Date of Award

2012

Degree Type

Dissertation

Department

Chemistry

First Advisor

Wang, Sihe

Subject Headings

Vitamin D -- Therapeutic use, Chronic renal failure -- Treatment, Kidneys -- Diseases -- Treatment, Vitamin D, ADMA, SDMA, GFR, iothalamate, chronic kidney disease, CKD, liquid chromatography, mass spectrometry, method development

Abstract

Chronic kidney disease (CKD) is highly prevalent in the US population and has high incidence of cardiovascular and all-cause mortality. A known complication of CKD is secondary hyperparathyroidism that is caused by bone and mineral imbalances, including vitamin D deficiency. Supplementation of CKD patients with vitamin D is based on guidelines issued by the Kidney Disease Quality Outcomes Initiative (K/DOQI), which recommend administration of vitamin D2 in variable doses depending on the severity of vitamin D deficiency. Retrospective and pilot studies have shown that vitamin D2 was not as effective as vitamin D3 in treating vitamin D deficiency. In Chapter I, we investigated the effectiveness of vitamin D2 versus vitamin D3 treatment in resolving vitamin D deficiency in the pre-dialysis CKD population. This study was a double blinded, randomized, single center study that involved 22 CKD subjects. Data showed that vitamin D3 elicited a more rapid increase in 25-hydroxyvitamin D (25OHD) levels than vitamin D2, but both forms became equivalent in terms of the number of people who reached target 25OHD levels by the end of study.Glomerular filtration rate (GFR) is the best overall index of kidney function. GFR is determined by measuring the urinary clearance of a radioactive exogenous biomarker, such as iothalamate, or estimated (eGFR) by measuring creatinine and adjusting for race, gender and age using equations. There are several known limitations to using creatinine-based equations and radioactive substances exposure for eGFR and GFR determinations. In the remaining Chapters, solutions are proposed for measurement of GFR and eGFR, which involve liquid chromatography-tandem mass spectrometry (LC-MS/MS). Chapter II discusses this technique and the process of development and validation of bioanlaytical methods by LC-MS/MS. Chapter III introduces a LC-MS/MS method for the measurement of L-arginine, symmetric dimethylarginine (SDMA), and asymmetric dimethylarginine (ADMA). SDMA was correlated with biomarkers of kidney

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