Constipation is one of the most frequent symptoms encountered in daily clinical practice and is implicated in the development of atherosclerosis, potentially through altered gut microbiota. However, ...little is known about its association with incident cardiovascular events.
In a nationally representative cohort of 3,359,653 US veterans with an estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2 between October 1, 2004 and September 30, 2006 (baseline period), with follow-up through 2013, we examined the association of constipation status (absence or presence; defined using diagnostic codes and laxative use) and laxative use (none, one, or ≥2 types of laxatives) with all-cause mortality, incident coronary heart disease (CHD), and incident ischemic stroke.
Among 3,359,653 patients, 237,855 (7.1%) were identified as having constipation. After multivariable adjustments for demographics, prevalent comorbidities, medications, and socioeconomic status, patients with (versus without) constipation had 12% higher all-cause mortality (hazard ratio HR, 1.12; 95% CI, 1.11–1.13), 11% higher incidence of CHD (HR, 1.11; 95% CI, 1.08–1.14), and 19% higher incidence of ischemic stroke (HR, 1.19; 95% CI, 1.15–1.22). Patients with one and ≥2 (versus none) types of laxatives experienced a similarly higher risk of all-cause mortality (HRs 95% CI, 1.15 1.13–1.16 and 1.14 1.12–1.15, respectively), incident CHD (HRs 95% CI, 1.11 1.07–1.15 and 1.10 1.05–1.15, respectively) and incident ischemic stroke (HRs 95% CI, 1.19 1.14–1.23 and 1.21 1.16–1.26, respectively).
Constipation status and laxative use are independently associated with higher risk of all-cause mortality and incident CHD and ischemic stroke.
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•Constipation and laxative use associate with higher risk of mortality.•They also associate with higher incidence of coronary heart disease and stroke.•Findings are robust to various sensitivity analyses.
Consumption of cannabis and various related products (cannabinoids) for both medicinal and recreational use is gaining popularity. Furthermore, regulatory changes are fostering a cultural shift ...toward increasing liberalization of cannabis use, thereby increasing the likelihood of even larger numbers of individuals being exposed in the future. The two different types of receptors (CB
and CB
) that are activated by the pharmacologically active ingredients of cannabis are found in numerous tissues, including the kidneys. Experimental studies suggest that stimulation of these receptors using pharmacologic agents or their naturally occurring ligands could have both deleterious and beneficial effects on the kidneys, depending on receptor distribution, type of renal insult, or the timing of the activation during acute or chronic states of kidney injury. To date, the mechanisms by which the CB
or CB
receptors are involved in the pathology of these renal conditions remain to be fully described. Furthermore, a better understanding of the impact of exocannabinoids and endocannabinoids on the renal system may lead to the development of new drugs to treat kidney disease and its complications. Given the increasing public health relevance of cannabis exposure, it is clear that more research is necessary to clarify the various physiological and pathophysiological effects of cannabis and related analogs on the kidney. This will help limit the deleterious effects of these substances while promoting their potential beneficial impact on renal function in various types of kidney diseases.
Constipation and Incident CKD Sumida, Keiichi; Molnar, Miklos Z; Potukuchi, Praveen K ...
Journal of the American Society of Nephrology,
04/2017, Letnik:
28, Številka:
4
Journal Article
Recenzirano
Odprti dostop
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 m
, 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 m
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.
ATP-binding cassette (ABC) transporters are transmembrane efflux transporters mediating the extrusion of an array of substrates ranging from amino acids and lipids to xenobiotics, and many ...therapeutic compounds, including anticancer drugs. The ABC transporters are also recognized as important contributors to pharmacokinetics, especially in drug-drug interactions and adverse drug effects. Drugs and xenobiotics, as well as pathologic conditions, can influence the transcription of ABC transporters, or modify their activity or intracellular localization. Kinases can affect the aforementioned processes for ABC transporters as do protein interactions. In this review, we focus on the ABC transporters ABCB1, ABCB11, ABCC1, ABCC4, and ABCG2 and illustrate how kinases and protein-protein interactions affect these transporters. The clinical relevance of these factors is currently unknown; however, these examples suggest that our understanding of drug-drug interactions will benefit from further knowledge of how kinases and protein-protein interactions affect ABC transporters.
Background Mortality is extremely high immediately after the transition to dialysis therapy, but the association of blood pressure (BP) before dialysis therapy initiation with mortality after ...dialysis therapy initiation remains unknown. Study Design Observational study. Setting & Participants 17,729 US veterans transitioning to dialysis therapy in October 2007 to September 2011, with a median follow-up of 2.0 years. Predictor Systolic (SBP) and diastolic BP (DBP) averaged over the last 1-year predialysis transition period as 6 (<120 to ≥160 mm Hg in 10−mm Hg increments) and 5 (<60 to ≥90 mm Hg in 10−mm Hg increments) categories, respectively, and as continuous measures. Outcomes & Measurements Postdialysis all-cause mortality, assessed over different follow-up periods (ie, <3, 3-<6, 6-<12, and ≥12 months after dialysis therapy initiation) using Cox regressions adjusted for demographics, comorbid conditions, medications, cardiovascular medication adherence, body mass index, estimated glomerular filtration rate, and type of vascular access. Results Mean predialysis SBP and DBP were 141.2 ± 16.1 (SD) and 73.7 ± 10.6 mm Hg, respectively. There was a reverse J-shaped association of SBP with all-cause mortality, with significantly higher mortality seen with SBP < 140 mm Hg. Mortality risks associated with lower SBP were greatest in the first 3 months after dialysis therapy initiation, with multivariable-adjusted HRs of 2.40 (95% CI, 1.96-2.93), 1.99 (95% CI, 1.66-2.40), 1.35 (95% CI, 1.13-1.62), 0.98 (95% CI, 0.78-1.22), and 0.76 (95% CI, 0.57-1.00) for SBP <120, 120 to <130, 130 to <140, 150 to <160, and ≥160 (vs 140-<150) mm Hg, respectively. No consistent association was observed between predialysis DBP and postdialysis mortality. Limitations Results cannot be inferred to show causality and may not be generalizable to women or the general US population. Conclusions Lower predialysis SBP is associated with higher all-cause mortality in the immediate postdialysis period. Predialysis DBP showed no consistent association with postdialysis mortality. Further studies are needed to clarify ideal predialysis SBP levels among incident dialysis patients as a potential means to improve the excessively high early dialysis mortality.
Background Medication nonadherence is a known risk factor for adverse outcomes in the general population. However, little is known about the association of predialysis medication adherence among ...patients with advanced chronic kidney disease and mortality following their transition to dialysis. Study Design Observational study. Setting & Participants 32,348 US veterans who transitioned to dialysis during 2007 to 2011. Predictors Adherence to treatment with cardiovascular drugs, ascertained from pharmacy database records using proportion of days covered (PDC) and persistence during the predialysis year. Outcomes Post–dialysis therapy initiation all-cause and cardiovascular mortality, using Cox models with adjustment for confounders. Results Mean age of the cohort was 72 ± 11 (SD) years; 96% were men, 74% were white, 23% were African American, and 69% had diabetes. During a median follow-up of 23 (IQR, 9-36) months, 18,608 patients died. Among patients with PDC > 80%, there were 14,006 deaths (mortality rate, 283 95% CI, 278-288/1,000 patient-years); among patients with PDC > 60% to 80%, there were 3,882 deaths (mortality rate, 294 95% CI, 285-304/1,000 patient-years); among patients with PDC ≤ 60%, there were 720 deaths (mortality rate, 291 95% CI, 271-313/1,000 patient-years). Compared with patients with PDC > 80%, the adjusted HR for post–dialysis therapy initiation all-cause mortality for patients with PDC > 60% to 80% was 1.12 (95% CI, 1.08-1.16), and for patients with PDC ≤ 60% was 1.21 (95% CI, 1.11-1.30). In addition, compared with patients showing medication persistence, adjusted HR risk for post–dialysis therapy initiation all-cause mortality for patients with nonpersistence was 1.11 (95% CI, 1.05-1.16). A similar trend was detected for cardiovascular mortality and in subgroup analyses. Limitations Large number of missing values; results may not be generalizable to women or the general US population. Conclusions Predialysis cardiovascular medication nonadherence is an independent risk factor for postdialysis mortality in patients with advanced chronic kidney disease transitioning to dialysis therapy. Further studies are needed to assess whether interventions targeting adherence improve survival after dialysis therapy initiation.
Patients with advanced CKD experience increased intestinal potassium excretion. This compensatory mechanism may be enhanced by laxative use; however, little is known about the association of laxative ...use with risk of dyskalemia in advanced CKD.
Our study population encompassed 36,116 United States veterans transitioning to ESKD from 2007 to 2015 with greater than or equal to one plasma potassium measurement during the last 1-year period before ESKD transition. Using generalized estimating equations with adjustment for potential confounders, we examined the association of time-varying laxative use with risk of dyskalemia (
., hypokalemia potassium <3.5 mEq/L or hyperkalemia >5.5 mEq/L) versus normokalemia (3.5-5.5 mEq/L) over the 1-year pre-ESKD period. To avoid potential overestimation of dyskalemia risk, potassium measurements within 7 days following a dyskalemia event were disregarded in the analyses.
Over the last 1-year pre-ESKD period, there were 319,219 repeated potassium measurements in the cohort. Of these, 12,787 (4.0%) represented hypokalemia, and 15,842 (5.0%) represented hyperkalemia; the time-averaged potassium measurement was 4.5 mEq/L. After multivariable adjustment, time-varying laxative use (compared with nonuse) was significantly associated with lower risk of hyperkalemia (adjusted odds ratio aOR, 0.79; 95% confidence interval 95% CI, 0.76 to 0.84) but was not associated with risk of hypokalemia (aOR, 1.01; 95% CI, 0.95 to 1.07). The results were robust to several sensitivity analyses.
Laxative use was independently associated with lower risk of hyperkalemia during the last 1-year pre-ESKD period. Our findings support a putative role of constipation in potassium disarrays and also support (with a careful consideration for the risk-benefit profiles) the therapeutic potential of laxatives in hyperkalemia management in advanced CKD.
Rheumatoid arthritis is associated with reduced kidney function, possibly due to chronic inflammation or the use of nephrotoxic therapies. However, little is known about the effects of using the ...newer novel non-nephrotoxic biologic agents on the risk of incident chronic kidney disease (CKD). To study this we used a cohort of 20,757 United States veterans diagnosed with rheumatoid arthritis with an estimated glomerular filtration rate (eGFR) of 60 mL/min/1.73m2 or more, recruited between October 2004 and September 2006, and followed through 2013. The associations of biologic use with incident CKD (eGFR under 60 with a decrease of at least 25% from baseline, and eGFR under 45 mL/min/1.73m2) and change in eGFR (<-3, -3 to <0 reference, and ≥0 mL/min/1.73m2/year) were examined in propensity-matched patients based on their likelihood to initiate biologic treatment, using Cox models and multinomial logistic regression models, respectively. Among 20,757 patients, 4,617 started biologic therapy. In the propensity-matched cohort, patients treated (versus not treated) with biologic agents had a lower risk of incident CKD (hazard ratios 0.95, 95% confidence interval 0.82-1.10 and 0.71 0.53-0.94 for decrease in eGFR under 60 and under 45 mL/min/1.73m2, respectively) and progressive eGFR decline (multinomial odds ratios 95% CI for eGFR slopes <-3 and ≥0 versus -3 to <0 mL/min/1.73m2/year, 0.67 0.58-0.79 and 0.76 0.69-0.83, respectively). A significant deceleration of eGFR decline was also observed after biologic administration in patients treated with biologics (-1.0 versus -0.4 mL/min/1.73m2/year before and after biologic use). Thus, biologic agent administration was independently associated with lower risk of incident CKD and progressive eGFR decline.
Abstract
Background
Constipation is highly prevalent in patients with chronic kidney disease (CKD), particularly among those with end-stage renal disease (ESRD), partly due to their dietary ...restrictions, comorbidities and medications. Laxatives are typically used for constipation management; however, little is known about laxative use and its associated factors in patients with advanced CKD transitioning to ESRD.
Methods
In a retrospective cohort of 102 477 US veterans transitioning to dialysis between October 2007 and March 2015, we examined the proportion of patients who filled a prescription for any type of laxative within each 6-month period over 36 months pre- and post-transition to ESRD. Factors associated with laxative use during the last 1-year pre-ESRD period were identified by multivariable logistic regression.
Results
The proportion of patients prescribed laxatives increased as patients progressed to ESRD, peaking at 37.1% in the 6 months immediately following ESRD transition, then remaining fairly stable throughout the post-ESRD transition period. Among laxative users, stool softeners were the most commonly prescribed (∼30%), followed by hyperosmotics (∼20%), stimulants (∼10%), bulk formers (∼3%), chloride channel activator (<1%) and several combinations of these. The use of anticoagulants, oral iron supplements, non-opioid analgesics, antihistamines and opioid analgesics were among the factors independently associated with pre-ESRD laxative use.
Conclusion
The use of laxatives increased considerably as patients neared transition to ESRD, likely mirroring the increasing burden of drug-induced constipation during the ESRD transition period. Findings may provide novel insight into better management strategies to alleviate constipation symptoms and reduce medication requirements in patients with advanced CKD.
To investigate the association of estimated glomerular filtration rate (eGFR) slopes before dialysis initiation with cause-specific mortality after dialysis initiation.
In this retrospective cohort ...study of 18,874 US veterans who had transitioned to dialysis from October 1, 2007, through September 30, 2011, we examined the association of pre-end-stage renal disease (ESRD) eGFR slopes with all-cause, cardiovascular, and infection-related mortality during the post-ESRD period over a median follow-up of 2.0 years (interquartile range, 1.1-3.2 years). Associations were examined using Cox models with adjustment for potential confounders.
Before the 18,874 patients transitioned to dialysis, 4485 (23.8%), 5633 (29.8%), and 7942 (42.1%) experienced fast, moderate, and slow eGFR decline, respectively, and 814 (4.3%) had increasing eGFR (defined as eGFR slopes of less than -10, -10 to less than -5, -5 to <0, and ≥0 mL/min per 1.73 m(2) per year). During the study period, a total of 9744 all-cause, 2702 cardiovascular, and 604 infection-related deaths were observed. Compared with patients with slow eGFR decline, those with moderate and fast eGFR decline had a higher risk of all-cause mortality (adjusted hazard ratio HR, 1.06; 95% CI, 1.00-1.11; and HR, 1.11; 95% CI, 1.04-1.18, respectively) and cardiovascular mortality (HR, 1.11; 95% CI, 1.01-1.23 and HR, 1.13; 95% CI, 1.00-1.27, respectively). In contrast, increasing eGFR was only associated with higher infection-related mortality (HR, 1.49; 95% CI, 1.03-2.17).
Rapid eGFR decline is associated with higher all-cause and cardiovascular mortality, and increasing eGFR is associated with higher infection-related mortality among incident dialysis cases.
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