NDT Advance Access published online on April 5, 2006
Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfl142
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Department of Urology, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA
* To whom correspondence should be addressed. Background. Primary hyperoxaluria type 2 (PH2) is a rare monogenic disorder characterized by an elevated urinary excretion of oxalate. Increased oxalate excretion in PH2 patients can cause nephrolithiasis and nephrocalcinosis, and can, in some cases, result in renal failure and systemic oxalate deposition. The disease is due to a deficiency of glyoxylate reductase/hydroxypyruvate reductase (GRHPR) activity. A definitive diagnosis of PH2 is currently made by the analysis of GR activity in a liver biopsy. GRHPR is expressed in virtually every tissue in the body, suggesting that utilization of more readily available cells could be used to determine GRHPR deficiency. In this study, we have evaluated the potential of determining GR and d-glycerate dehydrogenase (DGDH) activity in blood mononuclear cells (BMC) as a diagnostic indicator of PH2. Methods. Blood samples were obtained from 10 male and 10 female normal subjects, median age 31, range 21-63, at the Wake Forest University Medical Center and from primary hyperoxaluria patients at the Mayo Clinic. The BMC were isolated and GR and DGDH activities measured in cell lysates. Results. An assay of 20 normal individuals indicated that BMC contained a DGDH and GR activity of 0.97±0.20 (range 0.62-1.45), and 10.6±3.3 (range 8.3-16.6) nmol/min/mg protein, respectively. The intra-assay coefficient of variation for DGDH and GR activity was 8.2 and 11.5%, respectively. The BMC lysates from normal adult subjects and patients with PH1 showed similar GR and DGDH activities. This was confirmed by the presence of immunoreactive GRHPR protein by western blot analysis. In contrast, PH2 BMC lysates did not exhibit DGDH or GR activity, and showed no immunoreactive GRHPR by western blot analysis. Conclusion. These results suggest that the assay of DGDH or GR activity in BMC could be used as a minimally invasive diagnostic test for PH2.
Received February 13, 2006
Accepted March 6, 2006
Brief Report
Glyoxylate reductase activity in blood mononuclear cells and the diagnosis of primary hyperoxaluria type 2
John Knight 1 *,
Ross P. Holmes 1,
Dawn S. Milliner 2,
Carla G. Monico 2,
and
Scott D. Cramer 3
2 Mayo Clinic Hyperoxaluria Center, Departments of Pediatric and Adolescent Medicine and Internal Medicine, Division of Nephrology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA
3 Department of Cancer Biology, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA
John Knight, E-mail: jknight{at}wfubmc.edu
Abstract 
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  T. Takayama, M. Nagata, S. Ozono, K. Nonomura, and S. D. Cramer A novel mutation in the GRHPR gene in a Japanese patient with primary hyperoxaluria type 2 Nephrol. Dial. Transplant., August 1, 2007; 22(8): 2371 - 2374. [Full Text] [PDF]
|
|