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Csaba P Kovesdy - One of the best experts on this subject based on the ideXlab platform.
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Laxative use and change in estimated glomerular filtration rate in patients with advanced chronic kidney disease
Journal of Renal Nutrition, 2021Co-Authors: Keiichi Sumida, Ankur A Dashputre, Praveen K Potukuchi, Fridtjof Thomas, Yoshitsugu Obi, Miklos Z Molnar, Justin Gatwood, Elani Streja, Kamyar Kalantarzadeh, Csaba P KovesdyAbstract:Objectives Constipation is highly prevalent in advanced chronic kidney disease (CKD), due in part to dietary (e.g., fiber) restrictions, and is often managed by Laxatives; however, the effect of Laxative use on kidney function in advanced CKD remains unclear. We aimed to examine the association of Laxative use with longitudinal change in estimated glomerular filtration rate (eGFR) in patients with advanced CKD. Design and Methods In a retrospective cohort of 43,622 US veterans transitioning to end-stage renal disease (ESRD) from 2007 to 2015, we estimated changes in eGFR (slope) by linear mixed-effects models using ≥2 available outpatient eGFR measurements during the 2-year period before transition to ESRD. The association of Laxative use with change in eGFR was examined by testing the interaction of time-varying Laxative use with time for eGFR slope in the mixed-effects models with adjustment for fixed and time-varying confounders. Results Laxatives were prescribed in 49.8% of patients during the last 2-year pre-ESRD period. In the crude model, time-varying Laxative use was modestly associated with more progressive eGFR decline compared with non-use of Laxatives (median [interquartile interval] −7.1 [−11.9, −4.3] vs. −6.8 [−11.6, −4.0] mL/min/1.73 m2/year, P Conclusions There was a clinically negligible association of Laxative use with change in eGFR during the last 2-year pre-ESRD period, suggesting the renal safety profile of Laxatives in advanced CKD patients.
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Laxative use and risk of dyskalemia in patients with advanced ckd transitioning to dialysis
Journal of The American Society of Nephrology, 2021Co-Authors: Keiichi Sumida, Ankur A Dashputre, Praveen K Potukuchi, Fridtjof Thomas, Yoshitsugu Obi, Miklos Z Molnar, Justin Gatwood, Elani Streja, Kamyar Kalantarzadeh, Csaba P KovesdyAbstract:Background 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. Methods 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 (i.e., hypokalemia [potassium 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. Results 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. Conclusions 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.
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Laxative use in patients with advanced chronic kidney disease transitioning to dialysis
Nephrology Dialysis Transplantation, 2020Co-Authors: Keiichi Sumida, Ankur A Dashputre, Praveen K Potukuchi, Fridtjof Thomas, Yoshitsugu Obi, Miklos Z Molnar, Justin Gatwood, Elani Streja, Kamyar Kalantarzadeh, Csaba P KovesdyAbstract: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.
Cynthia M Nijenhuis - One of the best experts on this subject based on the ideXlab platform.
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disturbed development of the enteric nervous system after in utero exposure of selective serotonin re uptake inhibitors and tricyclic antidepressants part 2 testing the hypotheses
British Journal of Clinical Pharmacology, 2012Co-Authors: Cynthia M Nijenhuis, Peter G J Ter Horst, Nienke Van Rein, Bob Wilffert, Lolkje T W De Jongâ Van Den BergAbstract:WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Antidepressant use has increased in the last decade. Several studies have suggested a possible association between maternal antidepressant use and teratogenic effects. In a review of the pharmacologic literature we showed that antidepressant exposure might disturb the development of the enteric nervous system. WHAT THIS STUDY ADDS • In utero exposure to selective serotonin re-uptake inhibitors (SSRIs) in the second and third trimester or to tricyclic antidepressants (TCAs) in the first trimester leads to a significant increase in Laxative use compared with non-exposed children. SSRI exposure was not associated with significant increased antidiarrhoeal medication use, but TCA exposure was. AIMS Antidepressant use has increased in the last decade. Several studies have suggested a possible association between maternal antidepressant use and teratogenic effects. METHODS The pharmacy prescription database IADB.nl was used for a cohort study in which Laxative and antidiarrhoeal medication use in children after in utero exposure to antidepressants (TCA, SSRI, fluoxetine or paroxetine exposed) was compared with no antidepressant exposure. Laxatives and antidiarrhoeal medication use were applied as a proxy for constipation and diarrhoea respectively, which may be associated with disturbed enteric nervous system (ENS) development. RESULTS Children exposed in utero to SSRIs (mainly fluoxetine and paroxetine) in the second and third trimester or to TCAs in the first trimester, more often received Laxatives. Combined exposure to TCAs and SSRIs in pregnancy was associated with a 10-fold increase in Laxative use. In utero exposure to SSRIs is not associated with antidiarrhoeal medication use compared with non-exposed children. In contrast, antidiarrhoeal medication use was significantly higher in children exposed to TCAs anytime in pregnancy. CONCLUSIONS The increased Laxative use after second and third trimester exposure to SSRIs might be explained through the inhibitory effect of the serotonin re-uptake transporter (SERT) and because of selectivity for the 5-HT2B receptor which affects the ENS. TCA exposure during the first trimester leads to increased Laxative use probably through inhibition of the norepinephrine transporter (NET). Exposure of TCAs anytime in pregnancy leads to increase diarrhoeal use possibly through down-regulation of α2-adrenoceptors or up-regulation of the pore forming α1c subunit.
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disturbed development of the enteric nervous system after in utero exposure of selective serotonin re uptake inhibitors and tricyclic antidepressants part 2 testing the hypotheses
British Journal of Clinical Pharmacology, 2012Co-Authors: Cynthia M Nijenhuis, Bob Wilffert, Peter G J Ter Horst, Nienke Van Rein, Lolkje T W De Jongâ Van Den BergAbstract:WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Antidepressant use has increased in the last decade. Several studies have suggested a possible association between maternal antidepressant use and teratogenic effects. In a review of the pharmacologic literature we showed that antidepressant exposure might disturb the development of the enteric nervous system. WHAT THIS STUDY ADDS • In utero exposure to selective serotonin re-uptake inhibitors (SSRIs) in the second and third trimester or to tricyclic antidepressants (TCAs) in the first trimester leads to a significant increase in Laxative use compared with non-exposed children. SSRI exposure was not associated with significant increased antidiarrhoeal medication use, but TCA exposure was. AIMS Antidepressant use has increased in the last decade. Several studies have suggested a possible association between maternal antidepressant use and teratogenic effects. METHODS The pharmacy prescription database IADB.nl was used for a cohort study in which Laxative and antidiarrhoeal medication use in children after in utero exposure to antidepressants (TCA, SSRI, fluoxetine or paroxetine exposed) was compared with no antidepressant exposure. Laxatives and antidiarrhoeal medication use were applied as a proxy for constipation and diarrhoea respectively, which may be associated with disturbed enteric nervous system (ENS) development. RESULTS Children exposed in utero to SSRIs (mainly fluoxetine and paroxetine) in the second and third trimester or to TCAs in the first trimester, more often received Laxatives. Combined exposure to TCAs and SSRIs in pregnancy was associated with a 10-fold increase in Laxative use. In utero exposure to SSRIs is not associated with antidiarrhoeal medication use compared with non-exposed children. In contrast, antidiarrhoeal medication use was significantly higher in children exposed to TCAs anytime in pregnancy. CONCLUSIONS The increased Laxative use after second and third trimester exposure to SSRIs might be explained through the inhibitory effect of the serotonin re-uptake transporter (SERT) and because of selectivity for the 5-HT2B receptor which affects the ENS. TCA exposure during the first trimester leads to increased Laxative use probably through inhibition of the norepinephrine transporter (NET). Exposure of TCAs anytime in pregnancy leads to increase diarrhoeal use possibly through down-regulation of α2-adrenoceptors or up-regulation of the pore forming α1c subunit.
Lolkje T W De Jongâ Van Den Berg - One of the best experts on this subject based on the ideXlab platform.
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disturbed development of the enteric nervous system after in utero exposure of selective serotonin re uptake inhibitors and tricyclic antidepressants part 2 testing the hypotheses
British Journal of Clinical Pharmacology, 2012Co-Authors: Cynthia M Nijenhuis, Peter G J Ter Horst, Nienke Van Rein, Bob Wilffert, Lolkje T W De Jongâ Van Den BergAbstract:WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Antidepressant use has increased in the last decade. Several studies have suggested a possible association between maternal antidepressant use and teratogenic effects. In a review of the pharmacologic literature we showed that antidepressant exposure might disturb the development of the enteric nervous system. WHAT THIS STUDY ADDS • In utero exposure to selective serotonin re-uptake inhibitors (SSRIs) in the second and third trimester or to tricyclic antidepressants (TCAs) in the first trimester leads to a significant increase in Laxative use compared with non-exposed children. SSRI exposure was not associated with significant increased antidiarrhoeal medication use, but TCA exposure was. AIMS Antidepressant use has increased in the last decade. Several studies have suggested a possible association between maternal antidepressant use and teratogenic effects. METHODS The pharmacy prescription database IADB.nl was used for a cohort study in which Laxative and antidiarrhoeal medication use in children after in utero exposure to antidepressants (TCA, SSRI, fluoxetine or paroxetine exposed) was compared with no antidepressant exposure. Laxatives and antidiarrhoeal medication use were applied as a proxy for constipation and diarrhoea respectively, which may be associated with disturbed enteric nervous system (ENS) development. RESULTS Children exposed in utero to SSRIs (mainly fluoxetine and paroxetine) in the second and third trimester or to TCAs in the first trimester, more often received Laxatives. Combined exposure to TCAs and SSRIs in pregnancy was associated with a 10-fold increase in Laxative use. In utero exposure to SSRIs is not associated with antidiarrhoeal medication use compared with non-exposed children. In contrast, antidiarrhoeal medication use was significantly higher in children exposed to TCAs anytime in pregnancy. CONCLUSIONS The increased Laxative use after second and third trimester exposure to SSRIs might be explained through the inhibitory effect of the serotonin re-uptake transporter (SERT) and because of selectivity for the 5-HT2B receptor which affects the ENS. TCA exposure during the first trimester leads to increased Laxative use probably through inhibition of the norepinephrine transporter (NET). Exposure of TCAs anytime in pregnancy leads to increase diarrhoeal use possibly through down-regulation of α2-adrenoceptors or up-regulation of the pore forming α1c subunit.
Lolkje T W De Jongâ Van Den Berg - One of the best experts on this subject based on the ideXlab platform.
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disturbed development of the enteric nervous system after in utero exposure of selective serotonin re uptake inhibitors and tricyclic antidepressants part 2 testing the hypotheses
British Journal of Clinical Pharmacology, 2012Co-Authors: Cynthia M Nijenhuis, Bob Wilffert, Peter G J Ter Horst, Nienke Van Rein, Lolkje T W De Jongâ Van Den BergAbstract:WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Antidepressant use has increased in the last decade. Several studies have suggested a possible association between maternal antidepressant use and teratogenic effects. In a review of the pharmacologic literature we showed that antidepressant exposure might disturb the development of the enteric nervous system. WHAT THIS STUDY ADDS • In utero exposure to selective serotonin re-uptake inhibitors (SSRIs) in the second and third trimester or to tricyclic antidepressants (TCAs) in the first trimester leads to a significant increase in Laxative use compared with non-exposed children. SSRI exposure was not associated with significant increased antidiarrhoeal medication use, but TCA exposure was. AIMS Antidepressant use has increased in the last decade. Several studies have suggested a possible association between maternal antidepressant use and teratogenic effects. METHODS The pharmacy prescription database IADB.nl was used for a cohort study in which Laxative and antidiarrhoeal medication use in children after in utero exposure to antidepressants (TCA, SSRI, fluoxetine or paroxetine exposed) was compared with no antidepressant exposure. Laxatives and antidiarrhoeal medication use were applied as a proxy for constipation and diarrhoea respectively, which may be associated with disturbed enteric nervous system (ENS) development. RESULTS Children exposed in utero to SSRIs (mainly fluoxetine and paroxetine) in the second and third trimester or to TCAs in the first trimester, more often received Laxatives. Combined exposure to TCAs and SSRIs in pregnancy was associated with a 10-fold increase in Laxative use. In utero exposure to SSRIs is not associated with antidiarrhoeal medication use compared with non-exposed children. In contrast, antidiarrhoeal medication use was significantly higher in children exposed to TCAs anytime in pregnancy. CONCLUSIONS The increased Laxative use after second and third trimester exposure to SSRIs might be explained through the inhibitory effect of the serotonin re-uptake transporter (SERT) and because of selectivity for the 5-HT2B receptor which affects the ENS. TCA exposure during the first trimester leads to increased Laxative use probably through inhibition of the norepinephrine transporter (NET). Exposure of TCAs anytime in pregnancy leads to increase diarrhoeal use possibly through down-regulation of α2-adrenoceptors or up-regulation of the pore forming α1c subunit.
Keiichi Sumida - One of the best experts on this subject based on the ideXlab platform.
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Laxative use and change in estimated glomerular filtration rate in patients with advanced chronic kidney disease
Journal of Renal Nutrition, 2021Co-Authors: Keiichi Sumida, Ankur A Dashputre, Praveen K Potukuchi, Fridtjof Thomas, Yoshitsugu Obi, Miklos Z Molnar, Justin Gatwood, Elani Streja, Kamyar Kalantarzadeh, Csaba P KovesdyAbstract:Objectives Constipation is highly prevalent in advanced chronic kidney disease (CKD), due in part to dietary (e.g., fiber) restrictions, and is often managed by Laxatives; however, the effect of Laxative use on kidney function in advanced CKD remains unclear. We aimed to examine the association of Laxative use with longitudinal change in estimated glomerular filtration rate (eGFR) in patients with advanced CKD. Design and Methods In a retrospective cohort of 43,622 US veterans transitioning to end-stage renal disease (ESRD) from 2007 to 2015, we estimated changes in eGFR (slope) by linear mixed-effects models using ≥2 available outpatient eGFR measurements during the 2-year period before transition to ESRD. The association of Laxative use with change in eGFR was examined by testing the interaction of time-varying Laxative use with time for eGFR slope in the mixed-effects models with adjustment for fixed and time-varying confounders. Results Laxatives were prescribed in 49.8% of patients during the last 2-year pre-ESRD period. In the crude model, time-varying Laxative use was modestly associated with more progressive eGFR decline compared with non-use of Laxatives (median [interquartile interval] −7.1 [−11.9, −4.3] vs. −6.8 [−11.6, −4.0] mL/min/1.73 m2/year, P Conclusions There was a clinically negligible association of Laxative use with change in eGFR during the last 2-year pre-ESRD period, suggesting the renal safety profile of Laxatives in advanced CKD patients.
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Laxative use and risk of dyskalemia in patients with advanced ckd transitioning to dialysis
Journal of The American Society of Nephrology, 2021Co-Authors: Keiichi Sumida, Ankur A Dashputre, Praveen K Potukuchi, Fridtjof Thomas, Yoshitsugu Obi, Miklos Z Molnar, Justin Gatwood, Elani Streja, Kamyar Kalantarzadeh, Csaba P KovesdyAbstract:Background 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. Methods 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 (i.e., hypokalemia [potassium 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. Results 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. Conclusions 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.
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Laxative use in patients with advanced chronic kidney disease transitioning to dialysis
Nephrology Dialysis Transplantation, 2020Co-Authors: Keiichi Sumida, Ankur A Dashputre, Praveen K Potukuchi, Fridtjof Thomas, Yoshitsugu Obi, Miklos Z Molnar, Justin Gatwood, Elani Streja, Kamyar Kalantarzadeh, Csaba P KovesdyAbstract: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.
