Filtration Markers May Have Prognostic Value Independent of Glomerular Filtration Rate

Tangri, Navdeep; Inker, Lesley A.; Tighiouart, Hocine; Sorensen, Eric S.; Menon, Vandana; Beck, Gerald J.; Shlipak, Michael G.; Coresh, Josef; Levey, Andrew S.; Sarnak, Mark J.

doi:10.1681/asn.2011070663

Cited by 77 publications

(76 citation statements)

References 38 publications

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“…15 While most laboratories use the MDRD equation to calculate eGFR, neither the MDRD nor the CKD-EPI have been well validated in Black patients with a broad spectrum of HIV severity. [16][17][18][19] Furthersearch question using the outcome of all-cause mortality as a surrogate for chronic kidney disease as CKD has been shown to be strongly associated with death [22][23][24][25] in a national registry of HIV-infected veterans. Specifically, we evaluated the impact of removing the race coefficient from the MDRD and CKD-EPI equations on comparisons between Black and White HIV-infected veterans related to: 1) the prevalence of reduced eGFR; 2) the distribution of eGFR values; and 3) the relationship between eGFR and all-cause mortality.…”

Section: Racial Disparities In Estimating Gfr -Anker Et Almentioning

confidence: 99%

Racial Disparities in Creatinine-based Kidney Function Estimates Among HIV-infected Adults

Anker¹,

Scherzer²,

Peralta³

et al. 2016

Ethn Dis

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Objective: The aim of our study was to investigate whether current eGFR equations in clinical use might systematically overestimate the kidney function, and thus misclassify CKD status, of Black Americans with HIV. Specifically, we evaluated the impact of removing the race coefficient from the MDRD and CKD-EPI equations on comparisons between Black and White HIV-infected veterans related to: 1) the prevalence of reduced eGFR; 2) the distribution of eGFR values; and 3) the relationship between eGFR and all-cause mortality.Design: Retrospective cohort study.Setting: The Department of Veterans Affairs (VA) HIV Clinical Case Registry (CCR), which actively monitors all HIV-infected persons receiving care in the VA nationally.Patients/Participants: 21,905 treatmentnaïve HIV-infected veterans.Main Outcome Measures: Estimated glomerular filtration rate (eGFR) using the abbreviated Modification of Diet in Renal Disease (MDRD) formula with and without (MDRD-RCR) the race coefficient and allcause mortality.Results: Persons with eGFR <45 mL/ min/1.73m2 had a higher risk of death compared with those with eGFR >80 mL/ min/1.73m2 among both Blacks (HR=2.8, 95%CI: 2.4-3.3) and Whites (HR=1.9, 95%CI: 1.4-2.6), but the association appeared to be stronger in Blacks (P=.038, test for interaction). Blacks with eGFR 45- 60 mL/min/1.73m2 also had a higher risk of death (HR=1.7, 95%CI: 1.4-2.1) but Whites did not (HR=0.86, 95%CI: .67- 1.10; test for interaction: P<.0001). Racial differences were substantially attenuated when eGFR was re-calculated without the race coefficient.Conclusions: Our findings suggest that clinicians may want to consider estimating glomerular filtration rate without the race coefficient in Blacks with HIV. Ethn Dis. 2016;26(2):213-220; doi:10.18865/ ed.26.2.213

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Section: Racial Disparities In Estimating Gfr -Anker Et Almentioning

confidence: 99%

Racial Disparities in Creatinine-based Kidney Function Estimates Among HIV-infected Adults

Anker¹,

Scherzer²,

Peralta³

et al. 2016

Ethn Dis

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“…Cystatin C-based GFR estimates do not require correction for muscle bulk, sex, and race (6)(7)(8). Cystatin C predicts mortality in CKD independent of GFR (9). There has been interest in use of cystatin C as a marker of residual renal function (RRF) in both acute renal failure and ESRD (10)(11)(12).…”

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confidence: 99%

Removal and Rebound Kinetics of Cystatin C in High-Flux Hemodialysis and Hemodiafiltration

Vilar

Boltiador

Viljoen

et al. 2014

Clinical Journal of the American Society of Nephrology

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Background and objectives Cystatin C is a 13.3 kD middle molecule of similar size to b 2 -microglobulin and a marker of GFR in CKD. This study aimed to determine cystatin C kinetics in hemodialysis to understand whether blood concentrations may predict residual renal function and middle-molecule clearance.Design, setting, participants, & measurements Cystatin C removal and rebound kinetics were studied in 24 patients on high-flux hemodialysis or hemodiafiltration. To determine whether cystatin C concentrations are predictable, an iterative two-pool mathematical model was applied.Results Cystatin C was cleared effectively, although less than b 2 -microglobulin (reduction ratios6SD are 39%611 and 51%611). Cystatin C rebounded to 95%65% of predialysis concentration by 12 hours postdialysis. The two-pool kinetic model showed excellent goodness of fit. Modeled extracellular cystatin C pool volume is smaller than that predicted, comprising 25.5%69.2 of total body water. Iterated parameters, including nonrenal clearance, showed wide interindividual variation. Modeled nonrenal clearance was substantially higher than renal clearance in this population at 25.166.6 ml/min per 1.73 m 2 body surface area.Conclusions Plasma cystatin C levels may be used to measure middle-molecule clearance. Levels rebound substantially postdialysis and plateau in the interdialytic period. At low GFR, nonrenal clearance predominates over renal clearance, and its interindividual variation will limit use of cystatin C to predict residual renal function in advanced kidney disease.

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“…On the basis of prior work, we hypothesized that changes in iGFR would not consistently outperform changes in eGFR for the prediction of CKD-related outcomes. 1,[15][16][17][18][19] …”

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Change in Measured GFR Versus eGFR and CKD Outcomes

Ku¹,

Xie

Shlipak

et al. 2015

JASN

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Measured GFR (mGFR) has long been considered the gold standard measure of kidney function, but recent studies have shown that mGFR is not consistently superior to eGFR in explaining CKD-related comorbidities. The associations between longitudinal changes in mGFR versus eGFR and adverse outcomes have not been examined. We analyzed a subset of 942 participants with CKD in the Chronic Renal Insufficiency Cohort Study who had at least two mGFRs and two eGFRs determined concurrently by iothalamate and creatinine (eGFR cr ) or cystatin C, respectively. We compared the associations between longitudinal changes in each measure of kidney function over 2 years and risks of ESRD, nonfatal cardiovascular events, and all-cause mortality using univariate Cox proportional hazards models. The associations for all outcomes except all-cause mortality associated most strongly with longitudinal decline in eGFR cr. Every 5-ml/min per 1.73 m 2 decline in eGFR cr over 2 years associated with 1.54 (95% confidence interval, 1.44 to 1.66; P,0.001) times higher risk of ESRD and 1.23 (95% confidence interval, 1.12 to 1.34; P,0.001) times higher risk for cardiovascular events. All-cause mortality did not associate with longitudinal decline in mGFR or eGFR. When analyzed by tertiles of renal function decline, mGFR did not outperform eGFR cr in the association with any outcome. In conclusion, compared with declines in eGFR, declines in mGFR over a 2-year period, analyzed either as a continuous variable or in tertiles, did not consistently show enhanced association with risk of ESRD, cardiovascular events, or death.

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Filtration Markers May Have Prognostic Value Independent of Glomerular Filtration Rate

Cited by 77 publications

References 38 publications

Racial Disparities in Creatinine-based Kidney Function Estimates Among HIV-infected Adults

Racial Disparities in Creatinine-based Kidney Function Estimates Among HIV-infected Adults

Removal and Rebound Kinetics of Cystatin C in High-Flux Hemodialysis and Hemodiafiltration

Change in Measured GFR Versus eGFR and CKD Outcomes

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