Submitted on July 31, 2007
Accepted on August 1, 2008
Magnesium stimulates renal phosphate reabsorption
Julia Thumfart1, Susanne Jung1, Salah Amasheh2, Stephanie Kraemer3, Harm Peters4, Kerstin Sommer1, Jurg Biber5, Heini Murer5, Iwan Meij6, Uwe Querfeld1, Carsten A Wagner5, and Dominik N Muller1*
1 Pediatric Nephrology, Charite University Children's Hospital, Berlin, Germany
2 Clinical Physiology, Charite University Hospital, Berlin, Germany
3 Nephrology, Charite University Hospital, Berlin, Germany
4 Nephrology, Charite University Hospital, Germany
5 Institute of Physiology, University of Zurich, Zurich, Switzerland
6 Max-Delbrueck-Centre for Molecular Medicine, Berlin, Germany
* To whom correspondence should be addressed. E-mail: dominik.mueller{at}mdc-berlin.de.
In the kidney, about 80% of the filtered phosphate (Pi) is reabsorbed along the proximal tubule. Changes in renal Pi reabsorption are associated with modulation of the sodium dependent Pi cotransporter NaPi Type IIa (NaPi-IIa) and Type IIc (NaPi-IIc) protein abundance in the brush border membrane (BBM) of proximal tubule cells. NaPi-IIa is mainly regulated by dietary Pi intake and parathyroid hormone (PTH). The purpose of the present study was to elucidate the effect of alteration in dietary magnesium (Mg2+) intake on renal Pi handling. Urinary Pi excretion and renal expression of NaPi-IIa and NaPi-IIc were analyzed in rats fed with normal (0.2%) or high Mg2+ (2.5%) diet. High Mg2+ diet resulted in decreased renal Pi excretion and increased protein expression of NaPi-IIa and NaPi-IIc. Serum FGF-23 (fibroblast growth factor 23) levels were unchanged under high Mg2+ diet. Serum PTH levels were slightly decreased under high Mg2+ diet. To examine whether the observed changes in renal Pi reabsorption are PTH dependent, NaPi-IIa and NaPi-IIc expression were also analyzed in parathyroidectomized (PTX) rats fed with normal or high Mg2+ diet. In PTX rats Mg2+ had no significant effect on renal Pi excretion or NaPi-IIa protein expression. Mg2+ increased NaPi-IIc protein expression in PTX rats. This experiment shows for the first time on the molecular level how Mg2+ stimulates renal Pi reabsorption. Under high Mg2+ diet NaPi-IIa expression is dependent on PTH levels, whereas NaPi-IIc expression seems to be independent from PTH levels.
