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Clinical Kidney Journal May 2022In adults, primary hyperoxaluria (PH) does not always present as obviously as in children, leading to delayed or even missed diagnosis. When diagnosed in adulthood, PH... (Review)
Review
In adults, primary hyperoxaluria (PH) does not always present as obviously as in children, leading to delayed or even missed diagnosis. When diagnosed in adulthood, PH usually progresses at a slower rate and the focus is on the prevention of recurrent kidney stones as much as it is on the preservation of renal function. The most tragic presentation is when the diagnosis is made after primary non-function of a renal graft for treating previously unknown renal disease. Recurrent stones, nephrocalcinosis and features of systemic oxalosis can all be presenting features. For these reasons, consideration should be given to screening for this rare condition, using biochemical and/or genetic means, but being careful to exclude common differential diagnoses. Such efforts should be synchronized with diagnostic methods for other rare kidney diseases.
PubMed: 35711295
DOI: 10.1093/ckj/sfac068 -
Clinics and Research in Hepatology and... May 2024Enteric hyperoxaluria is a metabolic disorder resulting from conditions associated with fatty acid malabsorption and characterized by an increased urinary output of... (Review)
Review
Enteric hyperoxaluria is a metabolic disorder resulting from conditions associated with fatty acid malabsorption and characterized by an increased urinary output of oxalate. Oxalate is excessively absorbed in the gut and then excreted in urine where it forms calcium oxalate crystals, inducing kidney stones formation and crystalline nephropathies. Enteric hyperoxaluria is probably underdiagnosed and may silently damage kidney function of patients affected by bowel diseases. Moreover, the prevalence of enteric hyperoxaluria has increased because of the development of bariatric surgical procedures. Therapeutic options are based on the treatment of the underlying disease, limitation of oxalate intakes, increase in calcium salts intakes but also increase in urine volume and correction of hypocitraturia. There are few data regarding the natural evolution of kidney stone events and chronic kidney disease in these patients, and there is a need for new treatments limiting kidney injury by calcium oxalate crystallization.
Topics: Humans; Hyperoxaluria; Oxalates; Calcium Oxalate; Malabsorption Syndromes
PubMed: 38503362
DOI: 10.1016/j.clinre.2024.102322 -
Rhode Island Medical Journal (2013) Dec 2023Hyperoxaluria is a clinically relevant metabolic entity that portends a high morbidity burden. Primarily manifesting as kidney stone disease and chronic kidney disease,... (Review)
Review
Hyperoxaluria is a clinically relevant metabolic entity that portends a high morbidity burden. Primarily manifesting as kidney stone disease and chronic kidney disease, advanced hyperoxaluria can also affect major organs, including the brain, heart, liver, bone, and the skin. It is categorized based on etiology into primary and secondary hyperoxaluria. Pathology is attributed to excess de novo oxalate production in the former and multifactorial exogenous oxalate absorption or excess intake of its precursors in the latter. Diagnosis often involves demonstrating elevated urinary oxalate levels, especially in patients with normal kidney function. Here in this review, we will perform an in-depth discussion of various causes of hyperoxaluria and describe treatment options. In view of the significant morbidity burden associated with hyperoxaluria, patients could benefit from heightened clinician awareness to aid in the timely diagnosis and management of this condition.
Topics: Humans; Kidney Calculi; Hyperoxaluria; Oxalates
PubMed: 38015779
DOI: No ID Found -
Urolithiasis Dec 2020Measurement of oxalate in the blood is essential for monitoring primary hyperoxaluria patients with progressive renal impairment and on dialysis prior to... (Comparative Study)
Comparative Study
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.
Topics: Hematologic Tests; Humans; Hyperoxaluria, Primary; Oxalates
PubMed: 32472220
DOI: 10.1007/s00240-020-01197-4 -
Pediatric Nephrology (Berlin, Germany) Dec 2018Combined and sequential liver-kidney transplantation (CLKT and SLKT) is a definitive treatment in children with end-stage organ failure. There are two major indications:... (Review)
Review
Combined and sequential liver-kidney transplantation (CLKT and SLKT) is a definitive treatment in children with end-stage organ failure. There are two major indications: - terminal insufficiency of both organs, or - need for transplanting new liver as a source of lacking enzyme or specific regulator of the immune system in a patient with renal failure. A third (uncommon) option is secondary end-stage renal failure in liver transplant recipients. These three clinical settings use distinct qualification algorithms. The most common indications include primary hyperoxaluria type 1 (PH1) and autosomal recessive polycystic kidney disease (ARPKD), followed by liver diseases associated with occasional kidney failure. Availability of anti-C5a antibody (eculizumab) has limited the validity of CLKT in genetic atypical hemolytic uremic syndrome (aHUS). The liver coming from the same donor as renal graft (in CLKT) is immunologically protective for the kidney and this provides long-term rejection-free follow-up. No such protection is observed in SLKT, when both organs come from different donors, except uncommon cases of living donation of both organs. Overall long-term outcome in CLKT in terms of graft survival is good and not different from isolated liver or kidney transplantation, however patient survival is inferior due to complexity of this procedure.
Topics: Atypical Hemolytic Uremic Syndrome; Child; End Stage Liver Disease; Graft Rejection; Graft Survival; Humans; Hyperoxaluria, Primary; Kidney Failure, Chronic; Kidney Transplantation; Liver Transplantation; Polycystic Kidney, Autosomal Recessive; Survival Analysis; Tissue and Organ Procurement; Transplantation, Homologous; Treatment Outcome
PubMed: 29322327
DOI: 10.1007/s00467-017-3880-4 -
Journal of Managed Care & Specialty... Mar 2022Primary hyperoxaluria (PH) is a family of rare, life-threatening genetic liver disorders characterized by elevated production and excretion of oxalate. To date, the...
Primary hyperoxaluria (PH) is a family of rare, life-threatening genetic liver disorders characterized by elevated production and excretion of oxalate. To date, the clinical and economic burden associated with PH has not been well characterized due to the rarity of the disease and previous challenges with diagnostic coding that prevented proper identification of patients with PH in claims data. To characterize the clinical and economic costs, as well as health care resource utilization (HCRU), associated with PH relative to a matched cohort of patients without PH. Data from the IQVIA PharMetrics Plus Database were used to conduct a retrospective matched-cohort study to compare differences in clinical characteristics, HCRU, and pharmacy and medical costs in patients with PH compared with a matched cohort of patients without PH from January 2014 to December 2019. Overall, 324 patients were included in the PH cohort and 1,620 patients were in the non-PH cohort. The mean age of PH patients was 48.1 years, and approximately 58% of the sample were male. Significantly more patients in the PH cohort than the non-PH cohort were diagnosed with stage 2 chronic kidney disease (CKD; 3.1% vs 0.4%, respectively; < 0.001), stage 3 CKD (4.6% vs 0.5%; < 0.001), stage 4 CKD (2.5% vs 0.1%; < 0.001), and stage 5 CKD or end-stage renal disease (ESRD; 2.2% vs 0.1%; < 0.001). PH patients had a significantly higher mean Charlson Comorbidity Index composite score than patients in the non-PH cohort (0.79 vs 0.37; < 0.001). HCRU was significantly higher in patients with PH. The PH cohort had a significantly higher proportion of patients with at least 1 visit to clinicians specializing in nephrology (19% vs 0.4%, respectively; < 0.001), cardiology (22% vs 12%; < 0.001), ophthalmology (16% vs 7%; < 0.001), general surgery (9% vs 6%; = 0.011), and urology (65% vs 6%; < 0.001) compared with patients without PH. Mean total annual health care costs in the PH cohort were 65% higher than in the non-PH cohort ($22,549 vs $7,852, respectively; < 0.001). Similar results were found for total prescription drug costs ($4,125 vs $2,464; = 0.012). Despite the rarity of PH, patients with this disease incur substantial clinical and economic burden and may cause financial strain on the health care system. Additional research is warranted to understand the economic and clinical burden of PH stratified by the 3 subtypes of the disease. Funding for this research was provided by Dicerna Pharmaceuticals. Mucha and Hoppe are employed by Dicerna Pharmaceuticals. Silber Miyasoto, Skaar, and Wang are employed by Trinity Life Sciences, which was contracted by Dicerna Pharmaceuticals to conduct the study analysis. Langman is consultant to Dicerna Pharmaceuticals. This study was presented as a poster at the AMCP Nexus 2020 (virtual), October 19-23, 2020, and American Society of Nephrology 2020 (virtual), October 19-25, 2020.
Topics: Cohort Studies; Health Care Costs; Humans; Hyperoxaluria, Primary; Insurance Claim Review; Male; Middle Aged; Patient Acceptance of Health Care; Retrospective Studies; United States
PubMed: 35199581
DOI: 10.18553/jmcp.2022.28.3.316 -
Journal of Pediatric Urology Apr 2021Calcium oxalate stones are the most common type among stone-forming patients and in some cases result from predisposed genetic conditions. In this work, we examined the...
OBJECTIVE
Calcium oxalate stones are the most common type among stone-forming patients and in some cases result from predisposed genetic conditions. In this work, we examined the differences in structure and chemical composition between oxalate stones from patients from three groups: 1) pediatric patients that were genetically predisposed (primary hyperoxaluria) to form stones (PPH); 2) control pediatric patients that did not have such genetic predisposition (PN-PH); 3) adult patients that formed oxalate stones without the genetic predisposition (A-CaOx). A variety of instrumental analyses were conducted to identify physicochemical properties of stones characteristic of predisposed pediatric (PPH), pediatric hyperoxaluria (PN-PH), and adult (A-CaOx) patient populations.
METHODS
Genetic variants of 16 stone-forming patients were determined using whole-exome gene sequencing. Components of stones from PPH (n = 6), PN-PH (n = 5), and A-CaOx (n = 5) groups were identified using Fourier transform infrared (FTIR) spectroscopy. Stone morphology and density were evaluated using high resolution X-ray computed tomography (micro-XCT). Stone microstructure and elemental composition were mapped with scanning electron microscopy (SEM) and energy dispersive X-ray (EDX) spectroscopy, respectively.
RESULTS
Calcium oxalate bipyramidal crystals were found on stones from all groups. Stones from PPH patients with PH types I and II were composed of calcium oxalate monohydrate (COM) with relatively uniform mineral density (1224 ± 277 mg/cc) and distinct smooth surfaces. By contrast, micro-spherical calcium phosphate particles were found only on PN-PH stones, which also showed a broader range of mineral densities (1266 ± 342 mg/cc). Stones from the PN-PH group also contained phosphorus (P), which was absent in NP-PH stones. A-CaOx stones were of significantly lower mineral density (645 ± 237 mg/cc) than pediatric stones and were more heterogeneous in their elemental composition.
CONCLUSION
Unique structural and compositional characteristics were identified in stones from pediatric patients with primary hyperoxaluria. These include the absence of phosphorus, a narrower mineral density distribution, and a uniform elemental composition compared to stones from pediatric patients without the genetic predisposition. Thus, characterization of stones at the macro- and micro-scales in combination with genetic testing of patients can provide insights and accurate diagnosis to develop a treatment plan for effective patient care.
Topics: Adult; Calcium Oxalate; Child; Humans; Hyperoxaluria, Primary; Kidney Calculi; Tomography, X-Ray Computed
PubMed: 33495102
DOI: 10.1016/j.jpurol.2020.11.023 -
Frontiers in Pediatrics 2021Oxalate overproduction in Primary Hyperoxaluria type I (PH1) leads to progressive renal failure and systemic oxalate deposition. In severe infantile forms of PH1...
Oxalate overproduction in Primary Hyperoxaluria type I (PH1) leads to progressive renal failure and systemic oxalate deposition. In severe infantile forms of PH1 (IPH1), end-stage renal disease (ESRD) occurs in the first years of life. Usually, the management of these infantile forms is challenging and consists in an intensive dialysis regimen followed by a liver-kidney transplantation (combined or sequential). Medical records of all infants with IPH1 reaching ESRD within the first year of life, diagnosed and followed between 2005 and 2018 in two pediatric nephrology departments in Brussels and Paris, have been reviewed. Seven patients were included. They reached ESRD at a median age of 3.5 (2-7) months. Dialysis was started at a median age of 4 (2-10 months). Peritoneal dialysis (PD) was the initial treatment for 6 patients and hemodialysis (HD) for one patient. Liver transplantation (LT) was performed in all patients and kidney transplantation (KT) in six of them. A sequential strategy has been chosen in 5 patients, a combined in one. The kidney transplanted as part of the combined strategy was lost. Median age at LT and KT was 25 (10-41) months and 32.5 (26-75) months, respectively. No death occurred in the series. At the end of a median follow-up of 3 years, mean eGFR was 64 ± 29 ml/min/1.73 m. All patients presented retinal and bone lesions and five patients presented bones fractures. Despite encouraging survival figures, the morbidity in IPH1 patients remains extremely heavy and its management presents a huge challenge. Thanks to the newly developed RNA-interference drug, the future holds brighter prospects.
PubMed: 33959570
DOI: 10.3389/fped.2021.615183 -
Journal of Medical Case Reports Oct 2023Primary hyperoxaluria (PH) is a rare genetic disorder characterized by the excessive production and accumulation of oxalate. We present five cases of PH, each exhibiting...
BACKGROUND
Primary hyperoxaluria (PH) is a rare genetic disorder characterized by the excessive production and accumulation of oxalate. We present five cases of PH, each exhibiting varying manifestations of the disorder including a case presenting as postpartum kidney failure. Notably, three of these cases involve a previously unreported mutation.
CASE PRESENTATIONS
We evaluated five Indian patients who presented with varying manifestations of PH. The first case, a 30 year old woman, presented as post-partum kidney failure and was found to be having oxalate nephropathy precipitated by dietary oxalate overload in the setting of previously undiagnosed PH. Genetic analysis revealed a previously unreported mutation in the alanine-glyoxylate aminotransferase gene. The patient underwent simultaneous kidney liver transplant. The second and third cases, 26 and 28 year old women respectively, were asymptomatic siblings of the first patient, who were diagnosed through screening. The fourth case is a 12 year boy with PH type 1 presenting as nephrolithiasis and rapidly worsening kidney function requiring combined kidney liver kidney transplant. Case 5 is a 6 year old male child with type 2 PH presenting with nephrolithiasis, nephrocalcinosis and normal kidney function. All the patients were born to consanguineous parents.
CONCLUSIONS
Due to limited clinical suspicion and inadequate diagnostic resources in certain countries with limited resources, it is possible for PH to go undiagnosed. The manifestations of the disease can range from no noticeable symptoms to severe disease. Interestingly, in some individuals with primary hyperoxaluria, the disease may not exhibit any symptoms until it is triggered by a high intake of dietary oxalate.
Topics: Male; Child; Humans; Female; Adult; Hyperoxaluria, Primary; Kidney; Oxalates; Kidney Calculi; Renal Insufficiency
PubMed: 37803380
DOI: 10.1186/s13256-023-04129-z -
Pediatric Nephrology (Berlin, Germany) Mar 2023Accurate diagnosis of primary hyperoxaluria (PH) has important therapeutic consequences. Since biochemical assessment can be unreliable, genetic testing is a crucial... (Review)
Review
Accurate diagnosis of primary hyperoxaluria (PH) has important therapeutic consequences. Since biochemical assessment can be unreliable, genetic testing is a crucial diagnostic tool for patients with PH to define the disease type. Patients with PH type 1 (PH1) have a worse prognosis than those with other PH types, despite the same extent of oxalate excretion. The relation between genotype and clinical phenotype in PH1 is extremely heterogeneous with respect to age of first symptoms and development of kidney failure. Some mutations are significantly linked to pyridoxine-sensitivity in PH1, such as homozygosity for p.G170R and p.F152I combined with a common polymorphism. Although patients with these mutations display on average better outcomes, they may also present with CKD stage 5 in infancy. In vitro studies suggest pyridoxine-sensitivity for some other mutations, but confirmatory clinical data are lacking (p.G47R, p.G161R, p.I56N/major allele) or scarce (p.I244T). These studies also suggest that other vitamin B6 derivatives than pyridoxine may be more effective and should be a focus for clinical testing. PH patients displaying the same mutation, even within one family, may have completely different clinical outcomes. This discordance may be caused by environmental or genetic factors that are unrelated to the effect of the causative mutation(s). No relation between genotype and clinical or biochemical phenotypes have been found so far in PH types 2 and 3. This manuscript reviews the current knowledge on the genetic background of the three types of primary hyperoxaluria and its impact on clinical management, including prenatal diagnosis.
Topics: Humans; Hyperoxaluria, Primary; Pyridoxine; Mutation; Genetic Testing; Genotype; Transaminases
PubMed: 35695965
DOI: 10.1007/s00467-022-05613-2