COMMENTARY

Urinary Oxalate and CKD Progression: Is There an Association?

Nisha Bansal, MD, MAS

Disclosures

May 02, 2019

Does higher urinary oxalate excretion predispose patients to kidney failure? Elevated levels of oxalate, a metabolite eliminated through the kidney, can be toxic. Oxalate nephropathy is characterized by high concentrations of oxalate in kidney tubular fluid that leads to calcium oxalate crystals and injury to tubular epithelial cells, among other mechanisms.

Certain rare disorders, such as primary hyperoxaluria, create an overproduction of oxalate, which leads to end-stage renal disease (ESRD). In addition to rare disorders, urinary oxalate excretion is dependent on dietary oxalate intake, net intestinal absorption, and endogenous oxalate synthesis from the liver. Therefore, it is possible that urinary oxalate levels are elevated in more common forms of chronic kidney disease (CKD) and may be causal in loss of kidney function.

In a recent study published in JAMA Internal Medicine, Waikar and colleagues[1] investigated the association of 24-hour urinary oxalate excretion with progression of CKD in the large Chronic Renal Insufficiency Cohort. The study included 3121 participants with moderate CKD (mean estimated glomerular filtration rate [eGFR], 43 mL/min/1.73 m2). Median urinary oxalate excretion by 24-hour urine collections was 18.6 mg/24 hours (intraquartile range, 12.9-25.7 mg/24 hours).

Factors associated with higher urinary oxalate excretion included:

  • Nonblack race;

  • Diabetes;

  • Lower eGFR;

  • Higher urine proteinuria;

  • Use of thiazide diuretics;

  • Lower serum calcium;

  • Lower urinary calcium; and

  • High urine creatinine concentration.

With more than 22,318 person-years of follow-up, 752 participants progressed to ESRD and 940 participants reached the composite endpoint of ESRD or had a 50% decline in eGFR. In statistical models, participants in the highest quintile of urinary oxalate concentration (≥ 27.8 mg/24 hours) had a 33% higher risk for CKD progression and a 45% higher risk for ESRD. Significant associations were also seen in participants in the third and fourth highest quintile of urinary oxalate excretion (≥ 16.2 mg/24 hours).

The authors also reported that the associations were generally consistent across subgroups by demographics, level of kidney function, use of medications, and specific laboratory values. A secondary analysis found no association between urinary oxalate excretion and mortality.

The authors concluded that higher levels of urinary oxalate excretion were associated with greater risk for kidney disease progression and ESRD among patients with more common forms of CKD. These findings are supported by other studies that have identified oxalate as a causal mediator in kidney damage.[2] For example, calcium oxalate composes 80% of kidney stones, and there is a well-known association between kidney stones and increased risk for CKD.

What Can We Glean From This Study?

At least two possible mechanisms may explain the findings in this study. Calcium oxalate crystals can precipitate and cause obstruction in the tubular lumen.[3] Deposition of calcium oxalate can also induce an inflammatory response, which can lead to kidney damage.

Strengths of this study include a rigorous approach and a large, well-characterized CKD cohort. But some caution should be taken when interpreting the findings. The urinary oxalate levels were measured from frozen samples in a reference laboratory. Therefore, the absolute levels of urinary oxalate reported in the study may not be comparable to those reported in nonfrozen samples or different laboratories. There is known interlaboratory variability in urinary oxalate measurements. Furthermore, data on patients' histories of nephrolithiasis or kidney biopsies were not available.

The findings from this study highlight oxalate as a novel risk factor for CKD progression in common forms of CKD. Oxalate nephropathy may be an important contributor to loss of kidney function, even in patients without known nephrolithiasis. Further data are needed to determine whether interventions to reduce urinary oxalate excretion, such as pharmacologic or dietary measures, are beneficial in preserving kidney function.

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