Kidney failure 1.7X more likely - Vitamin D Binding Protein – Feb 2016

Biomarkers of Vitamin D Status and Risk of ESRD - Feb 2016

American Journal of Kidney Diseases, Volume 67, Issue 2, February 2016, Pages 235–242, doi:10.1053/j.ajkd.2015.08.026
Casey M. Rebholz, PhD, MS, MPH1, , , Morgan E. Grams, MD, PhD, MHS1, 2, Pamela L. Lutsey, PhD, MPH3, Andrew N. Hoofnagle, MD, PhD4, Jeffrey R. Misialek, MPH3, Lesley A. Inker, MD, MS5, Andrew S. Levey, MD5, Elizabeth Selvin, PhD, MPH1, 6, Chi-yuan Hsu, MD, MSc7, Paul L. Kimmel, MD8, Ramachandran S. Vasan, MD9, 10, John H. Eckfeldt, MD, PhD11, Josef Coresh, MD, PhD, MHS1, 6, on behalf of the Chronic Kidney Disease Biomarkers
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.

PDF is available free at Sci-Hub  10.1053/j.ajkd.2015.08.026

Kideny Cancer 3X more likely if poor Vitamin D Binding Protein - July 2018

Vitamin D binding protein and risk of renal cell carcinoma in the Cancer Prevention Study-II Cohort
Alison M. Mondul, Stephanie J. Weinstein, Dominick Parisi, Caroline Y Um, Marjorie L McCollough and Demetrius Albanes
DOI: 10.1158/1055-9965.EPI-18-0263

Background:Kidney cancer has several well-established risk factors including smoking, obesity, and hypertension. These factors do not, however, completely account for its etiology. One previous study of vitamin D binding protein (DBP) and risk of renal cell carcinoma found a striking inverse association that warranted replication. Methods:We conducted a nested case-control study in the American Cancer Society Cancer Prevention Study-II (CPS-II) Nutrition Cohort to prospectively examine circulating DBP concentration and renal cell carcinoma risk. Cases (n=87) were matched 1:1 to controls on gender, race, age (+/- 5 years), and date of blood collection (+/- 30 days). Odds ratios and 95% confidence intervals were estimated for quartiles of DBP using conditional logistic regression.

Results:There was a statistically significant inverse trend across quartiles of DBP (p-trend = 0.03) such that participants with higher DBP had a markedly decreased risk of renal cell carcinoma (vs. Q1: Q2 OR=0.93, 95% CI=0.41 - 2.11; Q3 OR=0.42, 95% CI=0.15 - 1.15; Q4 OR = 0.33, 95% CI=0.10 - 1.06; p-trend=0.03).

Conclusions:Our findings demonstrate a strong inverse association between circulating DBP and risk of renal cell carcinoma, supporting the findings from previous research. Impact:This is only the second study to examine vitamin D binding protein (DBP) and risk of kidney cancer, and one of only a handful of studies to examine circulating DBP and risk of cancer at any site. Our findings support emerging evidence for an etiologic role of DBP in cancer and may provide insights into the etiology of kidney and other cancers.

PDF is available free at Sci-Hub  10.1158/1055-9965.EPI-18-0263