CHICAGO (FRONTLINE MEDICAL NEWS) – Constipation was associated with poor kidney health in a large nationwide cohort of 3.5 million United States veterans, and researchers are considering whether effectively treating constipation could help prevent or treat kidney disease.

“In this large nationwide cohort … patients with constipation had higher risks of developing chronic kidney disease and end-stage renal disease, and were more likely to experience rapid decline in kidney function, even after adjusting for various known risk factors. We also found that more severe constipation was associated with an incrementally higher risk for both incident CKD (chronic kidney disease) and ESRD (end-stage renal disease),” said Keiichi Sumida, MD, a visiting scholar at the University of Tennessee Health Science Center in Memphis.

Dr. Sumida presented a poster describing the findings at the American Society of Nephrology’s Kidney Week 2016 meeting.

In a multivariable analysis, those with constipation had a 13% higher likelihood of developing CKD (Hazard Ratio, 1.13; 95% Confidence Interval, 1.11 to 1.14) and a 9% higher likelihood of developing ESRD (HR, 1.09; 95% CI, 1.01 to 1.18) compared to those without constipation. As well, those with constipation experienced a faster decline in estimated glomerular filtration ratio (eGFR).

Scrutiny of US Veterans Administration databases identified nearly 4.5 million patients with serum creatinine measurements obtained between October 2004 and September 2006. Of these, 3,504,732 patients had an eGFR greater than or equal to 60 ml/min/1.73 m2 but no other symptoms of CKD. All were followed through 2013.

Constipation was defined as at least two ICD-9-CM diagnoses for constipation made at least 60 days apart or two or more prescriptions for laxatives separated by 60 days for up to a year. The severity of constipation was based on the number of different type of laxatives prescribed, with no laxative use being considered as absence of constipation, one laxative type being indicative of mild constipation, and two or more types of laxatives being indicative of severe constipation.

Co-primary outcomes were incident CKD, incident ESRD, and change in eGFR from baseline. As expected in the propensity-matched cohort, baseline demographic and clinical characteristics were comparable for the 3,251,291 individuals who experienced constipation and the 253,441 individuals who did not.

“Our findings highlight the plausible link between the gut and the kidneys, and provide additional insights into the pathogenesis of kidney disease progression. Our results suggest the need for careful observation of kidney function in patients with constipation, particularly among those with more severe constipation,” Dr. Sumida concluded.

Dr. Sumida hypothesized that altered gut microflora in constipation may result in inflammation, changes in metabolites, or accumulation of toxins. Alternative explanations increased serotonin related to laxative use, nephrotoxicity, dehydration, or electrolyte imbalance.

These possibilities need to be examined, as does the idea that relieving constipation could prevent renal decline. “Given the high prevalence of constipation in the general population and the simplicity of its assessment in primary care settings, the management of constipation through lifestyle modifications and/or use of probiotics rather than laxatives could become a useful tool in preventing the development of CKD, or in retarding the progression of existing CKD,” Dr. Sumida said.