CLINICAL RESPONSE TO LUMASIRAN IN A PH1 PATIENT ON HEMODIALYSIS: CHALLENGES IN OXALATE CONTROL UNDER LIMITED DIALYSIS ACCESS

Primary hyperoxaluria type 1 (PH1) is a rare autosomal recessive disorder caused by mutations in the AGXT gene, leading to excessive hepatic oxalate production and progressive kidney damage. Calcium oxalate accumulation results in nephrocalcinosis, urolithiasis, and systemic oxalosis, especially after renal function declines. Traditional treatments include hyperhydration, citrate, and pyridoxine, which is effective in select genotypes. However, many patients progress to end-stage kidney disease (ESKD), particularly in settings with delayed diagnosis.

The emergence of RNA interference (RNAi) therapies, such as lumasiran, has significantly advanced PH1 management. Lumasiran inhibits glycolate oxidase, reducing glyoxylate and subsequent oxalate production. Clinical trials have demonstrated substantial reductions in plasma oxalate (POx), with mild adverse effects.

In dialysis-dependent patients, managing oxalate burden is particularly challenging, and treatment outcomes are influenced not only by pharmacologic response but also by dialysis access and intensity. This case highlights the clinical course of a PH1 patient treated with lumasiran under the constraints of Brazil’s public health system (SUS), which limits dialysis frequency.

This report describes the clinical response to lumasiran in an adult PH1 patient undergoing hemodialysis. Diagnosis was confirmed via genetic testing (heterozygous mutation p.Gly170Arg, pyridoxine-responsive and p.Lys12Argfs*34 genotype). Lumasiran was administered according to approved dosing protocols at 3 mg/kg monthly for four months, followed by quarterly maintenance doses. The patient was monitored over a 12-month period, with assessments including Plasma oxalate (POx) levels, cardiac function via echocardiography and treatment tolerability. Pyridoxine therapy was continued throughout.

Cardiac evaluations revealed preserved systolic function with mild structural changes, notably left atrial enlargement and ventricular hypertrophy. Initial echocardiograms showed severe hypertrophy, while follow-up exams indicated stability or slight improvement.

POx levels dropped sharply after lumasiran initiation (<5 μmol/L), but subsequently rebounded and remained elevated. Table 1 summarizes POx progression:

PH1 patients often require intensified dialysis—up to six sessions per week—to manage oxalate burden. However, Brazil’s public health system (SUS) covers only three weekly sessions, with a fourth allowed in specific cases. This patient received four sessions per week, a frequency likely insufficient to prevent systemic oxalosis.

In resource-limited settings, where access to intensive dialysis and liver transplantation is restricted, RNAi therapies like lumasiran offer a promising alternative due to their ease of administration and potential to improve outcomes. Although POx initially declined with lumasiran, levels later rose, suggesting POx alone may not reliably indicate treatment success in patients with systemic oxalosis. 

This case illustrates the limitations of relying solely on plasma oxalate (POx) to assess treatment efficacy in dialysis patients with systemic oxalosis. The patient received four dialysis sessions per week—above the SUS standard of three, yet still below the intensity often required in PH1. These findings underscore the need for individualized dialysis strategies and support the role of RNAi therapies in mitigating disparities in care delivery. In resource-limited settings, optimizing treatment outcomes requires not only access to novel therapies but also systemic improvements in dialysis infrastructure.