Circulating Oxalate Levels in Short Bowel Syndrome as a Severity Marker of CKD

Abstract

Introduction: Patients with short bowel syndrome (SBS) may exhibit enteric hyperoxaluria (EH), and the prevalence of oxalate nephropathy in SBS is likely underestimated. Plasma oxalate (POx) is a surrogate of systemic oxalate deposition and, consequently, may increase the risk of developing chronic kidney disease (CKD). The main objective of this study was to explore the distribution of POx levels in patients with SBS.

Methods: Patients followed for SBS were recruited prospectively in the OXAGO study (NCT04119765) to assess POx during their annual renal follow-up including iohexol clearance. The inclusion criteria were age ≥18 years, and SBS type 2 and type 3 for more than 6 months.

Results: A total of 47 patients were included but only 45 patients has a measured POx (55% males, 80% SBS type 2, 66% parenteral nutrition, 61% kidney stone history). POx levels were 6.8 ± 4.4 μmol/l, 29% of patients had POx ≥5 μmol/l. In the whole cohort, mean urinary oxalate (UOx) was 648±415 and 54% were >500 μmol/24h. In the group of patients with high POx levels (HPO), 24-hour urine oxalate was significantly higher than in the group with normal POx levels (NPO) (919 ± 566 vs. 526 ± 257 μmol/l; P = 0.003). Glomerular filtration rate (GFR) was 66 ± 22 ml/min per 1.73 m², and 91% had CKD. GFR was significantly lower in the HPO than in the NPO group (49 ± 23 vs. 73 ± 18 ml/min per 1.73 m²; P = 0.0005.

Conclusion: Patients with SBS can display increased POx levels even with GFR >30 ml/min per 1.73 m². POx may be an interesting biomarker to assess the severity of EH.

Keywords: enteric hyperoxaluria; plasma oxalate; short bowel.

Graphical abstract

Figure 1

Plasma oxalate distribution. (a) Plasma oxalate (POx) distribution. Mean plasma oxalate was 6.8 ± 4.4 μmol/l; (b) plasma oxalate repartition between patients with measurable POx (grey) and patients with POx < 5 umol/l. Among all patients, 29 % of patients had a plasma oxalate ≥5 μmol/l for a mean of 11.5 ± 6.1 μmol/l.

Figure 2

Relationship between plasma oxalate and mGFR. (a) Plasma oxalate concentration (POx) in function of measured GFR (mGFR) in the control cohort of patients with chronic kidney disease without malabsorption. POx was ≥5 μmol/l only when eGFR was below 10 ml/min per 1.73 m². (b) Plasma oxalate concentration (POx) in function of measured GFR (mGFR) in the SBS cohort; (c) comparison of POx between matched mGFR control patients and patients with SBS. (POx 5 ± 0 μmol/l for control group [mGFR of 61 ± 24 ml/min per 1.73 m²] vs. POx 6.8 ± 4.4 μmol/l for SBS group [66 ± 22 ml/min per 1.73 m²]; P = 0.02).

Figure 3

Renal determinants of plasma oxalate level. (a) In the group of patients with high plasma oxalate (HPO), 24-hour urine oxalate was significantly higher (919 ± 566 μmol/l) versus normal plasma oxalate group (NPO) (526 ± 257 μmol/l); P = 0.003. (b) Excretion fraction in HPO is increased more than in the NPO group (153% ± 9% vs. 100% ± 5%). (c) Mean mGFR was 49 ± 23 ml/min per 1.73 m² and was significantly lower in the HPO group than in the NPO group (73 ± 18 ml/min per 1.73 m²; P = 0.0005).