Abnormal Mineral Metabolism and Mortality in Hemodialysis Patients With Secondary Hyperparathyroidism: Evidence From Marginal Structural Models Used to Adjust for Time-Dependent Confounding

Fukagawa, Masafumi; Kido, Ryō; Komaba, Hirotaka; Ônishi, Yoshihiro; Yamaguchi, Takuhiro; Hasegawa, Takeshi; Kurita, Noriaki; Fukuma, Shingo; Akizawa, Tadao; Fukuhara, Shunichi

doi:10.1053/j.ajkd.2013.08.011

Cited by 75 publications

(78 citation statements)

References 39 publications

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“…In the long term, elevated calcium phosphate product is involved in the pathogenesis of vascular calcification, which impairs arterial wall structure [25,26] . Since impaired mineral metabolism is a strong and independent predictor of mortality in hemodialysis [27] , the intermittently higher calcium phosphate product during the long interdialytic interval may worsen the outcomes in these patients. Furthermore, recent studies have shown that high dialysate calcium concentrations acutely raise BP and worsen arterial compliance during dialysis [28] .…”

Section: Calcium and Phosphatementioning

confidence: 99%

Adverse Effects of Conventional Thrice-Weekly Hemodialysis: Is It Time to Avoid 3-Day Interdialytic Intervals?

et al. 2015

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Background: Maintenance hemodialysis is typically scheduled thrice weekly due to simple logistic reasons; thus, the vast majority of hemodialysis patients receive renal replacement therapy for two shorter 2-day intervals and a longer 3-day interval. As compared to the 2-day interval, we review the ill effects of the longer 3-day interdialytic interval in this report. Summary: Large-scale observational studies show that both cardiovascular-related hospital admissions and mortality occur more frequently on the day following the long interdialytic interval than on any other day of the week. Although the reasons for excess mortality are obscure, several pathophysiologic mechanisms may be involved, such as a greater magnitude of change during the long interdialytic interval in the following parameters: volume status, electrolyte and acid-base status, arterial wall and left ventricle mechanics. These data raise the need for re-examining the issue of timing and frequency of prescribed dialysis regimens in an attempt to improve patient outcomes. Although enhanced-frequency and/or extended-time dialysis schedules may mitigate the risks of the long interdialytic interval, the benefit of such dialytic modalities on survival is not yet proven. Key Message: This article summarizes currently available epidemiologic and pathophysiologic evidence on the adverse effects related to the long interdialytic interval of thrice-weekly hemodialysis and discusses the need to research further alternative dialysis practices that could mitigate these risks.

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Section: Calcium and Phosphatementioning

confidence: 99%

Adverse Effects of Conventional Thrice-Weekly Hemodialysis: Is It Time to Avoid 3-Day Interdialytic Intervals?

et al. 2015

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“…They are likely to have higher cardiovascular and mortality risk by exposure to abnormal mineral and bone metabolism represented by high iPTH levels or their treatments, partially through vascular calcification or fraction [43]. This might increase power to estimate the effect of RASI use for mortality in a precise manner.…”

Section: Discussionmentioning

confidence: 99%

Interactive Effectiveness of Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers or Their Combination on Survival of Hemodialysis Patients

Kido¹,

Akizawa

Fukagawa

et al. 2017

Am J Nephrol

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Background: Does the use of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers individually or as a combination confer a survival benefit in hemodialysis patients? The answer to this question is yet unclear. Methods: We performed a case-cohort study using data from the Mineral and Bone Disorder Outcomes Study for Japanese CKD stage 5D patients (MBD-5D), a 3-year multicenter prospective case-cohort study, including 8,229 hemodialysis patients registered from 86 facilities in Japan. All patients had secondary hyperparathyroidism, a condition defined as a parathyroid hormone level ≥180 pg/mL and/or receiving vitamin D receptor activators. We compared all-cause mortality rates between those receiving ACEI, ARB, and their combination and non-users with interaction testing. We used marginal structural Poisson regression (causal model) to estimate the causal effect and interaction adjusted for possible time-dependent confounding. Cardiovascular mortality was also evaluated. Results: Among 3,762 randomly sampled subcohort patients, those taking ACEI, ARB, and their combination at baseline accounted for 4.0, 31.6, and 3.8%, respectively. Over 3 years, 1,226 all-cause and 462 cardiovascular deaths occurred. Compared to non-users, ARB-alone users had a lower all-cause mortality rate (adjusted incident rate ratio [aIRR] 0.62, 95% CI 0.50–0.76), whereas ACEI-alone users showed a statistically similar rate (aIRR 1.01, 95% CI 0.57–1.77). On the contrary, combination users had a greater mortality rate (aIRR 2.56, 95% CI 1.22–5.37), showing significant interaction (p = 0.03). Analysis for cardiovascular mortality showed similar results. Conclusion: Among hemodialysis patients with secondary hyperparathyroidism, unlike ACEI use, ARB use was associated with greater survival than non-use. Conversely, combination use was associated with greater mortality. Controlled trials are warranted to verify the causality factors of these associations.

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“…The JSDT guideline recommends controlling phosphate and calcium levels first and only then controlling PTH levels. This is because the association of PTH levels with mortality is weaker than that of serum phosphorus and calcium [27] , which was also confirmed in another cohort of SHPT patients [31] . Furthermore, new roles for high PTH levels in the development of cachexia, sarcopenia [32] , and hyperuricemia [33] have recently been reported in addition to the classic concept of PTH as a uremic toxin [34] .…”

Section: Clinical Practice Pattern and Guideline For Ckd-mbd In Japanmentioning

confidence: 92%

Chronic Kidney Disease-Mineral and Bone Disorder in Asia

Fukagawa¹,

Komaba²

2017

Kidney Dis

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Background: Chronic kidney disease-mineral and bone disorder (CKD-MBD) is one of the most common complications in patients with CKD. As CKD-MBD is a systemic syndrome, prevention and management should be aimed at achieving better survival and less risk of cardiovascular events and fractures. Summary: Although target ranges for serum markers of mineral metabolism have been proposed in several global or local guidelines, these were mostly based on data from non-Asian patients. Additionally, there remain differences in medical and social systems as well as in economic status, even among Asian countries and areas. Key Message: Asian CKD patient data needs to be analyzed, published, and shared to establish optimal local strategies for CKD-MBD management.

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Abnormal Mineral Metabolism and Mortality in Hemodialysis Patients With Secondary Hyperparathyroidism: Evidence From Marginal Structural Models Used to Adjust for Time-Dependent Confounding

Cited by 75 publications

References 39 publications

Adverse Effects of Conventional Thrice-Weekly Hemodialysis: Is It Time to Avoid 3-Day Interdialytic Intervals?

Adverse Effects of Conventional Thrice-Weekly Hemodialysis: Is It Time to Avoid 3-Day Interdialytic Intervals?

Interactive Effectiveness of Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers or Their Combination on Survival of Hemodialysis Patients

Chronic Kidney Disease-Mineral and Bone Disorder in Asia

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