Primary and secondary hyperoxaluria: Understanding the enigma

Table 1 Comparison between primary and secondary hyperoxaluria

Clinical feature	Primary hyperoxaluria	Secondary hyperoxaluria
Etiology	Inborn error of metabolism with specific enzymatic defects	Increased dietary intake of oxalate or precursors
	PH 1: Alanine glyoxalate aminotransferase	Increased intestinal absorption
	PH 2: Glyoxalate/hydroxypyruvate reductase	Altered intestinal microflora
	PH 3: 4-hydroxy 2-oxoglutarate aldolase
Clinical presentation	PH 1: Recurrent stones, nephrocalcinosis, ESRD common	Recurrent renal stones, nephrocalcinosis, CKD and ESRD
	Clinical heterogeneity in presentation, varies from an infantile to an adult onset form
	PH 2: Recurrent stones, nephrocalcinosis less common, ESRD has been reported (approximately 20% cases)
	PH 3: Hypercalciuria with hyperoxaluria is reported, no reports to date of ESRD
Systemic oxalosis	Frequent part of the presentation	Less common but may occur in severe cases of inflammatory bowel disease or short bowel syndrome
Diagnosis: History	Family history is often suggestive with other affected relatives	Dietary history may be an important pointer towards the diagnosis
Urinary excretion	> 1.0 mmol/1.73 m2 BSA	Usually < 1.0 mmol/1.73 m2 BSA but in some cases of enteric hyperoxaluria may extend into the primary range
Composition of renal stones	95% calcium oxalate monohydrate (whewellite)	Mixed stones (whewellite and weddellite)
Other diagnostic points	Plasma oxalate levels in ESRD are > 60-80 mmol/L as compared from non-PH causes of ESRD	14C test can be used to assess for increased intestinal absorption
Treatment:
General measures:	Daily fluid intake > 3.0 L/d	Hydration and urinary alkalinization
	Pyridoxine in PH1	Renal replacement therapy when ESRD occurs
	Urinary alkalinization
	Thiazides for PH3
	Renal replacement therapy when ESRD occurs
Specific measures:	No role as dietary absorption is < 5%	Important role as dietary absorption is > 40%
Dietary management
O. formigenes	No role in management	No role demonstrated in human studies
Transplantation	PH1: Liver kidney transplant (combined or sequential)	Limited data available regarding transplants for treatment of SH
	Isolated kidney transplant in pyridoxine sensitive adult patients
	PH2: Isolated kidney transplant
	PH3: No role of kidney transplant

PH: Primary hyperoxaluria; SH: Secondary hyperoxaluria; CKD: Chronic kidney disease; ESRD: End stage renal disease; BSA: Body surface area.

Table 2 Additional resources for information on hyperoxaluria

Resource	Web address
Oxalosis and Hyperoxaluria Foundation	http://www.ohf.org/
Rare Disease Initiative of the Renal Association	http://rarerenal.org/
Rare Diseases Clinical Research Network (links to the Rare Kidney Stone Consortium)	http://www.rarediseasesnetwork.org/
Children Living with Inherited Metabolic Diseases	http://www.climb.org.uk/
Genetics Home Reference	http://ghr.nlm.nih.gov/
Office of Rare Diseases Research	http://rarediseases.info.nih.gov/
National Organization for Rare Disorders	http://www.rarediseases.org/