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

[primary hyperoxaluria type 1]

The sequence of events by which primary hyperoxaluria type 1 (PH 1 ) 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 PH 1 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 PH 1 patients without renal failure , we calculated oxalate secretion , and estimated PT CaOx SS . Plasma oxalate was elevated in all PH 1 patients and inverse to creatinine clearance . Renal secretion of oxalate was present in all PH 1 but rare in controls . PT CaOx SS was >1 in all nonpyridoxine-responsive PH 1 before transplant and most marked in patients who developed end stage renal disease (ESRD ). PT from PH 1 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 . PH 1 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 PH 1 .

Diseases
Validation

Diseases presenting "renal failure" symptom

cholangiocarcinoma

congenital diaphragmatic hernia

cystinuria

erdheim-chester disease

fabry disease

heparin-induced thrombocytopenia

homocystinuria without methylmalonic aciduria

junctional epidermolysis bullosa

kindler syndrome

legionellosis

oculocutaneous albinism

primary hyperoxaluria type 1

scrub typhus

systemic capillary leak syndrome

This symptom has already been validated