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Drug therapies to delay the progression of chronic kidney disease.

ABSTRACT: Chronic kidney disease (CKD) is associated with significant morbidity and mortality, impacted not alone by progression to end-stage kidney disease, but also by the high associated incidence of cardiovascular events and related mortality. Despite our current understanding of the pathogenesis of CKD and the treatments available, the reported incidence of CKD continues to rise worldwide, and is often referred to as the silent public healthcare epidemic. The significant cost to patient wellbeing and to the economy of managing the later stages of CKD have prompted efforts to develop interventions to delay the development and progression of this syndrome. In this article, we review established and novel agents that may aid in delaying the progression of CKD and improve patient outcomes.

SUBMITTER: Ward F

PROVIDER: S-EPMC4953257 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature

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Drug therapies to delay the progression of chronic kidney disease.

Ward Frank F Holian John J Murray Patrick T PT

Clinical medicine (London, England) 20151201 6

Chronic kidney disease (CKD) is associated with significant morbidity and mortality, impacted not alone by progression to end-stage kidney disease, but also by the high associated incidence of cardiovascular events and related mortality. Despite our current understanding of the pathogenesis of CKD and the treatments available, the reported incidence of CKD continues to rise worldwide, and is often referred to as the silent public healthcare epidemic. The significant cost to patient wellbeing and ...[more]

PMID: 26621944

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Project description:Background and objectivesPrevious studies suggest that tobacco, alcohol, and illicit drug use is associated with CKD. We examined the associations of substance use with CKD progression and all-cause mortality among patients with CKD.Design, setting, participants, & measurementsThe Chronic Renal Insufficiency Cohort Study is a prospective, longitudinal cohort study among 3939 participants with CKD in the United States. Self-reported tobacco smoking, alcohol drinking, marijuana use, and hard illicit drug (cocaine, heroin, or methamphetamine) use were obtained at baseline and annual follow-up visits. CKD progression was defined as incident ESKD or halving of eGFR. Substance use was modeled as the cumulative average exposure to capture both recent and long-term use in multivariable time-dependent Cox regression.ResultsOver a median 5.5-year follow-up, 1287 participants developed CKD progression, and 1001 died. Baseline proportions of tobacco smoking, alcohol drinking, marijuana use, and hard illicit drug use were 13%, 20%, 33%, and 12%, respectively. Compared with nonsmoking throughout follow-up, multivariable-adjusted hazard ratios for persistent tobacco smoking were 1.02 (95% confidence interval, 0.86 to 1.21) for CKD progression and 1.86 (95% confidence interval, 1.54 to 2.24) for all-cause mortality. Compared with nondrinking throughout follow-up, multivariable-adjusted hazard ratios for persistent alcohol drinking were 1.06 (95% confidence interval, 0.88 to 1.29) for CKD progression and 0.73 (95% confidence interval, 0.58 to 0.91) for all-cause mortality. Compared with nonuse throughout follow-up, multivariable-adjusted hazard ratios for persistent marijuana use were 0.94 (95% confidence interval, 0.82 to 1.07) for CKD progression and 1.11 (95% confidence interval, 0.96 to 1.30) for all-cause mortality. Compared with nonuse throughout follow-up, multivariable-adjusted hazard ratios for persistent hard illicit drug use were 1.25 (95% confidence interval, 1.00 to 1.55) for CKD progression and 1.41 (95% confidence interval, 1.10 to 1.81) for all-cause mortality.ConclusionsHard illicit drug use is associated with higher risk of CKD progression and all-cause mortality, tobacco smoking is associated with higher risk of all-cause mortality, and alcohol drinking is associated with lower risk of all-cause mortality among patients with CKD.

Project description:Chronic kidney disease (CKD) has been recognized as a leading public health problem worldwide. Through its effect on cardiovascular risk and end-stage kidney disease, CKD directly affects the global burden of morbidity and mortality. Classical optimal management of CKD includes blood pressure control, treatment of albuminuria with angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers, avoidance of potential nephrotoxins and obesity, drug dosing adjustments, and cardiovascular risk reduction. Diabetes might account for more than half of CKD burden, and obesity is the most important prompted factor for this disease. New antihyperglycemic drugs, such as sodium-glucose-cotransporter 2 inhibitors have shown to slow the decline of GFR, bringing additional benefit in weight reduction, cardiovascular, and other kidney outcomes. On the other hand, a new generation of non-steroidal mineralocorticoid receptor antagonist has recently been developed to obtain a selective receptor inhibition reducing side effects like hyperkalemia and thereby making the drugs suitable for administration to CKD patients. Moreover, two new potassium-lowering therapies have shown to improve tolerance, allowing for higher dosage of renin-angiotensin system inhibitors and therefore enhancing their nephroprotective effect. Regardless of its cause, CKD is characterized by reduced renal regeneration capacity, microvascular damage, oxidative stress and inflammation, resulting in fibrosis and progressive, and irreversible nephron loss. Therefore, a holistic approach should be taken targeting the diverse processes and biological contexts that are associated with CKD progression. To date, therapeutic interventions when tubulointerstitial fibrosis is already established have proved to be insufficient, thus research effort should focus on unraveling early disease mechanisms. An array of novel therapeutic approaches targeting epigenetic regulators are now undergoing phase II or phase III trials and might provide a simultaneous regulatory activity that coordinately regulate different aspects of CKD progression.

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Drug therapies to delay the progression of chronic kidney disease.

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Drug therapies to delay the progression of chronic kidney disease.

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