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Clinical Kidney Journal Jan 2021We report the case of a 31-year-old female with primary hyperoxaluria type 1 with end-stage kidney disease who developed severe peripheral vascular disease leading to...
We report the case of a 31-year-old female with primary hyperoxaluria type 1 with end-stage kidney disease who developed severe peripheral vascular disease leading to limb amputation initially thought to be secondary to calciphylaxis. However, polarized review of the pathologic specimen revealed calcium oxalate deposition in the lumen of blood vessels. This unusual presentation of systemic oxalosis demonstrates the adverse consequences of elevations of serum oxalate in patients with hyperoxaluria and that levels can acutely worsen with abrupt onset of kidney failure.
PubMed: 33564451
DOI: 10.1093/ckj/sfz190 -
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 -
Pediatric Nephrology (Berlin, Germany) Oct 2015Primary hyperoxalurias (PH) comprise a group of three distinct metabolic diseases caused by derangement of glyoxylate metabolism in the liver. Recent years have seen... (Review)
Review
Primary hyperoxalurias (PH) comprise a group of three distinct metabolic diseases caused by derangement of glyoxylate metabolism in the liver. Recent years have seen advances in several aspects of PH research. This paper reviews current knowledge of the genetic and biochemical basis of PH, the specific epidemiology and clinical presentation of each type, and therapeutic approaches in different disease stages. Potential future specific therapies are discussed.
Topics: Genetic Predisposition to Disease; Genetic Testing; Humans; Hyperoxaluria, Primary; Mutation; Nephrolithiasis; Oxalates; Renal Replacement Therapy; Transaminases
PubMed: 25519509
DOI: 10.1007/s00467-014-3030-1 -
Pediatric Nephrology (Berlin, Germany) Jan 2016Deposition of calcium oxalate crystals in the kidney and bone is a hallmark of primary hyperoxaluria (PH). Since the bone compartment can store massive amounts of... (Review)
Review
Deposition of calcium oxalate crystals in the kidney and bone is a hallmark of primary hyperoxaluria (PH). Since the bone compartment can store massive amounts of oxalate, patients present with recurrent low-trauma fractures, bone deformations, severe bone pains, and specific oxalate osteopathy on X-ray. Bone biopsy from the iliac crest displays specific features such as oxalate crystals surrounded by a granulomatous reaction corresponding to an invasion of bone surface by macrophages. The objective of this manuscript is therefore to provide an overview of bone impairment in PH, by reviewing the current literature on bone and dental symptoms as well as imaging techniques used for assessing bone disease.
Topics: Animals; Biopsy; Bone Density; Bone Diseases, Metabolic; Bone Remodeling; Bone and Bones; Calcium Oxalate; Crystallization; Diagnostic Imaging; Humans; Hyperoxaluria, Primary; Predictive Value of Tests; Prognosis; Risk Factors; Stomatognathic Diseases
PubMed: 25631241
DOI: 10.1007/s00467-015-3048-z -
Urolithiasis Aug 2022Autosomal recessive disorders are prevalent in Pakistan, a developing South Asian country where consanguineous marriages are common. This study seeks to determine the...
Autosomal recessive disorders are prevalent in Pakistan, a developing South Asian country where consanguineous marriages are common. This study seeks to determine the prevalence of monogenic causes in children presenting with nephrocalcinosis and nephrolithiasis at a dialysis and transplant center in Karachi, Pakistan. A retrospective analysis was conducted in children aged 1-18 years presenting with nephrocalcinosis, between 2010 and 2019. Demographic information, clinical profile, laboratory parameters and stone analysis were collected, on a pre-designed questionnaire. One hundred and twenty-six children were included, with 11 and 3 diagnosed with renal tubular acidosis and Bartter's syndrome respectively. Next-generation sequencing and Sanger sequencing was performed on 112 children. Eighty-seven patients were diagnosed with primary hyperoxaluria, with mutations in alanine-glyoxylate-aminotransferase gene found in 73, followed by glyoxylate reductase/hydroxy-pyruvate reductase in 13, and 4-hydroxy-2-oxaloglutarate aldolase in 1. Twenty-five patients reported negative for mutations. Sixty-four percent were males, with a statistically significant difference (p < 0.05). History of parental consanguineous marriage was found in 98% of the cohort. Fifty-four and 40 patients presented to the clinic with Chronic Kidney Disease Stage 1 and Stage 5, respectively, with a statistically significant difference p = 0.007. Mutations noted in our cohort are different and more severe than those reported in the developed world. The disease poses a major disease burden in developing world context with the only treatment option of combined liver-kidney transplantation not available in Pakistan.
Topics: Child; Cost of Illness; Female; Genetic Linkage; Humans; Hyperoxaluria; Hyperoxaluria, Primary; Kidney Calculi; Male; Nephrocalcinosis; Pakistan; Retrospective Studies
PubMed: 35678848
DOI: 10.1007/s00240-022-01338-x -
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 -
Urolithiasis May 2024Primary hyperoxaluria type 2 (PH2) is a rare hereditary disease that causes nephrolithiasis, nephrocalcinosis and kidney failure. This study aimed to investigate the... (Meta-Analysis)
Meta-Analysis
Primary hyperoxaluria type 2 (PH2) is a rare hereditary disease that causes nephrolithiasis, nephrocalcinosis and kidney failure. This study aimed to investigate the clinical features and mutational spectrum of Chinese patients with PH2. A retrospective cohort study was performed on PH2 patients admitted to our center over seven years. We also systematically reviewed all the articles on Chinese PH2 patients published from January 2000 to May 2023 and conducted a meta-analysis. A total of 25 PH2 patients (10 from our center and 15 from published studies) were included in this study. The median age of onset in patients from our center was 8.50 (1.00, 24.00) years, and 50% were male. Among the full cohort of 25 Chinese patients, the median age of onset was 8.00 (0.40, 26.00) years, and 64% of them were male. Seven patients progressed to end-stage kidney disease, with a median age of 27.50 (12, 31) years. The cumulative renal survival rates were 100%, 91.67%, 45.83% and 30.56% at 10, 20, 30 and 40 years of age, respectively. A total of 18 different variants were identified, and c.864_865del was the dominant variant, accounting for 57.69% of the total alleles. Patients who were heterozygous for c.864_865del were more susceptible to nephrocalcinosis than those who were homozygous for c.864_865del and those harboring other mutations (83.33% versus 33.3% and 0%, respectively) (p = 0.025). The clinical features and mutational spectrum of Chinese PH2 patients were described. This study helps to expand awareness of the phenotypes and genotypes of Chinese PH2 patients and contributes to the improvement of diagnostic and treatment strategies for PH2 patients.
Topics: Humans; Hyperoxaluria, Primary; Male; Female; Retrospective Studies; Mutation; Child; Adult; Adolescent; Young Adult; China; Child, Preschool; Asian People; Infant; Nephrocalcinosis; Age of Onset; Kidney Failure, Chronic; East Asian People; Transaminases
PubMed: 38727838
DOI: 10.1007/s00240-024-01579-y -
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 -
Current Opinion in Organ Transplantation Oct 2015The experience of combined liver-kidney transplantation (CLKT) is limited in pediatric populations. This strategy is, however, required in specific diseases such as... (Review)
Review
PURPOSE OF REVIEW
The experience of combined liver-kidney transplantation (CLKT) is limited in pediatric populations. This strategy is, however, required in specific diseases such as metabolic diseases (namely primary hyperoxaluria type one and methylmalonic acidemia), autosomal recessive polycystic kidney disease, miscellaneous ciliopathies and atypical hemolytic uremic syndrome.
RECENT FINDINGS
Different series and registry studies have confirmed the feasibility of pediatric CLKT with encouraging results in the long term, even in the youngest and smallest patients, provided that highly trained multidisciplinary teams are involved in this global management. As such, the long-term outcomes after CLKT are currently comparable to that of isolated liver or kidney transplantations, even though the immediate postoperative period remains challenging.
SUMMARY
Some questions remain nevertheless unanswered, such as the respective place of combined versus sequential liver-kidney transplantation, especially in primary hyperoxaluria and autosomal recessive polycystic kidney disease. The aim of this review was therefore to provide a 2015 update on pediatric CLKT. In the future, international collaborative studies and registries may help to improve our knowledge of this rare and still highly challenging technique.
Topics: Child; Humans; Hyperoxaluria, Primary; Kidney Diseases; Kidney Transplantation; Liver Diseases; Liver Transplantation; Registries
PubMed: 26270957
DOI: 10.1097/MOT.0000000000000225 -
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