Search

Background: Genetic testing is increasingly recognized as crucial in inherited nephropathies. Here, we report on an atypical presentation of a complex tubulopathy that led to an unexpected diagnosis of primary hyperoxaluria type 1 (PH1)., Case Diagnosis: At 2 weeks of age, a premature boy with stunted growth was diagnosed with complex tubulopathy associating hyponatremia, hypokalemia, hypomagnesemia, hypophosphatemia, metabolic acidosis, and acute kidney injury. Despite electrolyte replacement, severe hypomagnesemia persisted while massive parallel sequencing of genes involved in hypomagnesemia yielded negative results, including HNF1β. At 3 years of age, despite satisfactory growth, hypomagnesemia persisted and nephrocalcinosis appeared and progressed rapidly thereafter. Whole-genome analysis then revealed compound heterozygous mutations in the AGXT gene, thus leading to the diagnosis of PH1., Conclusion: Given the emergence of new targeted therapies, thorough genetic analysis including whole-genome analysis should be pursued, especially in case of atypical clinical presentation., Competing Interests: Declarations. Ethics approval: Lyon university hospital ethics committees. Conflict of interest: JB received consulting, research, and speaker fees from Alnylam, and consulting fees from Dicerna/Novonordisk and Biocodex. CAB and ALSL received consulting fees from Alnylam., (© 2024. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)

Background and Objectives: In the rare disease primary hyperoxaluria type 1, overproduction of oxalate by the liver causes kidney stones, nephrocalcinosis, kidney failure, and systemic oxalosis. Lumasiran, an RNA interference therapeutic, suppresses glycolate oxidase, reducing hepatic oxalate production. The objective of this first-in-human, randomized, placebo-controlled trial was to evaluate the safety, pharmacokinetic, and pharmacodynamic profiles of lumasiran in healthy participants and patients with primary hyperoxaluria type 1., Design, Setting, Participants, & Measurements: This phase 1/2 study was conducted in two parts. In part A, healthy adults randomized 3:1 received a single subcutaneous dose of lumasiran or placebo in ascending dose groups (0.3-6 mg/kg). In part B, patients with primary hyperoxaluria type 1 randomized 3:1 received up to three doses of lumasiran or placebo in cohorts of 1 or 3 mg/kg monthly or 3 mg/kg quarterly. Patients initially assigned to placebo crossed over to lumasiran on day 85. The primary outcome was incidence of adverse events. Secondary outcomes included pharmacokinetic and pharmacodynamic parameters, including measures of oxalate in patients with primary hyperoxaluria type 1. Data were analyzed using descriptive statistics., Results: Thirty-two healthy participants and 20 adult and pediatric patients with primary hyperoxaluria type 1 were enrolled. Lumasiran had an acceptable safety profile, with no serious adverse events or study discontinuations attributed to treatment. In part A, increases in mean plasma glycolate concentration, a measure of target engagement, were observed in healthy participants. In part B, patients with primary hyperoxaluria type 1 had a mean maximal reduction from baseline of 75% across dosing cohorts in 24-hour urinary oxalate excretion. All patients achieved urinary oxalate levels ≤1.5 times the upper limit of normal., Conclusions: Lumasiran had an acceptable safety profile and reduced urinary oxalate excretion in all patients with primary hyperoxaluria type 1 to near-normal levels., Clinical Trial Registry Name and Registration Number: Study of Lumasiran in Healthy Adults and Patients with Primary Hyperoxaluria Type 1, NCT02706886., (Copyright © 2021 by the American Society of Nephrology.)

Primary hyperoxaluria type 1 (PH1) is a genetic disorder characterized by overproduction of oxalate and eventual kidney failure. Kidney failure is usually irreversible in PH1. However, in patients with PH1 homozygous for the G170R mutation (in which the glycine at amino acid 170 is replaced by an arginine), pyridoxine is an enzyme cofactor and decreases urinary oxalate excretion by reducing hepatic oxalate production. We report recovery from dialysis in 3 patients with PH1 homozygous for the G170R mutation in response to pharmacologic-dose pyridoxine treatment. Median age at initiation or resumption of pyridoxine treatment was 37 (range, 20-53) years, and median daily pyridoxine dose was 8.8 (range, 6.8-14.0) mg per kilogram of body weight. Duration of hemodialysis before recovery of kidney function was 10 (range, 5-19) months. Plasma oxalate concentration improved after recovery of kidney function. At a median of 3 (range, 2-46) months following discontinuation of hemodialysis, estimated glomerular filtration rate was 34 (range, 23-52) mL/min/1.73m 2 , plasma oxalate concentration was 8.8 (range, 4.6-11.3) μmol/L, and urinary oxalate excretion was 0.93 (range, 0.47-1.03) mmol/d. Kidney function was maintained during a median of 3.2 (range, 1.3-3.8) years of follow-up. These observations suggest that kidney failure may be reversible in a subset of patients with PH1 homozygous for the G170R mutation treated with pharmacologic-dose pyridoxine., (Copyright © 2020 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Primary hyperoxaluria type 1 (PH1) is a rare genetic disease caused by hepatic overproduction of oxalate that leads to kidney stones, nephrocalcinosis, kidney failure, and systemic oxalosis. Lumasiran, an investigational RNA interference (RNAi) therapeutic agent, reduces hepatic oxalate production by targeting glycolate oxidase., Methods: In this double-blind, phase 3 trial, we randomly assigned (in a 2:1 ratio) patients with PH1 who were 6 years of age or older to receive subcutaneous lumasiran or placebo for 6 months (with doses given at baseline and at months 1, 2, 3, and 6). The primary end point was the percent change in 24-hour urinary oxalate excretion from baseline to month 6 (mean percent change across months 3 through 6). Secondary end points included the percent change in the plasma oxalate level from baseline to month 6 (mean percent change across months 3 through 6) and the percentage of patients with 24-hour urinary oxalate excretion no higher than 1.5 times the upper limit of the normal range at month 6., Results: A total of 39 patients underwent randomization; 26 were assigned to the lumasiran group and 13 to the placebo group. The least-squares mean difference in the change in 24-hour urinary oxalate excretion (lumasiran minus placebo) was -53.5 percentage points (P<0.001), with a reduction in the lumasiran group of 65.4% and an effect seen as early as month 1. The between-group differences for all hierarchically tested secondary end points were significant. The difference in the percent change in the plasma oxalate level (lumasiran minus placebo) was -39.5 percentage points (P<0.001). In the lumasiran group, 84% of patients had 24-hour urinary oxalate excretion no higher than 1.5 times the upper limit of the normal range at month 6, as compared with 0% in the placebo group (P<0.001). Mild, transient injection-site reactions were reported in 38% of lumasiran-treated patients., Conclusions: Lumasiran reduced urinary oxalate excretion, the cause of progressive kidney failure in PH1. The majority of patients who received lumasiran had normal or near-normal levels after 6 months of treatment. (Funded by Alnylam Pharmaceuticals; ILLUMINATE-A ClinicalTrials.gov number, NCT03681184.)., (Copyright © 2021 Massachusetts Medical Society.)

Measurement of oxalate in the blood is essential for monitoring primary hyperoxaluria patients with progressive renal impairment and on dialysis prior to transplantation. As no external quality assurance scheme is available for this analyte, we conducted a sample exchange scheme between six laboratories specifically involved with the investigation of primary hyperoxaluria to compare results. The methodologies compared were gas chromatography/mass spectrometry (GCMS), ion chromatography with mass spectrometry (ICMS), and enzymatic methods using oxalate oxidase and spectrophotometry. Although individual laboratories performed well in terms of reproducibility and linearity, there was poor agreement (absolute values) between centres as illustrated by a longer-term comparison of patient results from two of the participating laboratories. This situation was only partly related to differences in calibration and mainly reflected the lower recoveries seen with the ultrafiltration of samples. These findings lead us to conclude that longitudinal monitoring of primary hyperoxaluria patients with deteriorating kidney function should be performed by a single consistent laboratory and the methodology used should always be defined. In addition, plasma oxalate concentrations reported in registry studies and those associated with the risk of systemic oxalosis in published studies need to be interpreted in light of the methodology used. A reference method and external quality assurance scheme for plasma oxalate analysis would be beneficial.

Background: Primary hyperoxalurias are rare diseases with endogenous overproduction of oxalate, thus leading to hyperoxaluria, hyperoxalemia, urolithiasis, and/or nephrocalcinosis and eventually early kidney failure. Plasma oxalate (POx) is an important diagnostic parameter in clinical studies on primary hyperoxaluria (PH). This is especially the case in kidney failure, where urinary parameters are no longer suitable. We aimed to evaluate whether POx would be an adequate endpoint for clinical studies in PH patients with stable kidney function. In addition, the correlation of POx to serum creatinine (SCr) and calculated glomerular filtration rate (eGFR) was examined., Methods: We retrospectively analyzed follow-up of individual POx values over time, as well as POx correlation to SCr, eGFR, and vitamin B6 (VB6), a common therapeutic in PH1. Results from 187 blood samples taken between 2009 and 2017, during routine laboratory evaluations from 41 patients with PH1 who had neither undergone dialysis nor transplantation, were evaluated., Results: Negligibly low correlation coefficients (CCs) between POx vs. SCr (CC = -0.0950), POx vs. eGFR (CC = -0.1237), and POx vs. VB6 (CC = 0.1879) were found, with the exception of CKD stage 3a patients, who showed a positive correlation (CC of - 0.7329, POx vs eGFR). The intra-individual analysis of POx over time showed a high fluctuation of POx values., Conclusion: We conclude that POx has a limited validity as a primary endpoint for clinical studies in PH1 patients with stable kidney function. In addition, it does not correlate to SCr and eGFR in this group of patients.

This retrospective analysis investigated plasma oxalate (POx) as a potential predictor of end-stage kidney disease (ESKD) among primary hyperoxaluria (PH) patients. PH patients with type 1, 2, and 3, age 2 or older, were identified in the Rare Kidney Stone Consortium (RKSC) PH Registry. Since POx increased with falling estimated glomerular filtration rate (eGFR), patients were stratified by chronic kidney disease (CKD) subgroups (stages 1, 2, 3a, and 3b). POx values were categorized into quartiles for analysis. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) for risk of ESKD were estimated using the Cox proportional hazards model with a time-dependent covariate. There were 118 patients in the CKD1 group (nine ESKD events during follow-up), 135 in the CKD 2 (29 events), 72 in CKD3a (34 events), and 45 patients in CKD 3b (31 events). During follow-up, POx Q4 was a significant predictor of ESKD compared to Q1 across CKD2 (HR 14.2, 95% CI 1.8-115), 3a (HR 13.7, 95% CI 3.0-62), and 3b stages (HR 5.2, 95% CI 1.1-25), p < 0.05 for all. Within each POx quartile, the ESKD rate was higher in Q4 compared to Q1-Q3. In conclusion, among patients with PH, higher POx concentration was a risk factor for ESKD, particularly in advanced CKD stages.

Primary hyperoxalurias (PH) are inborn errors of glyoxylate metabolism characterized by an increase in endogenous oxalate production. Oxalate overproduction may cause calcium-oxalate crystal formation leading to kidney stones, nephrocalcinosis, and ultimately kidney failure. Twenty-four hour urine oxalate excretion is an inaccurate measure for endogenous oxalate production in PH patients and not applicable in those with kidney failure. Treatment efficacy cannot be assessed with this measure during clinical trials. We describe the development and validation of a gas chromatography-tandem mass spectrometry method to analyze the samples obtained following a stable isotope infusion protocol of 13 C 2 -oxalate and 1- 13 C-glycolate in both healthy individuals and PH patients. Isotopic enrichments of plasma oxalate, glycolate, and glyoxylate were measured on a gas chromatography-triple quadrupole mass spectrometry system using ethylhydroxylamine and N - tert -butyldimethylsilyl- N -methyltrifluoroacetamide (MTBSTFA) for analyte derivatization. Method precision was good for oxalate and glycolate (coefficients of variation [CV] were <6.3% and <4.2% for inter- and intraday precision, respectively) and acceptable for glyoxylate (CV <18.3% and <6.7% for inter- and intraday precision, respectively). The enrichment curves were linear over the specified range. Sensitivity was sufficient to accurately analyze enrichments. This new method allowed calculation of kinetic features of these metabolites, thus enabling a detailed analysis of the various pathways involved in glyoxylate metabolism. The method will further enhance the investigation of the metabolic PH derangements, provides a tool to accurately assess the therapeutic efficacy of new promising therapeutic interventions for PH, and could serve as a clinical tool to improve personalized therapeutic strategies.

Primary hyperoxaluria type 1 (PH1) is a rare but devastating autosomal recessive inherited disease caused by mutations in gene AGXT. Pathogenic mutations of AGXT were mostly reported in Caucasian but infrequently in Asian, especially in Chinese. To update the genotypes of PH1 in the Chinese population, we collected and identified 7 Chinese probands with PH1 from 2013 to 2017 in our center, five of whom had delayed diagnosis and failed in kidney transplantation. Samples of peripheral blood DNA from the 7 patients and their family members were collected and sequencing analysis was performed to test the mutations of gene AGXT. Western blotting and enzyme activity analysis were conducted to evaluate the function of the mutations. Furthermore, a systematic review from 1998 to 2017 was performed to observe the genetic characteristics between Chinese and Caucasian. The results showed that a total of 12 mutations were identified in the 7 pedigrees. To the best of our knowledge, 2 novel variants of AGXT, p.Gly41Trp and p.Leu33Met, were first reported. Bioinformatics and functional analysis showed that only 7 mutations led to a reduced expression of alanine-glyoxylate amino transferase (AGT) at a protein level. The systematic review revealed significant population heterogeneity in PH1. In conclusion, new genetic subtypes and genetic characteristics of PH1 are updated in the Chinese population. Furthermore, a genotype-phenotype correlation is found in PH1.

Primary hyperoxaluria (PH) patients overproduce oxalate because of rare genetic errors in glyoxylate metabolism. Recurrent urolithiasis and/or progressive nephrocalcinosis are PH hallmarks and can lead to kidney damage, systemic oxalosis and death. Based on previous studies, we hypothesised that treatment with the oxalate-metabolizing bacterium Oxalobacter formigenes would mediate active elimination of oxalate from the plasma to the intestine of PH patients, thereby reducing urinary oxalate excretion (Uox). The efficacy and safety of O. formigenes (Oxabact™ OC3) were evaluated for 24 weeks in a randomised, placebo-controlled, double-blind study. The primary endpoint was reduction in Uox. Secondary endpoints included change in plasma oxalate (Pox) concentration, frequency of stone events, number of responders, and Uox in several subgroups. Additional post hoc analyses were conducted. Thirty-six patients were randomised; two patients withdrew from placebo treatment. Both OC3 and placebo groups demonstrated a decrease in Uox/urinary creatinine ratio, but the difference was not statistically significant. No differences were observed with respect to change in Pox concentration, stone events, responders' number or safety measures. In patients with estimated glomerular filtration rate (eGFR) < 90 mL/min/1.73 m 2 , Pox increased by 3.25 µmol/L in the placebo group and decreased by -1.7 µmol/L in the OC3 group (p = 0.13). After 24 weeks, eGFR had declined to a greater degree in the placebo than in the OC3 group: -8.00 ± 2.16 versus -2.71 ± 2.50; p = 0.01. OC3 treatment did not reduce urinary oxalate over 24 weeks of treatment compared with placebo in patients with PH. The treatment was well tolerated.

Background: Since plasma oxalate (POx) concentrations increase at lower glomerular filtration rate (GFR) levels, even among those without enteric (EH) or primary hyperoxaluria (PH), the appropriate thresholds for considering a disorder of oxalate metabolism are poorly defined. The current study was completed to establish relationships between POx, GFR, and urine oxalate excretion (UOx) among patients with PH, EH, and routine urinary stone disease (USD)., Methods: The most recent POx measurement on all Mayo Clinic patients between 2005 and 2015 were electronically pulled from the Lab Information System together with the closest serum creatinine within 14days and 24h urine study within 60days. After exclusion of patients not in steady state at the time of blood draw, 270 patients were available for study. Records were reviewed for clinical diagnoses to categorize patients as PH, EH, or USD. Waste plasma for Pox was also obtained from controls without USD undergoing clinical GFR testing., Results: In all 3 groups POx increased as eGFR fell. For any given eGFR, POx was highest in the PH group and lowest in the USD and control groups (p<0.0001). POx was also influenced by UOx excretion (reflecting total body oxalate burden, absorption from diet and endogenous production). Generalized estimating equations of POx vs eGFR revealed higher average POx levels in PH compared to EH,USD or control, and for EH compared to USD or control. GEE prediction models were created that use POx, UOx, age, and serum creatinine to estimate the probability of a PH diagnosis., Conclusions: New models were developed to help interpret POx when considering PH in clinical practice even when it was not previously suspected and/or eGFR is reduced., (Copyright © 2017 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

Background: Patients with primary hyperoxaluria (PH) overproduce oxalate which is eliminated via the kidneys. If end-stage kidney disease develops they are at high risk for systemic oxalosis, unless adequate oxalate is removed during hemodialysis (HD) to equal or exceed ongoing oxalate production. The purpose of this study was to validate a method to measure oxalate removal in this unique group of dialysis patients., Methods: Fourteen stable patients with a confirmed diagnosis of PH on HD were included in the study. Oxalate was measured serially in hemodialysate and plasma samples in order to calculate rates of oxalate removal. HD regimens were adjusted according to a given patient's historical oxalate production, amount of oxalate removal at dialysis, residual renal clearance of oxalate, and plasma oxalate levels., Results: After a typical session of HD, plasma oxalate was reduced by 78.4 ± 7.7%. Eight patients performed HD 6 times/week, 2 patients 5 times/week, and 3 patients 3 times/week. Combined oxalate removal by HD and the kidneys was sufficient to match or exceed endogenous oxalate production. After a median period of 9 months, pre-dialysis plasma oxalate was significantly lower than initially (75.1 ± 33.4 vs. 54.8 ± 46.6 mmol/l, p = 0.02)., Conclusion: This methodology can be used to individualize the dialysis prescription of PH patients to prevent oxalosis during the time they are maintained on HD and to reduce risk of oxalate injury to a transplanted kidney.

Type 1 primary hyperoxaluria is a genetic disorder caused by deficiency of the liver-specific peroxisomal enzyme alanine-glyoxylate aminotransferase. This enzyme deficiency leads to excess oxalate production and deposition of calcium oxalate salts, resulting in kidney failure and systemic oxalosis. Aside from combined liver/kidney transplantation, no curative treatment exists. Various strategies for optimizing dialysis treatment have been evaluated, but neither conventional hemodialysis nor peritoneal dialysis can keep pace with oxalate production in this patient population. In this report, we describe a patient with end-stage renal disease from type 1 primary hyperoxaluria managed with nocturnal home hemodialysis. Performing hemodialysis 8-10 hours each night with blood flow of 350 mL/min and total dialysate volume of 60 L, she has maintained pre- and postdialysis serum oxalate levels at or below the level of supersaturation. We also review published literature regarding oxalate removal in various modalities of dialysis in patients with type 1 primary hyperoxaluria. In our patient, nocturnal hemodialysis has controlled serum oxalate levels better than conventional hemodialysis therapies. Home nocturnal hemodialysis should be considered an option for management of patients with end-stage renal disease from type 1 hyperoxaluria who are awaiting transplantation., (Copyright © 2013 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Primary hyperoxaluria (PH) is a rare genetic disease, in which high urinary oxalate (Uox) cause recurrent kidney stones and/or progressive nephrocalcinosis, often followed by early end-stage renal disease, as well as extremely high plasma oxalate, systemic oxalosis and premature death. Oxalobacter formigenes, an anaerobic oxalate degrading bacterium, naturally colonizes the colon of most humans. Orally administered O. formigenes (Oxabact) was found to significantly reduce urine and plasma oxalate. We aimed to evaluate its effect and safety in a randomized, double-blind, placebo-controlled multicenter study., Methods: Oral Oxabact was given to PH patients (>5 years old, Uox > 1.0 mmol/1.73 m(2)/day, glomerular filtration rate (GFR) > 50 mL/min) at nine PH referral sites worldwide. Primary endpoint was the change from baseline in Uox (mmol/1.73 m(2)/day) after 24 weeks of treatment (>20% reduction)., Results: Of the 43 subjects randomized, 42 patients received either placebo (23 subjects) or Oxabact (19 subjects). The change in Uox was <20% and not different between groups (P = 0.616). Ad hoc analysis was performed in 37 patients compliant with medication and urine processing. Change in Uox was -19% in subjects given Oxabact and -10% in placebo, (P = 0.288), but -21 and -7% with Uox expressed as molar creatinine ratio (Ox:Cr, mmol/mol, P = 0.06). Reduction of Ox:Cr was more obvious for patients with higher baseline values (>160 mmol/mol, Oxabact -28%, placebo -6%; P < 0.082). No serious adverse events were reported., Conclusion: Oxabact was safe and well tolerated. However, as no significant change in Uox was seen, further studies to evaluate the efficacy of Oxabact treatment are needed.

Primary hyperoxaluria (PH) is a rare genetic disorder characterized by overproduction of oxalate due to specific enzyme deficiencies in glyoxylate metabolism. The primary clinical presentation is in the form of recurrent urolithiasis, progressive nephrocalcinosis, end-stage renal disease, and systemic oxalosis. Herein, we present a case of PH who was diagnosed at 47 years of age after 6 years on hemodialysis. He presented with fatigue, anorexia, weight loss, and was found to have cachexia, diffuse edema, hepatomegaly, ascites, hypercalcemia, hyperphosphatemia, hypoalbuminemia, low parathyroid hormone levels, lytic and resorptive areas in the vertebrae, diffusely increased echogenity of the liver, multiple renal stones, and bilateral nephrocalcinosis. Bone marrow biopsy showed calcium oxalate crystals and crystal granulomas. The liver biopsy could not be performed. The absence of an identifiable reason for secondary forms, the severity of the clinical presentation, and pathological findings led to the diagnosis of PH2. He died while waiting for a potential liver and kidney donor. The presented case is consistent with the literature as he had renal stone disease in the third decade and end-stage renal disease in the fifth decade. Hypercalcemia was thought to be due to osteoclast-stimulating activity of macrophages constituting the granuloma. Erythropoietin-resistant anemia and hypothyroidism were thought to be due to accumulation of oxalate in the bone marrow and thyroid gland, respectively. It is very important to keep in mind the possibility of PH when faced with a patient with nephrocalcinosis and oxalate stone disease., (© 2011 The Authors; Hemodialysis International © 2011 International Society for Hemodialysis.)

Background: Patients with primary hyperoxaluria may need repeated kidney transplants due to damage from oxalic acid (oxalate) deposits. However, oxalate may also be potentially harmful in all transplant recipients. Determinants of oxalate following transplantation have not been well studied., Methods: Two hundred and twelve recipients admitted for transplantation were included in the study. Blood samples for measurement of oxalate and other relevant laboratory parameters were collected at baseline and subsequently 10 weeks after transplantation. For oxalate determination, samples were obtained in 99, 167 and 54 patients out of the 212 at baseline, at follow-up and at both time points, respectively. We examined the bivariate association between plasma oxalate at transplantation and preemptive transplantation, time on dialysis, recipient age, creatinine, urea, phosphate, haemoglobin, PTH, albumin and calcium. Oxalate 10 weeks after transplantation was tested likewise including also laboratory parameters at baseline, primary non-function, rejection episodes, live versus deceased donor, donor age and GFR at follow-up., Results: Median plasma oxalate concentration at transplantation was 35.0 micromol/L [95% confidence interval (95% CI) = 10.4-93.9] and 98% of the values were above normal limits (2.6-11.0). Oxalate concentration after 10 weeks was 9.0 micromol/L (4.0-25.5), still 37% being above the upper normal value. Multiple regression analysis revealed established dialysis treatment (P = 0.002) and creatinine (P < 0.000001) as independent positive determinants of oxalate at transplantation. Oxalate at 10 weeks was negatively associated to (51)Cr-EDTA absolute GFR (P = 0.023) and positively associated to donor age (P = 0.027) and plasma creatinine at 10 weeks (P = 0.03)., Conclusion: At transplantation, plasma oxalate was on average three times increased and above the upper normal limit in 98% of patients and were still above normal in 37% after 10 weeks. The reduction after 10 weeks is determined by GFR and donor age. Whether increased plasma oxalate following kidney transplantation may have long-term consequences needs further study.

A solid phase extraction (SPE)-LC-MSMS method for the routine determination of oxalic acid (OX) in plasma, a diagnostic marker of primary hyperoxaluria (PH), was developed and validated. The normal range of OX was found to be 3-11 micromol/L (n=67), with no differences attributable to gender or age. The effect of pre-analytical factors on the in vitro production of OX was investigated, and plasma was found to be stable for 1-2 h at room temperature, less after ingestion of vitamin C; the process was not completely stopped by preservation at either -20 or -70 degrees C.

Patients with end-stage renal failure owing to primary hyperoxaluria type 1 (PH1) receive dialysis while waiting for transplantation. So far, dialysis has not been shown to overcome the problem of ongoing oxalate production and deposition at extrarenal sites. We report on six children with PH1 who had to be dialyzed for a median period of 2.5 years while awaiting liver transplantation. Aiming at preventing oxalate tissue accretion, oxalate mass transfer was studied and dialysis intensified accordingly. Mean plasma oxalate concentration was between 51 and 137 micromol/l. In three of the six patients with a urinary output between 630 and 3140 ml, urinary removal of oxalate was between 5.6 and 12.4 mmol/week/1.73 m2. Hemodialysis (HD) in five of the six patients demonstrated a mean oxalate dialysance between 158 and 444 l/week/1.73 m2. Peritoneal dialysis (PD) in two of the six patients showed mean oxalate clearances of 66 and 103 l/week/1.73 m2. One patient received HD and PD. By adding all modes of elimination, a mean total oxalate mass between 10.1 and 24.1 mmol/week/1.73 m2 was removed. Dialysis is still necessary as a temporary therapy for a number of patients with PH1. Dialysis should be instituted pre-emptively and maximally exploited by intensified HD/PD treatment protocols, without, however, cutting back urinary output.

Primary hyperoxaluria is characterized by severe urolithiasis, nephrocalcinosis, and early renal failure. As treatment options are scarce, we aimed for a new therapeutic tool using colonic degradation of endogenous oxalate by Oxalobactor formigenes. Oxalobacter was orally administered for 4 weeks as frozen paste (IxOC-2) or as enteric-coated capsules (IxOC-3). Nine patients (five with normal renal function, one after liver-kidney transplantation, and three with renal failure) completed the IxOC-2 study. Seven patients (six with normal renal function and one after liver-kidney transplantation) completed the IxOC-3 study. Urinary oxalate or plasma oxalate in renal failure was determined at baseline, weekly during treatment and for a 2-week follow-up. The patients who showed >20% reduction both at the end of weeks 3 and 4 were considered as responders. Under IxOC-2, three out of five patients with normal renal function showed a 22-48% reduction of urinary oxalate. In addition, two renal failure patients experienced a significant reduction in plasma oxalate and amelioration of clinical symptoms. Under IxOC-3 treatment, four out of six patients with normal renal function responded with a reduction of urinary oxalate ranging from 38.5 to 92%. Although all subjects under IxOC-2 and 4 patients under IxOC-3 showed detectable levels of O. formigenes in stool during treatment, fecal recovery dropped directly at follow up, indicating only transient gastrointestinal-tract colonization. The preliminary data indicate that O. formigenes is safe, leads to a significant reduction of either urinary or plasma oxalate, and is a potential new treatment option for primary hyperoxaluria.

This is the first report of a cardiac manifestation of a primary hyperoxaluria type II (PH II) with the hemodynamic characteristics of a severe restrictive cardiomyopathy. PH II is a rare inherited metabolic disease characterized by a deficiency of D-glycerate dehydrogenase, which has also glyoxylate reductase activity. This defect causes an accumulation of hydroxypyruvate the precursor of oxalate. The renal excretion of oxalate is impaired causing a deposition of oxalate mainly in the kidneys. To date, less than fifty cases have been reported. Systemic oxalosis in PH II is an occasional finding; thus far, myocardial oxalosis due to PH II has never been reported. Described is the case of a 41 year old male with renal failure and severe neuropathy of unknown cause, who underwent endomyocardial biopsy under the suspicion of cardiac amyloidosis. Echocardiography and cardiac catheterization showed a severe restrictive cardiomyopathy; endomyocardial biopsy established the diagnosis of oxalosis. Plasma oxalate levels were markedly increased, therefore a liver biopsy was performed. Immunoreactivity for D-glycerate dehydrogenase/ glyoxylate reductase was absent and activity of the enzyme was < 5% of normal. In summary, these findings established the diagnosis of a restrictive cardiomyopathy due to PH II.

Calcium oxalate supersaturation of the blood is associated with deposition of crystals in various tissues. We measured the serum levels of oxalate, citrate, calcium, and magnesium to estimate their saturation in 112 hemodialysis patients without primary hyperoxaluria and two boys with primary hyperoxaluria. Serum levels of oxalate and citrate were determined by high-performance capillary electrophoresis, while calcium and magnesium were measured by ICP spectroscopy. The serum levels of oxalate, citrate, calcium, and magnesium were 44.9+/-16.5, 138.1+/-54.9 micromol/l, 2.30+/-0.28, and 1.07+/-0.18 mmol/l, respectively, while the levels in patients with primary hyperoxaluria were 83.9+/-34.3, 197.9+/-63.5 micromol/l, 2.53+/-0.15, and 1.14+/-0.34 mmol/l, respectively. Serum calcium oxalate saturation (SS), as calculated by the Equil program, was significantly correlated with the serum oxalate level. Most patients showed metastable supersaturation (1

Primary hyperoxaluria (PH1) is a condition caused by a hepatic-based enzyme defect which can lead to renal failure due to oxalate stone disease, obstructive uropathy and nephrocalcinosis. It has been shown that the underlying metabolic defect can be corrected by liver transplantation and in most cases (renal failure having already occurred) is accompanied by a kidney graft. This paper describes the current results of 127 liver transplants performed in 117 patients over a 20-year period from 1984 to 2004 in 35 European centres. The mean age at onset of symptoms was 5.6 +/- 7.8 years and the mean age at which a diagnosis was made was 8.8 +/- 9.5 years. The diagnosis was confirmed by liver biopsy proven decreased AGT activity in 68% of cases, hyperoxaluria in 74%, hyperglycolicaciduria in 37% and hyperoxalaemia in 50%. Patients were transplanted at a mean age of 16.5 +/- 11.4 years following a period of dialysis of 3.2 +/- 3.2 years (range 0-14.4 years). 1-, 5- and 10-year patient survival values were 86, 80 and 69%, respectively, and liver graft survival rates of 80, 72 and 60% at the same time intervals. There have been 27 deaths and 10 liver retransplants have been carried out. Patient outcomes are improved when prolonged periods on dialysis and the complications of systemic oxalosis have not occurred.

An 18-year-old woman diagnosed with piridoxine-resistent primary hyperoxaluria type 1 (PH-1) and progressive renal insufficiency complicated with acute renal failure of obstructive origin who developed systemic oxalosis affecting the heart (cardiomyopathy), the skin (cutaneous ulcers) and vascular system (lower limb ischemia, as well as pulmonary and cerebral microcirculatory blockage resulting in pulmonary hemorrhage and tonic-clonic general seizures. As conventional hemodialysis (HD) or peritoneal dialysis (PD) are unable to eliminate enough oxalate to avoid a continuous positive balance, long daily sessions (6-7 h) of high-flux hemodialysis (highly permeable polyamide membrane of 2.1 m2) for 67 consecutive days normalized blood oxalate levels and reversed the systemic complications secondary to the calcium oxalate crystals deposit. The patient underwent a combined liver-kidney transplantation and has progressed well to the present time. The most important factors in PH-1 treatment are analyzed. Even though combined liver-kidney transplantation is the treatment of choice and should be performed before the glomerular filtrate rate (GFR) falls below 25 mL/min/1.73 m2, intensive HD becomes necessary to prevent oxalosis in the face of acute renal failure. Also, as our case shows, intensive HD can achieve a negative oxalate balance and reverse both the systemic lesions and the oxalate deposits.

Differential diagnosis of primary hyperoxaluria type I (PH1) may become difficult once end-stage renal failure and anuria have occurred. Here we describe a rapid and sensitive method to simultaneously quantify glycolate and oxalate in plasma using a stable isotope dilution and gas chromatography-mass spectrometry. The results are provided within 2 h. The linearity of the method was validated up to 200 micromol/l of these compounds and the inter-assay precision for glycolate and oxalate was 2.4 and 2.6%, respectively (n=5), when the control plasma was spiked with 50 micromol/l of glycolate and oxalate. For healthy subjects, 1.0 ml of plasma was required and 0.1 ml for the PH1 patients. Using this method, plasma levels in non-PH1 patients under hemodialysis and in healthy subjects were determined. This method proved to be useful when used for differential diagnosis of PH1 and for monitoring the plasma levels of glycolate and oxalate in two PH1 patients before and after dialysis and liver transplantation. Plasma glycolate in these patients was dramatically decreased after liver transplantation, but plasma oxalate decreased more slowly due to remobilization of the calcium oxalate stores deposited throughout the body.

Background: Dialysis patients with primary hyperoxaluria are exposed to risks and hazards associated with calcium oxalate salt deposition in body tissues, since regular dialysis treatment does not adequately correct hyperoxalaemia. The purpose of this study was to evaluate oxalate mass removal using various dialysis modes in a patient suffering from primary hyperoxaluria type 1 (PH1)., Methods: Oxalate kinetics during daily haemodialysis was compared with that of standard haemodialysis (STD HD) and haemodiafiltration (HDF) using high flux dialysers (FB 170 H and FB 210 U, Transdial, Paris, France). All dialysis sessions lasted for 4 h. Blood was withdrawn and spent dialysate was collected in plastic bags every hour to evaluate mass removal. Oxalate concentration in plasma and in spent dialysate was determined by an enzymatic method. Oxalate generation, distribution volume and tissue deposition were calculated using single-pool models adapted from previous studies., Results: Although no significant difference was found in mass removal per session between dialysis strategies and dialyser types, weekly mass removal with daily HD was about 2 times greater than with STD HD or HDF. Even when daily HD was performed, the oxalate generation rate-mass removal ratio (G/R ratio) remained at a value of approximately 2., Conclusion: Although daily HD sessions led to a substantial increase in weekly oxalate removal, all three types of renal replacement therapy were insufficient to compensate for estimated oxalate generation. To eliminate sufficient amounts of oxalate generated in PH1 patients, at least 8 h of daily dialysis with a high-flux membrane would probably be required. Renal replacement therapy for PH1 patients needs be improved further.

Objective: To evaluate the short-term efficacy of (l)-2-oxothiaolidine-4-carboxylate (OTZ, which reduces urinary oxalate excretion in normal subjects) in the treatment of primary hyperoxaluria type 1 (PH1) in a phase II study., Patients and Methods: Two patients with PH1 received intravenous infusions of OTZ (100 mg/kg body weight for 2 h) given every 8 h for four doses. One patient also received a placebo treatment. Urine samples (24-h collections) were obtained before and during OTZ treatment and assayed for oxalate, citrate, creatinine, sulphate and pH. Daily blood samples were assayed for plasma oxalate and serum creatinine., Results: Urinary oxalate excretion was unaffected by OTZ treatment. Plasma oxalate declined in both individuals with OTZ treatment, but the effect was small. Plasma cysteine was normal in one patient, rising from a mean (sd) of 36 (3.7) micromol/L before treatment to a peak of 141 micromol/L after OTZ, but was not detected in samples from the other patient. The ratio of oxalate to creatinine clearances was high in both patients, with mean values of 3.1 and 3.8., Conclusions: Treatment with OTZ did not lead to clinically significant changes in urinary oxalate excretion. The high clearance of oxalate in these patients suggests a substantial renal secretion of oxalate.

Combined liver-kidney and kidney-only transplantation outcomes in primary hyperoxaluria (PH) are described. Strategies for the selection of type and timing of transplantation and pretransplantation and posttransplantation management are reviewed. Records were reviewed for 16 patients with PH who received 9 liver-kidney and 10 kidney-only transplants. Plasma oxalate values declined from 61 +/- 42 micromol/L pretransplantation to 9 +/- 6 micromol/L 1 month after transplantation in liver-kidney transplant recipients and 92 +/- 19 to 9 +/- 5 micromol/L in kidney-only transplant recipients. In most liver-kidney transplant recipients, hyperoxaluria persisted for 6 to 18 months after transplantation. Follow-up was 3.5 +/- 4.1 years in liver-kidney and 4.5 +/- 6.3 years in kidney-alone transplant recipients. Patient survival rates were 78% for liver-kidney and 89% for kidney-only transplant recipients. No hepatic allografts were lost. Three of 9 liver-kidney and 6 of 10 kidney-alone transplants lost renal allograft function. In those with functioning kidneys, renal clearance was 45.1 +/- 19.5 mL/min/1.73 m(2) in liver-kidney transplant recipients and 49.5 +/- 26.1 mL/min/1.73 m(2) in kidney-only transplant recipients at last follow-up. Kaplan-Meier 1-, 2-, 3-, and 5-year renal allograft survival rates for patients undergoing transplantation after 1984 were 78%, 78%, 52%, and 52% in liver-kidney transplant recipients and 86%, 71%, 54%, and 36% in kidney-only transplant recipients. Simultaneous grafting of liver and kidney after the development of renal insufficiency is recommended for the majority of patients with PH type I (PH-I). Kidney-alone transplantation is recommended for those with pyridoxine-responsive type I disease because pharmacological therapy allows favorable management of oxalate production in this situation. Kidney-alone transplantation also is recommended for PH type II (PH-II). This disease is less severe than PH-I, and it is currently unknown whether liver transplantation will correct the metabolic defect responsible for PH-II.

In order to identify additional genotypes in primary hyperoxaluria type 1, we sequenced the AGXT genes of 9 patients. We report 5 new mutations. Three are splice-site mutations situated at the end of intron 4 and 8 (647-1G>A, 969-1G>C, 969-3C>G), one is a missense mutation in exon 5 (D183N), and one is a short duplication in exon 2 (349ins7). Their consequence is always a lack of enzymatic activity of the Alanine-Glyoxylate Aminotransferase (AGT); for 4 of them, we were able to deduce that they were associated to the absence of AGT protein. These mutations are rare, as they have been found on one allele in our study (except 969-3C>G present in 2 unrelated families), and have not been previously reported.

Background: Children with primary hyperoxaluria type 1 (PH 1) are at great risk to develop systemic oxalosis in end-stage renal disease (ESRD), as endogenous oxalate production exceeds oxalate removal by dialytic therapy. As oxalate accumulates, calcium oxalate (CaOx) tissue deposition occurs. Children with other causes of ESRD, however, are not prone to CaOx deposition despite elevated plasma oxalate (POx) levels., Methods: Our study objective was to examine the potential mechanisms for these observations. We measured POx, sulfate, citrate, and calculated CaOx saturation (betaCaOx) in 7 children with ESRD caused by PH 1 and in 33 children with non-PH-related ESRD. Maintenance hemodialysis (HD) was performed in 6 PH 1 and 22 non-PH patients: Pre- and post-HD levels were analyzed at this point and were repeated twice within 12 months in 5 PH 1 and 14 non-PH patients. Samples were obtained only once in 12 patients (one PH 1) on peritoneal dialysis (PD). After liver-kidney or kidney transplantation, plasma levels were measured repetitively., Results: The mean POx was higher in PH 1 (125.7 +/- 17.9 micromol/liter) than in non-PH patients (44.2 +/- 3.3 micromol/liter, P < 10(-4)). All other determined anions did not differ between the two groups. betaCaOx was higher in PH 1 (4.71 +/- 0.69 relative units) compared with non-PH children (1.56 +/- 0.12 units, P < 10(-4)). POx and betaCaOx were correlated in both the PH 1 (r = 0.98, P < 2 x 10(-4)) and the non-PH group (r = 0.98, P < 10(-4)). POx and betaCaOx remained stable over time in the non-PH children, whereas an insignificant decline was observed in PH 1 patients after six months of more aggressive dialysis. betaCaOx was supersaturated (more than 1) in all PH 1 and in 25 out of 33 non-PH patients. Post-HD betaCaOx remained more than 1 in all PH 1, but in only 2 out of 22 non-PH patients. In non-PH children, POx and betaCaOx decreased to normal within three weeks after successful kidney transplantation, whereas the levels still remained elevated seven months after combined liver-kidney transplantation in two PH 1 patients., Conclusion: Systemic oxalosis in PH 1 children with ESRD is due to higher POx and betaCaOx levels. As betaCaOx remained supersaturated in PH 1 even after aggressive HD, oxalate accumulation increases, and CaOx tissue deposition occurs. Therefore, sufficient reduction of POx and betaCaOx is crucial in PH 1 and might only be achieved by early, preemptive, combined liver-kidney transplantation or liver transplantation alone.

We present the case of a young woman with end-stage renal disease secondary to primary hyperoxaluria type 1, who after 3 years and 6 months of maintenance hemodialysis, and despite intensification of the dialytic treatment, developed severe livedo reticularis in her extremities leading to ischemic cutaneous ulcerations, necessitating continuous intravenous infusion of narcotics for pain control. She received a liver transplant after native hepatectomy. However, due to positive crossmatch, she could not receive a kidney from that donor. After transplantation, following serial serum oxalate levels, the hemodialysis regimen was safely reduced from 4 h daily to 3 h three times weekly. Over the course of 6 weeks after liver transplantation, her livedo reticularis resolved, the ischemic ulcers markedly improved, she was weaned off all pain medications, and her erythropoietin-resistant anemia resolved. Our results suggest that in patients with primary hyperoxaluria type 1, who have received a liver transplant and are on maintenance hemodialysis, after serial serum oxalate determinations, some may safely be changed to a thrice-weekly maintenance hemodialysis regimen. Moreover, with this regimen the complications of systemic oxalosis can reverse.

This paper reports on a total of 61 patients receiving 64 liver grafts for primary hyperoxaluria type 1 (PH1) at 25 centres throughout Europe between 1984 and 1994 recorded in a central registry. Fifty-seven patients received simultaneous kidney grafts and one patient a delayed kidney graft, two patients received isolated liver grafts and a further three patients underwent retransplantation of the liver, a final patient receiving a liver alone dying intra-operatively before a planned kidney graft was performed. Results of such liver grafts are excellent, reversing the metabolic defect of PH1. Thirteen grafts have been lost and 10 patients have died, with actuarial graft and patient survival rates of 88% at 1 year and patient survival of 80% at 5 years. Early combined liver and kidney grafting appears to represent the optimal treatment for patients with PH1, avoiding the adverse effects of a prolonged period of dialysis and the development of the complications of systemic oxalosis. The registry will continue to collect and collate data on patients undergoing hepatic transplantation for PH1.

Reliable methods for the assaying of oxalate in biological fluids are now available. However, preanalytical sample collection and storage conditions are critical to produce meaningful results for the diagnosis and assessment of treatment modalities in primary hyperoxaluria. Spontaneous in vitro generation of oxalate from ascorbate is possible, especially in plasma measurements, where the ascorbate to oxalate ratio is considerably greater than that of urine. The pH of blood also favours the conversion of ascorbate to oxalate. Losses, as well as generation of oxalate can occur in urine when collection procedures are inadequate. Analysis of properly collected samples is of greater assistance in monitoring the efficacy of treatment modalities in oxaluric patients. Routine and reliable assays are still needed for other closely related organic acid anions such as glycolate and L-glycerate. Measurement of these anions can facilitate the diagnosis and assist in monitoring of treatment in the different forms of primary hyperoxaluria.

We describe the case of a patient in end-stage renal failure due to primary hyperoxaluria type I (PH1) who started hemodialysis in 1977 and is still alive and active. The diagnosis of PH1 was first suspected after a bone biopsy performed in 1981 to investigate hyperparathyroidism. Oxalosis recurred as early as 3 months after transplantation in a cadaver kidney grafted in 1987; nevertheless, graft function remained good enough to make possible the discontinuation of dialysis treatment for 5 months and thereafter to have only 1 dialysis a week for 17 months. The diagnosis of PH1 has been recently confirmed despite the patient being already anuric by means of the determination of plasma oxalate and glycolate levels as well as by determining hepatic alanine:glyoxylate amino-transferase.

We describe a liquid chromatographic technique to determine L-glycerate in body fluids. The method is based on the derivatisation of the L-glycerate by incubation with lactate dehydrogenase and nicotinamide-adenine dinucleotide in the presence of phenylhydrazine. Oxidation of L-glycerate forms beta-hydroxypyruvate which is converted in turn into the related phenylhydrazone. The UV-absorbing derivative is determined using reversed-phase high performance liquid chromatography. The sensitivity was 5 mumol/l and 50 microliters of sample were required. The imprecision relative standard deviation was 4.5% and the recovery was 96.5 +/- 6.8% for L-glycerate in plasma. L-Glycerate concentrations in urine and plasma were less than 5 mumol/l in both normal individuals and patients with glycolic aciduria. In a patient with systemic oxalosis and normal plasma glycolate, plasma L-glyceric acid was 887 mumol/l.

Hyperoxaluria type I (HPI) is a metabolic disorder secondary to liver alanine glyoxylate aminotransferase deficiency. Renal failure occurs due to the excessive production and precipitation of oxalate in the kidney. Combined liver-renal transplantation is the correct treatment for this condition when end-stage renal failure occurs as with renal transplantation alone the risk of recurrence of the same pathology in the transplanted kidney would be high. We report the case of a 4 year-old child with HPI suffering from terminal renal failure in whom a hepato-renal transplantation was performed: six months later, creatinine clearance was 62 ml/min/1.73 m2 and liver function tests were normal.

1. The serum oxalate concentration rises in chronic renal failure and it is only partially eliminated by regular dialysis treatment. However, the recent literature is not conclusive on whether progressive oxalate retention and secondary oxalosis should be expected in patients on regular dialysis treatment. 2. To further investigate this, we have estimated the state of saturation with respect to calcium oxalate monohydrate in plasma ultrafiltrates from 28 patients on maintenance haemodialysis and eight healthy control subjects, matched for sex and age. Five patients had type I primary hyperoxaluria and histologically proven oxalosis, whereas 23 had oxalosis-unrelated renal diseases. Dialysis efficiency was quantified as the KdTd/V of urea. Samples were obtained from each patient before, immediately after and 48 h after a dialysis session. Fasting samples were obtained from the control subjects. Oxalate was determined in both plasma ultrafiltrates and the whole dialysate by ion-exchange chromatography, after a non-delayed and [14C]oxalate-recovery-controlled procedure. The state of saturation with calcium oxalate monohydrate was estimated by means of a computer system which solved the interactions among 45 complex species. 3. The fasting plasma oxalate concentration (means +/- SD) in ultrafiltrates from healthy subjects was 3.8 +/- 1.5 (range 1.4-5.8) mumol/l, and the state of saturation with calcium oxalate monohydrate was 0.096 +/- 0.04.(ABSTRACT TRUNCATED AT 250 WORDS)

Purpose and Patients and Methods: The purpose of this article is to report the experience of three centers with combined hepatic and renal transplantation for pyridoxine-resistant primary hyperoxaluria type I (alanine:glyoxylate aminotransferase [EC 2.6.1.44] deficiency), with particular emphasis on the selection criteria and timing of the operation. Nine patients with this inherited disease were treated by combined hepatic and renal transplantation. The former replaces the enzyme-deficient organ while the latter replaces the functionally affected organ., Results: One patient with gross systemic oxalosis died in the immediate postoperative period and another died 8 weeks postoperatively of a generalized cytomegalovirus infection, having shown evidence of biochemical correction. One patient with particularly severe osteodystrophy at the time of the operation died 14 months postoperatively from renal failure due to progressive calcium oxalate nephrocalcinosis involving the transplanted kidney, plus thromboembolic disease. He also had very extensive systemic oxalosis. An additional patient with severe osteodystrophy died 9 months postoperatively. One patient developed hyper-rejection of the kidney and died later of gastrointestinal hemorrhage. The four long-term survivors (22 to 38 months) have remained asymptomatic from the standpoint of their renal disease, with resolution of any manifestations of systemic oxalosis that they may have had. They are either employed or continuing their education., Conclusions: A prolonged period of end-stage renal failure treated by dialysis regimens that are suitable for non-hyperoxaluric renal failure and extensive systemic oxalosis, particularly oxalotic osteodystrophy, are poor prognostic features. We propose that hepatic transplantation should be considered as definitive treatment before end-stage renal failure develops. This should be supplemented by renal transplantation with vigorous pre- and perioperative hemodialysis to deplete the body stores of oxalate. Although some authorities would reserve hepatic transplantation for patients in whom renal transplantation has failed, we suggest that combined liver and kidney transplantation is appropriate in patients who have never had a renal graft. Furthermore, the time has come to consider hepatic transplantation before any irreversible renal damage has occurred in these patients.

A liquid chromatographic procedure for the determination of glycolic acid in plasma is proposed. The system is based on pre-column derivatization of the alpha-keto acid by means of phenylhydrazine, coupled with the enzymatic oxidation of glycolate to glyoxylate. The phenylhydrazone formed is separated by reversed-phase liquid chromatography and detected by UV absorption. The measured within and between-batch CV imprecision was 2.6 and 11.3%, respectively, at 5.68 mumol/l glycolate concentration; the analytical recovery was 102.0 +/- 7.3% and the minimum detectable concentration of glycolate was 0.3 mumol/l. The reference interval for plasma glycolate was 4.51 to 12.20 mumol/l (n = 14). Results of determinations of plasma samples from uremic patients, patients with type I primary hyperoxaluria and patients with chronic renal failure secondary to systemic oxalosis are reported.

A 4.5-year-old boy received a combined liver and kidney transplant for correction of hyperoxaluria type 1. Both organs were from the same donor and functioned primarily. Three months after transplantation, urine oxalate excretion reached a maximum of 10,500 mumol/24 h and remained above 2300 mumol/24 h for the next 2 months. Two months later, oxalate excretion decreased to about 565 mumol/24 h, indicating exhaustion of a large oxalate pool. Six months after transplantation plasma oxalate is near normal (4.9 mumol/l). With the exception of one episode of acute rejection of the renal transplant, both organs were tolerated well and continue to have a unimpaired function 9 months after transplantation. However, there is increased echogenity on renal ultrasound, indicating oxalate deposits in the grafted kidney. This case illustrates that successful combined transplantation of both liver and kidney can be performed in infants, resulting in cure of the metabolic defect. The prolonged or acute excretion of oxalate may lead to oxalate deposition in the grafted kidney without impaired graft function or early graft loss.