Creatinine-based eGFR Research Articles

Cystatin C as a novel predictor of preterm labor in severe preeclampsia.

BackgroundThe most common cause of acute kidney injury (AKI) in pregnancy is preeclampsia. Serum cystatin C (CysC) is a potential biomarker of early kidney damage as its levels are not disturbed by volume status changes in pregnancy, and serum CysC levels could serve as a replacement for conventionally used creatinine. In this study, we investigated the serum levels of CysC in severe preeclampsia cases and the associations between CysC levels and poor obstetric outcomes.MethodsOur cohort included severe preeclampsia patients with a normal serum creatinine level. Creatinine was measured to calculate estimated glomerular filtration rate (eGFR) based on the Cockcroft and Gault, Modification of Diet in Renal Disease Study (MDRD), and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations, while CysC was measured to calculated eGFR based on a CysC-based equation. We then evaluated the correlations between serum CysC level, eGFR, and obstetric outcomes.ResultsTwenty-six patients were evaluated of which 38.5% delivered preterm and 30.8% had low-birth weight babies. Unlike creatinine-based eGFR and CysC-based eGFR, serum CysC demonstrate significant negative correlation with gestational age. Receiver operating characteristic curve analysis indicated that serum CysC is a potential biomarker of preterm delivery with a cut-off serum level of 1.48 mg/L with 80% sensitivity and 75% specificity.ConclusionGFR estimation using CysC is likely to be inaccurate in pregnancy. However, we found a significant correlation between preterm delivery and serum CysC level. Our results suggest that serum CysC level has the potential to predict preterm delivery in severe preeclampsia patients.

Cystatin C and creatinine-based eGFR levels and their correlation to long-term morbidity and mortality in older adults

BackgroundThe prevailing diagnostic criteria for CKD are age-independent, but have been challenged in light of the eGFR decline associated with normal aging. The stages of CKD communicate magnitude of risk of ESRD, cardiovascular morbidity, and mortality.AimsThis study aims to provide more insight into the morbidity and mortality associated with eGFR levels corresponding to the current CKD stages in older adults.MethodsThe 2931 older adults in the Good Aging in Skåne study were randomized from the general population. The exposure variable used was eGFR level (CKD-EPI based on creatinine and cystatin C) with eGFR 60–89 mL/min/1.73 m2 as a reference; the outcomes were mortality, acute cardiovascular disease, congestive heart failure, and rapid kidney function decline (RKFD; defined as a decline in eGFR by 3 mL/min/1.73 m2 per year or more).ResultsThe mean age at baseline was 73 (SD 11) and mean follow-up time 11 (SD 5) years. Mortality was higher at lower eGFR levels with adjusted HR (95% CI) being 1.58 (1.34–1.88), 1.22 (1.05–1.41), 1 (reference), and 0.90 (0.67–1.21) for eGFR < 45, 45–59, 60–89 and ≥ 90 mL/min/1.73 m2, respectively. For acute CVD the adjusted HR (95% CI) were 1.23 (0.81–1.87), 1.21 (0.87–1.69), 1 (reference), and 0.53 (0.28–1.00) for the same eGFR levels.ConclusionsThis study confirms that mortality in older adults increases with decreasing eGFR at eGFR levels below today’s threshold for CKD. The correlation was less certain for lower eGFR and incident cardiovascular disease.

Agreement between Creatinine and Cystatin C-Based Equations in the Estimation of Glomerular Filtration Rate among Malaysian Patients with Renal Impairment

Abstract: Background: Cystatin C-based equations have been proposed as an alternative for creatinine-based equations in the estimation of Glomerular Filtration Rate (eGFR). Limited studies were available with regards to the Asian population to evaluate the agreement of eGFR measured based on both biomarkers. This study aimed to evaluate the agreement between various cystatin C- and creatinine-based eGFR equations. Methods: Patients were recruited from the Nephrology Clinic Universiti Kebangsaan Malaysia Medical Centre. Serum cystatin C and creatinine levels were analysed by particle-enhanced immunoturbidimetry assay and kinetic alkaline picrate method, respectively. Various cystatin C-based (Hoek, Larsson, Grubb, Flodin, cystatin C-based Chronic Kidney Disease Epidemiology (CKD-EPI)) and creatinine-based eGFR equations (Cockcroft-Gault, Modification of Diet in Renal Disease, creatinine-based CKD-EPI) were compared by using the Pearson’s correlation and Bland-Altman plot. Results: A total of 118 patients included in this study have a mean age of 61±15 years and 57.6% were female. The mean serum cystatin C and creatinine levels were 2.00±1.06 mg/L and 2.21±1.63 mg/dL, respectively. The correlation between serum cystatin C and creatinine level was significant (r=0.78, P<0.01). All cystatin C-based eGFR correlated significantly with the creatinine-based eGFR equations. The strongest correlation was between creatininebased and cystatin C-based CKD-EPI equation (r=0.93, P<0.01). The Bland-Altman plot shows that cystatin C-based CKD-EPI equation had the least mean difference when compared with creatinine-based CKD-EPI equation. Conclusion: Significant correlation and good agreement were demonstrated between various cystatin C-based and creatininebased eGFR equations. The cystatin C-based equations are appropriate alternative for GFR measurement among Malaysian patients with renal impairment. Key words: Cystatin C, Creatinine, Estimated Glomerular Filtration Rate, Renal Function, Renal Elimination, Chronic Kidney Disease.

Creatinine-Based Renal Function Estimates and Dosage of Postoperative Pain Management for Elderly Acute Hip Fracture Patients.

Many analgesics and their metabolites are renally excreted. The widely used Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)-estimated glomerular filtration rate (eGFR) equations are not developed for use in the elderly, while the recent Berlin Initiative Study (BIS), Full Age Spectrum (FAS), and Lund-Malmö revised (LMR) equations are. This observational study investigated differences between creatinine-based eGFR equations and how the choice of equation influences dosage of analgesics in elderly (≥70 years) patients admitted with acute hip fracture. eGFR was calculated by the CKD-EPI, BIS, Cockcroft-Gault (CG), FAS, LMR, and Modification of Diet in Renal Disease (MDRD) equations. Standard daily dose for postoperative pain medications ibuprofen, morphine and gabapentin was simulated for each equation according to dosage recommendations in Renbase®. For 118 patients, mean eGFR from the CKD-EPI, BIS, CG, FAS, LMR, and MDRD equations was 67.3 mL/min/1.73 m2, 59.1 mL/min/1.73 m2, 56.9 mL/min/1.73 m2, 60.3 mL/min/1.73 m2, 58.9 mL/min/1.73 m2, and 79.1 mL/min/1.73 m2, respectively (p < 0.0001). Mean difference to CKD-EPI was −10.4 mL/min/1.73 m2 to 11.8 mL/min/1.73 m2. Choice of eGFR equation significantly influenced the recommended dose (p < 0.0001). Shifting to BIS, FAS, or LMR equations led to a lower recommended dose in 20% to 31% of patients. Choice of eGFR equation significantly influenced dosing of ibuprofen, morphine, and gabapentin.

Estimated glomerular filtration rate and functional status among older people: A systematic review

BackgroundThe association between chronic kidney disease (CKD) and functional status may change as a function of the equation used to estimate glomerular filtration rate (eGFR). We reviewed the predictive value of different eGFR equations in regard to frailty and disability outcomes. MethodsWe searched Pubmed from inception to March 2018 for studies investigating the association between eGFR and self-reported and/or objective measures of frailty or disability. Cross-sectional and longitudinal studies were separately analysed. ResultsWe included 16 studies, one of which reporting both cross-sectional and longitudinal data. Three out of 7 cross-sectional studies compared different eGFR equations in regard to their association with functional status: two studies showed that cystatin C-based, but not creatinine-based eGFR may be associated with hand-grip strength or frailty; another study showed that two different creatinine-based eGFR equations may be similarly associated with disability. Four out of 10 longitudinal studies provided comparative data: two studies reported similar association with disability for different creatinine-based eGFR equations; one study showed that creatinine-based eGFR was not associated with frailty, but a not significant trend for association was observed with cystatin C-based eGFR; one study showed that cystatin C-based but not creatinine-based eGFR may predict incident mobility disability, while both methods may predict gait speed decline. High heterogeneity was observed in regard to confounders included in reviewed studies. None of them included the most recently published equations. ConclusionAvailable data do not support the superiority of one of the eGFR equations in terms of measuring or predicting functional decline.

Association of cystatin C- and creatinine-based eGFR with osteoporotic fracture in Japanese postmenopausal women with osteoporosis: sarcopenia as risk for fracture.

Coexistence of chronic kidney disease (CKD) is regarded as a risk for osteoporotic fracture particularly in postmenopausal women, not only because of increased parathyroid hormone level but also uremic sarcopenia. We examined the relationships of cystatin C-based glomerular filtration rate (eGFRcys) and creatinine-based GFR (eGFRcr), as well as their ratio with occurrence of osteoporotic fracture in postmenopausal osteoporotic women. This cross-sectional study included 555 postmenopausal women with osteoporosis. eGFRcr and eGFRcys were simultaneously measured, while occurrence of osteoporotic fracture was obtained by a medical chart review. Patients with osteoporotic fractures (n=211) exhibited significantly lower levels of physical activity, eGFRcr, eGFRcys, and eGFRcys/eGFRcr ratios, while a higher percentage was CKD stage 3 or more, estimated by eGFRcr or eGFRcys (CKDcys), than those without (n=344). Lower eGFRcys, but not lower eGFRcr, was independently associated with osteoporotic fracture in the entire cohort and that association was retained in CKDcys patients. Of great interest, higher eGFRcr was associated with osteoporotic fracture independent of eGFRcys in CKDcys patients. Furthermore, lower eGFRcys/eGFRcr ratio was independently associated with osteoporotic fracture in both CKDcys patients and the entire cohort. eGFRcys reduction might be associated with osteoporotic fracture in postmenopausal osteoporotic women, indicating the involvement of renal osteopathy in its occurrence. Furthermore, the association of higher, but not lower, eGFRcr with osteoporotic fracture in CKDcys cases might be explained by underestimation of renal dysfunction by eGFRcr resulting from decreased muscle mass and quality in those patients.

Existing creatinine-based equations overestimate glomerular filtration rate in Indians

BackgroundAccurate estimation of glomerular filtration rate (GFR) is important for diagnosis and risk stratification in chronic kidney disease and for selection of living donors. Ethnic differences have required correction factors in the originally developed creatinine-based GFR estimation equations for populations around the world. Existing equations have not been validated in the vegetarian Indian population. We examined the performance of creatinine and cystatin-based GFR estimating equations in Indians.MethodsGFR was measured by urinary clearance of inulin. Serum creatinine was measured using IDMS-traceable Jaffe’s and enzymatic assays, and cystatin C by colloidal gold immunoassay. Dietary protein intake was calculated by measuring urinary nitrogen appearance. Bias, precision and accuracy were calculated for the eGFR equations.ResultsA total of 130 participants (63 healthy kidney donors and 67 with CKD) were studied. About 50% were vegetarians, and the remainder ate meat 3.8 times every month. The average creatinine excretion were 14.7 mg/kg/day (95% CI: 13.5 to 15.9 mg/kg/day) and 12.4 mg/kg/day (95% CI: 11.2 to 13.6 mg/kg/day) in males and females, respectively. The average daily protein intake was 46.1 g/day (95% CI: 43.2 to 48.8 g/day). The mean mGFR in the study population was 51.66 ± 31.68 ml/min/1.73m2. All creatinine-based eGFR equations overestimated GFR (p < 0.01 for each creatinine based eGFR equation). However, eGFR by CKD-EPICys was not significantly different from mGFR (p = 0.38). The CKD-EPICys exhibited lowest bias [mean bias: −3.53 ± 14.70 ml/min/1.73m2 (95% CI: -0.608 to −0.98)] and highest accuracy (P30: 74.6%). The GFR in the healthy population was 79.44 ± 20.19 (range: 41.90–134.50) ml/min/1.73m2.ConclusionExisting creatinine-based GFR estimating equations overestimate GFR in Indians. An appropriately powered study is needed to develop either a correction factor or a new equation for accurate assessment of kidney function in the Indian population.

Prevalence and determinants of differences in cystatin C and creatinine-based estimated glomerular filtration rate in community-dwelling older adults: a cross-sectional study

BackgroundDifferences in cystatin C and creatinine-based estimated glomerular filtration rate (eGFR) can lead to clinical uncertainty. Existing eGFR equations perform poorly in a subset of individuals. This study aims to describe the prevalence of differences between cystatin C-based (eGFRcys) and creatinine-based (eGFRcreat) eGFR in older adults and to explore which subsets of individuals may be most affected by differing estimations.MethodsIn this cross-sectional study, participants from a cohort of community-dwelling older adults were examined at a baseline visit in 2001-2004 as part of the larger “Good Aging in Skåne” study. Exposure variables were obtained from questionnaires, interviews, examinations, and medical records. Blood samples were taken during the baseline visit, cryopreserved, and analyzed at a later time for biomarkers. The CKD-EPI equations were used to estimate GFR. Initial descriptive analyses were performed on 2931 individuals. A total of 2532 participants were included in the final multiple linear regression.ResultsNearly two-thirds of participants had eGFR differences exceeding 10%, with nearly 20 % of participants having eGFR differences exceeding 30%. Smoking, age, body mass index (BMI), C-reactive protein (CRP), glucocorticoid use, and mean eGFR were correlated with differences between eGFRcreat and eGFRcys.ConclusionsDifferences between eGFRcreat and eGFRcys are common and often of large magnitude in this community-dwelling population of older adults. The finding of multiple non-GFR determinants correlated to differences in GFR estimations can help direct future research to improve eGFR equations for subgroups prone to conflicting GFR estimations or to guide choice of biomarker for GFR estimation in these subgroups.

Albuminuria and kidney function as prognostic marker of left ventricular mass among South Asians with hypertension

We aimed to evaluate the association of albuminuria and estimated glomerular filtration rate (eGFR) at baseline and changes in these parameters with left ventricular mass index (LVMI) at 7 years in adults with hypertension from communities in Pakistan. A nested cohort of 539 hypertensives aged 40 years and older from a community-living population in Karachi, Pakistan, followed up for 7 years in the Control of Blood Pressure and Risk Attenuation trial. Urine spot albumin-to-creatinine ratio (UACR) and serum creatinine-based eGFR were assessed at baseline and 7 years, and echocardiography at 7 years. Mean age of participants was 50.9 ± 9.1 (standard deviation) years; 63% were female. Mean eGFR was 91.0 ± 15.9 (standard deviation) mL/min/1.73 m2 and median (interquartile range) UACR 6.2 (3.9, 11.3) mg/g. In multivariate analysis, although baseline eGFR was marginally associated with LVMI, a strong association was found between higher LVMI with greater rate of decline in eGFR (β = −1.05; 95% confidence interval [CI]: [−1.94, −0.17]). Higher baseline UACR was significantly associated with higher follow-up LVMI (β = 2.26; 95% CI: [0.87, 3.65]), as was rate of UACR increase of ≥1.07 mg/g/y versus of <0.14 mg/g/y. (β = 4.19; 95% CI: [0.75, 7.63]). Associations with developing left ventricular hypertrophy were found for reduced baseline eGFR, higher baseline UACR, and greater rate of UACR increase, but not for rate of eGFR decline. Comparable results were observed for the outcomes of posterior wall thickness and septal wall thickness. Higher baseline albuminuria, lower baseline eGFR, and their longitudinal worsening were significantly associated with higher LVMI or the development of left ventricular hypertrophy among individuals with hypertension in Pakistan.

Establishing the presence or absence of chronic kidney disease: Uses and limitations of formulas estimating the glomerular filtration rate.

The development of formulas estimating glomerular filtration rate (eGFR) from serum creatinine and cystatin C and accounting for certain variables affecting the production rate of these biomarkers, including ethnicity, gender and age, has led to the current scheme of diagnosing and staging chronic kidney disease (CKD), which is based on eGFR values and albuminuria. This scheme has been applied extensively in various populations and has led to the current estimates of prevalence of CKD. In addition, this scheme is applied in clinical studies evaluating the risks of CKD and the efficacy of various interventions directed towards improving its course. Disagreements between creatinine-based and cystatin-based eGFR values and between eGFR values and measured GFR have been reported in various cohorts. These disagreements are the consequence of variations in the rate of production and in factors, other than GFR, affecting the rate of removal of creatinine and cystatin C. The disagreements create limitations for all eGFR formulas developed so far. The main limitations are low sensitivity in detecting early CKD in several subjects, e.g., those with hyperfiltration, and poor prediction of the course of CKD. Research efforts in CKD are currently directed towards identification of biomarkers that are better indices of GFR than the current biomarkers and, particularly, biomarkers of early renal tissue injury.

Possible risk of overestimation of renal function using cystatin C-based eGFR in testicular cancer survivors treated with cisplatin-based chemotherapy.

Chronic kidney disease (CKD) is a major long-term morbidity of testicular cancer (TC) survivors cured by cisplatin-based chemotherapy. We conducted the present study to elucidate the usefulness of cystatin-based estimated glomerular filtration rates (eGFRcys) for diagnosis of CKD compared to creatinine-based eGFR (eGFRcreat) in those patients. eGFRcys and eGFRcreat were measured in 53 TC survivors. The 24-h creatinine clearance (CrCl) was measured in 12 TC survivors and 17 CKD patients with medical disease; all of them had eGFRcreat <60m/min/1.73m2. Also, urinary beta2-microglobulin and albumin concentrations in spot urine specimens were measured. The mean eGFRcreat was significantly lower than eGFRcys, at 67.9 and 95.2ml/min/1.73m2, respectively (p<0.05). The prevalence of stage 3-5 CKD differed by GFR estimation methods. It was 47.2% with eGFRcreat and only 7.5% with eGFRcys. There were 21 patients with eGFRcreat <60ml/min/1.73m2 and eGFRcys ≥60ml/min/1.73m2. In all 12 TC survivors, the eGFRcys values were higher than both eGFRcreat and GFR (24-h CrCl). In contrast, no difference was observed among eGFR values in the 17 patients with CKD due to medical disease. Ten of 21 patients with eGFRcreat <60ml/min/1.73m2 and eGFRcys ≥60ml/min/1.73m2 showed significant beta2-microglobulinuria: a higher prevalence than that in patients with both eGFRs ≥60ml/min/1.73m2. Also, the incidence of microalbuminuria tended to be high in those patients. The present study suggests that eGFRcys may overestimate renal function in TC survivors cured by cisplatin-based chemotherapy.

Kidney function, bone-mineral metabolism markers, and future risk of peripheral artery disease

Background and aimsReduced kidney function is a risk factor for lower-extremity peripheral artery disease (PAD). However, the associations of novel filtration markers with PAD are yet to be quantified. Moreover, little is known on whether bone-mineral metabolism (BMM) markers are related to incident PAD beyond kidney function. MethodsUsing data from 12,472 participants at baseline (1990–1992) of the Atherosclerosis Risk in Communities (ARIC) study, we comprehensively quantified the associations of kidney related markers with incident PAD (defined as hospitalizations with diagnosis of lower-extremity atherosclerosis, revascularization, or amputation). Kidney related markers of interest included estimated glomerular filtration rate (eGFR) (based on creatinine, cystatin C, and both), cystatin C, beta-2 microglobulin (B2M), and BMM markers (serum fibroblast growth factor 23, parathyroid hormone, calcium, and phosphorus). ResultsDuring a median follow-up of 21 years, 471 participants developed incident PAD. Low eGFR was significantly associated with future PAD risk, with slightly stronger relationship when cystatin C was used (adjusted hazard ratio [HR] 6.3–8.3 for eGFR <30 and 2.4–3.5 for eGFR 30–59 vs. eGFR ≥90 mL/min/1.73 m2). Among all filtration markers, B2M had the strongest association with incident PAD (HR for top vs. bottom quartile 2.60 [95% CI: 1.91–3.54] for B2M vs. 1.20 [0.91–1.58] for creatinine-based eGFR). Among BMM markers, only phosphorus remained significant for PAD risk beyond potential confounders, including kidney function (HR 1.47 [1.11–1.94] in top quartile). ConclusionsKidney dysfunction was independently associated with future PAD risk, particularly when assessed with cystatin C and B2M. Among the BMM markers tested, phosphorus was most robustly associated with incident PAD beyond kidney function. Our results suggest the potential usefulness of novel filtration markers for PAD risk assessment and the possible role of phosphorus in the pathophysiology of PAD.

Kidney Function, Proteinuria, and Cancer Incidence: The Korean Heart Study

Reported associations of estimated glomerular filtration rate (eGFR) with cancer risk are inconsistent, and data for the proteinuria-cancer relationship are sparse. We sought to quantify the associations of cancer incidence with eGFR and with proteinuria in a large population-based cohort. A prospective cohort study. 242,583 adults (30-74 years old) without a diagnosis of cancer at baseline in the Korean Heart Study, based on health checkups in 1996 to 2004 with follow-up until2012. Creatinine-based eGFR (≥90, 60-89, 45-59, and<45mL/min/1.73m2) and dipstick proteinuria (undetectable/trace, 1+, 2+, and≥3+). Overall and site-specific cancer incidence based on ICD-10 codes. 15,165 cases of cancer were detected. The relationship between eGFR and incidence of any cancer was J shaped, with the lowest risk at 45 to 59mL/min/1.73m2. There was 44% higher risk for any cancer among those with eGFRs<45mL/min/1.73m2 compared with those with eGFRs≥90mL/min/1.73m2 (HR, 1.44; 95% CI, 1.11-1.87). High proteinuria was also associated with cancer risk, showing a dose-response relationship (HRs of 1.24 [95% CI, 1.13-1.35], 1.38 [95% CI, 1.17-1.63], and 1.66 [95% CI, 1.30-2.12] for 1+, 2+, and≥3+ vs undetectable/trace). Examining site-specific cancer, eGFR<45 (vs≥45) mL/min/1.73m2 was significantly associated with kidney and ureteral cancer, multiple myeloma, and leukemia, whereas proteinuria≥ 1+ (vsundetectable/trace) was related to a broader set of cancers (ie, stomach, rectal, liver, lung, ovarian, kidney, bladder, and multiple myeloma). After excluding study participants with follow-up less than 3 years, the associations remained consistent for kidney cancer and myeloma with eGFR and for rectal, liver, lung, and ovarian cancer with proteinuria. Relatively small number of participants with severely reduced eGFR or 70 years or older. Kidney measures, particularly proteinuria, were associated with increased incidence of cancer. Future studies are needed to better understand the pathophysiologic mechanisms underlying these associations.

Accurate eGFR reporting for children without anthropometric data

IntroductionReporting estimated glomerular filtration rate (eGFR) instead of serum concentrations is advised in current guidelines. Most creatinine-based eGFR equations for children require height, a parameter not readily available to laboratories. Combining height-dependent creatinine- and cystatin C-based eGFR improves performance. Recently, a height-independent creatinine-based eGFR equation has been developed. AimTo compare the combination of height-independent creatinine- and cystatin C-based equations with a combination of equations using anthropometric data. MethodsRetrospective analysis of 408 pediatric inulin clearance studies with simultaneous height, creatinine, cystatin C and urea measurements. eGFR calculation using the recalibrated Schwartzcrea (height-dependent), FASage (height-independent) and the Schwartzcys equation. The means (Schwartzcrea+Schwartzcys)/2 and (FASage+Schwartzcys)/2 were compared with the CKiD3 equation incorporating cystatin C, creatinine, urea, height and gender in terms of %prediction error and accuracy. ResultsAll three single parameter equations performed similarly (P30 accuracy around 80%). (FASage+Schwartzcys)/2 (P30 89.2%) and (Schwartzcrea+Schwartzcys)/2 (P30 89.0%), performed comparably to CKiD3 (P30 90.0%). If the difference between the creatinine- and the cystatine C based eGFR was <40%, P30 accuracy of the mean exceeded 90%. ConclusionCombining the height-independent FASage and SchwartzCys equations substantially improves accuracy and performs comparably to height-dependent equations. This allows laboratories to directly report eGFR in children.

Community burden and prognostic impact of reduced kidney function among patients hospitalized with acute decompensated heart failure: The Atherosclerosis Risk in Communities (ARIC) Study Community Surveillance.

BackgroundKidney dysfunction is prevalent and impacts prognosis in patients with acute decompensated heart failure (ADHF). However, most previous reports were from a single hospital, limiting their generalizability. Also, contemporary data using new equation for estimated glomerular filtration rate (eGFR) are needed.Methods and resultsWe analyzed data from the ARIC Community Surveillance for ADHF conducted for residents aged ≥55 years in four US communities between 2005–2011. All ADHF cases (n = 5, 391) were adjudicated and weighted to represent those communities (24,932 weighted cases). The association of kidney function (creatinine-based eGFR by the CKD-EPI equation and blood urea nitrogen [BUN]) during hospitalization with 1-year mortality was assessed using logistic regression. Based on worst and last serum creatinine, there were 82.5% and 70.6% with reduced eGFR (<60 ml/min/1.73m2) and 37.4% and 26.6% with severely reduced eGFR (<30 ml/min/1.73m2), respectively. Lower eGFR (regardless of last or worst eGFR), particularly eGFR <30 ml/min/1.73m2, was significantly associated with higher 1-year mortality independently of potential confounders (odds ratio 1.60 [95% CI 1.26–2.04] for last eGFR 15–29 ml/min/1.73m2 and 2.30 [1.76–3.00] for <15 compared to eGFR ≥60). The association was largely consistent across demographic subgroups. Of interest, when both eGFR and BUN were modeled together, only BUN remained significant.ConclusionsSeverely reduced eGFR (<30 ml/min/1.73m2) was observed in ~30% of ADHF cases and was an independent predictor of 1-year mortality in community. For prediction, BUN appeared to be superior to eGFR. These findings suggest the need of close attention to kidney dysfunction among ADHF patients.

Measures of chronic kidney disease and risk of incident peripheral artery disease: a collaborative meta-analysis of individual participant data

Some evidence suggests that chronic kidney disease is a risk factor for lower-extremity peripheral artery disease. We aimed to quantify the independent and joint associations of two measures of chronic kidney disease (estimated glomerular filtration rate [eGFR] and albuminuria) with the incidence of peripheral artery disease. In this collaborative meta-analysis of international cohorts included in the Chronic Kidney Disease Prognosis Consortium (baseline measurements obtained between 1972 and 2014) with baseline measurements of eGFR and albuminuria, at least 1000 participants (this criterion not applied to cohorts exclusively enrolling patients with chronic kidney disease), and at least 50 peripheral artery disease events, we analysed adult participants without peripheral artery disease at baseline at the individual patient level with Cox proportional hazards models to quantify associations of creatinine-based eGFR, urine albumin-to-creatinine ratio (ACR), and dipstick proteinuria with the incidence of peripheral artery disease (including hospitalisation with a diagnosis of peripheral artery disease, intermittent claudication, leg revascularisation, and leg amputation). We assessed discrimination improvement through c-statistics. We analysed 817 084 individuals without a history of peripheral artery disease at baseline from 21 cohorts. 18 261 cases of peripheral artery disease were recorded during follow-up across cohorts (median follow-up was 7·4 years [IQR 5·7-8·9], range 2·0-15·8 years across cohorts). Both chronic kidney disease measures were independently associated with the incidence of peripheral artery disease. Compared with an eGFR of 95 mL/min per 1·73 m2, adjusted hazard ratios (HRs) for incident study-specific peripheral artery disease was 1·22 (95% CI 1·14-1·30) at an eGFR of 45 mL/min per 1·73 m2 and 2·06 (1·70-2·48) at an eGFR of 15 mL/min per 1·73 m2. Compared with an ACR of 5 mg/g, the adjusted HR for incident study-specific peripheral artery disease was 1·50 (1·41-1·59) at an ACR of 30 mg/g and 2·28 (2·12-2·44) at an ACR of 300 mg/g. The adjusted HR at an ACR of 300 mg/g versus 5 mg/g was 3·68 (95% CI 3·00-4·52) for leg amputation. eGFR and albuminuria contributed multiplicatively (eg, adjusted HR 5·76 [4·90-6·77] for incident peripheral artery disease and 10·61 [5·70-19·77] for amputation in eGFR <30 mL/min per 1·73 m2 plus ACR ≥300 mg/g or dipstick proteinuria 2+ or higher vs eGFR ≥90 mL/min per 1·73 m2 plus ACR <10 mg/g or dipstick proteinuria negative). Both eGFR and ACR significantly improved peripheral artery disease risk discrimination beyond traditional predictors, with a substantial improvement prediction of amputation with ACR (difference in c-statistic 0·058, 95% CI 0·045-0·070). Patterns were consistent across clinical subgroups. Even mild-to-moderate chronic kidney disease conferred increased risk of incident peripheral artery disease, with a strong association between albuminuria and amputation. Clinical attention should be paid to the development of peripheral artery disease symptoms and signs in people with any stage of chronic kidney disease. American Heart Association, US National Kidney Foundation, and US National Institute of Diabetes and Digestive and Kidney Diseases.

Kidney dysfunction and silent brain infarction in generally healthy adults

BackgroundThe association between silent brain infarction (SBI) and estimated glomerular filtration rate (eGFR)-based kidney dysfunction has not yet been definitively confirmed. This study aimed to investigate the association in generally healthy adults without a previous history of stroke or overt kidney disease. MethodsThe data from the screening health check-up program in the Seoul National University Hospital Health Promotion Center from January 1, 2009 to December 31, 2013 were used. A total of 2594 subjects who underwent brain MRI as part of health screening were included. SBIs were identified using T2-weighted and FLAIR images. Kidney dysfunction was defined as eGFR<60ml/min/1.73m2. To assess the effect of kidney dysfunction on the small perforating branches of cerebral vessels, subgroup analysis was performed using the presence of SLI as a dependent variable. ResultsThe mean age was 56.8±9.3years, and 1422 subjects (54.8%) were male. The mean eGFR level was 81.9±15.4ml/min/1.73m2. The prevalence rates of kidney dysfunction and SBI were 5.1% and 7.1%, respectively. A higher proportion of subjects with SBI had kidney dysfunction than subjects without SBI (14.6% vs. 4.4%). The number of SBI lesions tended to increase with the progression of kidney dysfunction (p for trend<0.001). In multivariate logistic regression analyses, kidney dysfunction was significantly associated with the presence of SBI (adjusted odd ratio=1.99 to 2.21 in all four models). The same significant association was consistently identified in subgroup analyses using silent lacunar infarction (adjusted odd ratio=1.71 to 1.87 in all four models). ConclusionKidney dysfunction was found to be an independent risk factor for the presence and number of SBI in generally healthy adults. Physicians treating patients with a decreased creatinine-based eGFR level should try to identify and modify the coexisting risk factors of stroke followed by SBI.

Abstract TP173: Kidney Dysfunction and Silent Brain Infarction in Generally Healthy Adults

Purpose: The association between silent brain infarction (SBI) and estimated glomerular filtration rate (eGFR)-based kidney dysfunction has not yet been definitively confirmed. This study aimed to investigate the association in generally healthy adults without a previous history of stroke or overt kidney disease. Methods: A total of 2,594 subjects who underwent brain MRI as part of health screening were included. SBIs were identified using gradient-recalled echo MRI. Kidney dysfunction was defined as eGFR &lt; 60 ml/min/1.73 m 2 . Results: The mean age was 56.8 ± 9.3 years, and 1,422 subjects (54.8%) were male. The mean eGFR level was 81.9 ± 15.4 ml/min/1.73 m 2 . The prevalence rates of kidney dysfunction and SBI were 5.1% and 7.1%, respectively. A higher proportion of subjects with SBI had kidney dysfunction than subjects without SBI (14.6% vs. 4.4%). The number of SBI lesions tended to increase with the progression of kidney dysfunction (p for trend &lt; 0.001). In multivariate logistic regression analyses, kidney dysfunction was significantly associated with the presence of SBI (adjusted odd ratio = 1.99 to 2.21 in all four models). The same significant association was consistently identified in subgroup analyses using silent lacunar infarction (adjusted odd ratio = 1.71 to 1.87 in all four models). Conclusion: Kidney dysfunction was found to be an independent risk factor for the presence and number of SBI in generally healthy adults. Physicians treating patients with a decreased creatinine-based eGFR level should try to identify and modify the coexisting risk factors ofstroke followed by SBI.

Which creatinine-based estimated glomerular filtration rate equation best predicts all-cause mortality in Chinese subjects with type 2 diabetes?

In Chinese, ethnicity-based and/or diabetes specific modifications of the Modification of Diet in Renal Disease (MDRD) and the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations have been developed for determining estimated glomerular filtrate rate (eGFR). This study aimed to compare the performance of five different creatinine-based eGFR equations in predicting all-cause mortality among Chinese subjects with type 2 diabetes (T2DM). A total of 6739 Chinese subjects with T2DM were included. Their eGFR was calculated using the MDRD, CKD-EPI, their respective modified equations for Chinese, and the diabetes specific CKD-EPI Chinese T2DM equations. Multiple Cox regression analysis was used to evaluate the associations of eGFR with all-cause mortality. C-statistics, net reclassification index (NRI) and integrated discrimination index (IDI) were applied to assess the discrimination and reclassification of each eGFR equation in predicting mortality outcome. Over a follow-up of 5.7years, the incidence of all-cause mortality was 12.9% (N=867). The CKD-EPI equation discriminated all-cause mortality better than the MDRD equation (C-statistics: 0.714 vs. 0.689, p<0.0001), and Chinese modification of their respective equations did not improve discrimination. Among the five eGFR equations evaluated, the CKD-EPI Chinese T2DM equation provided the best discrimination in predicting all-cause mortality among Chinese subjects with T2DM, and was the only equation providing a significantly positive NRI and IDI relative to the CKD-EPI equation. Among Chinese subjects with T2DM, our findings suggested that the CKD-EPI Chinese T2DM equation best predicted all-cause mortality, and relative to the CKD-EPI equation, conferred improved discrimination and reclassification.

Cystatin C and the Risk of Frailty and Mortality in Older Men.

This study examines the association between cystatin C (cysC) levels and risks of progression of frailty status or death in older men. Prospective study of 2,613 men without overt frailty aged 67 years and older enrolled in the MrOS ancillary sleep study. Baseline measurements included serum cysC, serum creatinine, and frailty status. Repeat frailty status, performed an average of 3.4 years later, was assessed as an ordinal outcome of robust, intermediate stage (prefrail), frail or dead. Mean age was 75.7 years. Men with higher cysC were older and had a higher comorbidity burden. After adjusting for age, clinical site, and race, higher cysC was associated with nearly twofold greater odds of being classified as intermediate stage versus robust (OR quartile 4 vs 1; 1.82, 95% confidence interval [CI] 1.35-2.45), a threefold greater odds of frailty versus robust (OR quartile 4 vs 1; 3.13, 95% CI 2.03-4.82), and a more than fivefold greater odds of death versus robust (OR quartile 4 vs 1; 5.48, 95% CI 2.98-10.08). Results were similar for cysC-based estimated glomerular filtration rate (eGFR). This relationship was attenuated but persisted after adjusting for additional potential confounders including baseline frailty status, body mass index, smoking status, comorbidity burden, self-reported disability, and serum albumin. In contrast, neither serum creatinine nor creatinine-based eGFR was associated in a graded manner with higher risks of development of frailty or death. In this cohort of older men without overt frailty, higher cysC and cysC-based eGFR, but not creatinine or creatinine-based estimates of GFR, were associated with increased risks of frailty or death. These findings suggest that higher cysC level may be a promising biomarker for unsuccessful aging as manifested by increased risks of frailty and death.