Primary hyperoxaluria type 1: still challenging!
- 455 Downloads
Primary hyperoxaluria type 1, the most common form of primary hyperoxaluria, is an autosomal recessive disorder caused by a deficiency of the liver-specific enzyme alanine: glyoxylate aminotransferase (AGT). This results in increased synthesis and subsequent urinary excretion of the metabolic end product oxalate and the deposition of insoluble calcium oxalate in the kidney and urinary tract. As glomerular filtration rate (GFR) decreases due to progressive renal involvement, oxalate accumulates and results in systemic oxalosis. Diagnosis is still often delayed. It may be established on the basis of clinical and sonographic findings, urinary oxalate ± glycolate assessment, DNA analysis and, sometimes, direct AGT activity measurement in liver biopsy tissue. The initiation of conservative measures, based on hydration, citrate and/or phosphate, and pyridoxine, in responsive cases at an early stage to minimize oxalate crystal formation will help to maintain renal function in compliant subjects. Patients with established urolithiasis may benefit from extracorporeal shock-wave lithotripsy and/or JJ stent insertion. Correction of the enzyme defect by liver transplantation should be planned, before systemic oxalosis develops, to optimize outcomes and may be either sequential (biochemical benefit) or simultaneous (immunological benefit) liver–kidney transplantation, depending on facilities and access to cadaveric or living donors. Aggressive dialysis therapies are required to avoid progressive oxalate deposition in established end-stage renal disease (ESRD), and minimization of the time on dialysis will improve both the patient’s quality of life and survival.
KeywordsPrimary hyperoxaluria type 1 Alanine:glyoxylate aminotransferase Oxalate Urolithiasis Dialysis Liver transplantation Combined liver–kidney transplantation Oxalosis
- 6.Millan MT, Berquist WE, So SK, Sarwal MM, Wayman KI, Cox KL, Filler G, Salvatierra O Jr, Esquivel CO (2003) One hundred percent patient and kidney allograft survival with simultaneous liver and kidney transplantation in infants with primary hyperoxaluria: a single-center experience. Transplantation 76:1458–1463PubMedCrossRefGoogle Scholar
- 7.Cochat P, Rolland MO (2005) The primary hyperoxalurias. In: Davison AM, Cameron JS, Grünfeld JP, Ponticelli C, Ritz E, Winearls CG, van Ypersele C (eds) Oxford textbook of clinical nephrology (3rd edn). Oxford University Press, Oxford, pp 2374–2380Google Scholar
- 10.Wong PN, Law ELK, Tong GMW, Mak SK, Lo KY, Wong AKM (2003) Diagnosis of primary hyperoxaluria type 1 by determination of peritoneal dialysate glycolic acid using standard organic-acids analysis method. Perit Dial Int 23:S210–S213Google Scholar
- 12.Amoroso A, Pirulli D, Florian F, Puzzer D, Boniotto M, Crovella S, Zezlina S, Spano A, Mazzola G, Savoldi S, Ferrettini C, Berutti S, Petrarulo M (2001) AGXT gene mutations and their influence on clinical heterogeneity of type 1 primary hyperoxaluria. J Am Soc Nephrol 12:2072–2079PubMedGoogle Scholar
- 14.Danpure CJ, Rumsby G (1995) Enzymological and molecular genetics of primary hyperoxaluria type 1. Consequences for clinical management. In: Khan SR (ed) Calcium oxalate in biological systems. CRC Press, Boca Raton, pp 189–205Google Scholar