Constipation and Incident CKD

Abstract

Constipation is one of the most prevalent conditions in primary care settings and increases the risk of cardiovascular disease, potentially through processes mediated by altered gut microbiota. However, little is known about the association of constipation with CKD. In a nationwide cohort of 3,504,732 United States veterans with an eGFR ≥60 ml/min per 1.73 m², we examined the association of constipation status and severity (absent, mild, or moderate/severe), defined using diagnostic codes and laxative use, with incident CKD, incident ESRD, and change in eGFR in Cox models (for time-to-event analyses) and multinomial logistic regression models (for change in eGFR). Among patients, the mean (SD) age was 60.0 (14.1) years old; 93.2% of patients were men, and 24.7% were diabetic. After multivariable adjustments, compared with patients without constipation, patients with constipation had higher incidence rates of CKD (hazard ratio, 1.13; 95% confidence interval [95% CI], 1.11 to 1.14) and ESRD (hazard ratio, 1.09; 95% CI, 1.01 to 1.18) and faster eGFR decline (multinomial odds ratios for eGFR slope <-10, -10 to <-5, and -5 to <-1 versus -1 to <0 ml/min per 1.73 m² per year, 1.17; 95% CI, 1.14 to 1.20; 1.07; 95% CI, 1.04 to 1.09; and 1.01; 95% CI, 1.00 to 1.03, respectively). More severe constipation associated with an incrementally higher risk for each renal outcome. In conclusion, constipation status and severity associate with higher risk of incident CKD and ESRD and with progressive eGFR decline, independent of known risk factors. Further studies should elucidate the underlying mechanisms.

Keywords: Epidemiology and outcomes; chronic kidney disease; end-stage renal disease; glomerular filtration rate.

Figure 1.

Unadjusted Kaplan–Meier cumulative event curves for renal events. (A) Incident CKD and (B) incident ESRD according to (a) constipation status and (b) its severity. Cumulative incidences of (A) CKD and (B) ESRD were higher in patients with (versus without) constipation and with more severe constipation.

Figure 2.

Association of the presence of constipation with renal events. (A) Incident CKD, (B) incident ESRD, and (C) change in eGFR. The presence of constipation was associated with higher incidence rates of CKD and ESRD and faster eGFR decline, compared with the absence of constipation. Estimates were calculated using Cox proportional models (for incident CKD and ESRD) and multinomial logistic regression models (for change in eGFR). Models represent unadjusted association (model 1) and associations after adjustment for age, sex, race, and baseline eGFR (model 2); model 2 variables plus comorbidities (diabetes mellitus, hypertension, CHD, congestive heart failure, cerebrovascular disease, peripheral arterial disease, peptic ulcer disease, rheumatic disease, malignancy, depression, liver disease, chronic lung disease, HIV/AIDS, and bowel disorders; model 3); model 3 plus baseline body mass index, systolic BP, and diastolic BP (model 4); and model 4 plus socioeconomic parameters (mean per capita income, marital status, service connectedness, housing stress, low education, low employment, and persistent poverty), number of VA health care encounters, cumulative length of hospitalization, receipt of influenza vaccination(s), and use of angiotensin–converting enzyme inhibitors/angiotensin II receptor blockers, statins, antidepressants, nonopioid analgesics, and opioids (model 5).

Figure 3.

Association of the presence of constipation with renal events in predefined subgroups of the overall cohort. (A) Incident CKD, (B) incident ESRD, and (C) change in eGFR. The presence (versus absence) of constipation was associated with higher risk of incident CKD and ESRD and faster eGFR decline in most subgroups. Estimates were calculated using Cox proportional models (for incident CKD and ESRD) and multinomial logistic regression models (for eGFR slope [milliliter per minute per 1.73 m² per year]; <−10 versus −1 to <0 [reference]). Data were adjusted for age, sex, race, baseline eGFR, comorbidities (diabetes mellitus [DM], hypertension, CHD, congestive heart failure [CHF], cerebrovascular disease, peripheral arterial disease, peptic ulcer disease, rheumatic disease, malignancy, depression, liver disease, chronic lung disease, HIV/AIDS, and bowel disorders), baseline body mass index, systolic BP, diastolic BP, socioeconomic parameters (mean per capita income, marital status, service connectedness, housing stress, low education, low employment, and persistent poverty), number of VA health care encounters, cumulative length of hospitalization, receipt of influenza vaccination(s), and use of angiotensin–converting enzyme inhibitors/angiotensin II receptor blockers, statins, antidepressants, nonopioid analgesics, and opioids. HTN, hypertension.

Figure 4.

Algorithm used to define the study cohort. *Patients with the date of cohort entry later than the date of last encounter (n=32,038), those with the date of incident ESRD later than the date of last encounter (n=2236), or those with an eGFR slope <−55 (0.5th percentile) or ≥40 (99.5th percentile) ml/min per 1.73 m² per year (n=32,161).