Renal Fanconi Syndrome and Hypophosphatemic Rickets in the Absence of Xenotropic and Polytropic Retroviral Receptor in the Nephron.

Ansermet, Camille; Moor, Matthias B.; Centeno, Gabriel; Auberson, Muriel; Hu, Dorothy Zhang; Baron, Roland; Nikolaeva, Svetlana; Haenzi, Barbara; Katanaeva, Natalya; Gautschi, Ivan; Katanaev, Vladimir; Rotman, Samuel; Koesters, Robert; Schild, Laurent; Pradervand, Sylvain; Bonny, Olivier; Firsov, Dmitri (2017). Renal Fanconi Syndrome and Hypophosphatemic Rickets in the Absence of Xenotropic and Polytropic Retroviral Receptor in the Nephron. Journal of the American Society of Nephrology : JASN, 28(4), pp. 1073-1078. American Society of Nephrology 10.1681/ASN.2016070726

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Tight control of extracellular and intracellular inorganic phosphate (Pi) levels is critical to most biochemical and physiologic processes. Urinary Pi is freely filtered at the kidney glomerulus and is reabsorbed in the renal tubule by the action of the apical sodium-dependent phosphate transporters, NaPi-IIa/NaPi-IIc/Pit2. However, the molecular identity of the protein(s) participating in the basolateral Pi efflux remains unknown. Evidence has suggested that xenotropic and polytropic retroviral receptor 1 (XPR1) might be involved in this process. Here, we show that conditional inactivation of Xpr1 in the renal tubule in mice resulted in impaired renal Pi reabsorption. Analysis of Pi transport in primary cultures of proximal tubular cells or in freshly isolated renal tubules revealed that this Xpr1 deficiency significantly affected Pi efflux. Further, mice with conditional inactivation of Xpr1 in the renal tubule exhibited generalized proximal tubular dysfunction indicative of Fanconi syndrome, characterized by glycosuria, aminoaciduria, calciuria, and albuminuria. Dramatic alterations in the renal transcriptome, including a significant reduction in NaPi-IIa/NaPi-IIc expression, accompanied these functional changes. Additionally, Xpr1-deficient mice developed hypophosphatemic rickets secondary to renal dysfunction. These results identify XPR1 as a major regulator of Pi homeostasis and as a potential therapeutic target in bone and kidney disorders.

Item Type:	Journal Article (Original Article)
Division/Institute:	04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Nephrology and Hypertension
UniBE Contributor:	Moor, Matthias
Subjects:	600 Technology > 610 Medicine & health
ISSN:	1533-3450
Publisher:	American Society of Nephrology
Language:	English
Submitter:	Matthias Moor
Date Deposited:	08 Oct 2019 14:13
Last Modified:	05 Dec 2022 15:30
Publisher DOI:	10.1681/ASN.2016070726
PubMed ID:	27799484
Uncontrolled Keywords:	Fanconi syndrome hypophosphatemic rickets kidney phosphate homeostasis retroviral receptor XPR1
URI:	https://boris.unibe.ch/id/eprint/133425