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.