Hyperoxaluria and systemic oxalosis: an update on current therapy and future directions

Abstract

Due to lack of familiarity with PH and its heterogeneous clinical expression, diagnosis is often delayed until advanced disease is present, a condition, requiring intensive hemodialysis and timely transplantation. Achieving the most beneficial outcome largely depends on the knowledge of the clinical spectrum, early diagnosis, and initiation of treatment before renal failure ensues. A number of preconditions required for substantial improvement in the care of orphan disease like PH have now been achieved or soon will come within reach, so new treatment options can be expected in the near future.

Updated genetic testing of Italian patients referred with a clinical diagnosis of primary hyperoxaluria

“…Primary hyperoxaluria (PH) is a rare autosomal recessive disease (prevalence 1-3x10 -6 ) with onset mainly in childhood [1]. It is characterized by increased levels of urinary and plasma oxalate, nephrolithiasis and/or nephrocalcinosis leading to end stage renal disease (ESRD) and systemic oxalosis [2].…”

“…It is characterized by increased levels of urinary and plasma oxalate, nephrolithiasis and/or nephrocalcinosis leading to end stage renal disease (ESRD) and systemic oxalosis [2]. Three types of PH are currently known, but further genetic heterogeneity has been hypothesized, since in some patients the clinical suspicion of PH is not confirmed by molecular analysis [1].…”

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“…1 The PH-1 is caused by a deficiency of the liver-specific peroxisomal enzyme, alanine-glyoxylate aminotransferase (AGT), leading to excessive oxalate production, deposition of calcium oxalate crystals in the kidney, nephrocalcinosis, progressive renal failure, and systemic deposition of oxalate (oxalosis). 1,2 Neither dialysis nor isolated kidney transplant may remove calcium oxalate efficiently. 1 Isolated kidney transplant is followed by recurrence of nephrocalcinosis because of the overproduction of oxalate by the liver, leading to a high rate of graft loss.…”

“…1,2 Neither dialysis nor isolated kidney transplant may remove calcium oxalate efficiently. 1 Isolated kidney transplant is followed by recurrence of nephrocalcinosis because of the overproduction of oxalate by the liver, leading to a high rate of graft loss. 3 The only definitive treatment is combined liver and kidney transplant, which has improved patient and graft survival for patients with PH-1.…”

Apical Sparing of Longitudinal Strain, Left Ventricular Rotational Abnormalities, and Short-Axis Dysfunctionin Primary Hyperoxaluria Type 1

“…Diagnosis of primary hyperoxaluria type 1, a hereditary cause of calcium oxalate kidney stones or progressive nephrocalcinosis that frequently results in end-stage renal failure, 1 was made by liver biopsy (reduced alanine:glyoxylate aminotransferase activity, 3.0 µmol/h per milligram protein; normal, 19.1-47.9) and by genetic testing (homozygosity for the c.302 T>C, AGXT mutation). Her plasma oxalate level on regular hemodialysis (3× per week over 4 hours) was increased (86 µmol/L predialysis; normal, <10 µmol/L).…”