Kidney Stones Linked to Adverse Renal Outcomes

Nancy A. Melville

August 31, 2012

August 31, 2012 — A single kidney stone episode is associated with an increased risk of adverse renal events, including end-stage renal disease (ESRD), later in life according to new research published online August 30 in the British Medical Journal.

The study, led by R. Todd Alexander, MD, PhD, from the University of Alberta, in Edmonton, Canada, and colleagues in Canada and the United States, involved an analysis of more than 3 million patients enrolled in the Alberta (Canada) Kidney Disease Network database between 1997 and 2009.

The increase in risk associated with as little as a single kidney stone episode was small, but significant compared with those who did not have a kidney stone, although a greater risk was observed among women with a history of one or more kidney stones and among people younger than 50 years.

Patients with more than one kidney stone episode also showed a greater risk for adverse renal events that was independent of potential confounders including sex or age.

"These findings suggest that kidney stones are an important potential contributor to the risk of ESRD and that patients with prior kidney stones should be considered at increased risk for adverse renal outcomes — especially younger women or those with multiple symptomatic episodes," the authors write.

Hospital records from patients in the analysis, which included patients without ESRD at baseline or a history of pyelonephritis, showed that 23,706 (0.8%) had at least one kidney stone between 1997 and 2009.

A total of 5333 patients (0.2%) developed ESRD, 68,525 (4%) developed stage 3b–5 chronic kidney disease, and 6581 (0.3%) had a sustained doubling of serum creatinine concentration from baseline.

Compared with people who did not have kidney stones, the occurrence of one or more kidney stone episodes was associated with increased risk for ESRD (adjusted hazard ratio, 2.16; 95% confidence interval [CI], 1.79 - 2.62), new stage 3b–5 chronic kidney disease (hazard ratio, 1.74; 95% CI, 1.61 - 1.88), and a doubling of serum creatinine (hazard ratio, 1.94; 95% CI, 1.56 - 2.43).

The absolute increase in the risk for adverse outcomes among those with kidney stones, however, was said to be small, with an unadjusted rate of ESRD of 2.48 per million person days in people with one or more episodes of stones compared with 0.52 per million person days among those without stones.

Considering the heterogeneity of kidney stones and their formation, a variety of factors could explain the association with adverse renal outcomes, the authors say.

Rare monogenetic disorders such as primary hyperoxaluria and cystinuria are known to cause kidney stones, and therefore place people at an increased risk for ESRD, but the authors also speculate that progressive calcification in the renal interstitium could explain the role of calcium kidney stones in the progressive loss of kidney function.

Extension of such calcification into the tubular lumen might cause additional renal damage and progressive scarring, and crystallization in the tubular lumen itself could further cause damage to the tubular epithelium or obstruction leading to progressive scarring, the researchers add.

Other mechanisms could include progressive loss of renal function as the result of repeated urinary tract obstructions, and even treatment of kidney stones.

"[I]t is possible that surgical or percutaneous treatment of stones (rather than the stones themselves) accounts for the excess risk of kidney function loss," the authors write.

Limitations of the study include the fact that the database identified people who presented for health services, and therefore did not include those who did not seek care for a stone episode, and that some patients may have been misclassified regarding their number of presentations.

Given that kidney stones are common and considered to be potentially preventable, however, more studies should be conducted to better determine how they can be avoided, the authors conclude.

"Further research should be aimed at determining the mechanisms explaining this association and assessing the optimal way to prevent kidney stones in the general population, especially young women."

The study was supported by a team grant to the Interdisciplinary Chronic Disease Collaboration from the Alberta Heritage Foundation for Medical Research, the Kidney Foundation of Canada, and the University Hospital Foundation. The authors have disclosed no relevant financial relationships.

BMJ. Published online August 30, 2012. Full text


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