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Special Care in Dentistry : Official... Feb 2024Oro-dental manifestations of hyperoxaluria and dental management of affected patients are rarely reported in the literature. We describe a new oral presentation of...
OBJECTIVES
Oro-dental manifestations of hyperoxaluria and dental management of affected patients are rarely reported in the literature. We describe a new oral presentation of primary hyperoxaluria (PH) and review relevant literature about oro-dental manifestations and management of dental complications of hyperoxaluria.
METHODS
A case report of a 44-year-old female who presented with symptoms of temporomandibular joint dysfunction due to hyperoxaluria was described according to the CARE guidelines. In addition, an extensive search of biomedical databases (PubMed, Medline, Google Scholar, and Embase) for articles describing oro-dental manifestations and/or dental management in patients with hyperoxaluria was performed using the key words ("oral" and/or "hyperoxaluria" and/or "dental" and/or "oxalosis"). Included articles were reviewed and data about patient demographics, disease type and stage, oral and dental manifestations, and dental treatment outcome were retrieved and analyzed.
RESULTS
A total of 14 articles describing the oral and dental manifestations in 15 patients with hyperoxaluria were included. Tooth mobility, root resorption, and radiographic alterations were consistently described in all cases. Oral manifestations were described mainly in PH at late stages, and only after the onset of chronic renal disease. Dental management in all reported cases was palliative and aimed to relive pain and treat periodontal infection. Tooth loss due to extraction or uncontrolled mobility was the ultimate outcome in almost all reported cases.
CONCLUSION
Oral and dental manifestations in hyperoxaluria are rarely reported in the literature. Management of tooth mobility and root resorption in hyperoxaluria is challenging and clinical guidelines and evidence-based recommendations are lacking. Early diagnosis and treatment of hyperoxaluria might be the only effective approach to prevent dental and periodontal complications of the disease.
PubMed: 38321570
DOI: 10.1111/scd.12968 -
Kidney International Reports Jan 2024The RNA interference (RNAi) medication lumasiran reduces hepatic oxalate production in primary hyperoxaluria type 1 (PH1). Data outside clinical trials are scarce.
INTRODUCTION
The RNA interference (RNAi) medication lumasiran reduces hepatic oxalate production in primary hyperoxaluria type 1 (PH1). Data outside clinical trials are scarce.
METHODS
We report on retrospectively and observationally obtained data in 33 patients with PH1 (20 with preserved kidney function, 13 on dialysis) treated with lumasiran for a median of 18 months.
RESULTS
Among those with preserved kidney function, mean urine oxalate (Uox) decreased from 1.88 (baseline) to 0.73 mmol/1.73 m per 24h after 3 months, to 0.72 at 12 months, and to 0.65 at 18 months, but differed according to vitamin B6 (VB6) medication. The highest response was at month 4 (0.55, -70.8%). Plasma oxalate (Pox) remained stable over time. Glomerular filtration rate increased significantly by 10.5% at month 18. Nephrolithiasis continued active in 6 patients, nephrocalcinosis ameliorated or progressed in 1 patient each. At last follow-up, Uox remained above 1.5 upper limit of normal (>0.75 mmol/1.73 m per 24h) in 6 patients. Urinary glycolate (Uglyc) and plasma glycolate (Pglyc) significantly increased in all, urine citrate decreased, and alkali medication needed adaptation. Among those on dialysis, mean Pox and Pglyc significantly decreased and increased, respectively after monthly dosing (Pox: 78-37.2, Pglyc: 216.4-337.4 μmol/l). At quarterly dosing, neither Pox nor Pglyc were significantly different from baseline levels. An acid state was buffered by an increased dialysis regimen. Systemic oxalosis remained unchanged.
CONCLUSION
Lumasiran treatment is safe and efficient. Dosage (interval) adjustment necessities need clarification. In dialysis, lack of Pox reduction may relate to dissolving systemic oxalate deposits. Pglyc increment may be a considerable acid load requiring careful consideration, which definitively needs further investigation.
PubMed: 38312792
DOI: 10.1016/j.ekir.2023.10.004 -
Frontiers in Pediatrics 2023Primary hyperoxaluria type 1 (PH1) is a rare disease with autosomal recessive transmission, characterized by increased urinary excretion of oxalate, resulting in chronic...
BACKGROUND
Primary hyperoxaluria type 1 (PH1) is a rare disease with autosomal recessive transmission, characterized by increased urinary excretion of oxalate, resulting in chronic kidney disease secondary to recurrent urolithiasis, nephrocalcinosis, and accumulation of oxalate in various organs and tissues (systemic oxalosis). Since 2020, an innovative pharmacological approach, namely, lumasiran, has been added to the therapeutic armamentarium (dialysis and liver-kidney transplantation). The purpose of this paper is to describe the effect of lumasiran initiated at 10 days of life in a newborn with prenatally diagnosed PH1. A female fetus was prenatally diagnosed with hyperoxaluria type 1, based on family history and genetic testing. Her brother had the onset of the disease at 2 months of age and underwent liver and kidney transplantation at 13 months and 8 years of age, respectively. The baby was born late preterm at 36 weeks + 4 days of gestation via spontaneous labor, and lumasiran for compassionate use was started on the tenth day of life. At 20 months of age, the baby showed normal urinary oxalate values and kidney function, while the plasma oxalate level was under the threshold of oversaturation. There were no signs of systemic oxalosis.
CONCLUSIONS
Early use of lumasiran in young infants, who do not yet show signs of the disease, represents a therapeutic challenge for the pediatric nephrologist. The ability of the drug to act on the hepatocyte of the newborn and the most appropriate dosage to be used in these very young babies have yet to be clarified.
PubMed: 38293660
DOI: 10.3389/fped.2023.1338909 -
Nephrology (Carlton, Vic.) Apr 2024Primary hyperoxaluria type 1 (PH1) is characterized by increased endogenous oxalate production and deposition as calcium oxalate crystals. The main manifestations are...
BACKGROUND
Primary hyperoxaluria type 1 (PH1) is characterized by increased endogenous oxalate production and deposition as calcium oxalate crystals. The main manifestations are nephrocalcinosis/nephrolithiasis, causing impaired kidney function. We aimed to evaluate the clinical characteristics and overall outcomes of paediatric PH1 patients in Turkey.
METHODS
This is a nationwide, multicentre, retrospective study evaluating all available paediatric PH1 patients from 15 different paediatric nephrology centres in Turkey. Detailed patient data was collected which included demographic, clinical and laboratory features. Patients were classified according to their age and characteristics at presentation: patients presenting in the first year of life with nephrocalcinosis/nephrolithiasis (infantile oxalosis, Group 1), cases with recurrent nephrolithiasis diagnosed during childhood (childhood-onset PH1, Group 2), and asymptomatic children diagnosed with family screening (Group 3).
RESULTS
Forty-eight patients had a mutation consistent with PH1. The most common mutation was c.971_972delTG (25%). Infantile oxalosis patients had more advanced chronic kidney disease (CKD) or kidney failure necessitating dialysis (76.9% vs. 45.5%). These patients had much worse clinical course and mortality rates seemed to be higher (23.1% vs. 13.6%). Patients with fatal outcomes were the ones with significant comorbidities, especially with cardiovascular involvement. Patients in Group 3 were followed with better outcomes, with no kidney failure or mortality.
CONCLUSION
PH1 is not an isolated kidney disease but a systemic disease. Family screening helps to preserve kidney function and prevent systemic complications. Despite all efforts made with traditional treatment methods including transplantation, our results show devastating outcomes or mortality.
Topics: Humans; Child; Nephrocalcinosis; Retrospective Studies; Kidney Failure, Chronic; Renal Dialysis; Hyperoxaluria, Primary; Nephrolithiasis; Hyperoxaluria; Renal Insufficiency
PubMed: 38290500
DOI: 10.1111/nep.14273 -
Cureus Dec 2023Oxalate nephropathy occurs due to the deposition of calcium oxalate crystals in kidney tubules and/or the interstitium as a part of primary or secondary hyperoxaluria....
Oxalate nephropathy occurs due to the deposition of calcium oxalate crystals in kidney tubules and/or the interstitium as a part of primary or secondary hyperoxaluria. Secondary oxalate nephropathy can occur even with moderately high doses of ascorbic acid intake under yet unidentified clinical circumstances. Vitamin C, although traditionally considered an antioxidant, leads to the formation of superoxide and subsequent generation of reactive oxidant species at pharmacologic concentrations. Ascorbic acid is partly converted to oxalic acid, which is responsible for deposition and renal tubular injury. We report a case of a diabetic patient with normal kidney function who was put on a juice diet for a week due to upper gastrointestinal bleeding. He developed acute kidney injury due to biopsy-proven oxalate nephropathy requiring dialysis. Though he was lost to follow-up after two weeks on dialysis, he was expected to have only a slow recovery or become dependent on dialysis given his age, comorbidities, and extent of tubular involvement. Hence, caution should be exercised before supplementing vitamin C either in its natural form or as a drug. Risk factors for secondary oxalate nephropathy due to excessive intake of oxalate or its precursor are likely to be age, diabetes, dehydration, and underlying chronic kidney disease. Most of the patients do not have a complete recovery of kidney function, and many become dependent on dialysis.
PubMed: 38283477
DOI: 10.7759/cureus.51226 -
Clinical Journal of the American... Apr 2024Nephritis is a common manifestation of IgA vasculitis and is morphologically indistinguishable from IgA nephropathy. While MEST-C scores are predictive of kidney...
BACKGROUND
Nephritis is a common manifestation of IgA vasculitis and is morphologically indistinguishable from IgA nephropathy. While MEST-C scores are predictive of kidney outcomes in IgA nephropathy, their value in IgA vasculitis nephritis has not been investigated in large multiethnic cohorts.
METHODS
Biopsies from 262 children and 99 adults with IgA vasculitis nephritis ( N =361) from 23 centers in North America, Europe, and Asia were independently scored by three pathologists. MEST-C scores were assessed for correlation with eGFR/proteinuria at biopsy. Because most patients ( N =309, 86%) received immunosuppression, risk factors for outcomes were evaluated in this group using latent class mixed models to identify classes of eGFR trajectories over a median follow-up of 2.7 years (interquartile range, 1.2-5.1). Clinical and histologic parameters associated with each class were determined using logistic regression.
RESULTS
M, E, T, and C scores were correlated with either eGFR or proteinuria at biopsy. Two classes were identified by latent class mixed model, one with initial improvement in eGFR followed by a late decline (class 1, N =91) and another with stable eGFR (class 2, N =218). Class 1 was associated with a higher risk of an established kidney outcome (time to ≥30% decline in eGFR or kidney failure; hazard ratio, 5.84; 95% confidence interval, 2.37 to 14.4). Among MEST-C scores, only E1 was associated with class 1 by multivariable analysis. Other factors associated with class 1 were age 18 years and younger, male sex, lower eGFR at biopsy, and extrarenal noncutaneous disease. Fibrous crescents without active changes were associated with class 2.
CONCLUSIONS
Kidney outcome in patients with biopsied IgA vasculitis nephritis treated with immunosuppression was determined by clinical risk factors and endocapillary hypercellularity (E1) and fibrous crescents, which are features that are not part of the International Study of Diseases of Children classification.
Topics: Adult; Child; Humans; Male; Adolescent; Glomerulonephritis, IGA; IgA Vasculitis; Glomerular Filtration Rate; Kidney; Nephritis; Proteinuria; Biopsy; Retrospective Studies
PubMed: 38261310
DOI: 10.2215/CJN.0000000000000398 -
Pediatric Nephrology (Berlin, Germany) Jul 2024Lumasiran is the first RNA interference (RNAi) therapy of primary hyperoxaluria type 1 (PH1). Here, we report on the rapid improvement and even disappearance of...
BACKGROUND
Lumasiran is the first RNA interference (RNAi) therapy of primary hyperoxaluria type 1 (PH1). Here, we report on the rapid improvement and even disappearance of nephrocalcinosis after early lumasiran therapy.
CASE-DIAGNOSIS/TREATMENT
In patient 1, PH1 was suspected due to incidental discovery of nephrocalcinosis stage 3 in a 4-month-old boy. Bilateral nephrocalcinosis stage 3 was diagnosed in patient 2 at 22 months concomitantly to acute pyelonephritis. Urinary oxalate (UOx) and glycolate (UGly) were increased in both patients allowing to start lumasiran therapy before genetic confirmation. Nephrocalcinosis started to improve and disappeared after 27 months and 1 year of treatment in patients 1 and 2, respectively.
CONCLUSION
These cases illustrate the efficacy of early lumasiran therapy in infants to improve and even normalize nephrocalcinosis. As proposed in the 2023 European guidelines, the interest of starting treatment quickly without waiting for genetic confirmation may have an impact on long-term outcomes.
Topics: Humans; Nephrocalcinosis; Male; Infant; Hyperoxaluria, Primary; RNAi Therapeutics; Treatment Outcome; Glycolates
PubMed: 38261066
DOI: 10.1007/s00467-023-06268-3 -
Drugs Feb 2024Lumasiran (Oxlumo), a first-in-class synthetic, double-stranded, ribonucleic acid (RNA) interference molecule targeting glycolate oxidase through silencing HAO1 mRNA, is... (Review)
Review
Lumasiran (Oxlumo), a first-in-class synthetic, double-stranded, ribonucleic acid (RNA) interference molecule targeting glycolate oxidase through silencing HAO1 mRNA, is approved in several countries for patients of any age and stage of kidney function with primary hyperoxaluria type 1 (PH1). Approval was based on results from the phase III ILLUMINATE trials. In the double-blind, placebo-controlled, ILLUMINATE-A trial, subcutaneous lumasiran was significantly more effective than placebo in reducing 24-h urinary oxalate excretion in patients aged ≥ 6 years with PH1; this effect was sustained for ≥ 36 months in ongoing longer-term analyses. In the single-arm ILLUMINATE-B trial, lumasiran reduced urinary oxalate:creatinine ratios and plasma oxalate levels in patients aged < 6 years with PH1. In the single-arm ILLUMINATE-C trial, lumasiran reduced plasma oxalate levels in patients with PH1 receiving dialysis as well as those not receiving dialysis. In secondary and exploratory analyses of these trials, nephrocalcinosis grade, kidney stone event rates and estimated glomerular filtration rates were either stable or improved with lumasiran. Lumasiran had an acceptable tolerability profile that remained consistent in longer-term analyses; the most common adverse events were mild and transient injection-site reactions. Thus, lumasiran is an effective treatment option, with an acceptable tolerability profile, in patients with PH1.
Topics: Humans; Hyperoxaluria, Primary; Oxalates; RNA, Small Interfering; Randomized Controlled Trials as Topic
PubMed: 38252335
DOI: 10.1007/s40265-023-01987-1 -
Current Rheumatology Reviews 2024Primary hyperoxaluria consists of a group of inherited disorders with enzymatic defects in the glyoxylate pathway, leading to decreased oxalate metabolism. The resulting... (Review)
Review
BACKGROUND
Primary hyperoxaluria consists of a group of inherited disorders with enzymatic defects in the glyoxylate pathway, leading to decreased oxalate metabolism. The resulting oxalic deposition is specifically responsible for kidney disease and joint disease. Neonatal oxalosis is the most severe form of primary hyperoxia type 1, with the onset of end-stage renal disease in childhood.
CASE PRESENTATION
A 55-year-old hemodialysis man was referred to Nephrology because of inflammatory polyarthralgia and periarticular swelling evolving for six months. He had been on hemodialysis for six years for end-stage chronic renal failure, diagnosed at the same time as primary hyperoxaluria. Radiological investigation showed a rugby jersey appearance on the lumbar spine, budding calcium tone opacities next to large joints and clavicles, vascular calcifications and tumoral calcinosis. The synovial fluid contained a few cells with polymorphic intracellular crystals. We ruled out hyperparathyroidism, hypoparathyroidism, and related phosphocalcic disorders, and we retained arthropathy and tumoral calcinosis secondary to primary hyperoxaliuria. The patient also had congestive heart failure. Despite intensification of hemodialysis, he did not improve and died at the age of 56 in the context of cachexia.
CONCLUSION
This rare case documents the possible occurrence of late clinical presentation and long survival in primary oxalosis with extra renal complications.
Topics: Humans; Male; Middle Aged; Hyperoxaluria, Primary; Calcinosis; Renal Dialysis; Kidney Failure, Chronic; Fatal Outcome; Crystal Arthropathies; Joint Diseases
PubMed: 38243963
DOI: 10.2174/0115733971271874231118154332 -
FEBS Letters Feb 2024Primary hyperoxaluria type I (PH1) is caused by deficient alanine:glyoxylate aminotransferase (AGT) activity. PH1-causing mutations in AGT lead to protein mistargeting...
Primary hyperoxaluria type I (PH1) is caused by deficient alanine:glyoxylate aminotransferase (AGT) activity. PH1-causing mutations in AGT lead to protein mistargeting and aggregation. Here, we use hydrogen-deuterium exchange (HDX) to characterize the wild-type (WT), the LM (a polymorphism frequent in PH1 patients) and the LM G170R (the most common mutation in PH1) variants of AGT. We provide the first experimental analysis of AGT structural dynamics, showing that stability is heterogeneous in the native state and providing a blueprint for frustrated regions with potentially functional relevance. The LM and LM G170R variants only show local destabilization. Enzymatic transamination of the pyridoxal 5-phosphate cofactor bound to AGT hardly affects stability. Our study, thus, supports that AGT misfolding is not caused by dramatic effects on structural dynamics.
Topics: Humans; Hyperoxaluria, Primary; Mutation; Polymorphism, Genetic; Transaminases
PubMed: 38243391
DOI: 10.1002/1873-3468.14800