Dataset Information

Secondary hyperparathyroidism (CKD-MBD) treatment and the risk of dementia.

ABSTRACT:

Background

Elevated parathyroid hormone (PTH) levels have been reported as a potential risk factor for cognitive impairment. Compared with the general population, older adults with end-stage renal disease (ESRD) who are frequently affected by secondary hyperparathyroidism (SHPT) are at increased risk of developing dementia. The main objective of our study was to evaluate if the risk of dementia in older (age ≥66 years) ESRD patients differed if they were treated for SHPT.

Methods

Using the United States Renal Data System and Medicare claims, we identified 189 433 older adults without a diagnosis of dementia, who initiated dialysis between 2006 and 2016. SHPT treatment was defined as the use of vitamin D analogs, phosphate binders, calcimimetics or parathyroidectomy. We quantified the association between treated SHPT and incident dementia during dialysis using a multivariable Cox proportional hazards model with inverse probability weighting, considering SHPT treatment as a time-varying exposure.

Results

Of 189 433 older ESRD adults, 92% had a claims diagnosis code of SHPT and 123 388 (65%) were treated for SHPT. The rate of incident dementia was 6 cases per 100 person-years among SHPT treated patients compared with 11 cases per 100 person-years among untreated patients. Compared with untreated SHPT patients, the risk of dementia was 42% lower [adjusted hazard ratio (aHR) = 0.58, 95% confidence interval (CI): 0.56-0.59] among SHPT treated patients. The magnitude of the beneficial effect of SHPT treatment differed by sex (Pinteraction = .02) and race (Pinteraction ≤ .01), with females (aHR = 0.56, 95% CI: 0.54-0.58) and those of Asian (aHR = 0.51, 95% CI: 0.46-0.57) or Black race (aHR = 0.51, 95% CI: 0.48-0.53) having a greatest reduction in dementia risk.

Conclusion

Receiving treatment for SHPT was associated with a lower risk of incident dementia among older patients with ESRD. This work provides additional support for the treatment of SHPT in older ESRD patients.

SUBMITTER: Mathur A

PROVIDER: S-EPMC9585471 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature

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Publications

Secondary hyperparathyroidism (CKD-MBD) treatment and the risk of dementia.

Mathur Aarti A Ahn JiYoon B JB Sutton Whitney W Chu Nadia M NM Gross Alden L AL Segev Dorry L DL McAdams-DeMarco Mara M

Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association 20221001 11

<h4>Background</h4>Elevated parathyroid hormone (PTH) levels have been reported as a potential risk factor for cognitive impairment. Compared with the general population, older adults with end-stage renal disease (ESRD) who are frequently affected by secondary hyperparathyroidism (SHPT) are at increased risk of developing dementia. The main objective of our study was to evaluate if the risk of dementia in older (age ≥66 years) ESRD patients differed if they were treated for SHPT.<h4>Methods</h4> ...[more]

PMID: 35512551

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Project description:ObjectivesTo define groups of patients according to the changes of biochemical parameters, that is, serum calcium, phosphate and parathyroid hormone (PTH), over a 2-year follow-up period using group-based multi-trajectory modeling (GBMM) among a cohort of dialysis patients with newly diagnosed secondary hyperparathyroidism (SHPT) (ie, PTH≥500 ng/L for the first time) and to compare their patient characteristics and treatments.DesignPharmacoepidemiological study.SettingIn the 12 dialysis units located in the French region of Lorraine.ParticipantsA total of 269 dialysis patients with newly diagnosed SHPT were prospectively included from December 2009 to May 2012 and followed-up for 2 years.ResultsWe identified four distinct trajectory groups: 'rapid PTH drop' experiencing a rapid and sharp decrease (over weeks) in PTH level associated with decreasing phosphate level within normal range (n=34; 12.7%), 'gradual PTH decrease' experiencing a gradual and continuous decrease (over months) in PTH level and maintaining phosphate at a middle level throughout the study (n=98; 36.4%), 'slow PTH decrease with high phosphate' experiencing a slow decrease in PTH level associated with a relatively high phosphate level (n=105; 39.0%) and 'uncontrolled SHPT' with high levels of PTH and phosphate throughout the study (n=32; 11.9%). Patients in the 'uncontrolled SHPT' group were significantly (p<0.00001) younger than patients in other groups. Kidney Disease Improving Global Outcomes (KDIGO) targets for PTH, phosphate and calcium were reached simultaneously for 14.9% of patients at baseline and 16.7% at the end of the study. Patients were given cinacalcet more frequently at months 3 and 6 in the 'rapid PTH drop' and at month 24 in the 'uncontrolled SHPT' groups.ConclusionsOver 2 years following a new SHPT diagnosis, a younger age and a higher rate of alkaline phosphatase were associated to a continuous uncontrolled SHPT. Patients with the lowest PTH at the end of the follow-up tended to receive more often cinacalcet.Trial registration numberClinicalTrials.gov number, NCT02888639, post results.

Project description:ObjectivesAnemia is an important prognostic factor in hemodialysis patients. It has been reported that parathyroidectomy ameliorates anemia and reduces the requirement of postoperative erythropoiesis-stimulating agents. The objective of this study was to assess the effect of cinacalcet, which is considered as a pharmacological parathyroidectomy, on anemia in hemodialysis patients.MethodsWe used data from a prospective cohort of Japanese hemodialysis patients with secondary hyperparathyroidism; the criteria were: intact parathyroid hormone concentrations ≥ 180 pg/mL or use of an intravenous or oral vitamin D receptor activator. All patients were cinacalcet-naïve at study enrollment. The main outcome measure was achievement of the target hemoglobin level (≥10.0 g/dL), which was measured repeatedly every 6 months. Cinacalcet exposure was defined as cumulative time since initiation. Both conventional longitudinal models and marginal structural models were adjusted for confounding factors.ResultsAmong 3,201 cinacalcet-naïve individuals at baseline, cinacalcet was initiated in 1,337 individuals during the follow up. Cinacalcet users were slightly younger; included more patients with chronic glomerulonephritis and fewer with diabetes; were more likely to have a history of parathyroidectomy; and were more often on activated vitamin D agents, phosphate binders, and iron supplements. After adjusting for both time-invariant and time-varying potential confounders, including demographics, comorbidities, comedications, and laboratory values, each additional 6-month duration on cinacalcet was associated with a 1.1-fold increase in the odds of achieving the target hemoglobin level.ConclusionsCinacalcet may improve anemia in chronic hemodialysis patients with secondary hyperparathyroidism, possibly through pathways both within and outside the parathyroid hormone pathways. Further investigations are warranted to delineate the roles of cinacalcet not only in the management of chronic kidney disease-mineral and bone disorder but also in anemia control.

Project description:Background and objectivesCalcitriol is used to treat secondary hyperparathyroidism in patients with CKD. Paricalcitol is less calcemic and phosphatemic in preclinical studies and in some trials in dialysis patients, but head-to-head comparisons in nondialysis patients are lacking. A large meta-analysis of trials concluded that these agents did not consistently reduce parathyroid hormone (PTH) and increased the risk of hypercalcemia and hyperphosphatemia. Therefore, the objective of this multicenter trial was to compare the rate of hypercalcemia between calcitriol and paricalcitol, while suppressing PTH 40%-60%.Design, setting, participants, & measurementsPatients with stages 3-4 CKD (n=110) with a PTH level >120 pg/ml were recruited and randomized to 0.25 μg/d of calcitriol or 1 μg/d of paricalcitol between April 2009 and July 2011. Subsequent dose adjustments were by protocol to achieve 40%-60% PTH suppression below baseline. The primary endpoint was the rate of confirmed hypercalcemia of >10.5 mg/dl between groups.ResultsForty-five patients in each group completed the 24 weeks of treatment. Both agents suppressed PTH effectively (-52% with paricalcitol and -46% with calcitriol; P=0.17), although the paricalcitol group reached a 40% reduction in PTH sooner at a median 8 weeks (interquartile range [IQR], 4, 12) versus 12 weeks (IQR, 8, 18; P=0.02) and had a lower pill burden of 240 (IQR, 180, 298) versus 292 (IQR, 231, 405; P=0.01). Confirmed hypercalcemia was very low in both groups (three with paricalcitol and one with calcitriol) and was not significantly different (P=0.36). Both groups had small increases in calcium and phosphorus levels (0.3-0.4 mg/dl in each electrolyte) and significant decreases in alkaline phosphatase, a marker of high bone turnover, with no significant differences between groups.ConclusionsThese results show that both calcitriol and paricalcitol achieved sustained PTH and alkaline phosphatase suppression in stages 3-4 CKD, with small effects on serum calcium and phosphorus and a low incidence of hypercalcemia.

Dataset Information

Secondary hyperparathyroidism (CKD-MBD) treatment and the risk of dementia.

Background

Methods

Results

Conclusion

Publications

Secondary hyperparathyroidism (CKD-MBD) treatment and the risk of dementia.

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