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Clinical Kidney Journal May 2022The clinical presentation of primary hyperoxaluria in children ranges from mildly symptomatic nephrocalcinosis to very early onset end-stage kidney failure with systemic... (Review)
Review
The clinical presentation of primary hyperoxaluria in children ranges from mildly symptomatic nephrocalcinosis to very early onset end-stage kidney failure with systemic oxalosis, a devastating complication. We review the various manifestations of pediatric hyperoxaluria, treatment options for children with preserved kidney function and appropriate dialysis regimens. Liver or combined liver/kidney transplantation is currently the only definitive treatment for primary hyperoxaluria type 1, but novel RNA interference treatments offer hope for the future. Finally, we address the medical and ethical dilemmas facing pediatricians treating children with hyperoxaluria.
PubMed: 35592624
DOI: 10.1093/ckj/sfab231 -
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 -
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 -
Pediatric Nephrology (Berlin, Germany) Apr 2023Primary hyperoxaluria type 1 (PH1) is a rare genetic disease that causes progressive kidney damage and systemic oxalosis due to hepatic overproduction of oxalate....
BACKGROUND
Primary hyperoxaluria type 1 (PH1) is a rare genetic disease that causes progressive kidney damage and systemic oxalosis due to hepatic overproduction of oxalate. Lumasiran demonstrated efficacy and safety in the 6-month primary analysis period of the phase 3, multinational, open-label, single-arm ILLUMINATE-B study of infants and children < 6 years old with PH1 (ClinicalTrials.gov: NCT03905694 (4/1/2019); EudraCT: 2018-004,014-17 (10/12/2018)). Outcomes in the ILLUMINATE-B extension period (EP) for patients who completed ≥ 12 months on study are reported here.
METHODS
Of the 18 patients enrolled in the 6-month primary analysis period, all entered the EP and completed ≥ 6 additional months of lumasiran treatment (median (range) duration of total exposure, 17.8 (12.7-20.5) months).
RESULTS
Lumasiran treatment was previously reported to reduce spot urinary oxalate:creatinine ratio by 72% at month 6, which was maintained at 72% at month 12; mean month 12 reductions in prespecified weight subgroups were 89%, 68%, and 71% for patients weighing < 10 kg, 10 to < 20 kg, and ≥ 20 kg, respectively. The mean reduction from baseline in plasma oxalate level was reported to be 32% at month 6, and this improved to 47% at month 12. Additional improvements were also seen in nephrocalcinosis grade, and kidney stone event rates remained low. The most common lumasiran-related adverse events were mild, transient injection-site reactions (3 patients (17%)).
CONCLUSIONS
Lumasiran treatment provided sustained reductions in urinary and plasma oxalate through month 12 across all weight subgroups, with an acceptable safety profile, in infants and young children with PH1. A higher resolution version of the Graphical abstract is available as Supplementary information.
Topics: Child; Child, Preschool; Humans; Infant; Hyperoxaluria, Primary; Kidney Calculi; Oxalates
PubMed: 35913563
DOI: 10.1007/s00467-022-05684-1 -
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 Transplantation May 2024Recurrent disease after kidney transplant remains an important cause of allograft failure, accounting for 7-8% of graft loss and ranking as the fifth most common cause... (Review)
Review
BACKGROUND
Recurrent disease after kidney transplant remains an important cause of allograft failure, accounting for 7-8% of graft loss and ranking as the fifth most common cause of allograft loss in the pediatric population. Although the pathophysiology of many recurrent diseases is incompletely understood, recent advances in basic science and therapeutics are improving outcomes and changing the course of several of these conditions.
METHODS
Review of the literature.
RESULTS
We discuss the diagnosis and management of recurrent disease.
CONCLUSION
We highlight new insights into the pathophysiology and treatment of post-transplant primary hyperoxaluria, focal segmental glomerulosclerosis, immune complex glomerulonephritis, C3 glomerulopathy, lupus nephritis, atypical hemolytic uremic syndrome, and IgA nephropathy.
Topics: Humans; Kidney Transplantation; Recurrence; Child; Postoperative Complications; Kidney Diseases
PubMed: 38650536
DOI: 10.1111/petr.14676 -
Urolithiasis Oct 2023Based on the single-center case reports and all reported patients with primary hyperoxaluria type 1 (PH1) in China, this study discussed the clinical and genetic...
Based on the single-center case reports and all reported patients with primary hyperoxaluria type 1 (PH1) in China, this study discussed the clinical and genetic characteristics of this disease retrospectively. We reported and validated a novel genetic variation c.302 T > G: the clinical phenotypes of the two siblings were similar, in which both had onset in infancy, mainly manifested as renal insufficiency, and died within 6 months out of end-stage renal disease. The literature review is the first to summarize the Chinese patients with PH1 up to now. Forty-eight Chinese patients were included, containing 7 adults and 41 children. The median onset age was 51 months, and the ratio of male to female was 2.69:1. It showed a poor prognosis: 51.1% of Chinese primary hyperoxaluria type 1 patients suffered from end-stage renal disease, and 38.9% of patients died. Urolithiasis was the most common clinical manifestation both in adults and children, while infant-onset patients generally presented with renal insufficiency and had a higher mortality of 75.0%. One hundred and forty-nine AGXT mutant alleles are currently known in the Chinese population, c.33dupC and c.815_816insGA were the most common AGXT genes, accounting for 12.0% and 10.1% of allele frequencies, respectively. The exons 1, 2, 6, and 8 were the most common locations of gene variants, accounting for 78% of all variants, which will be promising targets of DNA sequencing for primary hyperoxaluria type 1.
Topics: Adult; Child; Child, Preschool; Female; Humans; Infant; Male; East Asian People; Hyperoxaluria; Hyperoxaluria, Primary; Kidney Failure, Chronic; Mutation; Retrospective Studies
PubMed: 37874369
DOI: 10.1007/s00240-023-01494-8 -
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 -
Pediatric Transplantation Feb 2024Combined liver-kidney transplantation (CLKT) is a surgical procedure that involves transplanting both liver and kidney organs. There are two types of CLKT: simultaneous... (Review)
Review
Combined liver-kidney transplantation (CLKT) is a surgical procedure that involves transplanting both liver and kidney organs. There are two types of CLKT: simultaneous liver-kidney transplantation (smLKT) and sequential LKT (sqLKT). CLKT accounts for a small percentage of liver transplantations (LTs), particularly in pediatric cases. Nevertheless, the procedure has demonstrated excellent outcomes, with high survival rates and lower rejection rates. The main indications for CLKT in pediatric patients differ somewhat from that in adults, in which end-stage kidney disease after LT is the major indication. In children, congenital diseases are common reason for performing CLKT; the examples of such diseases include autosomal recessive polycystic kidney disease with congenital hepatic fibrosis which equally affects both organs, and primary hyperoxaluria type 1, a primary liver disease leading kidney failure. The decision between smLKT or sqLKT depends on the dominant organ failure, the specific pathophysiology, and available organ sources. However, there remain significant surgical and societal challenges surrounding CLKT. Innovations in pharmacology and genetic engineering have decreased the necessity for CLKT in early-diagnosed cases without portal hypertension or kidney replacement therapy. Nonetheless, these advancements are not universally accessible. Therefore, decision-making algorithms should be crafted, considering region-specific organ allocation systems and prevailing medical environments.
Topics: Adult; Child; Humans; Kidney Transplantation; Liver Transplantation; Treatment Outcome; Kidney Diseases; Liver Failure; Hypertension, Portal; Kidney
PubMed: 38059323
DOI: 10.1111/petr.14666 -
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