Burden of Kidney Stone Disease in Patients with Enteric Hyperoxaluria

San Diego—Hyperoxaluria, a serious metabolic disorder, is a key risk factor for progression of kidney stone disease and other renal complications. Patients with malabsorptive gastrointestinal conditions, such as bariatric surgery or Crohn’s disease, are at risk of developing enteric hyperoxaluria due to over-absorption of oxalate. Current standard-of-care interventions are non-specific, and many have persistently high urine oxalate levels.

There are few data available that accurately describe the burden of kidney stone disease in patients with enteric hyperoxaluria. Sagar U. Nigwekar, MD, MMSc, and colleagues conducted analysis of data from  studies designed to define silent kidney stone burden in that patient population. They reported results during a poster presentation at Kidney Week 2018 in a poster titled Unmet Need in Enteric Hyperoxaluria: Clinical Characteristics and Stone Burden in Patients from ALLN-177 Studies.

Study participants (n=33) were enrolled in three phase 2 studies of ALLN-177, an oral, nonabsorbed, oxalate-specific enzyme therapy. All three studies examined medication use, 24-hour urine parameters, history of kidney stones, and dietary oxalate; two of the studies included computed tomography (CT) results (active renal colic was exclusionary).

Mean age of the study population was 64 years and 57.5% were female. Of the 33 participants, 73% (n=24) had bariatric surgery, 15% (n=5) had Crohn’s disease, 6% (n=2) had pancreatic insufficiency, and 6% (n=2) had other disease. Mean dietary oxalate level was 185 mg/d, urine volume was 1.9 L/d, and urinary oxalate was 102 mg/d. Overall, 21 participants were on calcium and/or citrate supplements, thiazides, allopurinol and/or pyridoxine.

Twenty-eight of the participants provided kidney stone medical history. Of those, 93% had at least one episode of kidney stone in the past 5 years. Of the 20 participants with CT results, 80% (=16) had at least one kidney stone and 40% (n=8) had kidney stone in both kidneys. Participants had three kidney stones on average. Four participants (20%) had kidney stone >10 mm, and eight (40%) had kidney stones 5 to 10 mm.

In conclusion, the researchers said, “Despite standard interventions, patients with enteric hyperoxaluria had persistently high urine oxalate levels. In addition, a substantial kidney stone burden was found on CT; many patients had multiple kidney stones, including some with larger kidney stones that could require urological intervention. Both hyperoxaluria and kidney stone burden are risk factors for progressive loss of kidney function. Our analysis highlights a significant unmet need in the enteric hyperoxaluria population, and the current ALLN-177 development program is focused on addressing this.”

Source: Nigwekar, SU, Lingeman JE, Easter L, Grujic D, Zhang, Z, Kausz AS. Unmet need in enteric hyperoxaluria: Clinical characteristics and stone burden in patients from ALLN-177 studies. Abstract of a poster (SA-PO685) presented at the American Society of Nephrology Kidney Week 2018, October 27, 2018, San Diego, California.

Funding for this analysis was provided by Allena Pharmaceuticals.