Editorial The merits of sequential transplantation for hyperoxaluria type I The three known forms of primary hyperoxaluria (PH) form a group of rare autosomal recessive disorders responsible for the overproduction of oxalate (1). Although the deficient enzyme is dif- ferent in each form, all three lead to hyperoxalu- ria. In PH type I (PH I, number 259 900 in the Online Mendelian Inheritance of Man [OMIM] database), the liver-specific peroxisomal alanine– glyoxylate aminotransferase (AGT) enzyme does not catalyze the conversion of glyoxylate and alanine to pyruvate and glycine, nor does it con- vert serine to hydroxypyruvate. This deficiency results in the accumulation of glyoxylate and excessive production of both oxalate and glyco- late (1). In PH type II (OMIM number, 260 000), the lack of glyoxylate reductase– hydroxypyruvate reductase (GRHPR), which catalyzes the reduction of glyoxylate to glycolate and hydroxypyruvate to D-glycerate, leads to the accumulation of oxalate and L-glyceric acid. Although the primary pathophysiological mech- anism behind PH type III has not yet been fully unraveled, it is now well established that the 4-hydroxy-2-oxoglutarate aldolase enzyme—a mitochondrial enzyme composed of 328 amino acids—is deficient in this condition (2). PH I is most common, with an incidence of about 1 case per 120 000 live births in a well-defined Cauca- sian cohort (3). The excessive production of oxa- late in PH type I will continue while the native liver is in situ since glyoxylate detoxification only takes place in the liver (1). As a result, isolated kidney transplantation in PH I is firmly associ- ated with a high rate of recurrence and graft loss (4). While pre-emptive liver transplantation is considered to avoid complications stemming from systemic oxalosis (5), PH I follows a hetero- geneous clinical course and properly timing the transplantation of the liver in relation to kidney function to avoid further damage to the kidneys remains challenging. PH I has responded to pyri- doxine in a few cases and may slow progression to end-stage chronic kidney disease (CKD) (6, 7). As a rule of thumb, PH I requires liver transplantation, which is often combined with renal transplantation, whereas PH II is commonly treated with isolated kidney transplantation. PH III rarely requires transplan- tation during childhood (8). Although combined liver and kidney transplants can yield excellent results (9), many centers consider sequential liver and kidney transplantation (8). The continued accumulation of oxalate substantially affects patients’ overall survival. In this edition of Pediatric Transplantation, Sasaki et al. (10) detail five cases of PH I at their institution. The authors describe the impact of organ shortages and wait times on the center’s decision to perform either combined or sequential liver and kidney transplantation, the former being ideal from an immunological perspective but more challenging considering the shortage of donors. In their case series, Sasaki et al. strongly argue in favor of imple- menting a two-step procedure in light of this donor shortage. Controlling plasma oxalate in PH patients with end-stage CKD is essential It is important to highlight several teachable moments present in Sasaki’s case series because this disorder is rare and can be approached in multiple different ways. For example, patients one and three were treated with peritoneal dialy- sis. Although it is understandable that peritoneal dialysis would be the therapy of choice in an infant, this method is ineffective at clearing oxa- late (11). As long as the patient retains his or her native liver, conventional hemodialysis and peri- toneal dialysis will not eliminate enough oxalate and a positive oxalate balance will remain. Therefore, strategies that are more intensive must be developed to limit both systemic involve- ment and further deposition of oxalate in organs other than the kidney (9, 11). The optimal 5 Pediatr Transplantation 2015: 19: 5–7 © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd Pediatric Transplantation DOI: 10.1111/petr.12404