Chronic Kidney Disease Epidemiology Collaboration Cystatin Research Articles

Cystatin C as a Predictor of Renal Function and Methotrexate-Associated Toxicities in Patients With Rheumatoid Arthritis.

Methotrexate (MTX) is an anchor drug for most patients with rheumatoid arthritis (RA); however, its use may be limited depending on renal function. Therefore, this study aimed to examine the discrepancy in the estimated glomerular filtration rate (eGFR) using conventional serum creatinine (SCr)-, cystatin C-, and MTX-associated toxicities in patients with RA. In total, 436 patients were enrolled, and eGFR was evaluated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation based on both cystatin C and SCr levels. The CKD and MTX dosing stages were classified according to eGFR. MTX-associated toxicities were also evaluated. The mean eGFR using CKD-EPI cystatin C (CKD-EPIcys) was 89.44 mL/min/1.73 m2, lower than the eGFR using CKD-EPI SCr (CKD-EPISCr) of 95.55 mL/min/1.73 m2. After converting eGFR to CKD-EPIcys by CKD-EPISCr, 29.8% of patients were reclassified to a higher stage according to the Kidney Disease: Improving Global Outcomes CKD stage. Also, according to the MTX guidelines, 6.4% of the group with an eGFR > 50 mL/min/1.73 m2 were reclassified to eGFR 10-50 mL/1.73 m2, requiring dose adjustment. The incidence of MTX-associated toxicities, such as anemia, leukopenia, and nephrotoxicity, was significantly higher in the CKD stage-changed group than in the nonstage-changed group. Our results showed that eGFR based on SCr was overestimated compared with eGFR based on cystatin C. In addition, we demonstrated that MTX-associated toxicities were significantly increased in the group with a changed stage when the eGFR was converted from CKD-EPISCr to CKD-EPIcys.

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

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

#4735 USEFULNESS OF CYSTATIN C IN MEASURING RENAL FUNCTION AND PREDICTING METHOTREXATE ASSOCIATED TOXICITIES IN PATIENTS WITH RHEUMATOID ARTHRITIS

Abstract Background and Aims Rheumatoid arthritis (RA) is a representative chronic disease accompanied by muscle loss, and cystatin C may be more useful than traditional creatinine (Cr) when measuring renal function. RA is affected not only by drug dose but also by side effects of treatment according to renal function. Therefore, we tried to compare the estimated glomerular filtrate rate (eGFR) using cystatin C and Cr and analyze the methotrexate (MTX) associated toxicities after treatment. Method A total of 436 RA patients was enrolled in this study. The eGFR was calculated using the Chronic kidney Disease Epidemiology Collaboration (CKD-EPI) equation based on cystatin C and serum Cr. According to eGFR, CKD stages and drug dosing stages were classified and MTX associated toxicities were evaluated. Results Mean eGFR using the CKD-EPI cr and CKD-EPI cystatin C equations were 95.36 and 89.44 mL/min. In the CKD-EPIcr group, there were 11 patients with eGFR less than 50 mL/min that required dosing reduction, and 38 patients in the CKD-EPI cystatin C group, showing a statistically significant difference (Table 1A). In addition, CKD stage 3B and 4 patients were also higher in the CKD-EPI cystatin C group compared to those in CKD-EPI cr group (Table 1B), and anemia and nephrotoxicity were high in the MTX related toxicity stage upgraded group. Conclusion Our study showed that eGFR by CKD-EPI Cr can be overestimated than that by CKD-EPI cystatin C, and also demonstrated higher MTX associated toxicities in the group, which the stage was changed upward. Therefore, this study suggests that cystatin C is useful predictor in measuring renal function and predicting MTX associated toxicities in RA patients

Performance of Creatinine and Cystatin C-Based Equations to Estimate Kidney Function in Renal Transplant Recipients

Background: Numerous equations are applied in order to estimate the glomerular filtration rate (GFR). Objectives: This study aimed to spot the optimal equation that accurately estimates GFR and, therefore, the chronic kidney disease (CKD) stage in renal transplant patients. Methods: This cross-sectional study was conducted on 58 renal transplant patients. Their venous blood samples were obtained for serum creatinine and cystatin C determination used to calculate estimated GFR (eGFR). The average contrast of GFR in each equation was calculated using the Bland-Altman method. The correlation, bias, imprecision, and 10% and 30% accuracy were compared between the eGFR cystatin C and creatinine. Concordance between both equations for CKD staging was assessed. The classification of patients was also investigated. Results: Bland-Altman plots and bias demonstrated that eGFR by the abbreviated modification of diet in renal disease (Ab-MDRD) was the most accurate compared with chronic kidney disease epidemiology collaboration (CKD-EPI) cystatin C, followed by CKD-EPI eGFR creatinine. With reference to CKD-EPI cystatin C, the imprecision of the equations was approximately similar to Ab-MDRD, and CKD-EPI creatinine is still better than the Cockcroft-gault (CG) formula. They also showed good 30% accuracy. Finally, our finding suggested that Ab-MDRD and CKD-EPI eGFR creatinine might be the best-performing equation in the classification of the CKD stages in a cutoff of 60 mL/min/1.73 m2. Conclusions: Due to the high cost and potential delay in measuring cystatin C, it would be much more appropriate to measure Ab-MDRD; after that, CKD-EPI eGFR creatinine as an alternative approach in order to facilitate rapid clinical decision in renal transplant patients.

Implications of the 2021 CKD-EPI cystatin C/creatinine eGFR equation for eligibility for therapy in HFrEF: insights from PARADIGM-HF

Abstract Background Estimated glomerular filtration rate (eGFR) is a key determinant of eligibility for many life-saving therapies in HFrEF. Recently, the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) provided new equations based on creatinine (CKD-EPIcr), cystatin C (CKD-EPIcys) or both (CKD-EPIcyscr) that do not include race. These new equations may reclassify individuals, irrespective of race, from one eGFR category to another, with implications for eligibility for HFrEF treatments. Purpose To assess the difference between eGFR estimation using the 2021 CKD-EPIcyscr equation and the 2009 CKD-EPIcr and Modification of Diet in Renal Disease Study (MDRD)-4 equations which are still standard in many European laboratories. Methods We included patients from PARADIGM-HF with cystatin C and creatinine values available at the time of randomization. For each patient, baseline eGFRs were calculated using the 3 equations described. Our focus was on patients with chronic kidney disease (CKD) stages III–V. Results Overall, 1910 patients were eligible. Mean age was 67.3 (10.1) year and 385 (18.7%) were female. Using 2009 CKD-EPIcr, 779 patients were in CKD stages 3–5, of which 233 (30%) were reclassified to a better CKD stage (higher eGFR) with the 2021 CKD-EPIcyscr equation (Table 1). Similar reclassification was seen when comparing MDRD-4 with the 2021 CKD-EPIcyscr equation: 277 (33%) of 831 patients in CKD stages 3–5 were reclassified to a better CKD stage (Figure 1). Conclusions The 2021 CKD-EPIcyscr equation favourably reclassified CKD stage in a large percentage of patients with HFrEF and a low eGFR, potentially increasing the proportion of these patients considered eligible for guideline-recommended therapies. Funding Acknowledgement Type of funding sources: None.

Altered kidney function induced by SARS-CoV-2 infection and acute kidney damage markers predict survival outcomes of COVID-19 patients: a prospective pilot study

Background Literature with regard to coronavirus disease 2019 (COVID-19) associated morbidities and the risk factors for death are still emerging. In this study, we investigated the presence of kidney damage markers and their predictive value for survival among hospitalized subjects with COVID-19. Methods Forty-seven participants was included and grouped as: ‘COVID-19 patients before treatment’, ‘COVID-19 patients after treatment’, ‘COVID-19 patients under treatment in intensive care unit (ICU)’, and ‘controls’. Kidney function tests and several kidney injury biomarkers were compared between the groups. Cumulative rates of death from COVID-19 were determined using the Kaplan–Meier method. The associations between covariates including kidney injury markers and death from COVID-19 were examined, as well. Results Serum creatinine and cystatin C levels, urine Kidney Injury Molecule-1 (KIM-1)/creatinine ratio, and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), CKD-EPI cystatin C, and CKD-EPI creatinine–cystatin C levels demonstrated significant difference among the groups. The most significant difference was noted between the groups ‘COVID-19 patients before treatment’ and ‘COVID-19 patients under treatment in ICU’. Advancing age, proteinuria, elevated serum cystatin C, and urine KIM-1/creatinine ratio were all significant univariate correlates of death (p < 0.05, for all). However, only elevated urine KIM-1/creatinine ratio retained significance in an age, sex, and comorbidities adjusted multivariable Cox regression (OR 6.11; 95% CI: 1.22–30.53; p = 0.02), whereas serum cystatin C showing only a statistically non-significant trend (OR 1.42; 95% CI: 0.00–2.52; p = 0.09). Conclusions Our findings clearly demonstrated the acute kidney injury related to COVID-19. Moreover, urine KIM-1/creatinine ratio was associated with COVID-19 specific death.

Targeted Cancer Therapies Causing Elevations in Serum Creatinine Through Tubular Secretion Inhibition: A Case Report and Review of the Literature

Rationale:Targeted cancer therapies have revolutionized the field of oncology by selecting for specific molecular pathways, thus improving overall clinical prognosis. However, many of these targeted treatments have been reported to have adverse kidney effects, including acute kidney injury, interstitial nephritis, and glomerular disease. Furthermore, some of these targeted therapies have also been found to cause an asymptomatic rise in serum creatinine levels through inhibition of active tubular secretion.Presenting concerns:A 79-year-old woman was being followed for stage 4 A2 chronic kidney disease secondary to type 2 diabetes and longstanding hypertension. She was diagnosed with invasive mammary carcinoma and was initiated on letrozole, an aromatase inhibitor, and palbociclib, a selective cyclin-dependent kinase inhibitor, was subsequently added. Prior to the initiation of her treatments, her baseline estimated glomerular filtration rate (eGFR) fluctuated between 25 and 28 mL/min/1.73 m2 over the previous year. After initiating palbociclib, her serum creatinine progressively increased, despite having well-controlled blood pressure and diabetes. In addition, there was no history of pre-renal events nor any sonographic evidence of obstruction. Within 7 months, her eGFR based on serum creatinine had decreased down to 12 mL/min/1.73 m2.Interventions:Given that there were no clinical or other biochemical changes suggestive of worsening renal function, a serum cystatin C was measured using an immunoturbidimetric assay, which was 1.71 mg/L and correlated with an eGFR of 33 mL/min/1.73 m2 based on the chronic kidney disease epidemiology collaboration (CKD-EPI) cystatin C equation (2012). This value was consistent with her previous baseline. Based on these findings, the significant decrease in eGFR measured by serum creatinine was attributed to the inhibitory effects of palbociclib on tubular creatinine secretion, rather than representing true kidney damage. Thus, a kidney biopsy was not performed in this context.Outcomes:Seven months later, a repeat serum cystatin C was repeated to assess for any worsening of the patient’s kidney function and revealed an eGFR of 35 mL/min/1.73 m2 based on the CKD-EPI cystatin C equation (2012), thus revealing stable kidney function and reinforcing the inhibitory effects of palbociclib on tubular creatinine secretion through its direct effects on kidney transporters.Teaching points:This case report and literature review acknowledges the importance of using alternative methods of assessing kidney function when patients are undergoing targeted cancer therapies known to affect tubular creatinine secretion, which include cyclin-dependent kinase 4/6 inhibitors, poly(adenosine diphosphate-ribose) polymerase inhibitors, tyrosine kinase inhibitors, and mesenchymal-epithelial transition inhibitors. The use of non–creatinine-based markers of glomerular filtration rate (GFR), such as cystatin C and nuclear renal scans, will allow for more accurate estimation of kidney function in the appropriate setting, thus avoiding invasive diagnostic tests and unnecessary adjustments of treatment plans. However, certain targeted cancer therapies have also been proven to cause true kidney injury; therefore, physicians must still maintain a high degree of suspicion and consider invasive investigations and/or cessation or reduction of treatments when alternative measurements of kidney function do not suggest an underestimation of GFR via serum creatinine.

Comparison of creatinine, cystatin, CKD-EPI cystatin C, CKD-EPI creatinine and MDRD equations in estimating glomerular filtration rate in patients with nephrotic syndrome

Objective: It’s recommended to use equations such as Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) by using creatinine level in estimating glomerular filtration rate (GFR). Here, we aimed to compare serum cystatin-C (Cys-C) and Cys-C based equations with creatinine and creatinine based equations in patients with chronic kidney disease (CKD) and nephrotic syndrome (NS).

DIFFERENTIAL PREVALENCE AND ASSOCIATIONS OF CHRONIC KIDNEY DISEASE BY FIVE ESTIMATORS IN A SOUTH AFRICAN POPULATION-BASED STUDY

Objective: The aim was to determine the prevalence, distribution, concordance and associations of chronic kidney disease (CKD) assessed by five glomerular filtration rate (GFR) formulae in urban black residents of Cape Town. Design and method: In this population-based cross-sectional study, stratified for age and gender, data collection included administered questionnaires, clinical measurements and biochemical analyses, including serum creatinine and cystatin C levels. GFR was based on the CKD Epidemiology Collaboration (CKD-EPI) equations (CKD-EPI creatinine (CKD-EPIcr), CKD-EPI cystatin C (CKD-EPIcys), CKD-EPI creatinine-cystatins (CKD-EPIcr-cys)), Modification of Diet in Renal Disease (MDRD) and Cockcroft-Gault formula (CGF). GFR &lt;60 mL/min/1.73 m2 defined CKD. Results: Mean estimated GFR, among 392 men and 700 women, was between 114.0 (CKD-EPIcr) and 135.4 mL/min/1.73 m2 (CGF) in men, and between 107.5 (CKD-EPIcr-cys) and 173.4 mL/min/1.73 m2 (CGF) in women. CKD prevalence ranged from 2.3% (CKD-EPIcr and MDRD) to 5.1% (CKD-EPIcys) in men and 1.6% (CGF) to 6.7% (CKD-EPIcr-cys) in women. Correlations between different estimates of GFR were positive and significant, and there were no significant differences between any two coefficients. The kappa statistic was high between CKD-EPIcr and MDRD (0.934), and CKD-EPIcys and CKD-EPIcr-cys (0.815), but fair-to-moderate between the other equations (0.353–0.565). In the basic regressions, older age and body mass index &gt;30 kg/m2, but not gender, were significantly associated with CKD-EPIcr-defined CKD. In the presence of these three variables, but in separate models, hypertension, heart rate &gt;90 beats/minute, diabetes and increasing low-density lipoprotein cholesterol were significant predictors of prevalent CKD by CKD-EPIcr and MDRD (except for diabetes). Metabolic syndrome, in the model with age and gender only, was significantly associated with CKD-EPIcr- and MDRD-defined CKD. No cardio-metabolic variable was associated with CKD determined by CKD-EPIcys, CKD-EPIcr-cys or CGF. Conclusions: The varying CKD prevalence estimates, on account of different GFR equations used, underscores the need to improve accuracy of CKD diagnoses. Moreover, considering the significant associations of cardio-metabolic diseases with CKD-EPIcr- and MDRD-defined CKD, screening for CKD should be incorporated into the routine assessment of high-risk patients such as those with hypertension or diabetes.

Prevalence, concordance and associations of chronic kidney disease by five estimators in South Africa

BackgroundTo determine the prevalence, distribution, concordance and associations of chronic kidney disease (CKD) determined by five glomerular filtration rate (GFR) formulae in urban black residents of Cape Town.MethodsData collection in this cross-sectional study included interviews, clinical measurements and biochemical analyses, including serum creatinine and cystatin C levels. GFR was based on the CKD Epidemiology Collaboration (CKD-EPI) equations (CKD-EPI creatinine (CKD-EPIcr), CKD-EPI cystatin C (CKD-EPIcys), CKD-EPI creatinine-cystatins (CKD-EPIcr-cys)), Modification of Diet in Renal Disease (MDRD) and Cockcroft-Gault formula (CGF). GFR < 60 mL/min/1.73 m2 defined CKD.ResultsAmong 392 men and 700 women, mean GFR, was between 114.0 (CKD-EPIcr) and 135.4 mL/min/1.73 m2 (CGF) in men, and between 107.5 (CKD-EPIcr-cys) and 173.4 mL/min/1.73 m2 (CGF) in women. CKD prevalence ranged from 2.3% (CKD-EPIcr and MDRD) to 5.1% (CKD-EPIcys) in men and 1.6% (CGF) to 6.7% (CKD-EPIcr-cys) in women. The kappa statistic was high between CKD-EPIcr and MDRD (0.934), and CKD-EPIcys and CKD-EPIcr-cys (0.815), but fair-to-moderate between the other eqs. (0.353–0.565). In the basic regressions, older age and body mass index ≥30 kg/m2, but not gender, were significantly associated with CKD-EPIcr-defined CKD. In the presence of these three variables, hypertension, heart rate ≥ 90 beats/minute, diabetes and low-density lipoprotein cholesterol were significant predictors of prevalent CKD.ConclusionsVarying CKD prevalence estimates, because of different GFR equations used, underscores the need to improve accuracy of CKD diagnoses. Furthermore, screening for CKD should be incorporated into the routine assessment of high-risk patients such as those with hypertension or diabetes.

Uric Acid Lowering and Biomarkers of Kidney Damage in CKD Stage 3: A Post Hoc Analysis of a Randomized Clinical Trial

Rationale & ObjectiveHyperuricemia is associated with chronic kidney disease (CKD) progression. We evaluated whether lowering serum uric acid levels improves levels of biomarkers of kidney damage.Study DesignPost hoc analysis of clinical trial participants.Setting & ParticipantsA double-blind randomized placebo-controlled study designed to lower serum uric acid levels. 80 patients with stage 3 CKD and asymptomatic hyperuricemia were randomly assigned to allopurinol treatment or placebo (300 mg/d) for 12 weeks.Exposure/PredictorAllopurinol treatment versus placebo.Outcomes & MeasuresWe evaluated the change from baseline for the following urinary biomarkers of kidney damage: albumin-creatinine ratio (ACR), neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule 1 (KIM-1), and transforming growth factor β1 (TGF-β1). Additionally, we evaluated CKD Epidemiology Collaboration (CKD-EPI)-estimated glomerular filtration rate (eGFR) and cystatin C eGFR.Analytical ApproachGeneralized linear mixed modeling was used.ResultsAfter 12 weeks, allopurinol (compared to placebo) significantly lowered serum uric acid levels with an estimate of −3.3 mg/dL (95% CI, −4.1 to −2.5 mg/dL; P < 0.001). Estimates for the change for allopurinol versus placebo over time were 1.09 (95% CI, 0.77-1.54) for ACR, 0.77 (95% CI, 0.36-1.63) for NGAL, and 2.36 (95% CI, 0.97-5.70) for TGF-β1. The model did not converge for KIM-1, but Wilcoxon signed rank test showed no significant difference in change from baseline between study groups. There was no significant change observed in CKD-EPI eGFR or cystatin C eGFR.LimitationsPost hoc analysis and short duration of the study.ConclusionsUric acid–lowering with allopurinol is not associated with improvement in levels of biomarkers of kidney damage in patients with asymptomatic hyperuricemia and stage 3 CKD.FundingThe study was funded by the National Institutes of Health through a career development award, K23DK088833, and the Clinical and Translational Science Award UL1TR002537.Trial RegistrationNCT01228903.

Comparison of different equations for estimated glomerular filtration rate in Han Chinese patients with chronic kidney disease.

To understand the agreement, precision, and accuracy between other estimated glomerular filtration rate (eGFR) equations and the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine-cystatin C equation (EPI_Cr_CysC). We conducted a cross-sectional study of 1,913 CKD patients. The eGFRs were calculated separately by creatinine clearance rate and Cockcroft-Gault equation corrected for standard body surface area (Ccr_BSA and eCcr_BSA); CKD-EPI creatinine equation (EPI_Cr); CKD-EPI cystatin C equation (EPI_CysC); EPI_Cr_CysC equation; Modification of Diet in Renal Disease (MDRD) Study equation with standardized serum creatinine; and full-age spectrum creatinine equation (FAS). The EPI_Cr_CysC equation was used as the reference. When compared with the EPI_Cr_CysC equation, the EPI_Cr equation achieved the highest agreement in eGFRs (Lin's concordance correlation coefficient = 0.936, 95% confidence interval (CI) = 0.930, 0.941). eCcr_BSA and EPI_Cr equations achieved the first and second highest percentage agreement in the accurate classification of CKD stage (72.55 vs. 71.25%). The MDRD equation had minimal bias and was closely followed by the EPI_Cr equation (median difference = -1.3, 95% CI = -2.0, -0.8 vs. median difference = 2.5, 95% CI = 1.7, 3.3 mL/min/1.73m2). The EPI_CysC and EPI_Cr equations achieved the first and second highest precision (interquartile range (IQR) of the difference = 12.2, 95% CI = 11.6, 12.9 vs. IQR of the difference = 15.5, 95% CI = 14.7, 16.3 mL/min/1.73m2). The EPI_Cr and MDRD equations performed similarly and both had the highest accuracy at 30% (1 - P30 = 18.6, 95% CI = 16.9, 20.4 vs. 1 - P30 = 18.6, 95% CI = 16.8, 20.3%). For assessment of renal function, the EPI_Cr equation performed the best and remained an acceptable alternative to the EPI_Cr_CysC equation in the absence of cystatin C. .

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.

Clinical Relevance of Differences in Glomerular Filtration Rate Estimations in Frail Older People by Creatinine- vs. Cystatin C-Based Formulae.

The risk of incorrect medication dosing is high in frail older people. Therefore, accurate assessment of the glomerular filtration rate is important. The objective of this study was to compare the estimated glomerular filtration rate using creatinine- and cystatin C-based formulae, the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations, in frail older people. We hypothesized that frailty determines the difference between the creatinine- and cystatin C-based formulae. The mean difference between CKD-EPI creatinine and cystatin C was determined using (cross-sectional) data of 55 patients (mean age 73years) admitted to a psychiatric ward for older adults. The level of agreement of these estimations was assessed by a Bland-Altman analysis. In all patients, the Rockwood's Frailty Index was derived and correlated with the mean difference between CKD-EPI creatinine and cystatin C. The mean difference between CKD-EPI creatinine (mean 71.2mL/min/1.73m2) and CKD-EPI cystatin C (mean 57.6mL/min/1.73m2) was 13.6mL/min/1.73m2 (p<0.0001). The two standard deviation limit in the Bland-Altman plot was large (43.2mL/min/1.73m2), which represents a low level of agreement. The Frailty Index did not correlate with the mean difference between the creatinine- and cystatin C-based glomerular filtration rate (Pearson correlation coefficient 0.182, p=0.184). There was a significant gap between a creatinine- and cystatin C-based estimation of glomerular filtration rate, irrespective of frailty. The range of differences between the commonly used estimated glomerular filtration rate formulae might result in clinically relevant differences in drug prescription and differences in chronic kidney disease staging.

Predictive performance of different kidney function estimation equations in lung transplant patients

BackgroundThere has been limited examination of the performance of glomerular filtration rate estimation (eGFR) equations in lung transplant populations. This study aimed to compare the performance of serum creatinine and cystatin C based eGFR equations with Tc-99m diethylenetriaminepentaacetic acid (DTPA) GFR measurements in individuals with end-stage lung disease, either prior to, or following, lung transplantation. MethodsIn this prospective observational study, participants underwent GFR measurements with Tc-99m Pentetate. Measured results were compared with GFR estimates derived from estimation equations [4-variable Modification of Diet in Renal Disease, Cockcroft-Gault, Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine, cystatin C and creatinine-cystatin C combined equations]. ResultsNinety-seven individuals were studied (77 post- and 20 wait-listed for transplantation). Median (range) radionucleotide GFR was 56.7ml/min/1.73m2 (22.8–109.2ml/min/1.73m2). In the study cohort as a whole, the CKD-EPI creatinine-cystatin C combined equation showed the highest performance, but was only slightly superior to the CKD-EPI creatinine equation. However, in individuals with cystic fibrosis, low arm muscle mass and/or low body mass index, all of the creatinine-based equations showed unacceptable performance. In these subgroups, improved GFR estimation was seen with the CKD-EPI cystatin C equation, and predictions were better still using the CKD-EPI creatinine-cystatin C combined equation. ConclusionsThis study shows adequate predictive ability of CKD-EPI creatinine in the cohort as a whole, but unacceptable performance in patients with cystic fibrosis, low arm muscle mass and/or low body mass index. Our findings demonstrate that cystatin C may be a preferable filtration marker in these subgroups.

GFR Estimation Using β-Trace Protein and β2-Microglobulin in CKD

β-Trace protein (BTP) and β2-microglobulin (B2M) are novel glomerular filtration markers that have stronger associations with adverse outcomes than creatinine. Comparisons of BTP and B2M to creatinine and cystatin C are limited by the absence of rigorously developed glomerular filtration rate (GFR) estimating equations for the novel markers. Study of diagnostic test accuracy. Pooled database of 3 populations with chronic kidney disease (CKD) with mean measured GFR of 48 mL/min/1.73 m2 (N=3,551; MDRD [Modification of Diet in Renal Disease] Study, AASK [African American Study of Kidney Disease and Hypertension], and CRIC [Chronic Renal Insufficiency Cohort] Study). GFR estimated using creatinine, cystatin C, BTP, or B2M level. GFR measured as the urinary clearance of iothalamate. For BTP and B2M, coefficients for age, sex, and race were smaller than for creatinine and were similar or smaller than for cystatin C. For B2M, coefficients for sex, age, and race were smaller than for creatinine and were similar (age and race) or smaller (sex) than for cystatin C. The final equations with BTP (BTP, age, and sex) or B2M (B2M alone) were less accurate than either the CKD-EPI (CKD Epidemiology Collaboration) creatinine or cystatin C equations. The combined BTP-B2M equation (BTP and B2M alone) had similar accuracy to the CKD-EPI creatinine or cystatin C equation. The average of the BTP-B2M equation and the CKD-EPI creatinine-cystatin C equation was not more accurate than the CKD-EPI creatinine-cystatin C equation. No external validation population, study population was restricted to CKD, few participants older than 65 years, or nonblack nonwhite race. BTP and B2M are less influenced by age, sex, and race than creatinine and less influenced by race than cystatin C, but provide less accurate GFR estimates than the CKD-EPI creatinine and cystatin C equations. The CKD-EPI BTP and B2M equation provides a methodological advance for their study as filtration markers and in their associations with risk and adverse outcomes, but further study is required before clinical use.

Potential Impact of Prescribing Metformin According to eGFR Rather Than Serum Creatinine.

OBJECTIVEMany societies recommend using estimated glomerular filtration rate (eGFR) rather than serum creatinine (sCr) to determine metformin eligibility. We examined the potential impact of these recommendations on metformin eligibility among U.S. adults.RESEARCH DESIGN AND METHODSMetformin eligibility was assessed among 3,902 adults with diabetes who participated in the 1999–2010 National Health and Nutrition Examination Surveys and reported routine access to health care, using conventional sCr thresholds (eligible if <1.4 mg/dL for women and <1.5 mg/dL for men) and eGFR categories: likely safe, ≥45 mL/min/1.73 m2; contraindicated, <30 mL/min/1.73 m2; and indeterminate, 30–44 mL/min/1.73 m2). Different eGFR equations were used: four-variable MDRD, Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine (CKD-EPIcr), and CKD-EPI cystatin C, as well as Cockcroft-Gault (CG) to estimate creatinine clearance (CrCl). Diabetes was defined by self-report or A1C ≥6.5% (48 mmol/mol). We used logistic regression to identify populations for whom metformin was likely safe adjusted for age, race/ethnicity, and sex. Results were weighted to the U.S. adult population.RESULTSAmong adults with sCr above conventional cutoffs, MDRD eGFR ≥45 mL/min/1.73 m2 was most common among men (adjusted odds ratio [aOR] 33.3 [95% CI 7.4–151.5] vs. women) and non-Hispanic Blacks (aOR vs. whites 14.8 [4.27–51.7]). No individuals with sCr below conventional cutoffs had an MDRD eGFR <30 mL/min/1.73 m2. All estimating equations expanded the population of individuals for whom metformin is likely safe, ranging from 86,900 (CKD-EPIcr) to 834,800 (CG). All equations identified larger populations with eGFR 30–44 mL/min/1.73 m2, for whom metformin safety is indeterminate, ranging from 784,700 (CKD-EPIcr) to 1,636,000 (CG).CONCLUSIONSThe use of eGFR or CrCl to determine metformin eligibility instead of sCr can expand the adult population with diabetes for whom metformin is likely safe, particularly among non-Hispanic blacks and men.

Markers of renal disease and function are associated with systemic inflammation in HIV infection.

Both renal disease and systemic inflammation predict non-AIDS-defining events and overall mortality in HIV-infected patients. Here, we sought to determine the relationships between renal disease and circulating inflammation markers. We performed a secondary analysis of AIDS Clinical Trials Group Study A5224s to determine if markers of renal disease [urine protein:creatinine ratio (uPCR), urine albumin:creatinine ratio (uACR), and estimated glomerular filtration rate (eGFR), using Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine and cystatin C-creatinine] were associated with markers of systemic inflammation [high-sensitivity C-reactive protein, interleukin-6, tumour necrosis factor (TNF)-α, soluble TNF-α receptor I (sTNFRI), sTNFRII, and soluble vascular cellular and intercellular adhesion molecules]. We correlated these renal and inflammatory markers prior to antiretroviral initiation and after 96 weeks of therapy. We found that eGFR (estimated using CKD-EPI cystatin C-creatinine), uPCR, and uACR were significantly correlated with most assessed markers of systemic inflammation prior to antiretroviral initiation. uPCR and eGFR (using CKD-EPI cystatin C-creatinine), but not uACR, remained significantly correlated with most of the assessed inflammatory markers after 96 weeks of antiretroviral therapy (ART). Most of these correlations, although statistically significant, were < 0.50. eGFR using CKD-EPI creatinine was much less frequently associated with inflammation markers and only significantly correlated with sTNFR1 at week 0 and with sTNFRI and II at week 96. Renal disease and function were associated with systemic inflammation in HIV infection, both before and after ART. Systemic inflammation may partially explain the relationships between proteinuria, albuminuria, and reduced renal function and future adverse outcomes.

Can cystatin C become an easy and reliable tool for anesthesiologists to calculate glomerular filtration rate?

Background and Aims:The aim was to evaluate the role of cystatin C as a noninvasive and easy marker of glomerular filtration rate (GFR) estimation in voluntary kidney donors.Materials and Methods:We retrospectively evaluated 40 voluntary kidney donors. They underwent complete biochemical and nuclear tests as a part of transplant workup. Serum cystatin C, serum creatinine, and Tc-99m diethylene-triamine-penta-acetic acid (DTPA) were used in our study. We calculated GFR using the chronic kidney disease epidemiology collaboration (CKD-EPI) formula based on creatinine only (GFR-CKD-EPI-creat), CKD-EPI formula using creatinine and cystatin C (GFR-CKD-EPI-cyst-creat), and modification of diet in renal disease (MDRD) and CKD-EPI cystatin C equation (2012) (GFR-cyst).Data was evaluated using the SPSS software (version 11.5). The correlation analysis and analysis of variance was used for statistical computation. Agreement was determined using analyze-it version 2.30 for MS-Excel 12+.Results:The mean age of the donors in our study was 49.83 ± 13.06. The mean cystatin C in females was 0.72 ± 0.12, the mean cystain C in males was 0.87 ± 0.23. On correlating GFR-cyst with GFR-DTPA the Pearson correlation coefficient (ρ) was found to be 0.388 this correlation was significant with P < 0.05. While comparing with DTPA the correlation coefficient of GFR-CKD-EPI-creat group was 0.587 which was significant with P < 0.01. The correlation coefficient of GFR-CKD-EPI-cyst-creat group compared with GFR-DTPA group was 0.543 which was also significant at P < 0.001. GFR-CKD-EPI-creat gave the highest correlation with DTPA in our study. The correlation coefficient of GFR-MDRD group with DTPA group was 0.576 this correlation was also significant with P < 0.01. The results obtained were further statistically analyzed by Bland-Altman analysis the percentage error for GFR-DTPA versus GFR-cyst-creat is 29.72%; for GFR-DTPA versus GFR-EPI-creat is 30.73%; or GFR-DTPA versus MDRD is 31.63% and for GFR-DTPA versus GFR-cyst is 34.37%.Conclusion:Cystatin C is a good endogenous marker for calculating GFR as it correlates very well with DTPA and CKD-EPI equation based GFR.

Glomerular filtration rate estimation using cystatin C alone or combined with creatinine as a confirmatory test

Glomerular filtration rate (GFR) estimating equations using the combination of creatinine and cystatin C (eGFRcr-cys) are more accurate than equations using either alone (eGFRcr or eGFRcys). New guidelines suggest measuring cystatin C as a confirmatory test when eGFRcr may be inaccurate, but do not specify demographic or clinical conditions in which eGFRcys or eGFRcr-cys are more accurate than eGFRcr nor which estimate to use in such circumstances. We compared the performance of the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations in 1119 subjects in the CKD-EPI cystatin C external validation dataset. Subgroups were defined by eGFRcr, age, sex, diabetes status and body mass index (BMI). The reference test was GFR measured using urinary or plasma clearance of exogenous filtration markers. Cystatin C and creatinine assays were traceable to primary reference materials. Accuracy was defined as the absolute difference in eGFR compared with mGFR. The mean mGFR was 70 ± 41 (SD) mL/min/1.73 m(2). eGFRcys was more accurate than eGFRcr at lower BMI and less accurate at higher BMI, especially at higher levels of eGFRcr. There were small differences in accuracy in people according to the diabetes status. eGFRcr-cys was as accurate or more accurate than eGFRcr or eGFRcys in these and all other subgroups. eGFRcr-cys, but not eGFRcys, is more accurate than eGFRcr in most subgroups we studied, suggesting preferential use of eGFRcr-cys when serum cystatin C is measured as a confirmatory test to obtain more accurate eGFR. Further studies are necessary to evaluate diagnostic strategies for using eGFRcys and eGFRcr-cys.