ESKD in a Young Patient with Chronic Bilateral Flank Pain

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Case Description

A 27-year-old man presented with a 2-week history of generalized weakness, nausea, decreased urine output, and 4/10 chronic bilateral flank pain. Initial investigations showed a creatinine of (14.3 mg/dl) 1267 μmol/L. He had a long-standing history of primary hyperoxaluria type 1, with liver biopsy–confirmed alanine glyoxylate aminotransferase deficiency, and had progressive CKD despite multiple surgical interventions, including lithotripsy, ureteroscopy, and percutaneous nephrolithotomy procedures. Abdominal x-ray (Figure 1A) and a computed tomography scan of the abdomen (Figure 1B) showed extensive medullary nephrocalcinosis with enlarged communicating cystic spaces around the calcified medulla.

Figure 1.

Abdominal imaging of patient with bilateral flank pain. (A) Abdominal radiograph demonstrates bilateral medullary nephrocalcinosis. (B) Axial computed tomography of the abdomen reveals bilateral medullary nephrocalcinosis.

Discussion

The primary hyperoxalurias (PH) are a group of autosomal recessive disorders involving the overproduction of oxalate, primarily by the liver. PH1 is caused by a deficiency of alanine glyoxylate aminotransferase, which converts glyoxylate to glycine (1). Individuals with PH develop progressive nephrocalcinosis and CKD. Our patient had been on treatment with pyridoxine, potassium citrate, sodium potassium phosphate but continued to progress. He was recently started on nedosiran, an interfering RNA (RNAi) therapy that inhibits hepatic lactate dehydrogenase A, a key enzyme in the metabolic pathway for oxalate production. Unfortunately, he continued to progress toward ESKD. He was thus started on nocturnal hemodialysis.

Treatment considerations for patients with hyperoxaluria include intensive dialysis and transplantation. It is imperative that such patients receive adequate clearance of oxalate to prevent extrarenal deposition of oxalate in organs such the heart, eyes, central nervous system, and joints (1). The optimal RRT is frequent nocturnal hemodialysis (2). Patients with early hyperoxaluria are candidates for a liver transplant, which overcomes the enzymatic deficiency. Novel RNAi therapy targeting the oxalate metabolic pathway has shown promising results when used early in the disease course. Other than nedosiran, a second RNAi molecule—lumasiran—is available, which targets glycolate oxidase (3). Kidney transplant alone is ineffective because the calcinosis will recur. Combined liver-kidney transplantation in ESKD patients is the definitive treatment. More evidence is required for the efficacy of kidney transplant combined with RNAi therapy.

Teaching Points

• Primary hyperoxaluria type I is a genetic defect in liver alanine glyoxylate aminotransferase that can lead to progressive renal decline due to nephrocalcinosis and oxalate nephrolithiasis.

• Individuals with hyperoxalosis and ESKD require intensive dialysis (e.g., frequent nocturnal dialysis) to clear oxalate in order to prevent extrarenal deposition of oxalate in tissues such as the eyes, heart, central nervous system, and joints.

• Novel treatments include novel interfering RNA therapy that inhibits enzymes in the oxalate metabolic pathway, whereas definitive treatment is a liver transplant with or without kidney transplant.

Disclosures

The authors have nothing to disclose.

Funding

None.

Author Contributions

Both authors wrote the original draft of the manuscript and reviewed and edited the manuscript.