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Frontiers in Pediatrics 2023Incidence and prevalence of urolithiasis is apparently increasing worldwide, also among children and adolescents. Nevertheless, robust data have only been obtained in a...
Incidence and prevalence of urolithiasis is apparently increasing worldwide, also among children and adolescents. Nevertheless, robust data have only been obtained in a few countries. In Spain, a voluntary Registry for Pediatric Renal Lithiasis has been active since 2015. Irregular participation limits its applicability, as well as its limitation to patients with a stone available for morphocompositional study, to obtain data about incidence and prevalence. On the other hand, findings about typology of stones and clinical and analytical characteristics of these subjects have been communicated in several meetings. Other valuable efforts in this field are the elaboration of guidelines for the collection and processing of urine samples for the study of urolithiasis in pediatric patients with the consensus of the Spanish Society for Pediatric Nephrology (AENP) as well as the Spanish Society for Laboratory Medicine (SEQC), the collaborative network RenalTube for the diagnosis of primary tubulopathies and the registry of patients with Primary Hyperoxaluria (OxalSpain). In many hospitals from the public healthcare system, pediatric nephrologists are the specialists in charge of the management of children with kidney stones, but there is no formal regulation on this competence. Other specialists, such as urologists, pediatric surgeons or pediatric urologists, in many cases do not offer a complete insight into the etiopathogenic mechanisms and the consequent medical treatment. Access to medication according to standards of treatment is warranted, provided a correct diagnosis is achieved, but criteria for the reimbursement of certain therapies, such as RNAi drugs for primary hyperoxaluria, are arguable.
PubMed: 38143536
DOI: 10.3389/fped.2023.1294319 -
Indian Journal of Nephrology 2023Hypercalcemia in infants presents with a variety of clinical features and the etiology of hypercalcemia varies with age. Here we present a case of hypercalcemia in an...
Hypercalcemia in infants presents with a variety of clinical features and the etiology of hypercalcemia varies with age. Here we present a case of hypercalcemia in an infant presenting with nephrocalcinosis and nephrolithiasis. Our investigations led us to a diagnosis of primary hyperoxaluria (PH) type 2, a rare metabolic disorder, along with hypercalcemia, a never before reported association. A 9-month-old female presented with urinary tract infection and systemic features requiring hospitalization and parenteral antibiotics. Investigations revealed bilateral medullary nephrocalcinosis. Genetic testing revealed a diagnosis of Primary hyperoxaluria type 2 with two possible mutations. Sanger sequencing of the parents identified the pathogenic mutation in the mother. This is the first report of a genetically proven case of primary hyperoxaluria type 2 associated with hypercalcemia.
PubMed: 37881736
DOI: 10.4103/ijn.ijn_140_22 -
BMC Nephrology Oct 2023Without effective intervention, primary hyperoxaluria type 1 (PH1) causes oxalate-induced kidney damage, leading to end-stage kidney disease and serious complications... (Observational Study)
Observational Study
BACKGROUND
Without effective intervention, primary hyperoxaluria type 1 (PH1) causes oxalate-induced kidney damage, leading to end-stage kidney disease and serious complications throughout the body. Although PH1 carries a heavy burden that impacts quality of life, literature on the experiences of those living with PH1 and caring for patients with PH1 is limited. This study aimed to describe the diagnostic journey in PH1 and characterize patients' and caregivers' self-reported experiences throughout the disease course.
METHODS
This was an observational study involving in-depth, semi-structured telephone interviews. Dominant trends were assessed using constant comparative analysis to identify themes in interviewees' descriptions of their experiences. Individuals aged ≥ 12 years and caregivers of children aged 6-17 years with genetically confirmed PH1 were eligible. Informed consent/assent and ability to read and speak English were required.
RESULTS
Interviewees (16 patients, 12 caregivers) reported a prolonged diagnostic journey due to low disease awareness, among other factors. Upon diagnosis, PH1 was frequently symptomatic, typically involving kidney stone-related symptoms but also potentially symptoms arising beyond the kidneys. PH1 most commonly led to worry and social impairment in adolescents, impaired physical function in adults, and a range of impacts on caregivers. In late-stage disease, dialysis was the most burdensome aspect of living with PH1 (due to time requirements, limitations from living with a catheter, etc.), and this burden was exacerbated by the COVID-19 pandemic. Benefits desired from PH1 management included reductions in laboratory measures of oxalate burden, kidney stone and urination frequency, and oxalate-related skin ulcers.
CONCLUSIONS
PH1 greatly impacts patients' and caregivers' lives, primarily due to burdensome disease manifestations and associated emotional, physical, and practical impacts, as well as disease management challenges - particularly those related to dialysis in late-stage disease.
Topics: Child; Adult; Adolescent; Humans; Pandemics; Quality of Life; Renal Dialysis; Hyperoxaluria, Primary; Oxalates; Kidney Calculi; Patient Outcome Assessment
PubMed: 37884879
DOI: 10.1186/s12882-023-03365-1 -
Journal of Nephrology Jul 2023Primary hyperoxaluria is a genetic disorder of the metabolism of glyoxylate, the precursor of oxalate. It is characterized by high endogenous production and excessive...
Diagnostic policies on nephrolithiasis/nephrocalcinosis of possible genetic origin by Italian nephrologists: a survey by the Italian Society of Nephrology with an emphasis on primary hyperoxaluria.
BACKGROUND
Primary hyperoxaluria is a genetic disorder of the metabolism of glyoxylate, the precursor of oxalate. It is characterized by high endogenous production and excessive urinary excretion of oxalate, resulting in the development of calcium oxalate nephrolithiasis, nephrocalcinosis, and, in severe cases, end-stage kidney disease and systemic oxalosis. Three different forms of primary hyperoxaluria are currently known, each characterized by a specific enzymatic defect: type 1 (PH1), type 2 (PH2), and type 3 (PH3). According to currently available epidemiological data, PH1 is by far the most common form (about 80% of cases), and is caused by a deficiency of the hepatic enzyme alanine:glyoxylate aminotransferase.
METHODS
A survey on rare forms of nephrolithiasis and nephrocalcinosis with a focus on primary hyperoxaluria in the setting of Italian Nephrology and Dialysis Centers, using an online questionnaire, was recently conducted by the Project Group "Rare Forms of Nephrolithiasis and Nephrocalcinosis" of the Italian Society of Nephrology, with the aim of assessing the impact and management of this disorder in clinical practice in Italy.
RESULTS
Forty-five public and private Italian Centers participated in the survey, and responses to the questionnaire were provided by 54 medical professionals. The survey results indicate that 21 out of the 45 participating Centers are managing or have managed primary hyperoxaluria patients, most of whom are on dialysis, or are recipients of kidney transplants.
CONCLUSIONS
The data of this survey indicate the need to implement genetic testing in suspected cases of primary hyperoxaluria, not only in the setting of dialysis or transplantation, but also with the aim of encouraging early diagnosis of PH1, which is the only type of primary hyperoxaluria for which specific drug therapy is currently available.
Topics: Humans; Nephrocalcinosis; Hyperoxaluria, Primary; Nephrologists; Nephrology; Oxalates; Kidney Calculi
PubMed: 37358729
DOI: 10.1007/s40620-023-01693-x -
Case Reports in Nephrology and Dialysis 2023The primary hyperoxalurias (PHs) are a group of diseases characterized by kidney stones, nephrocalcinosis, and chronic kidney disease. At stages of advanced kidney...
The primary hyperoxalurias (PHs) are a group of diseases characterized by kidney stones, nephrocalcinosis, and chronic kidney disease. At stages of advanced kidney disease, glomerular filtration of oxalate becomes insufficient, plasma levels increase, and tissue deposition may occur. Hemodialysis is often unable to overcome the excess hepatic oxalate production. The current surgical management of primary hyperoxaluria type 1 (PH1) is combined liver kidney transplantation. In a subset of PH1 patients who respond to pyridoxine, kidney-only transplantation has been successfully performed. Recently, kidney-only transplantation has also been performed in PH1 patients receiving a small interfering RNA therapy called lumasiran. This drug targets the hepatic overproduction of oxalate, making kidney-only transplantation a potentially practical novel approach for managing PH1 patients with advanced kidney disease. It is unknown if similar effects could be seen with a different small interfering RNA agent called nedosiran. This article will briefly review PH1, describe the small interfering RNA therapies being used to treat PH, summarize the reported cases of kidney-only transplantation performed with lumasiran, and detail a case of kidney-only transplantation performed in a PH1 patient receiving nedosiran.
PubMed: 37497389
DOI: 10.1159/000531053 -
Cureus Oct 2023Primary hyperoxaluria-1 (PH1) is an autosomal recessively inherited rare genetic condition due to the deficiency of the hepatic enzyme alanine:glyoxylate...
Primary hyperoxaluria-1 (PH1) is an autosomal recessively inherited rare genetic condition due to the deficiency of the hepatic enzyme alanine:glyoxylate aminotransferase which leads to high systemic levels of oxalate and subsequently, early end-stage renal disease and death. Here, we present a case of a three-month-old male infant who presented with loose stools, reduced oral intake, and decreased activity for 12-13 days along with edema and a peeling rash on cheeks, lips, and genitalia. During the entire duration of the inpatient stay, the child was oligoanuric. Kidney ultrasound (USG) was suggestive of bilateral hyperechoic kidneys with increased cortical echogenicity and a computed tomography scan showed bilateral diffusely calcified renal cortices with well-preserved renal architecture. A diagnosis of "oxalate nephropathy" was made from renal biopsy and genetic testing confirmed it to be "primary hyperoxaluria-1". The child was initially managed conservatively, and then peritoneal dialysis was done, following which the child was shifted to intermittent hemodialysis.
PubMed: 37954792
DOI: 10.7759/cureus.46827 -
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 -
Clinical Case Reports Jan 2024Cutaneous oxalosis is a rare manifestation of systemic oxalosis, typically associated with primary or secondary hyperoxaluria. We present a rare case of a 23-year-old...
Cutaneous oxalosis is a rare manifestation of systemic oxalosis, typically associated with primary or secondary hyperoxaluria. We present a rare case of a 23-year-old female diagnosed with primary hyperoxaluria and end-stage renal disease, who presented with papules on the palms without any vascular complications. The skin can be affected by oxalate deposition, resulting in various manifestations such as vascular complications or calcified nodules. In our case, the patient had primary hyperoxaluria and end-stage renal disease but exhibited atypical features of cutaneous oxalosis. Histopathology confirmed the presence of oxalate crystals in the dermis, subcutis, and medium-sized arteries. The mechanism of oxalate deposition in this case remains unclear. This case underscores the importance of considering cutaneous oxalosis in the differential diagnosis of patients with renal failure and skin lesions, and highlights the variability of clinical presentations in primary hyperoxaluria.
PubMed: 38188849
DOI: 10.1002/ccr3.8423 -
Cureus Jul 2023Primary hyperoxaluria (PH) is a rare genetic condition that disrupts the normal process of glyoxylate metabolism, resulting in an overproduction of oxalate. This...
Primary hyperoxaluria (PH) is a rare genetic condition that disrupts the normal process of glyoxylate metabolism, resulting in an overproduction of oxalate. This excessive oxalate production leads to the accumulation of calcium oxalate (known as oxalosis) throughout various organs in the body. The urinary tract, specifically the renal parenchyma, is the first location where the deposition of calcium oxalate begins in PH. These deposits are responsible for nephrocalcinosis and tubule‑interstitial nephritis which leads to end‑stage renal failure. This is then followed by the accumulation of oxalate in other organs including the bone marrow. Herein, we report the case of a 22-year-old male patient who presented with bicytopenia; he had a history of end-stage renal disease preceded by recurrent urolithiasis and nephrolithiasis episodes since the age of 3 years. A bone marrow biopsy was performed for evaluation of the bicytopenia which led to the diagnosis of PH.
PubMed: 37637636
DOI: 10.7759/cureus.42469 -
Kidney International Reports May 2024Primary hyperoxaluria (PH) is a rare genetic disorder of hepatic glyoxylate metabolism. Nedosiran is an RNA interference (RNAi) therapeutic that the US Food and Drug...
INTRODUCTION
Primary hyperoxaluria (PH) is a rare genetic disorder of hepatic glyoxylate metabolism. Nedosiran is an RNA interference (RNAi) therapeutic that the US Food and Drug Administration has approved for treatment of PH1. PHYOX3 is a trial evaluating monthly nedosiran in patients with PH.
METHODS
In this PHYOX3 interim analysis, participants with PH1 who continued from a single-dose nedosiran trial (PHYOX1), with no previous kidney or liver transplantation, dialysis, or evidence of systemic oxalosis were eligible. The safety and efficacy of once-monthly nedosiran was assessed over 30 months.
RESULTS
Thirteen participants completed PHYOX1 and continued into PHYOX3. At baseline, the mean (SD) and median (range) age was 24.2 (6.6) years and 23.0 (14-39) years, respectively; 53.8% were female and 61.5% were White. Mean estimated glomerular filtration rate (eGFR) remained stable (62-84.2 mL/min per 1.73 m) to month 30. Mean 24-hour urinary oxalate (Uox) excretion showed a sustained reduction from baseline of ≥60% at every visit (months 2-30). From month 2, at least 10 of 13 (76.9%) participants achieved normal (<0.46 mmol/24h; upper limit of assay-normal [ULN]) or near-normal (≥0.46 to <0.60 mmol/24h; ≥ULN to <1.3 × ULN) 24-hour Uox excretion. All participants experienced ≥1 adverse event (AE), mostly mild or moderate in severity (primarily, injection site events). Three serious, not treatment-related AEs were reported; there were no deaths or study discontinuations due to AEs.
CONCLUSION
Nedosiran was well-tolerated in patients with PH1, and treatment resulted in a sustained, substantial reduction in Uox excretion for at least 30 months in this long-term study. No safety signals have been identified to date. The PHYOX3 study is ongoing.
PubMed: 38707801
DOI: 10.1016/j.ekir.2024.02.1439