Creatinine-based Chronic Kidney Disease Epidemiology Research Articles

Formulae for estimation of kidney function as an approach to calculating drug doses: A scoping review

Background: The kidneys are the main organ for drug excretion, and it is critical to assess kidney function when designing dosage regimens for drugs that undergo renal elimination. Various formulae have been used to estimate kidney function and safely adjust doses. Objective: This research reviewed studies that assessed patients' kidney function with various approaches to provide appropriate choices of kidney function estimation formulas based on patients' age and clinical conditions. Method: The search involved browsing scientific articles in PubMed and ScienceDirect with the keywords (("assessment") AND ("GFR") AND ("formula")) OR ("renal function") AND ("human")) AND (“Creatinine”). The articles included were those available in full text and English. Thirty articles addressing the formulae for kidney function assessment were reviewed. Result: The Schwartz formula is more appropriate for pediatric and adult patients, whereas the creatinine-based chronic kidney disease epidemiology (CKD-EPI) formula can be used in geriatrics, obese patients, and patients already known to have decreased kidney function. The cystatin C-based CKD-EPI formula is for patients with HIV and post-transplant patients. Conclusion: This study identified that physiological conditions, especially patients’ age and pathology, should be considered in devising formulae to estimate kidney function to accurately calculate safe drug doses.

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.

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 and old GFR equations: a European perspective.

Glomerular filtration rate (GFR) is estimated in clinical practice from equations based on the serum concentration of endogenous biomarkers and demographic data. The 2009 creatinine-based Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI2009) was recommended worldwide until 2021, when it was recalibrated to remove the African-American race factor. The CKD-EPI2009 and CKD-EPIcr2021 equations overestimate GFR of adults aged 18-30 years, with a strong overestimation in estimated GFR (eGFR) at age 18 years. CKD-EPICr2021 does not perform better than CKD-EPI2009 in US population, overestimating GFR in non-Black subjects, and underestimating it in Black subjects with the same magnitude. CKD-EPICr2021 performed worse than the CKD-EPI2009 in White Europeans, and provides no or limited performance gains in Black European and Black African populations. The European Kidney Function Consortium (EKFC) equation, which incorporates median normal value of serum creatinine in healthy population, overcomes the limitations of the CKD-EPI equations: it provides a continuity of eGFR at the transition between pediatric and adult care, and performs reasonably well in diverse populations, assuming dedicated scaling of serum creatinine (Q) values is used. The new EKFC equation based on cystatin C (EKFCCC) shares the same mathematical construction, namely, it incorporates the median cystatin C value in the general population, which is independent of sex and ethnicity. EKFCCC is therefore a sex-free and race-free equation, which performs better than the CKD-EPI equation based on cystatin C. Despite advances in the field of GFR estimation, no equation is perfectly accurate, and GFR measurement by exogenous tracer clearance is still required in specific populations and/or specific clinical situations.

Decrease in estimated glomerular filtration rates in non-small cell lung cancer patients treated with crizotinib.

Crizotinib is a tyrosine kinase inhibitor used in patients with non-small cell lung cancer, and there are uncertainties about its effect on kidney function. In this study, it was aimed to document the possible adverse effect of the drug on kidney functions. The estimated glomerular filtration rates (eGFRs) of the patients were calculated by creatinine-based Chronic Kidney Disease Epidemiology Collaboration and compared by months using the paired samples t-test. Kaplan-Meier survival method was used for progression-free survival and overall survival (OS) analysis. Twenty-six patients who received crizotinib were included in the study, and the median progression-free survival time with crizotinib was 14.2 months and the median OS time was 27.4 months. There was a significant reduction of eGFR after the 1st month of crizotinib treatment when compared to the rate before treatment initiation (P < 0.001). The eGFR values at the end of the 1st month and the 2nd month of treatment and the 2nd and 3rd months of treatment were statistically similar (P = 0.086, P = 0.663; respectively). This decrease in eGFR values was reversible, and there was no difference detected between pretreatment and posttreatment discontinuation (P = 0.100). A reversible decrease in renal functions was detected in patients using crizotinib. When the literature data are examined, it is thought that the reason for this decrease may be related to the increase in renal inflammation or a pseudo decrease due to the decrease in creatinine excretion. When evaluating renal functions in these patients, using noncreatine-based (iothalamate, etc.) calculations can give more accurate results.

Creatinine and cystatin C-based estimated glomerular filtration rate estimates of kidney function in Black people with HIV on antiretroviral therapy.

To reduce health inequalities, the creatinine-based chronic kidney disease epidemiology collaboration 2021 formula for estimated glomerular filtration rate (eGFR) is replacing the 2009 formula, which required adjustment specifically for Black individuals. We compared the 2021 and 2009 creatinine-based formulae with cystatin C-based eGFR in Black people on antiretroviral therapy (ART) with HIV RNA <200 c/ml. Cross-sectional analysis of paired serum creatinine and cystatin C measurements. Bias, imprecision, accuracy, and performance for identifying individuals with eGFR cystatin C <60 (units: ml/min per 1.73 m 2 ) were determined. The effects of ART with no, mild-moderate, or marked effect on tubular creatinine secretion on the performance of the 2021 formula was assessed. We included 362 individuals (mean age 51 years, 56% female, mean eGFR-cystatin C 88.3). Overall, the 2021 (vs. the 2009 race-adjusted) formula was less biased and had improved imprecision and accuracy compared with eGFR-cystatin C but underestimated eGFR-cystatin C in those with eGFR ≥90 and overestimated eGFR-cystatin C in those with eGFR <60. The 2021 (vs. the 2009) formula had high specificity (95% vs. 97%) and negative predictive value (97% vs. 96%), but low sensitivity (56% vs. 52%) and positive predictive value (44% vs. 54%) for identifying individuals with eGFR-cystatin C <60 ( P > 0.25). Performance at the eGFR <60 cut-off was minimally affected by ART exposure group. The CKD-EPI 2021 creatinine-based formula was better aligned with eGFR-cystatin C than the 2009 formula. eGFR-cystatin C may provide clinically useful information in Black people with eGFR <60 irrespective of ART regimen.

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

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.

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.

Association of the Estimated Glomerular Filtration Rate With vs Without a Coefficient for Race With Time to Eligibility for Kidney Transplant

Kidney transplant is associated with improved survival and quality of life among patients with kidney failure; however, significant racial disparities have been noted in transplant access. Common equations that estimate glomerular filtration rate (eGFR) include adjustment for Black race; however, how inclusion of the race coefficient in common eGFR equations corresponds with measured GFR and whether it is associated with delayed eligibility for kidney transplant listing are unknown. To compare eGFR with measured GFR and evaluate the association between eGFR calculated with vs without a coefficient for race and time to eligibility for kidney transplant. This prospective cohort study used data from the Chronic Renal Insufficiency Cohort, a multicenter cohort study of participants with chronic kidney disease (CKD). Self-identified Black participants from that study were enrolled between April 2003 and September 2008, with follow-up through December 2018. Statistical analyses were completed on November 11, 2020. Estimated GFR, measured annually and estimated using the creatinine-based Chronic Kidney Disease-Epidemiology (CKD-EPI) equation with and without a race coefficient. Iothalamate GFR (iGFR) measured in a subset of participants (n = 311) and time to achievement of an eGFR less than 20 mL/min/1.73 m2, an established threshold for kidney transplant referral and listing. Among 1658 self-identified Black participants, mean (SD) age was 58 (11) years, 848 (51%) were female, and mean (SD) eGFR was 44 (15) mL/min/1.73 m2. The CKD-EPI eGFR with the race coefficient overestimated iGFR by a mean of 3.1 mL/min/1.73 m2 (95% CI, 2.2-3.9 mL/min/1.73 m2; P < .001). The mean difference between CKD-EPI eGFR without the race coefficient and iGFR was of smaller magnitude (-1.7 mL/min/1.73 m2; 95% CI, -2.5 to -0.9 mL/min/1.73 m2). For participants with an iGFR of 20 to 25 mL/min/1.73 m2, the mean difference in eGFR with vs without the race coefficient and iGFR was 5.1 mL/min/1.73 m2 (95% CI, 3.3-6.9 mL/min/1.73 m2) vs 1.3 mL/min/1.73 m2 (95% CI, -0.3 to 2.9 mL/min/1.73 m2). Over a median follow-up time of 4 years (interquartile range, 1-10 years), use of eGFR calculated without vs with the race coefficient was associated with a 35% (95% CI, 29%-41%) higher risk of achieving an eGFR less than 20 mL/min/1.73 m2 and a shorter median time to this end point of 1.9 years. In this cohort study, inclusion of the race coefficient in the estimation of GFR was associated with greater bias in GFR estimation and with delayed achievement of a clinical threshold for kidney transplant referral and eligibility. These findings suggest that nephrologists and transplant programs should be cautious when using current estimating equations to determine kidney transplant eligibility.

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.

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.

Estimated Glomerular Filtration Rate Using Creatinine-Based Chronic Kidney Disease Epidemiology Collaboration Equation.

Estimated Glomerular Filtration Rate Using Creatinine-Based Chronic Kidney Disease Epidemiology Collaboration Equation.

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.

Understanding kidney function assessment: The basics and advances

Multiple kidney function assessment modalities are available, but their appropriateness is constantly questioned. This review provides practitioners with in-depth understanding of kidney function assessment methods, their clinical utility, and comparisons. PUBMED search was conducted by relevant subject headings. Glomerular filtration rate (GFR) is the best indicator of kidney function. Exogenous compounds like inulin help measure GFR, but endogenous substances (like creatinine) are more convenient, although exhibiting greater variability. Cystatin C is advocated as a functional marker; its clinical significance is under study. Proteinuria adds value to GFR estimation. There are commonly used equations estimating GFR like the creatinine-based Cockcroft-Gault and the modification of diet in renal disease. The new creatinine-based Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation demonstrates higher accuracy of patient classification in earlier stages of disease. Recently, the Chronic Renal Insufficiency Cohort (CRIC) study has devised an equation combining serum creatinine and cystatin C in longitudinal modeling of kidney function. Current GFR estimation methods have limitations, and are useful for populations they have been tested in. Practitioners should be well informed on emerging equations that provide greater accuracy in CKD diagnosis; this would help implement appropriate prevention and intervention strategies.

Inverse association of estimated cystatin C- and creatinine-based glomerular filtration rate with left ventricular mass: Results from the Study of Health in Pomerania

BackgroundLeft ventricular hypertrophy (LVH) is an independent predictor of cardiovascular disease in the general population and in patients with chronic kidney disease. The objective of this study was to investigate the association of estimated glomerular filtration rate (eGFR) with left ventricular mass index (LVMI), LVH and left ventricular geometry. A question of clinical relevance is whether estimated glomerular filtration rate based on cystatin C (eGFRcystatinC) is a better marker for cardiovascular risk than estimated glomerular filtration rate based on creatinine (eGFRcreatinine). MethodsThe study sample included 2830 individuals from the population-based Study of Health in Pomerania (SHIP). LVH was defined as echocardiographic LVMI >48g/m2.7 in men and >44g/m2.7 in women. Kidney function, as assessed by eGFR, was determined from established equations: the creatinine-based Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation and a cystatin-based multivariable equation. ResultsWe found an inverse association between eGFR and LVMI. This association was stronger in models with eGFRcystatinC than in models with eGFRcreatinine. Subjects with moderately-to-severely decreased kidney function (defined as eGFR 15–<60mL/min per 1.73m2) had higher odds for abnormal geometric patterns of the left ventricle than subjects with normal eGFR when eGFRcystatinC was used. ConclusionsThe findings suggest that eGFRcystatinC is superior to eGFRcreatinine for assessing the risk of cardiovascular disease.