A test of the hypothesis that oxalate secretion produces proximal tubule crystallization in primary hyperoxaluria type I

Elaine M. Worcester, Andrew Evan, Fredric L. Coe, James E. Lingeman, Amy Krambeck, Andre Sommers, Carrie Phillips, Dawn Milliner

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

The sequence of events by which primary hyperoxaluria type 1 (PH1) causes renal failure is unclear. We hypothesize that proximal tubule (PT) is vulnerable because oxalate secretion raises calcium oxalate (CaOx) supersaturation (SS) there, leading to crystal formation and cellular injury. We studied cortical and papillary biopsies from two PH1 patients with preserved renal function, and seven native kidneys removed from four patients at the time of transplant, after short-term (2) or longer term (2) dialysis. In these patients, and another five PH1 patients without renal failure, we calculated oxalate secretion, and estimated PT CaOx SS. Plasma oxalate was elevated in all PH1 patients and inverse to creatinine clearance. Renal secretion of oxalate was present in all PH1 but rare in controls. PT CaOx SS was >1 in all nonpyridoxine-responsive PH1 before transplant and most marked in patients who developed end stage renal disease (ESRD). PT from PH1 with preserved renal function had birefringent crystals, confirming the presence of CaOx SS, but had no evidence of cortical inflammation or scarring by histopathology or hyaluronan staining. PH1 with short ESRD showed CaOx deposition and hyaluronan staining particularly at the corticomedullary junction in distal PT while cortical collecting ducts were spared. Longer ESRD showed widespread cortical CaOx, and in both groups papillary tissue had marked intratubular CaOx deposits and fibrosis. CaOx SS in PT causes CaOx crystal formation, and CaOx deposition in distal PT appears to be associated with ESRD. Minimizing PT CaOx SS may be important for preserving renal function in PH1.

Original languageEnglish
JournalAmerican Journal of Physiology - Renal Physiology
Volume305
Issue number11
DOIs
StatePublished - Dec 1 2013

Fingerprint

Calcium Oxalate
Oxalates
Crystallization
Chronic Kidney Failure
Kidney
Hyaluronic Acid
Renal Insufficiency
Primary hyperoxaluria type 1
Staining and Labeling
Transplants
Cicatrix
Dialysis
Creatinine
Fibrosis

Keywords

  • Calcium oxalate
  • Primary hyperoxaluria
  • Proximal tubule
  • Renal histopathology

ASJC Scopus subject areas

  • Physiology
  • Urology

Cite this

A test of the hypothesis that oxalate secretion produces proximal tubule crystallization in primary hyperoxaluria type I. / Worcester, Elaine M.; Evan, Andrew; Coe, Fredric L.; Lingeman, James E.; Krambeck, Amy; Sommers, Andre; Phillips, Carrie; Milliner, Dawn.

In: American Journal of Physiology - Renal Physiology, Vol. 305, No. 11, 01.12.2013.

Research output: Contribution to journalArticle

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