Primary Hyperoxaluria (PH)
Description
●Introduction:
➣The uncommon autosomal recessive inborn defects in glyoxylate metabolism that cause primary hyperoxaluria (PH) result in an excess of oxalate, which damages the kidneys.
➣Types and Enzymes:
•PH1 → Alanine-glyoxylate aminotransferase deficiency (AGXT) gene defect → the most severe, early ESRD.
•PH2 → (glyoxylate reductase/hydroxypyruvate reductase deficit) GRHPR gene defect.
• PH3 - HOGA1 gene abnormality.
➣Epidemiology: Infrequent globally (PH1 incidence: 1/120,000 births in Europe; prevalence: 1-3 million). Because of underdiagnosis, unknown in India.
➣Natural history: progressive CKD leading to ESRD, nephrolithiasis, and nephrocalcinosis.
• The median age for ESRD is about 24. At diagnosis, 20–50% already had ESRD.
➣Options for treatment include:
• Conservative: potassium citrate, pyridoxine, and a high fluid intake (only in certain PH1 versions).
• Dialysis: poor effectiveness for oxalate clearance.
• The only cure for PH1 is a liver-kidney transplant (LKT), which restores AGXT enzyme function.
• New treatment: FDA/EMA-approved Lumasiran (RNA interference medication) lowers hepatic oxalate production (PH1).
●Discussions:
➣The average delay between the onset of symptoms and genetic confirmation is approximately five years.
➣The spectrum includes asymptomatic carriers (as shown in Cases 2 and 3) as well as early infantile nephrocalcinosis.
➣Highlight of Case 1: severe worsening following consumption of oxalate-rich liquorice.
➣ Mutation results:
• Case 1: first report of a new mutation in AGXT exon 9.
•Case 4: a known PH1 mutation in India (p. Leu101Pro).
• GRHPR mutation (PH2) in Case 5.
➣Insights into treatment:
• Pyridoxine works exclusively for certain AGXT mutations (not Case 4).
• In PH1, LKT is curative.
•Although Lumasiran is a promising new medicine, its use in India is still quite limited.
➣ Significance: Genetic testing can stop the advancement of oxalate nephropathy, consanguinity, or recurring stones if detected early.
●Summaries of Cases
➣Case 1 (30F – postpartum, PH1)
•Symptoms include oliguria and vomiting within a week of giving birth, metabolic acidosis, elevated creatinine (15.5 mg/dl), and urine crystals of oxalate.
• Biopsy: 40% interstitial fibrosis, oxalate crystal deposits.
• Genetics: pathogenicity due to a new AGXT homozygous exon 9 frameshift mutation (p.Ala295SerfsTer22).
• Treatment options include haemodialysis and combination liver and kidney transplantation.
➣Cases 2 and 3 (asymptomatic, PH1 carriers, 26F and 28M siblings)
Findings: high urine oxalate (110 & 95 mg/day), normal renal function, and no stones.
• Genetics: identical frameshift mutation in AGXT exon 9 as in Case 1.
• Conservative management (hydration, pyridoxine, potassium citrate). Lost to follow-up.
➣Case 4 (12M-PH1)
Bilateral renal calculi and azotemia (eGFR 31 ml/min) are the presentation.
• Calcium oxalate monohydrate (90%) is the stone.
• Genetics: India's severe PH1 variation is caused by the AGXT missense mutation (c.302T>C; p.Leu101Pro).
• Treatment: pyridoxine (no response) → advanced to end-stage renal disease → received combination LKT.
➣Case 5 (6M-PH2)
•Presentation: creatinine 0.67 mg/dl (eGFR 68), nephrolithiasis + nephrocalcinosis, and recurring flank discomfort.
• Calcium oxalate monohydrate (90%) is the stone.
GRHPR homozygous missense mutation (c.494G>A; p.Gly165Asp) → PH2 is the genetic basis.
• Conservative management (potassium citrate, hydration).
Protocol
➣Issues Encountered
•Primary hyperoxaluria type 1 patients usually exhibit reduced urine production and vomiting, which frequently leads to chronic kidney failure in the early stages of infancy.
•End-stage renal illness that need dialysis right away.
•Genetic variables like consanguinity and family history may raise the risk and prevalence of illness.
•Severe hyperoxaluria causes gradual renal failure, severe nephrocalcinosis, and recurring kidney stones.
• Frequent pain episodes, an increased risk of infection, and abnormalities in fluid and electrolyte balance are among manifestations of this.
●Nursing therapies and care
➣A variety of evidence-based therapies are used in nursing care of infantile renal failure and primary hyperoxaluria.
➣Dialysis Care: Nurses keep an eye on haemodialysis or peritoneal treatments, making sure the patient's fluid and electrolyte levels are constant, guarding against infections at access points, and educating patients about the procedures and possible risks of dialysis.
➣Pain Management: Nephrocalcinosis or renal colic pain is managed with both non-pharmacological and pharmaceutical methods. Comfort is enhanced by customized therapies and routine pain assessments.
➣ Patient and Family Education: Because the condition is inherited, education focusses on the disease process, available treatments, symptoms of infection or complications, and genetic counselling.
➣ Fluid Balance and Nutrition: Constant input/output monitoring and nutritional assistance help avoid malnutrition and dehydration brought on by vomiting and impaired kidney function. Dietary changes could be required to reduce oxalate consumption and promote kidney health.
➣Infection Control: Vigilance for infections associated to dialysis is maintained, along with strict hand hygiene practices and wound care.
➣ Medication Administration and Monitoring: Nurses give out drugs like pyridoxine and keep an eye out for any negative effects. Drug interactions and adverse effects are avoided by medication reconciliation.
Psychosocial Support: Helping patients and their families deal with the stress of critical care and chronic illness on an emotional level. Ongoing assistance is ensured through coordination with interdisciplinary teams.
Notes
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