Serum Alkaline Phosphatase Levels and Mortality of Chronic Hemodialysis Patients
Tetsuri Yamashita, Junichi Shizuku, Takashi Ohba, Takashi Kabaya, Kosaku Nitta
DOI: 10.4236/ijcm.2011.24065   PDF    HTML   XML   7,747 Downloads   14,905 Views   Citations


Objective: Alkaline phosphatase (ALP) is considered a biomarker of high bone turnover in hemodialysis (HD) patients with secondary hyperparathyroidism. This study was conducted to determine whether high serum ALP levels are associated with increased all-cause mortality of HD patients. Patients and Methods: This was a retrospective cohort study conducted at a single center. The subjects were 195 patients on chronic HD therapy who were followed up for a 5 years, and relationships between their baseline data and outcomes were assessed statistically. The serum ALP level was used as the predictor, and the primary end point was all-cause mortality. Results: Based on the median serum ALP of 236 IU/L, the subjects were divided into a low-ALP group (<236 IU/l) and a high-ALP group (≥236 IU/l). The high-ALP group was older and had a longer dialysis vintage, lower serum phosphorus concentrations, and higher serum parathyroid hormone levels, and they also had lower serum albumin levels and higher C-reactive protein values. In a multivariate Cox model in which the baseline serum ALP levels were used adjusted for age, gender, HD vintage, comorbidity, bone metabolism parameters, and serum liver enzyme levels, each doubling of the serum ALP level was associated with a significant increase in the hazard of all-cause mortality (hazard ratio 10.70, 95% CI 1.53 - 74.24). Conclusion: High baseline serum ALP levels are associated with increased mortality of HD patients, independent of bone metabolism parameters and serum liver enzyme levels. ALP is a potential target for the treatment of HD patients.

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T. Yamashita, J. Shizuku, T. Ohba, T. Kabaya and K. Nitta, "Serum Alkaline Phosphatase Levels and Mortality of Chronic Hemodialysis Patients," International Journal of Clinical Medicine, Vol. 2 No. 4, 2011, pp. 388-393. doi: 10.4236/ijcm.2011.24065.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] C. P. Kovesdy, S. Ahmadzadeh, J. E. Anderson and K. Kalantar-Zadeh, “Secondary Hyperparathyroidism is Associated with Higher Mortality in Men with Moderate to Severe Chronic Kidney Disease,” Kidney International, Vol. 73, No. 11, 2008, pp. 1296-1302. doi:10.1038/ki.2008.64
[2] G. M. Chertow, P. Raggi, S. Chasan-Taber, J. Bommer, H. Holzer and S. K. Burke, “Determinants of Progressive Vascular Calcification in Haemodialysis Patients,” Nephrology Dialysis Transplantation, Vol. 19, No. 6, 2004, pp. 1489-1496. doi:10.1093/ndt/gfh125
[3] K. A. Lomashvili, P. Garg, S. Narisawa, J. L. Millan and W. C. O’Neill, “Upregulation of Alkaline Phosphatase and Pyrophosphate Hydrolysis: Potential Mechanism for Uremic Vascular Calcification,” Kidney International, Vol. 73, No. 9, 2008, pp. 1024-1030. doi:10.1038/ki.2008.26
[4] K. Kalantar-Zadeh, N. Kuwae, D. L. Regidor, et al., “Survival Predictability of Time-Varying Indicators of Bone Disease in Maintenance Hemodialysis Patients,” Kidney International, Vol. 70, No. 4, 2006, pp. 771-780. doi:10.1038/
[5] S. Beddhu, B. Baird, X. Ma, A. K. Cheung and T. Greene, “Serum Alkaline Phosphatase and Mortality in Hemodialysis Patients,” Clinical Nephrology, Vol. 74, No. 2, 2010, pp. 91-96.
[6] M. Schoppet and C. M. Shanahan, “Role for Alkaline Phosphatase as an Inducer of Vascular Calcification in Renal Failure?” Kidney International, Vol. 73, No. 9, 2008, pp. 989-991. doi:10.1038/ki.2008.104
[7] P. Magnusson, C. A. Sharp, M. Magnusson, J. Risteli, M. W. Davie and L. Larsson, “Effect of Chronic Renal Failure on Bone Turnover and Bone Alkaline Phosphatase Isoforms,” Kidney International, Vol. 60, No. 1, 2001, pp. 257-265. doi:10.1046/j.1523-1755.2001.00794.x
[8] S. Fletcher, R. G. Jones, H. C. Rayner, et al., “Assessment of Renal Osteodystrophy in Dialysis Patients: Use of Bone Alkaline Phosphatase, Bone Mineral Density and Parathyroid Ultrasound in Comparison with Bone Histology,” Nephron, Vol. 75, No. 4, 1997, pp. 412-419.
[9] M. Reslerova and S. M. Moe, “Vascular Calcification in Dialysis Patients: Pathogenesis and Consequences,” American Journal of Kidney Disease, Vol. 41, No. 3, pp. S96-S99. doi:10.1053/ajkd.2003.50094
[10] S. Narisawa, D. Harmey, M. C. Yadav, W. C. O’Neill, M. F. Hoylaerts and J. L. Millan, “Novel Inhibitors of Alkaline Phosphatase Suppress Vascular Smooth Muscle Cell Calcification,” Journal of Bone Mineral Research, Vol. 22, No. 11, 2007, pp. 1700-1710. doi:10.1359/jbmr.070714
[11] G. P. Fadini, P. Pauletto, A. Avogaro and M. Rattazzi, “The Good and the Bad in the Link between Insulin Resistance and Vascular Calcification,” Atherosclerosis, Vol. 193, No. 2, 2007, pp. 241-244.
[12] M. K. Sigrist, M. W. Taal, P. Bungay and C. W. McIntyre, “Progressive Vascular Calcification over 2 Years Is Associated with Arterial Stiffening and Increased Mortality in Patients with Stages 4 and 5 Chronic Kidney Disease,” Clinical Journal of American Society of Nephrology, Vol. 2, No. 6, 2007, pp. 1241-1248. doi:10.2215/CJN.02190507
[13] M. J. Blayney, R. L. Pisoni, J. L. Bragg-Gresham, et al., “High Alkaline Phosphatase Levels in Hemodialysis Patients are Associated with Higher Risk of Hospitalization and Death,” Kidney International, Vol. 74, No. 5, 2008, pp. 655-663. doi:10.1038/ki.2008.248
[14] D. L. Regidor, C. P. Kovesdy, R. Mehrotra R, et al., “Serum Alkaline Phosphatase Predicts Mortality among Maintenance Hemodialysis Patients,” Journal of American Society of Nephrology, Vol. 19, No. 11, 2008, pp. 2193-2203. doi:10.1681/ASN.2008010014
[15] A. Kerner, O. Avizohar, R. Sella, et al., “Association between Elevated Liver Enzymes and C-reactive Protein: Possible Hepatic Contribution to Systemic Inflammation in the Metabolic Syndrome,” Arteriosclerosis Thrombosis Vascular Biology, Vol. 25, No. 1, 2005, pp. 193-197.
[16] B. M. Cheung, K. L. Ong, R. V. Cheung, et al., “Association between Elevated Liver Enzymes and C-reactive Protein in Hong Kong Chinese,” Clinical Chemistry and Laboratory Medicine, Vol. 46, No. 4, 2008, pp. 523-527. doi:10.1515/CCLM.2008.111
[17] E. G. Lowrie and N. L. Lew, “Death Risk in Hemodialysis Patients: The Predictive Value of Commonly Measured Variables and an Evaluation of Death Rate Differences between Facilities,” American Journal of Kidney Disease, Vol. 15, No. 5, 1990, pp. 458-482.
[18] J. Zimmermann, S. Herrlinger, A. Pruy, T. Metzger and C. Wanner, “Inflammation Enhances Cardiovascular Risk and Mortality in Hemodialysis Patients,” Kidney Internation, Vol. 55, No. 2, 1999, pp. 648-658.
[19] J. Y. Yeun, R. A. Levine, V. Mantadilok and G. A. Kaysen, “C-Reactive Protein Predicts All Cause and Cardiovascular Mortality in Hemodialysis Patients,” American Journal Kidney Disease, Vol. 35, No. 3, 2000, pp. 469- 476. doi:10.1016/S0272-6386(00)70200-9

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