Low serum calcium is associated with poor renal outcomes in chronic kidney disease stages 3–4 patients

BMC Nephrology

Hung-Chun Chen²  Chi-Chih Hung³  Jer-Chia Tsai²  Shang-Jyh Hwang²  Jia-Jung Lee³  Yi-Wen Chiu²  Mei-Chuan Kuo³  Hung-Tien Kuo²  Lee-Moay Lim¹ 

[1]Department of Internal Medicine, Pingtung Hospital, Ministry of Health and Welfare, No. 270 Zihyou Road, Pingtung City, Pingtung County, Taiwan

[2]Faculty of Renal Care, College of Medicine, Kaohsiung Medical University, No. 100, Shih-Chuan 1st Road, Kaohsiung 807, Taiwan

[3]Division of Nephrology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, No. 100, Tzyou 1st Road, Kaohsiung 807, Taiwan

关键词: Renal replacement therapy;    Chronic kidney disease;    Calcium;   

Others  :  1082564
DOI  :  10.1186/1471-2369-15-183

 received in 2014-06-25, accepted in 2014-10-28,  发布年份 2014

【 摘 要 】

Background

Mineral disorders are associated with adverse renal outcomes in chronic kidney disease (CKD) patients. Previous studies have associated hypercalcemia and hypocalcemia with mortality; however, the association between serum calcium and renal outcome is not well-described. Whether adding calcium besides phosphorus or in the form of calcium-phosphorus (Ca × P) product into the model of survival analysis could improve the prediction of renal outcomes is not known.

Methods

A prospective cohort of 2144 outpatients with CKD stages 3–4 was evaluated. Cox proportional hazard analysis was performed according to calcium quartiles.

Results

The mean calcium level was 9.2 ± 0.7 mg/dL. Low serum calcium (<9.0 mg/dL) was associated with increased risk of requiring renal replacement therapy (RRT) (hazards ratio [HR]:2.12 (95% CI: 1.49–3.02, P <0.05) and rapid renal function progression (odds ratio [OR]: 1.65 (95% CI: 1.19–2.27, P <0.05) compared with high serum calcium (>9.8 mg/dL). Adding calcium into the survival model increased the integrated discrimination improvement by 0.80% (0.12% – 1.91%) while calcium-phosphorus product did not improve risk prediction.

The combination of high serum phosphorus (>4.2 mg/dL) and low serum calcium (<9.1 mg/dL) was associated with the highest risk of RRT (HR:2.31 (95% CI: 1.45–3.67, P < 0.05).

Conclusion

Low serum calcium is associated with increased risk of RRT and rapid renal function progression in CKD stage 3–4 patients. The integration of serum calcium and phosphorus, but not calcium-phosphorus product should be considered in a predictive model of renal outcome.

【 授权许可】

   
2014 Lim et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

【 参考文献 】

• [1]Kovesdy CP, Kalantar-Zadeh K: Bone and mineral disorders in pre-dialysis CKD. Int Urol Nephrol 2008, 40(2):427-440.
• [2]Schwarz S, Trivedi BK, Kalantar-Zadeh K, Kovesdy CP: Association of disorders in mineral metabolism with progression of chronic kidney disease. Clin J Am Soc Nephrol 2006, 1(4):825-831.
• [3]Menon V, Greene T, Pereira AA, Wang X, Beck GJ, Kusek JW, Collins AJ, Levey AS, Sarnak MJ: Relationship of phosphorus and calcium-phosphorus product with mortality in CKD. Am J Kidney Dis 2005, 46(3):455-463.
• [4]Bellasi A, Mandreoli M, Baldrati L, Corradini M, Di Nicolo P, Malmusi G, Santoro A: Chronic kidney disease progression and outcome according to serum phosphorus in mild-to-moderate kidney dysfunction. Clin J Am Soc Nephrol 2011, 6(4):883-891.
• [5]Voormolen N, Noordzij M, Grootendorst DC, Beetz I, Sijpkens YW, van Manen JG, Boeschoten EW, Huisman RM, Krediet RT, Dekker FW: High plasma phosphate as a risk factor for decline in renal function and mortality in pre-dialysis patients. Nephrol Dial Transplant 2007, 22(10):2909-2916.
• [6]Norris KC, Greene T, Kopple J, Lea J, Lewis J, Lipkowitz M, Miller P, Richardson A, Rostand S, Wang X, Appel LJ: Baseline predictors of renal disease progression in the African American Study of Hypertension and Kidney Disease. J Am Soc Nephrol 2006, 17(10):2928-2936.
• [7]Ravani P, Malberti F, Tripepi G, Pecchini P, Cutrupi S, Pizzini P, Mallamaci F, Zoccali C: Vitamin D levels and patient outcome in chronic kidney disease. Kidney Int 2009, 75(1):88-95.
• [8]Kendrick J, Cheung AK, Kaufman JS, Greene T, Roberts WL, Smits G, Chonchol M: Associations of plasma 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D concentrations with death and progression to maintenance dialysis in patients with advanced kidney disease. Am J Kidney Dis 2012, 60(4):567-575.
• [9]Ferro CJ, Chue CD, Steeds RP, Townend JN: Is lowering phosphate exposure the key to preventing arterial stiffening with age? Heart 2009, 95(21):1770-1772.
• [10]Moe SM, Chen NX: Pathophysiology of vascular calcification in chronic kidney disease. Circ Res 2004, 95(6):560-567.
• [11]Young EW, Humes HD: Calcium and acute renal failure. Miner Electrolyte Metab 1991, 17(2):106-111.
• [12]Moyses-Neto M, Guimaraes FM, Ayoub FH, Vieira-Neto OM, Costa JA, Dantas M: Acute renal failure and hypercalcemia. Ren Fail 2006, 28(2):153-159.
• [13]Hurley K, Baggs D: Hypocalcemic cardiac failure in the emergency department. J Emerg Med 2005, 28(2):155-159.
• [14]Kazmi AS, Wall BM: Reversible congestive heart failure related to profound hypocalcemia secondary to hypoparathyroidism. Am J Med Sci 2007, 333(4):226-229.
• [15]National Kidney Foundation: K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Am J Kidney Dis 2002, 39(2 Suppl 1):S1-S266.
• [16]Payne RB, Little AJ, Williams RB, Milner JR: Interpretation of serum calcium in patients with abnormal serum proteins. Br Med J 1973, 4(5893):643-646.
• [17]Devereux RB: Detection of left ventricular hypertrophy by M-mode echocardiography: anatomic validation, standardization, and comparison to other methods. Hypertension 1987, 9(2 Pt 2):II19-II26.
• [18]Pencina MJ, D’Agostino RB Sr, D’Agostino RB Jr, Vasan RS: Evaluating the added predictive ability of a new marker: from area under the ROC curve to reclassification and beyond. Stat Med 2008, 27(2):157-172. discussion 207–112
• [19]Eddington H, Kalra PA: The association of chronic kidney disease-mineral bone disorder and cardiovascular risk. J Ren Care 2010, 36(Suppl 1):61-67.
• [20]Fliser D, Kollerits B, Neyer U, Ankerst DP, Lhotta K, Lingenhel A, Ritz E, Kronenberg F, Kuen E, Konig P, Kraatz G, Mann JF, Muller GA, Kohler H, Riegler P: Fibroblast growth factor 23 (FGF23) predicts progression of chronic kidney disease: the Mild to Moderate Kidney Disease (MMKD) Study. J Am Soc Nephrol 2007, 18(9):2600-2608.
• [21]Lundberg S, Qureshi AR, Olivecrona S, Gunnarsson I, Jacobson SH, Larsson TE: FGF23, albuminuria, and disease progression in patients with chronic IgA nephropathy. Clin J Am Soc Nephrol 2012, 7(5):727-734.
• [22]Titan SM, Zatz R, Graciolli FG, dos Reis LM, Barros RT, Jorgetti V, Moyses RM: FGF-23 as a predictor of renal outcome in diabetic nephropathy. Clin J Am Soc Nephrol 2011, 6(2):241-247.
• [23]Isakova T, Xie H, Yang W, Xie D, Anderson AH, Scialla J, Wahl P, Gutierrez OM, Steigerwalt S, He J, Schwartz S, Lo J, Ojo A, Sondheimer J, Hsu CY, Lash J, Leonard M, Kusek JW, Feldman HI, Wolf M: Fibroblast growth factor 23 and risks of mortality and end-stage renal disease in patients with chronic kidney disease. JAMA 2011, 305(23):2432-2439.
• [24]Nakano C, Hamano T, Fujii N, Matsui I, Tomida K, Mikami S, Inoue K, Obi Y, Okada N, Tsubakihara Y, Isaka Y, Rakugi H: Combined use of vitamin D status and FGF23 for risk stratification of renal outcome. Clin J Am Soc Nephrol 2012, 7(5):810-819.
• [25]Mehrotra R, Kermah D, Budoff M, Salusky IB, Mao SS, Gao YL, Takasu J, Adler S, Norris K: Hypovitaminosis D in chronic kidney disease. Clin J Am Soc Nephrol 2008, 3(4):1144-1151.
• [26]Melamed ML, Astor B, Michos ED, Hostetter TH, Powe NR, Muntner P: 25-hydroxyvitamin D levels, race, and the progression of kidney disease. J Am Soc Nephrol 2009, 20(12):2631-2639.
• [27]de Boer IH, Katz R, Chonchol M, Ix JH, Sarnak MJ, Shlipak MG, Siscovick DS, Kestenbaum B: Serum 25-hydroxyvitamin D and change in estimated glomerular filtration rate. Clin J Am Soc Nephrol 2011, 6(9):2141-2149.
• [28]Levin A, Bakris GL, Molitch M, Smulders M, Tian J, Williams LA, Andress DL: Prevalence of abnormal serum vitamin D, PTH, calcium, and phosphorus in patients with chronic kidney disease: results of the study to evaluate early kidney disease. Kidney Int 2007, 71(1):31-38.
• [29]Block GA, Klassen PS, Lazarus JM, Ofsthun N, Lowrie EG, Chertow GM: Mineral metabolism, mortality, and morbidity in maintenance hemodialysis. J Am Soc Nephrol 2004, 15(8):2208-2218.
• [30]Kalantar-Zadeh K, Kuwae N, Regidor DL, Kovesdy CP, Kilpatrick RD, Shinaberger CS, McAllister CJ, Budoff MJ, Salusky IB, Kopple JD: Survival predictability of time-varying indicators of bone disease in maintenance hemodialysis patients. Kidney Int 2006, 70(4):771-780.
• [31]Kovesdy CP, Ahmadzadeh S, Anderson JE, Kalantar-Zadeh K: Secondary hyperparathyroidism is associated with higher mortality in men with moderate to severe chronic kidney disease. Kidney Int 2008, 73(11):1296-1302.
• [32]Shigematsu T, Caverzasio J, Bonjour JP: Parathyroid removal prevents the progression of chronic renal failure induced by high protein diet. Kidney Int 1993, 44(1):173-181.
• [33]Schumock GT, Andress DL, Marx SE, Sterz R, Joyce AT, Kalantar-Zadeh K: Association of secondary hyperparathyroidism with CKD progression, health care costs and survival in diabetic predialysis CKD patients. Nephron Clin Pract 2009, 113(1):c54-c61.
• [34]Gromadzinski L, Januszko-Giergielewicz B, Pruszczyk P: Hypocalcemia is related to left ventricular diastolic dysfunction in patients with chronic kidney disease. J Cardiol 2014, 63(3):198-204.
• [35]Bers DM: Cardiac excitation-contraction coupling. Nature 2002, 415(6868):198-205.
• [36]Tentori F, Blayney MJ, Albert JM, Gillespie BW, Kerr PG, Bommer J, Young EW, Akizawa T, Akiba T, Pisoni RL, Robinson BM, Port FK: Mortality risk for dialysis patients with different levels of serum calcium, phosphorus, and PTH: the Dialysis Outcomes and Practice Patterns Study (DOPPS). Am J Kidney Dis 2008, 52(3):519-530.
• [37]Kovesdy CP, Kuchmak O, Lu JL, Kalantar-Zadeh K: Outcomes associated with serum calcium level in men with non-dialysis-dependent chronic kidney disease. Clin J Am Soc Nephrol 2010, 5(3):468-476.
• [38]Block RA, Zakay D, Hancock PA: Human aging and duration judgments: a meta-analytic review. Psychol Aging 1998, 13(4):584-596.
• [39]Ganesh SK, Stack AG, Levin NW, Hulbert-Shearon T, Port FK: Association of elevated serum PO(4), Ca x PO(4) product, and parathyroid hormone with cardiac mortality risk in chronic hemodialysis patients. J Am Soc Nephrol 2001, 12(10):2131-2138.
• [40]O’Neill WC: The fallacy of the calcium-phosphorus product. Kidney Int 2007, 72(7):792-796.