Editorial Combined liver–kidney transplantation for hyperoxaluria type II? In this edition of Pediatric Transplantation, Naderi et al. (1) published an unusual case of end- stage renal disease (ESRD) in a relatively young patient with primary hyperoxaluria (PH) type II. Although the patient was considered for an iso- lated kidney transplant, the standard of care for this condition, evidence suggesting immediate recurrence and subsequent graft loss was found (2). Thus, as is common practice in PH type I, the authors question whether combined liver transplantation should also be considered for PH type II. In PH type I, the excessive production of oxa- late will continue as long as the native liver is in situ because the liver is the sole organ responsi- ble for glyoxylate detoxification (2). Consequently, it is well established that isolated kidney trans- plantation in PH type I is associated with a high rate of recurrence and graft loss (3). While pre-emptive liver transplantation is considered to avoid the complications of systemic oxalosis (4), PH I follows a heterogeneous clinical course and properly timing of the liver transplant in relation to the kidney function and to avoid further kidney damage remains challenging. Thus, most centers opt for combined or sequential liver and kidney transplantation. Although this has become stan- dard of care and can yield excellent results in PH type I (5), there is no experience with combined liver and kidney transplantation in patients with PH type II. Type II PH originates from a different mutation and the ubiquitous tissue distribution of the resultant enzyme deficiency favors isolated kidney transplantation (2, 6). It should be noted that there have been case reports detailing oxalate- related graft loss in patients with PH type II (7). This accompanying editorial aims to review current knowledge surrounding the three PHs and to discuss the feasibility of a combined liver– kidney transplant for this particular case, and was prompted by the possible link between the case presented by Dr. Naderi’s group and exces- sive oxalate burden prior to the transplantation. This editorial will summarize what is known about the three PHs, discuss management during dialysis, and will outline the supporting and opposing rationale for combined liver–kidney transplantation. Primary hyperoxaluria types I, II, and III The three known forms of primary hyperoxaluria form a group of rare autosomal recessive disor- ders responsible for the overproduction of oxa- late (2). PH type I is most common, with an incidence of about 1 case per 120 000 live births in a well-defined Caucasian cohort (8). No acceptable epidemiological studies have been performed to study the disease in other ethnici- ties, but prevalence appears higher in some North African and Middle Eastern nations in which consanguineous marriages are more com- mon (9). Recent studies suggest the emergence of PH III as the second most common form (10). Although each of the three forms is caused by a different enzyme deficiency, all lead to hyperoxal- uria. In hyperoxaluria type I (number 259900 in the Online Mendelian Inheritance of Man [OMIM] database), the liver-specific peroxisomal alanine-glyoxalate aminotransferase (AGT) enzyme does not catalyze the conversion of glyox- alate and alanine to pyruvate and glycine nor does it convert serine to hydroxypyruvate. This deficiency results in the accumulation of glyoxy- late and excessive production of both oxalate and glycolate (2). In PH type II (OMIM number, 260000), 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 enzyme 4-hydroxy-2-oxoglutarate aldolase—a mitochondrial enzyme of 328 amino acids—is 237 Pediatr Transplantation 2014: 18: 237–239 © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd Pediatric Transplantation DOI: 10.1111/petr.12243