Acute and long term mineral metabolism adaptation in living kidney donors: a prospective study.
BACKGROUND
Living kidney donors (LKDs) experience an abrupt decline in glomerular filtration rate (GFR). Mineral metabolism adaptations in early CKD are still debated and not well studied in LKDs. We prospectively studied acute and long term mineral metabolism adaptation of LKDs.


METHODS
From May 2010 to December 2012, we included 27 adult LKDs. Their mineral parameters and renal function were repeatedly measured at days 0, 1, 2, 3, 180 and 360 after donation. We also measured in uninephrectomized rats' Klotho in the remnant kidney and FGF23 circulating levels.


RESULTS
In the first days after nephrectomy, LKDs experience transient dilution hypocalcemia and secondary hyperparathyroidism. Urinary phosphate reabsorption decreases in spite of an abrupt decline in circulating FGF23 and Klotho. In a more chronic stage, at days 180 and 360 after donation, LKDs have lower GFR and 1,25(OH)2D compared to pre-donation levels, with unchanged 25(OH)D. PTH levels increase, resulting in decreased plasma phosphate levels and renal tubular reabsorption of phosphate. In comparison to pre-donation, FGF23 levels are not significantly changed whereas circulating Klotho levels are lower than pre-donation but higher than immediately post-donation. In uninephrectomized rats, Klotho kidney expression increases after three weeks, whereas circulating FGF23 levels are unchanged.


CONCLUSIONS
From six months after kidney donation, LKDs develop secondary hyperparathyroidism related to a decrease in 1,25(OH)2D, and decreased plasma phosphate levels. FGF23 levels do not rise in LKDs. Middle term mineral metabolism adaptations to decreased eGFR in donors include decrease in 1,25(OH)2D and increase in PTH and fractional excretion of phosphate resulting in lowered plasma phosphate levels, independently of FGF23. These adaptations differ from those described in CKD patients.
Service of Nephrology, Department of Internal Medicine Specialties, Geneva University Hospitals and Faculty of Medicine, Geneva, Switzerland.
B
B
Ponte
Service of Bone Disease, Department of Internal Medicine Specialties, Geneva University Hospitals and Faculty of Medicine, Geneva, Switzerland.
A
A
Trombetti
Service of Nephrology, Department of Internal Medicine Specialties, Geneva University Hospitals and Faculty of Medicine, Geneva, Switzerland.
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Hadaya
Service of Nephrology, Department of Internal Medicine Specialties, Geneva University Hospitals and Faculty of Medicine, Geneva, Switzerland.
T
T
Ernandez
Service of Nephrology, Department of Internal Medicine Specialties, Geneva University Hospitals and Faculty of Medicine, Geneva, Switzerland.
D
D
Fumeaux
Service of Urology, Department of Surgery, Geneva University Hospitals and Faculty of Medicine, Geneva, Switzerland.
C
C
Iselin
Service of Nephrology, Department of Internal Medicine Specialties, Geneva University Hospitals and Faculty of Medicine, Geneva, Switzerland.
P-Y
PY
Martin
Service of Nephrology, Department of Internal Medicine Specialties, Geneva University Hospitals and Faculty of Medicine, Geneva, Switzerland. Electronic address: sophie.deseigneux@hcuge.ch.
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de Seigneux
D000222:Adaptation, Physiological; D000328:Adult; D000818:Animals; D015153:Blotting, Western; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000097:blood; D005500:Follow-Up Studies; D005966:Glucuronidase / Q000097:blood; D006801:Humans; D007668:Kidney / Q000378:metabolism* / Q000601:surgery; D016030:Kidney Transplantation; D000090265:Klotho Proteins; D019520:Living Donors; D008297:Male; D008875:Middle Aged; D008903:Minerals / Q000378:metabolism*; D009392:Nephrectomy; D019990:Perioperative Care; D011446:Prospective Studies; D051381:Rats
C000717427:FGF23 protein, human; D008903:Minerals; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; D005966:Glucuronidase; D000090265:Klotho Proteins
FGF23; Kidney reduction; Klotho; Living donors