FAS equations showed equivalent analytical and clinical performances in the Korean adult population.

Comparisons between the 2012 New CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) Equations and Other Four Approved Equations

ObjectiveThe Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) reported two equations in 2012: one based on cystatin C concentration (CKD-EPI2012cys) and the other using both serum creatinine and cystatin C concentrations (CKD-EPI2012Scr-cys). We compared the adaptability of new formulae with other four equations.MethodsParticipants (n = 788; median age, 54 [range, 19–94] years) were recruited from the First Affiliated Hospital of Nanjing Medical University. The reference glomerular filtration rate (rGFR) was measured by a 99mTc-DTPA renal dynamic imaging method, and the estimated glomerular filtration rate (eGFR) was calculated separately by the Chinese adapted Modification of Diet in Renal Disease equation (C-MDRD), MacIsaac, Ma, serum creatinine-based CKD-EPI equation (CKD-EPI2009Scr), CKD-EPI2012cys and CKD-EPI2012Scr-cys equations. We compared the performance of six equations with rGFR.ResultsMedian rGFR was 76.35 (interquartile range, 59.03–92.50) mL/min/1.73 m2. Compared with CKD-EPI2009Scr, CKD-EPI2012Scr-cys formula had better diagnostic value with larger area under the receiver operating characteristic curve (ROCAUC, 0.879, p = 0.006), especially in young participants (ROCAUC, 0.883, p = 0.005). CKD-EPI2012cys equation did not perform better than other available equations. Accuracy (the proportion of eGFR within 30% of rGFR [P30]) of the CKD-EPI2012Scr-cys equation (77.03%) was inferior only to MacIsaac equation (80.2%) in the entire participants, but performed best in young participants with normal or mildly-injured GFR. Neither of the two new CKD-EPI equations achieved any ideal P30 in the elderly participants with moderately-severely injured GFR. Linear regression analysis demonstrated a consistent result. In this study, CKD-EPI2012Scr-cys had a relatively better diagnosis consistency of GFR stage between the eGFR and rGFR in the whole cohort.ConclusionCKD-EPI2012Scr-cys appeared less biased and more accurate in overall participants. Neither of the new CKD-EPI equations achieved ideal accuracy in senior participants with moderately-severely injured GFR. A large-scale study with more subjects and cooperating centers to develop new formulae for the elderly is assumed to be necessary.