Background

Using change in estimated glomerular filtration rate (eGFR) based on creatinine concentration as a surrogate outcome in clinical trials of chronic kidney disease has been proposed. Risk for end-stage renal disease (ESRD) and all-cause mortality associated with change in concentrations of other filtration markers has not been studied in chronic kidney disease populations.

Study design

Observational analysis of 2 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) were measured in serum samples collected at the 12- 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 4 markers.

Results

1-year decline in mGFR, eGFR_cr, eGFR_BTP, and the average of the 4 filtration markers was significantly associated with increased risk for incident ESRD in both studies (all P≤0.02). Compared to mGFR, only decline in eGFR_BTP was statistically significantly more strongly associated with ESRD risk in both studies (both P≤0.03). Decline in eGFR_cr, but not mGFR or the other filtration markers, was significantly associated with risk for 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_cr, eGFR_BTP, and the average of 4 filtration markers (creatinine, cystatin C, BTP, and B2M) were consistently associated with progression to ESRD.

Background

Disordered mineral metabolism is characteristic of decreased kidney function. However, the prospective associations between circulating levels of vitamin D binding protein, vitamin D, and end-stage renal disease (ESRD) have not been extensively evaluated in epidemiologic studies.

Study design

Nested case-control study.

Setting & participants

Middle-aged black and white men and women from 4 US communities.

Predictors

Baseline levels of vitamin D binding protein, 25-hydroxyvitamin D (25[OH]D), and 1,25-dihydroxyvitamin D (1,25[OH]2D) were measured in blood samples collected at study visit 4 (1996-1998) of the ARIC (Atherosclerosis Risk in Communities) Study.

Outcome

ESRD cases (n=184) were identified through hospitalization diagnostic codes from 1996 to 2008 and were frequency matched to controls (n=251) on categories of estimated glomerular filtration rate, albuminuria, diabetes mellitus, sex, and race.

Measurements

Logistic regression was used to estimate the association between mineral metabolism biomarkers (vitamin D binding protein, 25(OH)D, and 1,25(OH)2D) and incident ESRD, adjusting for age, sex, race, estimated glomerular filtration rate, albuminuria, diabetes mellitus, hypertension, education, specimen type, and serum levels of calcium, phosphate, and parathyroid hormone.

Results

Higher vitamin D binding protein levels were associated with elevated risk for incident ESRD (OR, 1.76; 95% CI, 1.22-2.54; P=0.003). Higher free and bioavailable 25(OH)D levels were associated with reduced risk for incident ESRD (ORs of 0.65 [95% CI, 0.46-0.92; P=0.02] and 0.63 [95% CI, 0.43-0.91; P=0.02] for free and bioavailable 25[OH]D, respectively). There was no association between ESRD and overall levels of 25(OH)D (OR, 0.83; 95% CI, 0.58-1.19; P=0.3) or 1,25(OH)2D (OR, 0.73; 95% CI, 0.48-1.13; P=0.2).

Limitations

Lack of direct measurement of free and bioavailable vitamin D.

Conclusions

In the general population, blood levels of vitamin D binding protein were positively associated and blood levels of free and bioavailable 25(OH)D were inversely associated with new-onset ESRD during follow-up.