Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Nephrol. May 6, 2015; 4(2): 235-244
Published online May 6, 2015. doi: 10.5527/wjn.v4.i2.235
Primary and secondary hyperoxaluria: Understanding the enigma
Bhavna Bhasin, Hatice Melda Ürekli, Mohamed G Atta
Bhavna Bhasin, Division of Nephrology, Medical University of South Carolina, Charleston, SC 29425, United States
Hatice Melda Ürekli, Suleyman Demirel University Faculty of Medicine, 32260 Isparta, Turkey
Mohamed G Atta, Division of Nephrology, Johns Hopkins University, Baltimore, MD 21287, United States
Author contributions: Bhasin B generated the figures and tables and wrote the manuscript; Ürekli HM contributed to the writing of the manuscript; Atta MG provided critical appraisal of the manuscript for scientific ideas and clinical relevance for publication; Atta MG also edited the manuscript in preparation for submission and publication.
Conflict-of-interest: The authors declare that they have no competing interests.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Correspondence to: Dr. Mohamed G Atta, MD, MPH, Division of Nephrology, Johns Hopkins University, 1830 E. Monument Street, Suite 416, Baltimore, MD 21287, United States.
Telephone: +1-410-9555268 Fax: +1-410-9550485
Received: July 24, 2014
Peer-review started: July 24, 2014
First decision: August 14, 2014
Revised: August 29, 2014
Accepted: February 4, 2015
Article in press: February 9, 2015
Published online: May 6, 2015

Hyperoxaluria is characterized by an increased urinary excretion of oxalate. Primary and secondary hyperoxaluria are two distinct clinical expressions of hyperoxaluria. Primary hyperoxaluria is an inherited error of metabolism due to defective enzyme activity. In contrast, secondary hyperoxaluria is caused by increased dietary ingestion of oxalate, precursors of oxalate or alteration in intestinal microflora. The disease spectrum extends from recurrent kidney stones, nephrocalcinosis and urinary tract infections to chronic kidney disease and end stage renal disease. When calcium oxalate burden exceeds the renal excretory ability, calcium oxalate starts to deposit in various organ systems in a process called systemic oxalosis. Increased urinary oxalate levels help to make the diagnosis while plasma oxalate levels are likely to be more accurate when patients develop chronic kidney disease. Definitive diagnosis of primary hyperoxaluria is achieved by genetic studies and if genetic studies prove inconclusive, liver biopsy is undertaken to establish diagnosis. Diagnostic clues pointing towards secondary hyperoxaluria are a supportive dietary history and tests to detect increased intestinal absorption of oxalate. Conservative treatment for both types of hyperoxaluria includes vigorous hydration and crystallization inhibitors to decrease calcium oxalate precipitation. Pyridoxine is also found to be helpful in approximately 30% patients with primary hyperoxaluria type 1. Liver-kidney and isolated kidney transplantation are the treatment of choice in primary hyperoxaluria type 1 and type 2 respectively. Data is scarce on role of transplantation in primary hyperoxaluria type 3 where there are no reports of end stage renal disease so far. There are ongoing investigations into newer modalities of diagnosis and treatment of hyperoxaluria. Clinical differentiation between primary and secondary hyperoxaluria and further between the types of primary hyperoxaluria is very important because of implications in treatment and diagnosis. Hyperoxaluria continues to be a challenging disease and a high index of clinical suspicion is often the first step on the path to accurate diagnosis and management.

Keywords: Primary hyperoxaluria, Transplantation, Renal stones, Secondary hyperoxaluria, Renal failure

Core tip: Hyperoxaluria is a disorder characterized by increased urinary oxalate excretion. Primary hyperoxaluria is an inherited defect of oxalate metabolism while secondary hyperoxaluria is seen in states of increased ingestion of oxalate, its precursors or altered gut flora. These disorders can lead to recurrent renal stones, nephrocalcinosis and eventually end stage renal disease. Despite these common features, the sub types of hyperoxaluria differ in their pathogenesis, severity of clinical presentation and treatment plan. Prompt clinical recognition and distinction between these disorders is essential not only for timely intervention but also impacts prognosis in patients with hyperoxaluria.