Primary hyperoxaluria diagnosed after kidney transplant: A review of the literature and case report of aggressive renal replacement therapy and lumasiran to prevent allograft loss

Abstract

Primary hyperoxaluria type 1 is a rare inherited disorder caused by abnormal liver glyoxalate metabolism leading to overproduction of oxalate, progressive kidney disease, and systemic oxalosis. While the disorder typically presents with nephrocalcinosis, recurrent nephrolithiasis, and/or early chronic kidney disease, the diagnosis is occasionally missed until it recurs after kidney transplant. Allograft outcomes in these cases are typically very poor, often with early graft loss. Here we present the case of a child diagnosed with primary hyperoxaluria type 1 after kidney transplant who was able to maintain kidney function, thanks to aggressive renal replacement therapy as well as initiation of a new targeted therapy for this disease. This case highlights the importance of having a high index of suspicion for primary hyperoxaluria in patients with chronic kidney disease and nephrocalcinosis/nephrolithiasis or with end stage kidney disease of uncertain etiology, as initiating therapies early on may prevent poor outcomes.

Lumasiran for Advanced Primary Hyperoxaluria Type 1: Phase 3 ILLUMINATE-C Trial

“…37 More recently, in a young patient diagnosed with PH1 following a kidney transplant, graft kidney function stabilized following lumasiran and aggressive kidney replacement therapy, allowing for discontinuation of dialysis. 38 The challenge the community J o u r n a l P r e -p r o o f now faces is to understand what might be a suitable POx level at which kidney-only transplant could be considered for patients with PH1, acknowledging that such a decision would not rely on a POx level alone. POx levels may fluctuate during follow-up, unrelated to changes in serum creatinine or eGFR 39 ; in addition, there is poor agreement in POx values between laboratories.…”

Improving Treatment Options for Primary Hyperoxaluria

“…So far, experiences with Oxlumo ® treatment (outside long-term studies from the company itself) have been reported only in ten PH1 cases, both children (n = 7) [85][86][87][88] and adults (n = 3) [89-91] (Table 3) with the time under treatment reported as from 1 to 18 months. Good tolerance, reduced urinary oxalate/creatinine ratio, and stability (or even slight improvement) of renal function were reported only in the children treated.…”

“…Glycolate values (in urine or plasma) were not provided in any case. In one case, however, metabolic acidosis was reported during a 5-month administration period (measured by low HCO 3 − values and negative base excess) and treatment with sodium bicarbonate was needed [ 88 ]. Here, we may speculate that acidosis might possibly be due to very high plasma glycolic acid levels (Table 3 ).…”

“…Currently, there is only minor experience with Oxlumo ® or compassionate use with nedosiran reported in the literature (Table 3 ). Reports show the decline in Uox and Pox, as per reported in the pivotal studies, but emerging evidence also shows that careful and personalized strategies have to be applied, to, for example, avoid recurrence of oxalosis in a kidney graft [ 85 , 88 , 91 ], or to adequately reduce Uox excretion by adaptation of medication [ 85 ].…”

Recurrence of rare disease after kidney transplant

“…Delayed graft function caused by the deposition of oxalate in allograft is easily misdiagnosed as acute rejection and needs kidney biopsy for accurate diagnosis. For this reason, a high index of suspicion for the diagnosis of PH is very important in patients with CKD and/or ESRD with uncertain etiology especially accomplished with nephrocalcinosis or nephrolithiasis (13). Such patients need exact preoperative screening for PH and proper treatment in both kidneys before KTx (13).…”