Primary Hyperoxaluria – The German Experience

Abstract

Background: Primary hyperoxaluria (PH) is a heterogeneous disease with variable age of onset and inconsistent progression into renal failure (ESRF). Aims: In 1994 we initiated a survey within our Pediatric Nephrology working group to ascertain epidemiologic data and current practices. Updates were performed in 2000 and 2004. Results: Diagnosis of PH was made in 65 patients (42 with PH type I, 3 with PH type II, 12 unclassified and 8 reported dead), which suggests a minimum prevalence of 0.7 per 1 million of the population. First symptoms were urolithiasis, nephrocalcinosis, urinary tract infection or hematuria. Diagnosis was often delayed and was made only in ESRF in 11% of patients. Measurement of urine metabolites or plasma oxalate in ESRF was performed in 76 and 57%, respectively. Determination of enzyme activity in liver biopsy (55% overall) and mutation analysis have increasingly been performed since 2000 (84.2 and 51%). Treatment included high fluid intake, pyridoxine, citrate and magnesium preparations. Pyridoxine response was reported in 21% of patients. No genotype/phenotype correlation was seen. Most patients (39) do not require renal replacement therapy, 5 patients receive chronic hemodialysis. Preemptive liver (n = 5) and combined liver-kidney transplantation (n = 9) were the preferred transplantation procedures. Conclusion: Despite increasing knowledge and awareness, diagnosis of PH is still too often delayed and diagnosis only made in ESRF. Most German patients, however, do currently not require renal replacement therapy. Genotype/phenotype correlations were not found. Combined liver kidney transplantation is the preferred procedure, but has its specific risks. Additional treatment options are clearly needed.

The primary hyperoxalurias

“…Although disease severity and resulting phenotype varies widely even within affected families, about 90 % of all (western) PH I cases become symptomatic in childhood to adolescence with the cardinal features being recurrent urolithiasis and/or nephrocalcinosis [6–8, 24]. In some cases, however, the disease may go unrecognized for years either due to the absence, subtlety, or misinterpretation of symptoms.…”

“…Approximately 30 % of PH I patients have some degree of sensitivity to pyridoxine [4, 24, 35]. Patients with certain mutations in particular, respond to pyridoxine, and may even demonstrate normalization of urinary oxalate [33, 38].…”

Kidney Stones in Primary Hyperoxaluria: New Lessons Learnt

“…PH I regularly causes end-stage renal disease (ESRD) and curative treatment requires combined liver kidney and/or pre-emptive liver transplantation [15]. Even in industrialized countries there is a high rate of late diagnosis in advanced renal failure or after kidney graft failure in the setting of isolated kidney transplantation (up to 40% in adults), which denotes underreporting [6]–[10]. Infantile oxalosis occurring with generalized nephrocalcinosis and ESRD within the first 3 years of life constitutes the most severe PH I subgroup (up to 20% of cases) and still poses a major therapeutic challenge [1], [2], [16].…”

Primary and secondary hyperoxaluria: Understanding the enigma

“…Administration of supraphysiological doses of pyridoxine may stabilize this enzyme and also enhance its enzymatic activity [57] . The recommended initial dose of pyridoxine is 5 mg/kg with a maximum dose of 20 mg/kg [79] . Pyridoxine has been demonstrated to be effective in only 30% of the patients [80,81] and therapeutic success is noted by a approximately 30% reduction in urine oxalate excretion after 3 mo of pyridoxine supplementation at the maximal dose [53,60] .…”