Modulation of Parathyroid Hormone by Aldosterone Antagonist may lead to Better Outcomes in Chronic Kidney Disease Related Secondary Hyperparathyroidism

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SUN 234-256-Bone & Calcium Metabolism: Clinical Trials & Case Series
Clinical
Sunday, June 16, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SUN-253
Mona Hassan*1, Laila Shiekh Sroujieh1, Meghan Liroff2, Derar Albashaireh1 and Waqas Qureshi1
1Henry Ford Hospital, Detroit, MI, 2Wayne State University
Background

Hyperparathyroidism has been associated with cardiovascular morbidity and mortality. Recently basic science models have shown a direct relationship of parathyroid hormone (PTH) with aldosterone. However it is not known if blocking aldosterone receptor leads to suppression of parathyroid hormone (PTH) in clinical setting and if it has clinical benefits.

Methods

This is a incidence case – control study where cases were all the consecutive patients with chronic kidney disease on aldosterone antagonists (AA). Controls were matched (1:1) on age, gender, race, estimated GFR and number of medications for hypertension from the insurance database >2 million patients not on AA that had PTH measured in the same year as that of the corresponding cases. PTH was measured within 1 year of starting AA and within 1 year after initiation of AA. Cox proportional hazard modeling was performed for outcomes; decrease in PTH, rates of new onset heart failure (HF), rates of heart failure related readmissions, and cardiovascular specific mortality. Analyses were adjusted for 25 OH vitamin D, hypertension, diabetes, smoking, and alkaline phosphatase. Time dependent covariate analysis was used to compare various levels of PTH in the year prior and after the initiation of aldosterone antagonist.

Results

Out of 850 patients, 425 patients (mean age 67±13, women 60.2%) were started on AA. Compliance was >80% with a mean follow up of 4.6±3.2 years. Mean PTH prior to initiation of AA was 141±133ng/dL which decreased by a mean of 40±113ng/dL compared to a change of 0.1 ± 64 ng/dL in controls (p<0.0001). The decrease in PTH was associated with decreased cardiovascular mortality (HR 0.71;95% CI 0.53 – 0.97, p = 0.03). Increase in PTH was associated with risk of new onset HF (HR 1.93; 95% CI 1.32 – 2.83, p = 0.001) and heart failure related readmission (HR 1.73; 95% CI 1.15 – 2.60, p = 0.009) but not with non fatal myocardial infarctions (p = 0.88). Kaplan – Meier’s showed worse survival of patients that did not have a decrease in PTH by 30% within 2 years (log rank p – value = 0.03). On post hoc analysis, there was no interaction of outcomes with degree of chronic kidney disease and vitamin D supplements, phosphate binding, bisphosophonates or calcimimetic medications.

Conclusion

In conclusion, modulating PTH via AA may provide another therapeutic way to improve hormonal imbalance in the patients with secondary hyperparathyroidism from renal disease. This modulation has important clinical implications.

(1) J Am Coll Cardiol. 2011 Sep 27;58(14):1433-41. doi: 10.1016/j.jacc.2011.03.069. Vitamin D, parathyroid hormone, and cardiovascular events among older adults. Kestenbaum B, Katz R, de Boer I, Hoofnagle A, Sarnak MJ, Shlipak MG, Jenny NS, Siscovick DS. Source Kidney Research Institute, University of Washington, Seattle, WA, USA. brk@u.washington.edu. (2) JAMA. 2011 Mar 16;305(11):1119-27. doi: 10.1001/jama.2011.308. Serum levels of phosphorus, parathyroid hormone, and calcium and risks of death and cardiovascular disease in individuals with chronic kidney disease: a systematic review and meta-analysis. Palmer SC, Hayen A, Macaskill P, Pellegrini F, Craig JC, Elder GJ, Strippoli GF. (3) Expert Opin Pharmacother. 2011 Dec;12(18):2801-15. doi: 10.1517/14656566.2011.631524. Epub 2011 Nov 14. Mineralocorticoid receptor antagonists for heart failure. Richards AM. (4) Eur J Clin Invest. 2007 Aug;37(8):607-22. Mineral metabolism disturbances in patients with chronic kidney disease. Kestenbaum B, Belozeroff V. (5) Am J Kidney Dis. 2011 Mar;57(3):403-14. doi: 10.1053/j.ajkd.2010.10.047. Epub 2010 Dec 24. Association of plasma aldosterone with cardiovascular mortality in patients with low estimated GFR: the Ludwigshafen Risk and Cardiovascular Health (LURIC) Study. Tomaschitz A, Pilz S, Ritz E, Grammer T, Drechsler C, Boehm BO, März W.

Nothing to Disclose: MH, LS, ML, DA, WQ

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