Project 2

An observational study to examine changes in Serum Bone profile following Unilateral Nephrectomy

Background: CKD-MBD (chronic Kidney disease associated mineral bone disease) increases the risk of fractures. It is also linked with extra calcium deposition around the blood vessels and with increased risk of heart attacks and strokes. That a protein called FGF23 (Fibroblast Growth Factor 23) is an important player in the CKD-MBD complex has been known for sometime. The mechanism of disease in CKD-MBD is poorly understood.

A literature search revealed that there is little information available on blood levels of FGF23, or indeed any other markers of disease of the CKD-MBD complex and there are no population studies to determine the normal blood levels of FGF23. While there is one study examining longitudinal changes of blood levels of FGF23 in mice with chronic kidney disease8, there are no similar human studies. FGF23 levels have been studied in renal transplant recipients and found to normalise by 3-12 months post transplant6.

We wish to perform serial measurements of blood levels of FGF23 and other proteins related to bone metabolism in patients who have donated one kidney, from before the operation to a period of time after the operation in order to determine what compensatory mechanisms are in play. This is because this group of patients will have the compensatory mechanisms in place in the short term but will not develop the disease in the long term. About 100 living donor nephrectomies are performed every year at our transplant centre. We hence have a pool of well informed subjects who are temporarily in-patients for around 5 days, and from whom we could acquire blood samples for this purpose. This would be a longitudinal study that increases our understanding of the course of events in CKD-MBD, potentially informing us of the time-period when FGF23 blockade might be an effective therapeutic intervention.

Hypothesis: Unilateral nephrectomy will result in a temporary rise in PTH and FGF23, with a secondary increase in excretion of urine phosphate.

Study Design: Observational study of subjects who have given written informed consent.

Sample size: 50 subjects who have undergone unilateral nephrectomy for kidney donation. They will be recruited over the period of one year.

Variable measured:

	Pre-nephrectomy	6 hours post Nephrectomy	24 hours Post	48 hours post	72 hours post	96 hours post	120 hours post
FGF23	√	√	√	√	√	√	√
PTH	√	√	√	√	√	√	√
Standard Renal Profile	√	√	√	√	√	√	√
24 hour urine creatininephosphate and calcium	√		√	√	√	√	√

This study will generate data which will be used to apply for the MRC or the KRUK PhD Fellowship for the research fellow. As part of the PhD, we would obtain similar data from a larger cohort of subjects over a 3 year period. The serum will be saved to do metabolomics and proteomic studies in order to elucidate the signal for renal hypertrophy as part of the larger study.