Crystalline Nephropathy Due to 2, 8-Dihydroxyadeninuria: An Under-Recognized Cause of Irreversible Renal Failure
SH Nasr, S Sethi, LD Cornell, DS Milliner, ME Fidler. Mayo Clinic, Rochester, MN
Background: 2, 8 dihydroxyadeninuria (DHA) is a rare autosomal recessive disorder caused by APRT deficiency, typically manifesting as recurrent stones. Only rare cases of DHA stones have been reported from the U.S. Here, we report 3 American pts with DHA crystalline nephropathy leading to ESRD with recurrence in the allograft.
Design: 3 cases of DHA crystalline nephropathy were identified from our Nephropathology archives.
Results: All 3 pts were white adults with no history of obstruction. 2 pts had no history of stones and 1 had a single episode of stones 36 yrs prior to presentation. All pts presented with renal failure with a mean creatinine of 7.5 mg/dl. Renal biopsies showed numerous tubulointerstitial DHA crystals, tubular degenerative changes, and moderate tubulointerstitial scarring. DHA crystals stained brown with H&E [fig 1] and were strongly birefringent [fig 2]. In the tubular lumina, they formed fan-like or irregular shapes. Within the tubular cytoplasm, they appeared as small single crystals with rod or rhomboidal shapes. In the interstitium, both single crystals and aggregates were seen. 2 pts were initially misdiagnosed, one as primary hyperoxaluria and the other as chronic interstitial nephritis. The diagnosis of DHA disease was confirmed by finding complete absence of APRT enzyme activity on blood spot. All 3 pts progressed to ESRD, within one month following biopsy in 2 and after 9 months in 1. All 3 pts underwent renal transplant with early disease recurrence in 3 allografts in 2 pts.
Conclusions: DHA disease is an under-recognized condition that can lead to irreversible renal failure and recurs in the allograft. It must be considered in the differential diagnosis of crystalline nephropathy, even in the absence of history of stones. Pathologists should be familiar with the characteristic brownish and birefringent tubulointerstitial crystals of this rare condition.
Category: Kidney (does not include tumors)
Monday, March 22, 2010 2:00 PM
Platform Session: Section H, Monday Afternoon