Estimating GFR in adult patients with hematopoietic cell transplant: comparison of estimating equations with an iohexol reference standard.
ABSTRACT: Formal evaluation of kidney function before and after hematopoietic cell transplant is important to determine conditioning regimens, type of transplant, and medication dosing. Serum creatinine and estimating equations may not accurately assess kidney function.Existing estimating equations for GFR were compared with an iohexol measure of GFR in a prospective cohort study of 50 patients undergoing hematopoietic cell transplant and subsequent care at the Fred Hutchinson Cancer Research Institute from 2009 to 2013. Patients underwent iohexol GFR, serum creatinine, and cystatin C determination at baseline and day 100 posthematopoietic cell transplant. Iohexol GFR measurements were compared with the CKD Epidemiology Collaboration, Inker CKD Epidemiology Collaboration cystatin C with and without serum creatinine, Modification of Diet in Renal Disease, and Cockcroft-Gault estimating equations using Bland-Altman analysis and McNemar's test. The iohexol measurements were also compared with blood samples collected simultaneously on filter paper.Mean differences between iohexol GFR and eGFR on the basis of Bland-Altman analyses ranged from -20.6 to +15.4 ml/min per 1.73 m(2) at baseline and -12.7 to +12.9 ml/min per 1.73 m(2) at day 100. The CKD Epidemiology Collaboration and Modification of Diet in Renal Disease estimating equations classified 64% of patients with a GFR<90 at baseline compared with 38% by iohexol GFR (P=0.003 and P<0.01, respectively). No statistically significant differences were seen at day 100. The filter paper GFR had a mean difference of 0 at baseline and 5.9 at day 100. Additionally, 21%-37% and 57%-89% of eGFRs were within 10% and 30%, respectively, of the iohexol GFR at baseline, and 16%-34% and 72%-84% were within 10% and 30%, respectively, of the iohexol GFR at day 100; 98% of the filter paper estimates at baseline were within 30%, and 46% were within 10% of iohexol GFR.The estimating equations are neither accurate nor precise in the hematopoietic cell transplant population, and clinical decision may require measurement of GFR.
Project description:Accurate assessment of kidney function is important for the management of solid-organ transplant recipients. In other clinical populations, glomerular filtration rate (GFR) most commonly is estimated using the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) creatinine or the 4-variable MDRD (Modification of Diet in Renal Disease) Study equation. The accuracy of these equations compared with other GFR estimating equations in transplant recipients has not been carefully studied.Diagnostic test study.Solid-organ transplant recipients longer than 6 months posttransplantation from 5 clinical populations (N=3,622, including recipients of kidney [53%], liver [35%], and other or multiple organs [12%]).Estimated GFR (eGFR) using creatinine-based GFR estimating equations identified from a systematic review of the literature. Performance of the CKD-EPI creatinine and the MDRD Study equations was compared with alternative equations.Measured GFR (mGFR) from urinary clearance of iothalamate or plasma clearance of iohexol.Error (difference between mGFR and eGFR) expressed as P30 (proportion of absolute percent error <30%) and mean absolute error.We identified 26 GFR estimating equations. Mean mGFR was 55.1±22.7 (SD) mL/min/1.73 m(2). P30 and mean absolute error for the CKD-EPI and the MDRD Study equations were 78.9% (99.6% CI, 76.9%-80.8%) for both and 10.6 (99.6% CI, 10.1-11.1) versus 11.0 (99.6% CI, 10.5-11.5) mL/min/1.73 m(2), respectively; these equations were more accurate than any of the alternative equations (P <0.001 for all pairwise comparisons for both measures). They performed better than or as well as the alternative equations in most subgroups defined by demographic and clinical characteristics, including type of transplanted organ.Study population included few nonwhites and people with solid-organ transplants other than liver and kidneys.The CKD-EPI creatinine and the MDRD Study equations perform better than the alternative creatinine-based estimating equations in solid-organ transplant recipients. They can be used for clinical management.
Project description:Aims: It remains controversial to choose the optimal equation to estimate glomerular filtration rate (GFR) in chronic kidney disease (CKD) patients with diabetes. Materials and Methods: Two hundred and fifteen diabetic CKD patients and 192 non-diabetic CKD patients were enrolled in this study. Iohexol GFR, serum creatinine (SCr), and Cystatin C(CysC) were measured simultaneously for each patient. SCr- and CysC-based estimated GFR (eGFR) were calculated through eight equations, including three CKD-EPI equations, Revised Lund-Malmö study equation (RLM), CAPA equation, and three Full Age Spectrum (FAS) equations. Bias, precision, and accuracy were compared among eGFR equations with iohexol-GFR serving as measured GFR (mGFR). Independent predictive factors of accuracy were explored using multivariate logistic regression analysis. Results: In the diabetic group, CKD-EPISCr-CysC showed the best performance among three CKD-EPI equations (interquartile range of 13.88 ml/min/1.73 m2 and 30% accuracy of 72.56%). Compared to CKD-EPISCr-CysC, the other five equations did not significantly improve the performance of GFR estimates. Mostly, eGFR equations were less accurate in diabetic group than in non-diabetic group. Significant differences were found in different mGFR range (P < 0.001). The multivariate logistic regression analysis identified that BMI, mGFR, and diabetic kidney disease (DKD) status were independent predictors of accuracy of three equations in diabetic group. HbA1c was a predictor of accuracy of CKD-EPISCr and CKD-EPICysC in diabetic group. Conclusions: This study showed that eGFR equations were less accurate in the diabetic group than in the non-diabetic group. CKD-EPIScr-CysC had the best performance among CKD-EPI equations in Chinese diabetic CKD patients. The other five equations did not significantly improve the performance of GFR estimates. BMI, mGFR, DKD status, and HbA1c were independent factors associated with accuracy in eGFR equations.
Project description:OBJECTIVE:To evaluate the performance of Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine, cystatin C, and creatinine-cystatin C estimating equations in HIV-positive patients. METHODS:We evaluated the performance of the Modification of Diet in Renal Disease (MDRD) Study and CKD-EPI creatinine 2009, CKD-EPI cystatin C 2012, and CKD-EPI creatinine-cystatin C 2012 glomerular filtration rate (GFR) estimating equations compared with GFR measured using plasma clearance of iohexol in 200 HIV-positive patients on stable antiretroviral therapy. Creatinine and cystatin C assays were standardized to certified reference materials. RESULTS:Of the 200 participants, median (IQR) CD4 count was 536 (421) and 61% had an undetectable HIV viral load. Mean (SD) measured GFR (mGFR) was 87 (26) mL/min per 1.73 m. All CKD-EPI equations performed better than the MDRD Study equation. All 3 CKD-EPI equations had similar bias and precision. The cystatin C equation was not more accurate than the creatinine equation. The creatinine-cystatin C equation was significantly more accurate than the cystatin C equation, and there was a trend toward greater accuracy than the creatinine equation. Accuracy was equal or better in most subgroups with the combined equation compared to either alone. CONCLUSIONS:The CKD-EPI cystatin C equation does not seem to be more accurate than the CKD-EPI creatinine equation in patients who are HIV-positive, supporting the use of the CKD-EPI creatinine equation for routine clinical care for use in North American populations with HIV. The use of both filtration markers together as a confirmatory test for decreased estimated GFR based on creatinine in individuals who are HIV-positive requires further study.
Project description:<h4>Background</h4>Equations to estimate GFR have not been well validated in the elderly and may misclassify persons with chronic kidney disease (CKD). We measured GFR and compared the performance of the Modification of Diet in Renal Disease (MDRD), the Chronic Kidney Disease-Epidemiology Collaboration (CKD-Epi) and the Berlin Initiative Study (BIS) equations based on creatinine and/or cystatin C in octogenarians and nonagenarians.<h4>Methods</h4>Using cross-sectional analysis we assessed 95 very elderly persons (mean 85 years) living in the community. GFR was measured by iohexol (mGFR) and compared with estimates using six equations: MDRD, CKD-Epi_creatinine, CKD-Epi_cystatin, CKD-Epi_creatinine-cystatin, BIS_creatinine and BIS_creatinine-cystatin.<h4>Results</h4>Mean mGFR was 55 (range,19-86) ml/min/1.73 m(2). Bias was smaller with the CKD-Epi_creatinine-cystatin and the CKD-Epi_creatinine equations (-4.0 and 1.7 ml/min/1.73 m(2)). Accuracy (percentage of estimates within 30% of mGFR) was greater with the CKD-Epi_creatinine-cystatin, BIS_creatinine-cystatin and BIS_creatinine equations (85%, 83% and 80%, respectively). Among the creatinine-based equations, the BIS_creatinine had the greatest accuracy at mGFR?< 60 ml/min/1.73 m(2) and the CKD-Epi_creatinine was superior at higher GFRs (79% and 90%, respectively). The CKD-Epi_creatinine-cystatin, BIS_creatinine-cystatin and CKD-Epi_cystatin equations yielded the greatest areas under the receiver operating characteristic curve at GFR threshold = 60 ml/min/1.73 m 2 (0.88, 0.88 and 0.87, respectively). In participants classified based on the BIS_creatinine, CKD-Epi_cystatin, or BIS_creatinine-cystatin equations, the CKD-Epi_creatinine-cystatin equation tended to improve CKD classification (net reclassification index: 12.7%, p = 0.18; 6.7%, p = 0.38; and 15.9%; p = 0.08, respectively).<h4>Conclusions</h4>GFR-estimating equations CKD-Epi_creatinine-cystatin and BIS_creatinine-cystatin showed better accuracy than other equations using creatinine or cystatin C alone in very elderly persons. The CKD-Epi_creatinine-cystatin equation appears to be advantageous in CKD classification. If cystatin C is not available, both the BIS_cr equation and the CKD-Epi_cr equation could be used, although at mGFR?< 60 ml/min/1.73 m(2), the BIS_cr equation seems to be the best alternative.
Project description:The glomerular filtration rate (GFR) estimating equation incorporating both cystatin C and creatinine perform better than those using creatinine or cystatin C alone in patients with reduced GFR. Whether this equation performs well in kidney transplant recipients cross-sectionally, and more importantly, over time has not been addressed.We analyzed four GFR estimating equations in participants of the Angiotensin II Blockade for Chronic Allograft Nephropathy Trial (NCT 00067990): Chronic Kidney Disease Epidemiology Collaboration equations based on serum cystatin C and creatinine (eGFR (CKD-EPI-Creat+CysC)), cystatin C alone (eGFR (CKD-EPI-CysC)), creatinine alone (eGFR (CKD-EPI-Creat)) and the Modification of Diet in Renal Disease study equation (eGFR (MDRD)). Iothalamate GFR served as a standard (mGFR).mGFR, serum creatinine, and cystatin C shortly after transplant were 56.1 ± 17.0 ml/min/1.73 m(2), 1.2 ± 0.4 mg/dl, and 1.2 ± 0.3 mg/l respectively. eGFR (CKD-EPI-Creat+CysC) was most precise (R(2) = 0.50) but slightly more biased than eGFR (MDRD); 9.0 ± 12.7 versus 6.4 ± 15.8 ml/min/1.73 m(2), respectively. This improved precision was most evident in recipients with mGFR >60 ml/min/1.73 m(2). For relative accuracy, eGFR (MDRD) and eGFR (CKD-EPI-Creat+CysC) had the highest percentage of estimates falling within 30% of mGFR; 75.8 and 68.9%, respectively. Longitudinally, equations incorporating cystatin C most closely paralleled the change in mGFR.eGFR (CKD-EPI-Creat+CysC) is more precise and reflects GFR change over time reasonably well. eGFR (MDRD) had superior performance in recipients with mGFR between 30 and 60 ml/min/1.73 m(2).
Project description:BACKGROUND:Estimating glomerular filtration rate (GFR) is important for clinical management in kidney transplantation recipients (KTR). However, very few studies have evaluated the performance of the new GFR estimating equations (Lund-Malmö Revised-LMR, and Full Age Spectrum-FAS) in KTR. METHODS:GFR was estimated (eGFR) using CKD-EPI, MDRD, LMR, and FAS equations and compared to GFR measurement (mGFR) by reference methods (inuline urinary and iohexol plasma clearance) in 395 deceased-donor KTR without corticosteroids. The equations performance was assessed using bias (mean difference of eGFR and mGFR), precision (standard deviation of the difference), accuracy (concordance correlation coefficient-CCC), and agreements (total deviation index-TDI). The area under receiver operating characteristic curves (ROC) and the likelihood ratio for a positive result were calculated. RESULTS:In the total population, the performance of the CKD-EPI, MDRD and FAS equations was significantly lower than the LMR equation regarding the mean [95%CI] difference in bias (-2.0 [-4.0; -1.5] versus 9.0 [7.5; 10.0], 5.0 [3.5; 6.0] and 10.0 [8.5; 11.0] mL/min/1.73m2, P<0.005) and TDI (17.10 [16.41; 17.88], 25.91 [24.66; 27.16], 21.23 [19.48; 23.13] and 25.84 [24.16; 27.57], respectively). Concerning the CCC, all equation had poor agreement (<0.800) without statically difference between them. However, all equations had excellent area under the ROC curve (>0.900), and LMR equation had the best ability to correctly predict KTR with mGFR<45 mL/min/1.73 m2 (positive likelihood ratio: 8.87 [5.79; 13.52]). CONCLUSION:Among a referral group of subjects KTR, LMR equation had the best mean bias and TDI, but with no significant superiority in other agreement tools. Caveat is required in the use and interpretation of PCr-based equations in this specific population.
Project description:In the estimation of glomerular filtration rate (GFR), ethnicity is an important determinant. However, all existing equations have been built solely from Caucasian and Afro-American populations and they are potentially inaccurate for estimating GFR in African populations. We therefore evaluated the performance of different estimated GFR (eGFR) equations in predicting measured GFR (mGFR).In a cross-sectional study, 93 healthy adults were randomly selected in the general population of Kinshasa, Democratic Republic of the Congo, between June 2015 and April 2016. We compared mGFR by plasma clearance of iohexol with eGFR obtained with the Modified Diet in Renal Disease (MDRD) equation with and without ethnic factor, the Chronic Kidney Disease Epidemiology (CKD-EPI) serum creatinine (SCr)-based equation, with and without ethnic factor, the cystatin C-based CKD-EPI equation (CKD-EPI SCys) and with the combined equation (CKD-EPI SCrCys) with and without ethnic factor. The performance of the equations was studied by calculating bias, precision and accuracy within 30% (P30) of mGFR.There were 48 women and 45 men. Their mean age was 45.0±15.7 years and the average body surface area was 1.68±0.16m2. Mean mGFR was 92.0±17.2 mL/min/1.73m2 (range of 57 to 141 mL/min/1.73m2). Mean eGFRs with the different equations were 105.5±30.1 and 87.2±24.8 mL/min/1.73m2 for MDRD with and without ethnic factor, respectively; 108.8±24.1 and 94.3x20.9 mL/min/1.73m2 for CKD-EPI SCr with and without ethnic factor, respectively, 93.5±18.6 mL/min/1.73m2 for CKD-EPI SCys; 93.5±18.0 and 101±19.6 mL/min/ 1.73m2 for CKD-EPI SCrCys with and without ethnic factor, respectively. All equations slightly overestimated mGFR except MDRD without ethnic factor which underestimated by -3.8±23.0 mL/min /1.73m2. Both CKD-EPI SCr and MDRD with ethnic factors highly overestimated mGFR with a bias of 17.9±19.2 and 14.5±27.1 mL/min/1.73m2, respectively. There was a trend for better P30 for MDRD and CKD-EPI SCr without than with the ethnic factor [86.0% versus 79.6% for MDRD (p = 0.21) and 81.7% versus 73.1% for the CKD-EPI SCr equations (p = 0.057)]. CKD-EPI SCrCys and CKD-EPI SCys were more effective than creatinine-based equations.In the Congolese healthy population, MDRD and CKD-EPI equations without ethnic factors had better performance than the same equations with ethnic factor. The equations using Cys C (alone or combined with SCr) performed better than the creatinine-based equations.
Project description:Accurate 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.GFR 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.A 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.Existing 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.
Project description:BACKGROUND:Chronic kidney disease (CKD) is a substantial cause of morbidity and mortality worldwide with disproportionate effects in sub-Saharan Africa (SSA). The optimal methods to estimate glomerular filtration rate (GFR) and therefore to determine the presence of CKD in SSA are uncertain. We plan to measure iohexol excretion to accurately determine GFR in Malawi, South Africa and Uganda. We will then assess the performance of existing equations to estimate GFR and determine whether a modified equation can better improve estimation of GFR in sub-Saharan Africa. METHODS:The African Research on Kidney Disease (ARK) study is a three-country study embedded within existing cohorts. We seek to enrol 3000 adults >?18?years based on baseline serum creatinine. Study procedures include questionnaires on socio-demographics and established risk factors for kidney disease along with anthropometry, body composition, blood pressure, blood chemistry and urine microscopy and albuminuria. We will measure GFR (mGFR) by plasma clearance of iohexol at 120, 180 and 240?min. We will compare eGFR determined by established equations with mGFR using Bland-Altman plots. We will use regression methods to estimate GFR and compare the newly derived model with existing equations. DISCUSSION:Through the ARK study, we aim to establish the optimal approach to estimate GFR in SSA. The study has the advantage of drawing participants from three countries, which will increase the applicability of the findings across the region. It is also embedded within established cohorts that have longitudinal information and serial measures that can be used to characterize kidney disease over a period of time. This will help to overcome the limitations of previous research, including small numbers, selected population sub-groups, and lack of data on proteinuria. The ARK collaboration provides an opportunity for close working partnerships across different centres, using standardized protocols and measurements, and shared bio-repositories. We plan to build on the collaboration for this study for future work on kidney disease in sub-Saharan Africa, and welcome additional partners from across the continent.
Project description:Background:Validation studies comparing glomerular filtration rate (GFR) equations based on standardized creatinine and cystatin C assays in the elderly are needed. The Icelandic Age, Gene/Environment Susceptibility-Kidney cohort was used to compare two pairs of recently developed GFR equations, the revised Lund-Malmö creatinine equation (LMRCr) and the arithmetic mean of the LMRCr and Caucasian, Asian, Paediatric and Adult cystatin C equations (MEANLMR+CAPA), as well as the Full Age Spectrum creatinine equation (FASCr) and its combination with cystatin C (FASCr+Cys), with the corresponding pair of Chronic Kidney Disease Epidemiology Collaboration equations (CKD-EPICr and CKD-EPICr+Cys). Methods:A total of 805 individuals, 74-93 years of age, underwent measurement of GFR (mGFR) using plasma clearance of iohexol. Four metrics were used to compare the performance of the GFR equations: bias, precision, accuracy [including the percentage of participants with estimated GFR (eGFR) within 30% of mGFR (P30)] and the ability to detect mGFR <60 mL/min/1.73 m2. Results:All equations had a P30 >90%. LMRCr and FASCr yielded significantly higher precision and P30 than CKD-EPICr, while bias was significantly worse. LMRCr, FASCr and CKD-EPICr showed similar ability to detect mGFR <60 mL/min/1.73 m2 based on the area under the receiver operating characteristic curves. MEANLMR+CAPA, FASCr+Cys and CKD-EPICr+Cys all exhibited consistent improvements compared with the corresponding creatinine-based equations. Conclusion:None of the creatinine-based equations was clearly superior overall in this community-dwelling elderly cohort. The addition of cystatin C improved all of the creatinine-based equations.