Constipation linked with kidney disease

Last Updated: 2016-11-14

By David L. Levine

NEW YORK (Reuters Health) - Researchers have discovered a link between constipation and kidney disease based on a study of a large nationwide cohort of US veterans.

As reported online November 10th in the Journal of the American Society of Nephrology, Drs. Keiichi Sumida and Csaba Kovesdy of the University of Tennessee Health Science Center and Memphis VA Medical Center and colleagues analyzed data on more than 3.5 million US veterans with normal kidney function.

During a median follow-up of 7.0 years, there were a total of 360,541 events of incident CKD, including 46,022 in patients with constipation (crude rate, 33.9 per 1000 patient-years) and 314,519 in patients without constipation (crude rate, 16.1 per 1000 patient-years).

Compared to veterans without constipation, patients with constipation had a 13% higher risk of developing chronic kidney disease (CKD) and a 9% higher risk of end-stage renal disease (ESRD); they were also more likely to experience rapid decline in kidney function, even after adjusting for various known risk factors.

More severe constipation was associated with an incrementally higher risk for both incident CKD and ESRD, the research team found.

In email to Reuters Health, Dr. Kovesdy said he and his colleagues were surprised by the finding.

"Although constipation is one of the most common conditions in primary care settings, and has been shown to increase the risk of cardiovascular disease, potentially through processes mediated by altered gut microbiota, little is known about its association with chronic kidney disease," Dr. Kovesdy said. "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."

"Given the high prevalence of constipation in the general population and the simplicity of its assessment in primary care settings," he added, "the management of constipation through lifestyle modifications (e.g., exercise and high-fiber diet) 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. Kovesdy admitted to some limitations of the study, the chief being that it was observational and that most participants were male. "The results may not be generalizable to women. Additionally, because constipation status and its severity were defined using ICD-9-CM codes and laxative prescription records, but not by subjective symptoms, there might be exposure misclassification," Dr. Kovesdy said.

Dr. Dominic Rajm, chief of renal diseases and hypertension at George Washington University, told Reuters Health by email that he was not surprised by the findings.

Dr. Rajm, who was not involved with the study, said the gastro-renal connection has been known to nephrologists for a very long time.

"Gut functions as a second kidney and allows excretion of urea, creatinine, potassium and number of other potential toxins," he said. "Gut is also the source of a number of uremic toxins, derived from microbiome. Impaired gut motility and constipation allows proliferation of microbiome, some unfavorable leading to generation of more uremic toxins. Furthermore, there is emerging data that dysbiosis could contribute to hypertension due to increased production of specific metabolites such as catecholamines and decreased generation of others such as short chain fatty acids."

Dr. Rajm said it's unclear whether the increased comorbidity was the cause of CKD. 'It may be that the laxative could have contributed to the findings, as the authors acknowledge. Unfortunately, we do not know what class of laxatives was used. Information about dietary fiber intake is important because a number of studies have showed increased dietary fiber intake reduces inflammation and inflammation predicts progression of CKD," Dr. Rajm said.

SOURCE: http://bit.ly/2ez8Swy

J Am Soc Nephrol 2016.