Risk of ESRD and Mortality Associated With Change in Filtration Markers

Abstract

Background Using change in estimated glomerular filtration rate (eGFR) based on creatinine as a surrogate outcome in clinical trials of chronic kidney disease has been proposed. Risk of end-stage renal disease (ESRD) and all-cause mortality associated with change in other filtration markers has not been studied in chronic kidney disease populations. Study Design Observational analysis of two clinical trials Setting & Participants Participants in the MDRD (Modification of Diet in Renal Disease; n=317) Study and AASK (African American Study of Kidney Disease and Hypertension; n=373) Predictors Creatinine, cystatin C, β-trace protein (BTP), and β2-microglobulin (B2M) levels were measured in serum samples collected at the 12-month and 24-month follow-up visits, along with measured GFR (mGFR) at these time points. Outcomes ESRD and all-cause mortality Measurements Poisson regression was used to estimate incidence rate ratios and 95% CIs for ESRD and all-cause mortality during long-term follow-up (10–16 years) per 30% decline in mGFR or eGFR for each filtration marker and the average of all four markers. Results One-year decline in mGFR, eGFRcr, eGFRBTP, and the average of the four filtration markers was significantly associated with an increased risk of incident ESRD in both studies (all p≤0.02). Compared to mGFR, only decline in eGFRBTP was statistically significantly more strongly associated with ESRD risk in both studies (both p≤0.03). Decline in eGFRcr, but not mGFR or the other filtration markers, was significantly associated with risk of all-cause mortality in AASK only (incidence rate ratio per 30% decline, 4.17; 95% CI, 1.78–9.74; p<0.001), but this association was not significantly different from decline in mGFR (p=0.2). Limitations Small sample size Conclusions Declines in mGFR, eGFR based on serum creatinine and BTP, and the average of four filtration markers (creatinine, cystatin C, BTP, and B2M) were consistently associated with progression to ESRD.

Multiplexed MRM-based protein quantification of putative prognostic biomarkers for chronic kidney disease progression in plasma

“…In line with our study, gradual increase in B2M levels across stages of CKD has been shown 38 . Furthermore, several associations between B2M levels and death, dialysis or cardiovascular events have been reported 39,42,43 , in agreement with our findings. 37 [n = 15 patients of CKD5 with haemodialysis (HD) were compared to n = 14 patients with stage 2-3 37 ] and LC-MRM-MS data [CKD stage 5 patients with HD (N = 24) versus CKD2-3].…”

“…The selection of the specific markers was guided by the existence of mass spectrometry-based data for these proteins 37 , their expected abundance levels based on the existent literature, targeting to avoid extensive pre-fractionation, as well as levels of evidence for the association of these proteins with unfavorable outcome. Using the study by Glorieux et al 37 as a basis, involving high resolution LC-MS/MS analysis of plasma proteome from patients with CKD and reporting on associations to outcome, in combination to the aforementioned criteria, the tested panel includes B2M [38][39][40][41][42][43][44][45][46] and SERPINF1 [47][48][49][50] , having been largely studied in CKD and serving as positive controls for the approach, as well as AMBP, LYZ, HBB, and IGHA1 with some earlier reported associations 37 , nevertheless not been validated yet in association with disease progression via absolute quantification.…”

Beta Trace Protein does not outperform Creatinine and Cystatin C in estimating Glomerular Filtration Rate in Older Adults

“…One possible explanation why this was not the case might be that the development population of both equations were not the same: amongst others, the Inker (BTP) study population included individuals with a higher mean age and reported a diabetes prevalence of 21%, both of which corresponds more closely to the characteristics of our BIS population compared to the CKD-EPI study population. Also, one prominent non-GFR determinant in old age certainly is inflammation by which BTP is known to be less influenced compared to cystatin C 11 . This could be another possible explanation why the Inker (BTP) equation performed better than the combined creatinine/cystatin C- based equation.…”

“…With regard to its renal metabolism, BTP has been shown to be freely filtered through the glomerular basement membrane with little if any tubular reabsorption or non-renal elimination 7 . Also, ß2-microglobulin (B2M), another low molecular weight protein, has been found to be highly correlated with measured GFR (mGFR) and like BTP, is less affected by age and sex 10 , 11 . Other research groups have investigated the approach of “biomarker-panels” using several, still unspecified, markers simultaneously, although these markers are not yet established for standard laboratory analysis 12 .…”

Perioperative Acute Kidney Injury: Prevention, Early Recognition, and Supportive Measures

“…Nonetheless, measurement of GFR in clinical practice is unpractical. Urine collection over 24 h with measurement of the excretion of SCr has been accepted as the best clinical approach to determine GFR [19]. However, one of the main requirements of GFR assessment is a steady state AKI stage that might often not be the case in rapidly evolving renal dysfunction [8].…”