CKD-EPI Cystatin Research Articles

Urinary abnormalities and renal function in pregnant women with chronic hypertension.

Renal involvement in pregnant women with chronic hypertension is not widely known. 1- To describe the epidemiological profile of pregnant women with chronic hypertension; 2- To evaluate urinary abnormalities (by urinalysis), renal function (serum creatinine and cystatin C, and estimated glomerular filtration rate (eGFR); 3- To evaluate the pregnancy outcome in chronic hypertension. 103 pregnant women with chronic hypertension (blood pressure over 140/90 mmHg, detected previously to pregnancy or until the 20th week) were submitted to clinical and laboratorial evaluation. Pregnant women were 21-45 (mean: 34) years-old. Protein/creatinine ratio in random urine was elevated in 5.2% (0.0-6.4g/g), serum creatinine in 19.6% and cystatin C in 14.7% of them. It was observed that characteristics of pregnant patients and their newborns (vs. frequencies of the cases with CKD-EPI cystatin C < 60 ml/min/1.73 m2) were: 20.5% (33.3%) of preterm birth < 37 weeks, 17.5% (22.2%) of birth weight < 2500g and 17.5% (22.2%) of small for gestational age; superimposed preeclampsia-eclampsia occurred in 24.7% (22.2%) of the cases. Renal abnormalities were detected by proteinuria, determinations of serum creatinine and cystatin C in 5.2, 19.6 and 14.7% of the cases. The results suggest that the formulas CKD-EPI and MDRD can have applicability in assessing renal function in pregnant women. It was also shown a high frequency of preterm birth or with < 2500g at birth or small for gestational age, as well as of superimposed preeclampsia-eclampsia (24.7%) in pregnant women with chronic hypertension.

Abstract 10756: Chronic Kidney Disease in Long-term Survivors After Fontan Palliation

Background: The Fontan operation is a palliative procedure for children with congenital single ventricle heart disease. With advances in prenatal diagnosis and surgical techniques, more children are surviving into adulthood with unique cardiovascular physiology. Little is currently known about long-term kidney function in these patients. Hypothesis: We hypothesize that long-term survivors after Fontan palliation will have a higher prevalence of chronic kidney disease (CKD) compared to healthy controls. Methods: We performed a retrospective cohort study of subjects evaluated through the Single Ventricle Survivorship Program (SVSP) at the Children’s Hospital of Philadelphia between July 1, 2010 and December 5, 2014 and healthy children similar in sex and age. The primary outcome was CKD, defined as eGFR &lt;90 ml/min/1.73m2 calculated with age-appropriate estimating equations using creatinine and cystatin C. Secondary outcomes included proteinuria and hyperparathyroidism. Results: The Fontan cohort included 68 subjects with mean age of 13.9 years (SD 5.8) at SVSP visit who were 11.2 years (SD 5.7) from Fontan operation. The healthy cohort included 70 patients with mean age of 15.9 years (SD 3.9). Mean eGFR was 102.6 versus 101.9ml/min/1.73m2 (p=0.89) in pediatric Fontan versus healthy subjects using the complete CKiD equation, and 128.5 versus 129.7ml/min/1.73m2 (p=0.56) in adult Fontan versus healthy subjects using the CKD-EPI creatinine and cystatin formula. 10% of Fontan subjects had an eGFR&lt;90 ml/min/1.73m2. Mean intact parathyroid hormone level was higher at 68.0pg/mL (SD 35.4) in the Fontan group compared to 26.0pg/mL (SD 13.6) in the healthy group. Proteinuria was found within 34% of the Fontan group compared to 4.6% within the control group. Conclusion: We found that 10% of subjects have eGFR &lt;90ml/min/1.73m2 after Fontan palliation which would indicate CKD if this remained persistent over time. Although the majority of the cohort had normal kidney function by eGFR, we found a higher proportion with proteinuria and increased parathyroid hormone levels which may indicate early kidney disease. Future studies will focus on evaluating changes in kidney function over time in long-term survivors after Fontan palliation.

KDIGO Guidelines and Kidney Transplantation: Is the Cystatin-C Based Recommendation Relevant?

The KDIGO guidelines propose a new approach to diagnose chronic kidney disease (CKD) based on estimated glomerular filtration rate (GFR). In patients with a GFR value comprised between 45 and 59 mL/min/1.73 m(2) as estimated by the CKD-EPI creatinine equation (eGFRcreat ), it is suggested to confirm the diagnosis with a second estimation using the CKD-EPI cystatin C-based equations (eGFRcys /eGFRcreat-cys) . We sought to determine whether this new diagnostic strategy might extend to kidney transplant recipients (KTR) and help to identify those with decreased GFR. In 670 KTR for whom a measured GFR was available, we simulated the detection of CKD using the two-steps approach recommended by the guidelines in comparison to the conventional approach relying on creatinine equation. One hundred forty-five patients with no albuminuria had eGFRcreat between 45 and 59 mL/min/1.73 m(2) . Among them, 23% had inulin clearance over 60 mL/min/1.73 m(2) and were thus incorrectly classified as CKD patients. When applying the Kidney Disease: Improving Global Outcomes (KDIGO) strategy, 138 patients were confirmed as having a GFR below 60 mL/min with eGFRcreat-cys . However, 21% of them were misclassified in reference to measured GFR. Our data do no not support the use of cystatin C as a confirmatory test of stage 3 A CKD in KTR.

APOL1 Genotype and Glomerular and Tubular Kidney Injury in Women With HIV

APOL1 genotype is associated with advanced kidney disease in African Americans, but the pathogenic mechanisms are unclear. Here, associations of APOL1 genotype with urine biomarkers of glomerular and tubular injury and kidney function decline were evaluated. Observational study. 431 human immunodeficiency virus (HIV)-infected African American women enrolled in Women's Interagency HIV Study (WIHS). APOL1 genotype. Albumin-creatinine ratio (ACR), 4 tubular injury biomarkers (interleukin 18 [IL-18], kidney injury molecule 1 [KIM-1], neutrophil gelatinase-associated lipocalin [NGAL], and α1-microglobulin [A1M]), and kidney function estimated using the CKD-EPI cystatin C equation. Participants were genotyped for APOL1 single-nucleotide polymorphisms rs73885319 (G1 allele) and rs71785313 (G2 allele). Urine biomarkers were measured using stored samples from 1999-2000. Cystatin C was measured using serum collected at baseline and 4- and 8-year follow-ups. At baseline, ACRs were higher among 47 women with 2 APOL1 risk alleles versus 384 women with 0/1 risk allele (median, 24 vs 11mg/g; P<0.001). Compared with women with 0/1 risk allele, women with 2 risk alleles had 104% higher ACRs (95% CI, 29-223mg/g) and 2-fold greater risk of ACR>30 (95% CI, 1.17-3.44) mg/g after multivariable adjustment. APOL1 genotype showed little association with urine IL-18:Cr ratio, KIM-1:Cr ratio, and NGAL:Cr ratio (estimates of-5% [95% CI,-24% to 18%],-20% [95% CI,-36% to -1%], and 10% [95% CI,-26% to 64%], respectively) or detectable urine A1M (prevalence ratio, 1.13; 95% CI, 0.65-1.97) in adjusted analyses. Compared with women with 0/1 allele, women with 2 risk alleles had faster eGFR decline, by 1.2 (95% CI,0.2 to2.2) mL/min/1.73m(2) per year, and 1.7- and 3.4-fold greater rates of incident chronic kidney disease (95% CI, 1.1 to 2.5) and 10% annual eGFR decline (95% CI, 1.7 to 6.7), respectively, with minimal attenuation after adjustment for glomerular and tubular injury biomarker levels. Results may not be generalizable to men. Among HIV-infected African American women, APOL1-associated kidney injury appears to localize to the glomerulus, rather than the tubules.

Impact of Baroreflex Activation Therapy on Renal Function - A Pilot Study

Background/Aims: Resistant hypertension and chronic kidney disease (CKD) are interlinked via sympathetic overdrive. Baroreflex activation therapy (BAT) has been shown to chronically reduce blood pressure (BP) in patients with resistant hypertension. The effect of BAT on renal function in CKD patients with resistant hypertension has not been reported. The aim of this study was to investigate the effect of sympathetic inhibition on renal function in CKD patients. Methods: 23 CKD patients with resistant hypertension were prospectively treated with BAT. Analyses were performed before and 6 months after the start of BAT. The renal function was analyzed by creatinine, cystatin C, glomerular filtration rate (GFR), renin, aldosterone, fractioned and 24-hour sodium excretion and analyses of urine marker proteins. The purpose of the control group was to investigate the influence of treating patients in a center for hypertension and regression to the mean on investigated variables. Results: The office mean BP decreased from 116.9 ± 20.9 mm Hg to 104.2 ± 22.2 mm Hg (p < 0.01), while the number of prescribed antihypertensive classes decreased from 6.6 ± 1.6 to 6.1 ± 1.7 (p = 0.02). Proteinuria and albuminuria decreased from a median of 283.9 and 47.7 to 136.5 (p = 0.01) and 45.0 mg/g creatinine (p = 0.01) with pronounced effects in higher CKD stage III + IV compared to I + II (p < 0.01). CKD-EPI cystatin C equation improved from 53.6 ± 22.7 to 60.4 ± 26.1 ml/min (p = 0.02). While creatinine and GFR were impaired after a period of 6 months, no changes of proteinuria, albuminuria, or BP were obtained in control patients. Conclusion: The data of this prospective trial demonstrate potential nephroprotective effects of BAT in therapy-resistant hypertension in CKD patients by a reduction of BP, proteinuria and moreover, a stabilization of estimated GFR.

Glomerular Filtration Rate Estimation in Prospective Living Kidney Donors: Preliminary Study

IntroductionKidney transplantation prolongs life expectancy in end-stage renal disease patients at a lesser cost than dialysis. Estimation of kidney function is crucial in the evaluation of prospective living kidney donors. Although unsurpassed in their precision methods of glomerular filtration rate (GFR) measurement with exogenous substances are invasive, expensive, and carry a risk for anaphylactic reactions. Alternatively, kidney function can also be assessed by GFR estimation formulas based on serum creatinine or novel markers such as cystatin C or β-trace protein (BTP). The aim of this study was to compare the performance of GFR estimation methods with reference scintigraphy-measured GFR in population of living kidney donor candidates. MethodsWe included 25 prospective kidney donors (aged 28–64 years) and measured GFR with the following equations: Cockcroft-Gault, Modification of Diet in Renal Disease (MDRD), Mayo Clinic, Nankivell, Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI; including cystatin C), and BTP based. GFR were assessed by 99mTc-DTPA for reference. All estimation methods were compared with a reference by general linear models. ResultsThe precision of GFR estimation by all methods is unsatisfactory (30% margin of reference held in <50% of cases). Direction of regression coefficients is negative for some of the methods even when adjusted for body mass index (BMI). Of the study subjects, 64% were overweight/obese. BMI value is significantly correlated with measured GFR (P < .01). CKD-EPI estimation equations are the most precise methods of GFR estimation in this analysis; in addition, CKD-EPI cystatin C and combined creatinine/cystatin C estimators are robust to overweight/obesity. ConclusionsThe precision of GFR estimation is unsatisfactory, in part because of overweight, which adversely influences measured GFR, but also renders estimation methods unusable, except for CKD-EPI cystatin C and combined creatinine/cystatin C formulae. GFR measurement with exogenous substances remains the method of choice in the assessment of kidney function in prospective kidney donors. In addition, it provides useful information on differential (split) renal function.

ABC goal achievement predicts microvascular but not macrovascular complications over 6-years in adults with type 1 diabetes: The Coronary Artery Calcification in Type 1 Diabetes Study

HypothesisVascular complications of type 1 diabetes are thought to cluster. We examined the prevalence and incidence of vascular complications and American Diabetes Association's ABC goal achievements in a prospective cohort of adults with type 1 diabetes. We hypothesized that ABC achievement at baseline would predict both micro- and macrovascular complications over 6-years. MethodsParticipants (N=652) were 19–56 year old at baseline and re-examined 6-years later. Microvascular complications included diabetic nephropathy (DN), defined as incident albuminuria (AER≥20μg/min) or rapid GFR decline (>3.3%/year) by CKD-EPI cystatin C and proliferative diabetic retinopathy (PDR), defined as laser eye-therapy. Macrovascular complications were defined as coronary artery calcium progression (CACp), measured by electron-beam computed-tomography. ABC goals were defined as HbA1c<7.0%, BP<130/80mmHg and LDL-C<100mg/dL. ResultsABC control was suboptimal with only 6% meeting all goals. Meeting no ABC goals at baseline compared to meeting all goals was associated with increased odds of developing microvascular complications (OR: 8.5, 2.3–31.5, p=0.001), but did not reach significance for CACp (OR: 1.7, 0.8–3.9, p=0.19). ConclusionABC achievement at baseline strongly predicted microvascular but not macrovascular complications over 6-years in adults with type 1 diabetes, suggesting a need for novel therapeutic targets to complement conventional risk factors in treating macrovascular complications.

Cystatin C-based renal function changes after antiretroviral initiation: a substudy of a randomized trial.

Background. The effects of antiretrovirals on cystatin C-based renal function estimates are unknown.Methods. We analyzed changes in renal function using creatinine and cystatin C-based estimating equations in 269 patients in A5224s, a substudy of study A5202, in which treatment-naive patients were randomized to abacavir/lamivudine or tenofovir/emtricitabine with open-label atazanavir/ritonavir or efavirenz.Results. Changes in renal function significantly improved (or declined less) with abacavir/lamivudine treatment compared with tenofovir/emtricitabine using the Cockcroft-Gault formula (P = .016) and 2009 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI; P = .030) and 2012 CKD-EPI cystatin C-creatinine (P = .025). Renal function changes significantly improved (or declined less) with efavirenz compared with atazanavir/ritonavir (P < .001 for all equations). Mean (95% confidence interval) renal function changes specifically for tenofovir/emtricitabine combined with atazanavir/ritonavir were −8.3 (−14.0, −2.6) mL/min with Cockcroft-Gault; −14.9 (−19.7, −10.1) mL/min per 1.732 with Modification of Diet in Renal Disease; −12.8 (−16.5, −9.0) mL/min per 1.732 with 2009 CKD-EPI; +8.9 (4.2, 13.7) mL/min per 1.732 with 2012 CKD-EPI cystatin C; and −1.2 (−5.1, 2.6) mL/min per 1.732 with 2012 CKD-EPI cystatin C-creatinine. Renal function changes for the other treatment arms were more favorable but similarly varied by estimating equation.Conclusions. Antiretroviral-associated changes in renal function vary in magnitude and direction based on the estimating equation used.

Glomerular filtration rate as a determinant of free light chains in renal transplantation

BackgroundTransplant patients have an increased incidence of lymphoproliferative disorders. The development of a sensitive immunoassay for serum free light chain (sFLC) determination has improved the diagnosis of monoclonal gammapathy. However, metabolism of FLC largely depends on renal function which could lead to misinterpretation of results. The aim of this study was to assess polyclonal FLC in kidney transplant recipients in relation to markers of renal function. Materials and methods97 renal transplant patients (median transplantation follow-up of 2.2years) were included in this study. Kappa FLC, lambda FLC and cystatin C were measured by particle-enhanced turbidimetric immunoassay (PETIA) using kits from a Binding Site (Birmingham, UK) SPAPLUS® analyzer. Glomerular filtration rate was measured using urinary clearance of 99mTc-DTPA and estimated using CKD-EPI creatinine 2009, CKD-EPI cystatin C 2012 and CKD-EPI creatinine–cystatin C 2012. ResultsSerum kappa FLC was 22.38 [6.39–68.91] mg/L and serum lambda FLC was 15.66 [7.29–50.81] mg/L. Both levels of kappa and lambda were correlated with renal function. Median κ/λ ratio was 1.34 [0.57 to 2.67] leaving 19.6% of renal transplant patients outside the normal reference range [0.26–1.65]. However, using a reference interval normalized by renal function [0.37–3.1], none of our patients was classified as abnormal. Conclusionκ/λ ratio should be cautiously analyzed in renal transplantation and renal function, estimated by creatinine/cystatin C equations should be taken into account.

Validation of a new standardized cystatin C turbidimetric assay: Evaluation of the three novel CKD-EPI equations in hypertensive patients

ObjectivesAnalytical and clinical performances of the new standardized cystatin C particle-enhanced turbidimetric immunoassay (PETIA) using DiaSys reagents on Olympus AU2700® analyzer were evaluated. Design and methodsWe have studied imprecision, linearity, limit of detection and limit of quantification of this new immunoassay. Method comparison was assessed in relation to results generated by the standardized Siemens-particle-enhanced nephelometric immunoassay (PENIA). In order to evaluate the clinical relevance of this assay, estimated glomerular filtration rate (GFR) was calculated using MDRD, CKD-EPI creatinine, CKD-EPI cystatin C 2012 and CKD-EPI creatinine–cystatin C 2012 equations and compared to GFR measured using urinary clearance of 99mTc-DTPA in 100 hypertensive patients. ResultsCystatin C measurements using DiaSys reagents have reliable analytical performances and are comparable to the standardized Siemens-PENIA method (bias of 0.01mg/L). The mean measured GFR was 90.0±29.7mL/min/1.73m2. Bias and accuracy of the three CKD-EPI equations were better than the MDRD. Both CKD-EPI creatinine-based and cystatin C-based formulae had similar bias, precision and accuracy. The combined creatinine–cystatin C equation was significantly more accurate and precise than the CKD-EPI creatinine equation in patients with GFR above 60mL/min/1.73m2. ConclusionsThe use of cystatin C in a combined equation with creatinine could improve the accuracy of eGFR in the reference interval.

Impact of Cardiovascular Organ Damage on Cortical Renal Perfusion in Patients with Chronic Renal Failure

Introduction. Properly preserved renal perfusion is the basic determinant of oxygenation, vitality, nutrition, and organ function and its structure. Perfusion disorders are functional changes and are ahead of the appearance of biochemical markers of organ damage. The aim of this study was to evaluate a relationship between the renal cortex perfusion and markers of cardiovascular organ damage in patients with stable chronic renal failure (CKD). Methods. Seventeen patients (2 F; 15 M; age 47 ± 16) with stable CKD at 2–4 stages and hypertension or signs of heart failure were enrolled in this study. Blood tests with an estimation of renal and cardiac functions, echocardiographic parameters, intima-media thickness (IMT), renal resistance index (RRI), and total (TPI), proximal (PPI), and distal (DPI) renal cortical perfusion intensity measurements were collected. Results. DPI was significantly lower than PPI. TPI significantly correlated with age, Cys, CKD-EPI (cystatin), and IMT, whereas DPI significantly depended on Cystain, CKD-EPI (cystatin; cystatin-creatinine), IMT, NT-proBNP, and troponin I. In multiple stepwise regression analysis model only CKD-EPI (cystatin) independently influenced DPI. Conclusions. Cardiovascular and kidney damage significantly influences renal cortical perfusion. Ultrasound measurement of renal perfusion could be a sensitive method for early investigation of cardiovascular and renal injuries.

Limitations of compensated Jaffe creatinine assays in cirrhotic patients

This study aimed to evaluate the impact of two creatinine measurement methods on the Model for End Stage Liver Disease (MELD) score and glomerular filtration rate estimation (eGFR) in cirrhotic patients. We focused on ID-MS traceable method such as compensated Jaffe (cJafCreat) and enzymatic (EnzCreat) methods. Potential protein-related interferences in creatinine determination were evaluated using dialysates spiked with albumin. MELD score, CKD-EPI formula creatinine-based eGFR and cystatin C-based eGFR were evaluated in 100 cirrhotic patients. In vitro model demonstrated that low protein levels result in an underestimation of creatinine levels using cJafCreat. In patients, cJafCreat created a negative bias of -6.1 μmol/L that led to higher eGFR and lower MELD scores. cJafCreat contributes to an overestimation of renal function in cirrhotic patients and may alter cirrhosis-severity assessment. Compensated Jaffe assays should therefore be replaced by enzymatic methods.

Simple Cystatin C Formula Compared to Sophisticated CKD‐EPI Formulas for Estimation of Glomerular Filtration Rate in the Elderly

Despite the fact that the serum creatinine level is notoriously unreliable for the estimation of glomerular filtration rate (GFR) in the elderly, the serum creatinine concentration and serum creatinine-based formulas, such as the Modification of Diet in Renal Disease study equation (MDRD) are the most commonly used markers to estimate GFR. Recently, serum cystatin C-based formulas, the newer creatinine formula (the Chronic Kidney Disease Epidemiology Collaboration formula (CKD-EPI creatinine formula), and an equation that uses both serum creatinine and cystatin C (CKD-EPI creatinine and cystatin formula) were proposed as new GFR markers. The aim of our study was to compare the MDRD formula, CKD-EPI creatinine formula, CKD-EPI creatinine and cystatin formula, and simple cystatin C formula (100/serum cystatin C) against (51) Cr-EDTA clearance in the elderly. A total of 317 adult Caucasian patients aged >65 years were enrolled. In each patient, (51) Cr-EDTA clearance, serum creatinine, and serum cystatin C were determined, and the GFR was calculated using the MDRD formula, CKD-EPI formulas, and simple cystatin C formula. Statistically significant correlations between (51) Cr-EDTA clearance and all formulas were found. In the receiver operating characteristic (ROC) curve analysis with a cut-off of GFR 45 mL/min/1.73 m(2), a higher diagnostic accuracy was achieved with the equation that uses both serum creatinine and cystatin C (CKD-EPI creatinine and cystatin formula) than the MDRD formula (P < 0.013) or CKD-EPI creatinine formula (P < 0.01), but it was not higher than that achieved for the simple cystatin C formula (P = 0.335). Bland and Altman analysis for the same cut-off value showed that the creatinine formulas underestimated and the simple cystatin C formula overestimated measured GFR. All equations lacked precision. The accuracy within 30% of estimated (51) Cr-EDTA clearance values differ according to the stage of CKD. Analysis of the ability to correctly predict GFR below and above 45 mL/min/1.73 m(2) showed a high prediction for all formulas. Our results indicate that the simple cystatin C formula, which requires just one variable (serum cystatin C concentration), is a reliable marker of GFR in the elderly and comparable to the creatinine formulas, including the CKD-EPI formulas.

Chronic Kidney Disease in Octogenarians

There are limited data on the prevalence of chronic kidney disease (CKD) and its clinical importance in the very old. We examined the prevalence of CKD in octogenarians and its association with cardiovascular disease (CVD). In a cross-sectional analysis of 1028 participants from the Cardiovascular Health Study All Stars, we evaluated association of prevalent CKD with CVD using multivariable logistic regression. CKD was defined as eGFR of <60 ml/min per 1.73 m(2). GFR was estimated using CKD-Epi creatinine and cystatin C equations that incorporate coefficients for age, gender, and race (eGFR(EPI), eGFR(CYS3var)) and the one-variable cystatin C equation (eGFR(CYS1var)). Prevalent CVD was defined as a composite of coronary heart disease, heart failure, and stroke. Mean age was 86 years, 64% were women, 86% were Caucasians, 14% had diabetes, and 39% had prevalent CVD. Mean eGFR(EPI), eGFR(CYS3var), and eGFR(CYS1var) were 59, 62, and 70 ml/min per 1.73 m(2), and 51%, 46%, and 33% had CKD, respectively. Associations of CKD with CVD varied by equation in adjusted analyses: CKD(EPI) (OR, 1.53; 95% CI, 1.15 to 2.03), CKD(CYS3var) (OR, 1.67; 95% CI, 1.25, 2.23), and CKD(CYS1var) (OR, 2.09; 95% CI, 1.55, 2.83). Reduced eGFR is highly prevalent in octogenarians, and the eGFR(CYS1var) equation yielded the lowest prevalence of CKD but the strongest association with prevalent CVD. Because there are no validated estimating equations in the elderly, estimation of kidney function on the basis of on any one equation should be interpreted with caution.