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Background: Primary hyperoxaluria type 3 (PH3) is a recently described cause of childhood renal calculi. It results from mutations in the HOGA1 gene and most cases have been diagnosed after clinical ascertainment, exclusion of other genetic hyperoxalurias and mutation testing. Metabolite testing has not been widely applied but holds promise for the rapid screening and diagnosis of patients who are not specifically suspected to have PH3.Case-Diagnosis/Treatment: Two cases presented with renal calculi. Urine metabolite testing by tandem mass spectrometry was performed as part of the routine diagnostic work-up for this condition. Both had significantly increased levels of the PH3 urine marker 4-hydroxyglutamate and related metabolites. The diagnosis of PH3 was confirmed by the finding of bi-allelic damaging HOGA1 mutations.Conclusions: Urine screening by tandem mass spectrometry is a rapid, high-throughput test that can detect PH3 cases that may otherwise not be diagnosed. [ABSTRACT FROM AUTHOR]

The deposition of calcium oxalate crystals in the kidney and bone is a hallmark of primary hyperoxaluria type 1 (PH1). We report here an evaluation of the bone status of 12 PH1 children based on bone biomarkers [parathyroid hormone, vitamin D, fibroblast growth factor 23 (FGF23)] and radiological assessments (skeletal age, three-dimensional high-resolution peripheral quantitative computed tomography, HR-pQCT) carried out within the framework of a cross-sectional single-center study. The controls consisted of healthy and children with chronic kidney disease already enrolled in local bone and mineral metabolism studies. The mean age (±standard deviation) age of the patients was 99 (±63) months. Six children suffered from fracture. Bone maturation was accelerated in five patients, four of whom were <5 years. The combination of new imaging techniques and biomarkers highlighted new and unexplained features of PH1: advanced skeletal age in young PH1 patients, increased FGF23 levels and decreased total volumetric bone mineral density with bone microarchitecture alteration. [ABSTRACT FROM AUTHOR]

In recent years the incidence of pediatric stone disease has increased several fold, mostly due to hypercalciuria and hypocitraturia. The goal of medical treatment is to protect the patient from formation of new stones and expansion of existing ones. The non-pharmacological means to address stone disease include high fluid intake and, frequently, modification of nutritional habits. The pharmacological treatment is based on the chemical composition of the stone and the biochemical abnormalities causing its formation; hence, chemical analysis of the stone, urine and blood is of paramount importance and should be done when the first stone is detected. This review discusses the current options of medical treatment of pediatric urolithiasis. [ABSTRACT FROM AUTHOR]

Idiopathic hypercalciuria is the most important predisposing risk factor for calcium oxalate (CaOx) renal stone formation. We assessed the associations between spontaneous CaOx crystallization based on the Bonn Risk Index (BRI), urinary pH, calciuria, oxaluria, and citraturia in 140 Caucasian patients with hypercalciuria, aged 4–17 years, and compared the findings with those in 210 normocalciuric controls. Of the 140 hypercalciuric patients, 58 had renal stones, and 82 had recurrent erythrocyturia, renal colic, or urinary obstructive symptoms—but without stones. Urinary ionized calcium ([Ca2+]) levels were measured using a selective electrode, while the onset of crystallization was determined using a photometer and titration with 40 mmol/L ammonium oxalate (Ox2−). The calculation of the BRI was based on the [Ca2+]:Ox2− ratio. The BRI values were 12-fold higher in hypercalciuric children than in healthy controls, but no differences were found in the BRI between subjects with urinary stones and those with urolithiasis-like symptoms. An increased BRI suggested an association with hypercalciuria, lower urinary pH, hypocitraturia, and hypooxaluria. These data indicate that hypercalciuria is an important factor associated with increased urinary CaOx crystallization, although the causal pathways need further investigation. Determination of the BRI in children with hypercalciuria may improve the risk assessment of kidney stones. [ABSTRACT FROM AUTHOR]

Primary hyperoxaluria (PH) is a heterogeneous disease with a variable age of onset and a variable progression into kidney failure. Early diagnosis is mandatory to avoid the damaging effects of systemic calcium oxalate deposition. In 1997, we initiated a nationwide survey of American nephrologists to ascertain epidemiological data and current practices. PH was reported in only 102 patients, with PH I in 79 and PH II in 9; 14 patients were not classified. Most patients were Caucasian (84%). Main symptoms at diagnosis were urolithiasis (54.4%) and nephrocalcinosis (30%). A significant delay of diagnosis was seen in 42% of patients and 30% of patients were diagnosed only at end-stage renal disease (ESRD). Diagnosis was usually based on history and urinary oxalate excretion. Glycolate and l-glyceric acid excretion were rarely determined. To determine the enzyme defect, a liver biopsy was performed in 40%. Even at ESRD, only 56% of patients received an adequate diagnostic work-up. Half of the patients showed 'good' or 'fair' pyridoxine sensitivity. In addition to B[sub 6], most patients received either citrate or orthophosphate. Kidney transplantation (KTx) failed in 19 of 32 transplants (n=27 patients) and was due to recurrent oxalosis in 8 transplants. Liver Tx was performed after KTx in 5 patients (1 patient died). Combined liver-kidney Tx in 21 patients (in 9 patients after failure of KTx) achieved good organ function in 13 patients; 7 patients, however, died shortly after transplantation. In conclusion, the time between first symptom and diagnosis of PH must be minimized, and the diagnostic procedures have to be improved. The cases of unclassified hyperoxaluria suggest the possibility of additional type(s) of PH. As isolated KTx failed in 59% of patients, combined liver-kidney Tx seems to be the better choice in place of isolated KTx as the primary transplant procedure. [ABSTRACT FROM AUTHOR]

Three patients with primary hyperoxaluria type I received therapy consisting of vitamin B[sub 6], magnesium oxide, and high oral fluid intake. Sonographic follow-up showed a variable response to treatment, ranging from normalization of renal tissue to no change at all. However, there is evidence of a correlation between laboratory findings and ultrasound findings during treatment. [ABSTRACT FROM AUTHOR]

Focuses on hyperoxaluria in patients with primary distal renal tubular acidosis (RTA). Increase in luminal hydrogen-ion concentration leading to increase in tubular citrate reabsorption; Risk factors for nephrocalcinosis; Secondary development of distal RTA in hyperoxaluria patients; Increase in the risk of developing progressive nephrocalcinosis due to hyperoxaluria in patients with distal RTA.

Criticizes the article 'Genetic analysis: a diagnostic tool for primary hyperoxaluria type 1 (PH1),' published in the October 9, 2002 issue of the journal 'Pediatric Nephrology,' by Danko Milosevic et al. Difficulty in the clinical diagnosis of PH1; Benefits of genetic analysis of PH1 patients; Unavailability of direct cycle sequencing of the entire coding region in several parts of the world.

Discourages performance of liver biopsy on patients diagnosed with hyperoxaluria type 1 (PH1). Comparison of statistics in developing and developed countries of PH1 patients who were subjected to liver biopsy; Procedures that can make prevention and diagnosis of PH1 easier; Comments of authors on the cost involved in mutation screening.

Addresses problems associated with diagnosis and management of primary hyperoxaluria (PH). Details of a case of PH where the patient reported solitary calculus in the right kidney; Description of medication given to the patient; Result of DNA analysis of the patient.