2026-08-12 | Case Report: A rare AGXT pathogenic variant associated with young-adult-onset end-stage kidney disease.
Primary hyperoxaluria type 1 (PH1) is a rare autosomal recessive metabolic disorder caused by pathogenic variants in AGXT, leading to hepatic oxalate overproduction, recurrent nephrolithiasis, nephrocalcinosis, progressive kidney dysfunction, and, in advanced stages, systemic oxalosis. Here, we report a family in which two brothers developed recurrent nephrolithiasis and progressed to end-stage kidney disease (ESKD) in young adulthood. The proband, a 32-year-old man, presented with bilateral kidney stones, rapidly progressive renal failure, and extensive extra-renal tissue oxalate deposition on follow-up imaging. Genetic testing identified a homozygous AGXT variant, c.740T>G, p.(Leu247Arg), in both affected siblings, while the proband's mother and daughter were heterozygous carriers, consistent with autosomal recessive inheritance. Plasma oxalate levels were markedly higher in the proband than in his brother and in non-PH ESKD controls. During follow-up, the proband received maintenance hemodialysis alone, whereas his older brother underwent combined hemodialysis, hemofiltration, and hemoperfusion, and appeared to achieve better plasma oxalate control. These findings suggest that intensified blood purification may serve as a potential bridging strategy in advanced PH1 while definitive treatment is being arranged. This report expands the genotypic and phenotypic spectrum of PH1 and underscores the importance of early genetic evaluation in patients with recurrent or early-onset nephrolithiasis, especially when accompanied by rapid renal decline or a positive family history.
Open article ↗
2026-07-14 | Clinical Characteristics, Genetic Spectrum, and Treatment Outcomes in Children With Primary Hyperoxaluria: Results From a National Turkish Registry.
Primary hyperoxaluria (PH) is a rare autosomal recessive disorder characterized by excessive oxalate production, leading to nephrolithiasis, nephrocalcinosis, and kidney failure. Data from large pediatric cohorts remain limited. This national, multicenter, retrospective study included 88 pediatric patients with PH followed in 15 centers in Türkiye between 2010 and 2024. Clinical, genetic, and treatment-related data were collected via a web-based registry, and disease progression and outcomes were analyzed. The median age at diagnosis was 2.6 (IQR: 0.5-8.4) years in PH1, with an approximate diagnostic delay of 2 years. At diagnosis, nearly half (49.4%) had kidney failure. Genetic diagnosis was performed in 59 (71.1%) patients. The most frequently detected variants were p.Val324Glyfs (n = 12, 20.3%) and p.Gly170Arg (n = 9, 15.2%). During a median follow-up of 58 months (IQR: 24-109), dialysis was initiated at 51.8% and mortality reached 27.7%, particularly among patients presenting with kidney failure. Pyridoxine was used in 55.4% of patients, although response rates were limited, partly due to late diagnosis and non-genotype-guided use. Transplantation was performed in 24.1% of patients. Sequential liver-kidney transplantation provided favorable long-term renal outcomes and remains the most effective treatment for advanced disease by correcting the underlying metabolic defect. Patients with PH2 and PH3 exhibited a milder clinical course, preserved kidney function, and no mortality during follow-up. Delayed diagnosis remains a major challenge in pediatric PH. Early recognition, genotype-guided therapy, and timely implementation of appropriate transplantation strategies are essential to improve outcomes.
Open article ↗
2026-07-03 | Primary hyperoxaluria type 1-current practice in the siRNA era: an ERA Genes & Kidney Working Group survey.
Primary hyperoxaluria type 1 (PH1) is a rare inherited metabolic disorder leading to the formation of kidney stones, nephrocalcinosis, and kidney failure. Besides, PH1 poses the risk of developing systemic oxalosis, a life-threatening condition with oxalate deposits in multiple organ systems. The rarity of the disorder combined with recent major additions to therapeutic options based on small interfering RNA (siRNA) therapeutics make a formal assessment of current practice and implementation of treatment recommendations an important asset. An international questionnaire survey was conducted among medical doctors involved in the treatment of patients with chronic kidney disease. The survey included 32 questions addressing demographics, diagnostics and therapeutics, and educational needs related to the care for PH1 patients. 176 participants from 43 countries completed the survey, the majority of them were from Europe. The results indicate clear shortcomings in the availability of recommended diagnostics, especially with regards to plasma oxalate. Genetic testing strategies often do not include patients who may have PH1, e.g. when the underlying cause of kidney failure is unknown or in patients with nephrolithiasis or nephrocalcinosis. Treatment modalities are only partly harmonized and intensified dialysis is not fully implemented across centers. Strategies toward combination of conventional therapeutics such as hyperhydration and pyridoxine with new siRNA therapeutics depend on the treating physician's expertise. The survey identifies clear needs regarding implementation of current treatment recommendations as well as important educational gaps. The advent of targeted treatment opportunities for PH1 comes with an increased need to provide guidance to the field. Filling the existing gaps will ensure that a growing number of patients get access to optimal care and novel life-changing therapies.
Open article ↗
2026-06-08 | From recurrent flank pain to systemic oxalosis: a case of primary hyperoxaluria type 1 requiring dual organ transplantation.
Primary hyperoxalurias (PH) are rare autosomal recessive inherited disorders that disrupt the metabolism of glyoxylate and oxalate. The most common type, primary hyperoxaluria type 1 (PH1), is caused by a deficiency in the liver enzyme alanine-glyoxylate aminotransferase (AGT), leading to the overproduction and excessive urinary excretion of oxalate. On routine evaluation, the patient presented with deranged renal function and echogenic kidneys. Imaging via KUB X-ray revealed radio-opaque kidney stones, small shrunken kidneys, and nephrocalcinosis, indicating progression to end-stage kidney disease (ESKD). Additional systemic manifestations included increased lumbar bone density and pulmonary fibrosis. Diagnosis was definitively confirmed through elevated 24-hour urinary oxalate levels and genetic screening showing an AGXT gene mutation. This necessitated combined liver-kidney transplantation (CLKT): the liver graft provides the missing AGT enzyme to stop oxalate production, while the kidney graft replaces damaged organs and discontinues chronic dialysis. PH1 must be suspected in pediatric patients presenting with recurrent urolithiasis or nephrocalcinosis, especially in clinical cases of consanguinity. Early interventions - high fluid intake, crystallization inhibitors, and pyridoxine - can help preserve kidney function. For patients reaching ESKD, combined transplantation is the most effective approach to correct the underlying metabolic error and stop oxalate accumulation. This case highlights the diagnostic challenge of PH1, where the initial presentation with flank pain and urinary symptoms may mimic a urinary tract infection, placing the patient at potential risk of urosepsis if misdiagnosed or untreated. CLKT remains the definitive treatment in advanced disease.
Open article ↗
2026-06-01 | P102 From stone disease to survival: sequential liver and kidney transplantation for type i primary hyperoxaluria in a resource-limited setting
Introduction
Type I primary hyperoxaluria is a rare autosomal recessive metabolic disorder caused by hepatic alanine-glyoxylate aminotransferase deficiency, leading to excessive oxalate production resulting in nephrolithiasis, nephrocalcinosis, end-stage renal disease, and systemic oxalosis. Definitive treatment is sequential or combined liver–kidney transplantation, where liver replacement corrects the metabolic defect and kidney transplantation restores renal function. We aimed to evaluate clinical characteristics and transplant outcomes of patients undergoing sequential liver with or without kidney transplantation in a resource-limited setting where diagnostic delay is common.
Methods
We retrospectively analyzed patients with primary hyperoxaluria who underwent liver transplantation with or without kidney transplantation at a tertiary care transplant center. The variables in our study are demographics, age at renal stone onset, diagnostic delay, age at time of liver transplant, prior urological interventions, duration of hemodialysis pre-liver transplant, graft-recipient weight ratio (GRWR), cold ischemia time, liver graft type, biliary ductal anatomy (single duct vs ductoplasty), cardiac involvement, one-year survival, liver-to-kidney transplant interval, and causes of mortality. Continuous variables are reported as mean ± standard deviation and categorical variables as frequencies and percentages.
Results
Fourteen patients were included, with a mean age at transplantation of 24.1 ± 11.4 years; 12 (85.7%) were male. Mean age at first renal stone was 10.79±8.78 years, while mean age at diagnosis was 23.29±11.17 years, resulting in a mean diagnostic delay of 11.89±13.40 years. Prior urological interventions were present in 11(78.6%). Mean duration of hemodialysis prior to liver transplantation was 17.07±9.07 months. Living donor liver transplantation was performed in all patients; mean GRWR was 1.26±0.72 and mean cold ischemia time was 35.71±18.80 minutes. Most grafts had single bile duct anatomy, with ductoplasty required in a minority. Cardiac involvement was common and predominantly manifested by diastolic dysfunction and pulmonary hypertension, with less frequent non-ischemic cardiomyopathy and largely preserved systolic function. One-year survival after liver transplantation was 10(71.4%). Mortality occurred early and was primarily attributable to sepsis, cardiac complications, and multiorgan failure
Conclusion
When contrasted with European registry cohorts that register earlier diagnosis and >85% one-year survival, patients in low-middle income settings present later with prolonged dialysis exposure and cardiac involvement yet can achieve acceptable short-term outcomes. Early metabolic screening, reduced diagnostic delay, and rigorous cardiac stratification may help to improve outcomes.
Open article ↗
