SciELO - Scientific Electronic Library Online

 
vol.81 issue2Collaborative registry of pulmonary hypertension in Argentina (RECOPILAR). Final analysisClinical characteristics and prognostic factors in an argentinian cohort with ANCA-associated vasculitis author indexsubject indexarticles search
Home Pagealphabetic serial listing  

Services on Demand

Journal

Article

Indicators

  • Have no cited articlesCited by SciELO

Related links

  • Have no similar articlesSimilars in SciELO

Share


Medicina (Buenos Aires)

Print version ISSN 0025-7680On-line version ISSN 1669-9106

Medicina (B. Aires) vol.81 no.2 Ciudad Autónoma de Buenos Aires June 2021

 

ORIGINAL ARTICLE

Biomarkers of bone and mineral disorders (FGF-23, fetuin-A) and vascular calcification scores as predictive tools for cardiovascular death in dialysis patients, at 10 years of follow-up

Biomarcadores del metabolismo mineral óseo (FGF-23, fetuína-A) y calcificaciones vasculares como herramientas predictivas de muerte cardiovascular de pacientes en diálisis, a 10 años de seguimiento

Pehuén Fernández1  2  3  * 

Walter Douthat1  2  3 

Mauro Castellano1  2 

Gabriela Cardozo1  2 

Gabriela Garay4 

Javier De Arteaga1  2 

Carlos Chiurchiu1  2 

Jorge De La Fuente1  2  3 

1 Servicio de Nefrología, Hospital Privado Universitario de Córdoba

2 Universidad Católica de Córdoba

3 Instituto Universitario de Ciencias Biomédicas de Córdoba (IUCBC)

4 Laboratorio de Química Clínica, Hospital Privado Universitario de Córdoba, Córdoba, Argentina

Abstract

Cardiovascular disorders represent the leading cause of death in dialysis patients. Alterations of bone and mineral metabolism (BMM) and vascular calcifications play a fundamental role in it. The objective of this study was to evaluate the predictive role on cardiovascular mortality of the measurement of biomarkers of BMM and vascular calcifications. A prospective cohort study was performed. All prevalent patients on chronic dialysis in September 2009 at our institution, who completed the total of the complementary stud ies, were studied. BMM biomarkers were measured (FGF 23, fetuin A, PTH, calcium and phosphorus) and the vascular calcifications were evaluated using the Kauppila and Adragao scores. Follow-up was carried out until 1/1/2019, death or transplant. Of the 30 patients included, 7 (23.3%) died due to cardiovascular causes. The follow-up time was 44.1 ± 30.4 (range = 1.4-112) months. The Adragao score was the only predictive variable of long-term cardiovascular mortality (area under the curve = 0.82; 95% CI 0.64-0.94; p < 0.001). The best cut-off point was 5 (sensitivity = 85.7%; specificity = 78.3%). It was also an independent risk factor for cardiovascular mortality adjusted for age, diabetes mellitus, coronary heart disease, aortic calcifications, time spent on dialysis and follow-up time (adjusted OR = 1.77; 95% CI = 1.06-2.96; p = 0.028). The vascular calcifications quantified from the Adragao score were the only independent predictor of long-term cardiovascular mortality. This score represents a simple, useful and superior tool to the biomarkers of BMM.

Key words: Chronic renal failure; Bone and mineral metabolism; Mortality; Vascular calcifications; FGF 23; Fetuin A

Resumen

Los trastornos cardiovasculares representan la primera causa de muerte en los pacientes en diálisis. Las alteraciones del metabolismo óseo y mineral (MOM) y las calcificaciones vasculares juegan un papel fundamental en la misma. El objetivo de este estudio fue evaluar el rol predictor sobre la mortalidad car diovascular de la medición de los biomarcadores del MOM y las calcificaciones vasculares. Se realizó un estudio de cohorte prospectivo. Se estudiaron todos los pacientes prevalentes en diálisis crónica en septiembre del 2009 en nuestra institución que completaron el total de los estudios complementarios. Se midieron biomarcadores del MOM (FGF 23, fetuína A, PTH, calcio y fósforo) y se evaluaron las calcificaciones vasculares mediante los scores de Kauppila y de Adragao. Se realizó un seguimiento hasta el 1/1/2019, la muerte o el trasplante. De los 30 pacientes incluidos, 7 (23.3%) fallecieron por causa cardiovascular. El tiempo de seguimiento fue de 44.1 ± 30.4 (rango = 1.4-112) meses. El score de Adragao fue la única variable predictiva de muerte cardiovascular a largo plazo (área bajo la curva = 0.82; IC95% = 0.64-0.94; p<0.001). El mejor punto de corte fue de 5 (sensibili dad = 85.7%; especificidad = 78.3%). Además, fue un factor de riesgo independiente de muerte cardiovascular ajustado por edad, diabetes mellitus, enfermedad coronaria, calcificaciones aorticas, tiempo de permanencia en diálisis y tiempo de seguimiento (OR ajustado = 1.77; IC95% = 1.06-2.96; p = 0.028). Las calcificaciones vasculares cuantificadas a partir del score de Adragao fueron el único predictor independiente de mortalidad cardiovascular a largo plazo. Este score representa una herramienta simple, útil y superior a los biomarcadores del MOM.

Palabras clave: Insuficiencia renal crónica; Metabolismo óseo y mineral; Mortalidad; Calcificaciones vasculares; FGF 23; Fetuína A

KEY POINTS

Current knowledge

• Cardiovascular disorders represent the leading cause of death in dialysis patients.

• Alteration of FGF 23, fetuin A, PTH, calcium, phosphorus and vascular calcifications play a fundamental role in cardiovascular mortality in these patients.

Contribution of the article to current knowledge

• The vascular calcifications quantified by the Adragao score were the only independent predictor of cardiovas cular mortality at 10 years of follow-up in end-stage renal disease patients.

• This score represents a simple, useful and superior tool to the biomarkers of bone and mineral metabolism.

The first cause of death in patients with chronic kidney disease (CKD) is cardiovascular events1,2. The risk of their appearance increases progressively according to the stage of CKD, reaching up to 20 times higher than the general population3. Data from the Argentine Registry of Dialysis and Transplants reflects something similar, showing that the cardiovascular and cerebrovascular causes represent 46.8% of the total deaths on chronic dialysis in Argentina4.

Both bone and mineral metabolism (BMM) alterations, and vascular calcifications (VCs) have an important role in long-term mortality in subjects with CKD5-10.

The VCs detected by simple radiographs of the hands and pelvis have a good correlation with coronary calcifications and vascular territories in dialysis patients. They are also good predictors of hospitalization-free survival, cardiovascular mortality and long-term global mortality11. In patients with CKD vascular calcifications occur decades earlier than in the general population and their progression accelerates at the beginning of dialysis treatment12,13.

Recent studies found that BMM biomarkers, such as fibroblast growth factor 23 (FGF 23) and fetuin A, can also be predictors of mortality in patients at different stages of CKD14-16. In these studies, elevated levels of FGF 23 were associated with mortality, regardless of serum phosphorus values and other known risk factors14. Likewise, high levels of fetuin A were significantly associated with lower valve and coronary calcifications and reduced mortality from any cause17. However, these biomarkers are not yet available for use in clinical practice in our setting and are used only in the field of research.

It is very useful, for a correct diagnosis and manage ment of these patients, to analyze the risk factors associ ated with death and cardiovascular events and to know the usefulness of the new BMM biomarkers and the effect of the presence of vascular calcifications to predict events that affect long-term morbidity and mortality.

The objective of this study was to analyze the role of biomarkers of BMM and VCs as predictors of long-term cardiovascular cause mortality, and find the best cut-off point for these biomarkers, in patients with end stage CKD.

Material and methods

A prospective, observational and analytical cohort study was performed.

The inclusion criteria were: patients with end stage CKD in renal replacement therapy for at least three months of perma nence prior to inclusion in the study, in the hemodialysis (HD) or peritoneal dialysis (PD) modality, prevalent in September 2009, at the Hospital Privado Universitario de Córdoba.

Subjects under 18 years of age, pregnant women, patients requiring renal replacement therapy for less than three months of stay, or for acute renal failure, or for delayed graft function (in the case of kidney transplants) were excluded. In addition, the patients who were hospitalized at the time of the study, those who refused to participate in it and those who did not complete the total of the required complementary studies were excluded. Among the subjects that met the selection criteria, they were invited to participate voluntarily in the study, after signing the informed consent.

Baseline clinical variables were relieved: age (years), sex, body mass index (kg/m2), modality and time of renal replace ment therapy (months), history of arterial hypertension, diabe tes mellitus, coronary heart disease, stroke, disease peripheral vascular, etiology of chronic kidney disease and presence of hemodialysis catheter. Biochemical determinations were performed in peripheral blood: hemoglobin (g/dl), albumin (g/ dl), calcium (mg/dl), phosphorus (mg/dl), PTH (pg/ml), FGF 23 (pg/ml) and fetuin A (g/l). And different radiographic sets were evaluated to assess the degree of vascular calcifications (Adragao and Kauppila scores).

Each subject was followed up until the kidney transplant, dialysis center change (loss of follow-up), death, until the cut of the study on 1/1/2019 or whichever came first.

Adragao score18: It was determined from a simple radio graphic set of hands and pelvis, measuring the absence or presence of VCs. Both radiographs were divided into 4 quad rants, giving each quadrant 1 point when the presence of VCs is detected. This score analyzes the presence of VCs of iliac, femoral, radial and digital arteries and the final value ranges between 0 and 8 points (0-4 image of both hands; 0-4 image of hips; where 0 means absence of VCs and 8 presence in all quadrants).

Kauppila score19: was determined from a lateral abdominal x-ray that includes from T10 to the first two sacral vertebrae. The aorta is identified as a tubular structure in front of the spine, only the segments of the aorta that are in front of the first four lumbar vertebrae (L1-L4) are analyzed. The score allows to divide into mild calcification (corresponds to 1/3 of the length of the vertebral body), moderate (corresponds to 2/3 of the length of the vertebral body) and severe (more than 2/3 of the vertebral body), according with the length of each calcified plaque detected. The anterior and posterior wall of the aorta is taken into account and a score ranging from 0-24 points is obtained, where 0 means absence of VCs and 24 the presence of these in both walls of the aorta and in the entire length it covers the height of the named vertebrae. All images were evaluated by the same operator.

FGF 23: ALPCO ELISA (enzyme immunosorbent assay) was used, which measures the intact FGF 23 molecule. The assay is a “sandwich” technique that uses two polyclonal anti-bodies directed towards epitopes of the amino and carboxylends of the FGF23 molecule. Plasma with EDTA is used for the measurement, and samples in freezer were preserved at -70 degrees until measurement.

Ultrasensitive fetuin-A: Ultrasensitive ELISA of ALPCO was used. The assay is a “sandwich” technique that uses two polyclonal antibodies that bind different epitopes of human fetuin-A, for the measurement of fetuin-A serum was used without special preparation of the patient and like the mea surement of FGF 23 the samples were preserved in serum at -70 degrees until the time of measurement.

Calcium and phosphorus levels were measured with an autoanalyzer (Hitachi 917; Hitachi, Ltd., Tokyo, Japan) and those of intact PTH with electrochemiluminescence (Nichol`s Institute, San Juan Capistrano, Calif., USA).

To analyze the categorical variables, absolute (n) and relative (%) frequencies were used, and for continuous vari ables, mean (X) and standard deviation (SD), or median (M) and interquartile range (IQR), as appropriate. To compare the categorical variables, the X2 test or Fisher’s exact test was used, as appropriate.

As predictors of mortality, the values of calcium, phos phorus, PTH, FGF 23, Fetuin-A, Kauppila score and Adragao score were evaluated. The area under the curve (AUC) of the ROC (receiver operating characteristic) curve analysis and its 95% confidence interval (95% CI) was used. The calculation of the AUC was performed using the method of Hanley and Mac Neil. ROC curves were plotted. Of the predictive variables with statistical significance, the best cut-off point was established using the Youden Index J criterion20. In turn, sensitivity, speci ficity, positive likelihood ratio, negative likelihood ratio, positive predictive value and negative predictive value were evaluated. The risk of cardiovascular mortality from the best cut-off point was quantified using the relative risk (RR) with its 95% CI.

The association between all the variables included in the database and the best predictive tool for cardiovascular mortality were analyzed. To evaluate the association between continuous variables, Pearson’s correlation (r) was used and for the dichoto mous variables the odd ratio (OR) with its 95% CI. Both the best predictive tool for cardiovascular mortality, and its associated variables, were included in the multivariate logistic regression analysis. To this analysis the variables were added: months of permanence in dialysis at the beginning of the study and months of follow-up at the end of the study, at the discretion of the researcher, regardless of the previous association analysis.

All tests were two-tailed and a value of p less than 0.05 was considered statistically significant.

Statistical analysis was performed with the Stata 14 program (StataCorp. LP. College Station, TX) and Medcalc 15.11.4 (MedCalc Software, Ostend, Belgium).

The study was approved by the Research Committee of the Private University Hospital of Córdoba (number 2018_53).

Results

Of the 82 patients undergoing renal replacement therapy at our institution in September 2009, six met some exclu sion criteria (One had started renal replacement therapy less than 3 months before, two with acute renal failure, one with delayed function of the graft, one under 18 years old and one hospitalized patient). Of the 76 that met the eligibility criteria, 30 subjects complied with all necessary complementary studies. All of them agreed to participate in the study (Fig. 1). Baseline characteristics, pathological personal history, specific dialysis characteristics, blood tests in general and specific bone mineral metabolism, and calcification scores of the subjects are summarized in Table 1.

Fig. 1 Flow chart of the inclusion of the subjects in the study 

Table 1 Baseline demographic and laboratory data of the population studied 

At the end of the follow-up, of the 30 patients, 11 (36.7%) had received a kidney transplant, 2 (6.7%) continued on chronic dialysis, 17 (56.7%) had died, and of these 7 (41.2%) were due to cardiovascular causes. The average follow-up time was 44.1 ± 30.4 months (range = 1.4-112 months).

In the ROC analysis, although calcium (AUC = 0.69; p = 0.082), phosphorus (AUC = 0.61; p = 0.465), PTH (AUC = 0.65; p = 0.175), FGF 23 (AUC = 0.68; p = 0.175), Fetuin-A (AUC = 0.61; p = 0.433) and the Kauppila score (AUC = 0.61; p = 0.461) had high AUC values, the same they did not reach statistical significance to predict long-term cardiovascular death. The only predic tive variable in the ROC analysis for cardiovascular death was the Adragao score (AUC = 0.82; 95% CI = 0.64-0.94; p < 0.001) (Table 2). Figure 2 shows the ROC curves of the different variables in predicting cardiovascular mortality.

Table 2 Ability to predict cardiovascular mortality of the different methods according to the area under the ROC curve 

Fig. 2 ROC curves to predict cardiovascular mortality of: A: Calcium. B: Phosphorus. C: FGF 23. D: Fetuin A. E: PTH. F: Kauppila score. G: Adragao score. 

According to the Youden Index J analysis, the best cut-off point for the Adragao score to predict cardiovascular mortality was 5 points or more, with a sensitivity of 85.7%, specificity of 78.3%, positive likelihood ratio of 3.94, nega tive likelihood ratio of 0.18, a positive predictive value of 54.5% and a negative predictive value of 94.7%.

The incidence of cardiovascular death in the group of patients with an Adragao score below 5 points was 5.3% (1/19) and in the group with a score of 5 points or more, it was 54.6% (6/11), there being a significant differ ence between both groups (p = 0.002). Subjects with an Adragao score of 5 points or more have a 10-fold higher risk of cardiovascular mortality than those with a score lower than 5 (RR = 10.36; 95% CI = 1.4-75.2; p = 0.002).

Of all the variables included in our database, the only ones associated with an increase in the Adragao score were: age (r = 0.43; p = 0.018), Kauppila score (r = 0.39; p = 0.034), the history of diabetes mellitus (OR = 10.2; p = 0.008) and coronary heart disease (OR = 7.1; p = 0.029). In multivariate analysis, Adragao score was a predictive tool for cardiovascular death regardless of the variables mentioned above, and also adjusted for the time spent on dialysis at the beginning of inclusion in the study and follow-up time during the study (Adjusted OR = 1.77; 95% CI = 1.06-2.96; p = 0.028) (Table 3).

Table 3 Association between the Adragao score and cardiovascular mortality, adjusted for the possible confusing variables. Multivariate logistic regression analysis 

Discussion

Cardiovascular disease is the leading cause of death in patients with CKD on dialysis1-4 and alterations in BMM and VCs play an important role in its development.

Over time, new molecules involved in MOM and in the physio pathogenesis of VCs such as FGF 23 and Fetuin A have been discovered. According to recent studies, both high FGF 23 values and decreased Fetuin A values increase the risk of cardiovascular events21-23 and death14-16 in patients with CKD. Currently, serum determination of these markers is expensive and there is little availability for use in clinical practice. In our study, neither of the two determinations was useful to predict cardiovascular mor tality over time in patients with terminal CKD in different dialysis modalities.

In Argentina, there is a high prevalence of VCs in sub jects with CKD on dialysis detected by plain radiography24. A recent meta-analysis shows that the Kauppila score is a significant predictor of all-cause mortality and cardio vascular events in dialysis patients25. However, this score does not appear to be higher than the Adragao score to predict mortality26, as our study also shows. Adragao et al.18 showed that patients with CKD in hemodialysis who have an Agragao score greater than 3 have almost four times greater risk of cardiovascular mortality than those with a lower score. This paper also evaluates the role of the phospho-calcium product and PTH in cardiovascular mortality, but not of FGF 23 and fetuin A, since at the time of that study, these molecules were still poorly understood. In our trial, the cut-off point of the Adragao score with the best predictive capacity for cardiovascular death was somewhat higher than 3 points (5 points or more), with a risk of cardiovascular death increased 10 times in these patients. This tool was superior in predictive capacity not only of the traditional MOM analytical determinations such as calcium, phosphorus and PTH, but also of the new biomarkers such as FGF 23 and Fetuin A, and that the Kauppila score.

It is important to keep in mind that while BMM biomark ers reflect the risk to which an individual is exposed at the time of measurement27, VCs images quantified from the scores represent the cumulative result of prolonged exposure to multiple factors of risk over time28.

The increase in the Adragao score was associated with traditional clinical variables such as age, history of diabetes mellitus and coronary heart disease, and also calcifications in other territories such as the aorta (Kaup pila score). Like the time spent on dialysis at the beginning of each patient’s study and the follow-up time at the end of the study, these variables mentioned above could also be risk factors for cardiovascular death and therefore could function as confounding factors for predictive ability of the Adragao score on cardiovascular death. To avoid this bias and evaluate the true role of the score, the adjusted multivariate analysis was performed taking into account all these variables and thus demonstrating their true utility.

Both the recommendations of the Spanish Society of Nephrology in 201129, the Argentine Society of Nephrology in 201730, the KDIGO guides in 201731, and other authors28,32 consider reasonable the use of VCs information to guide the management of BMM alterations.

The main strengths of our study are the evaluation of new biochemical markers of BMM such as FGF 23 and fetuin A, as there are few publications evaluating these measurements in dialysis patients as predictors of cardiovascular mortality, and prospective follow-up with prediction of long-term hard events.

In conclusion, vascular calcifications quantified from the Adragao score were the only independent predictor of long-term cardiovascular mortality. The best cut-off point for the Adragao score was 5, with a high predictive value. This score represents a simple, low cost, useful, accurate and superior tool to the new BMM biomarkers.

Acknowledgments:

To the Fundación Nefrológica de Córdoba and Instituto Universitario de Ciencias Biomédicas de Córdoba (IUCBC) for the support to cover publication costs.

References

1. Tonelli M, Wiebe N, Culleton B, et al. Chronic kidney dis ease and mortality risk: a systematic review. J Am Soc Nephrol 2006; 17: 2034-47. [ Links ]

2. Collins AJ, Foley RN, Herzog C, et al. Excerpts from the US Renal Data System 2009 Annual Data Report. Am J Kidney Dis 2010; 55: S1-420. [ Links ]

3. Foley RN, Parfrey PS, Sarnak MJ. Clinical epidemiology of cardiovascular disease in chronic renal failure. Am J Kidney Dis 1998; 32: 112-9. [ Links ]

4. Marinovich S, Bisigniano L, Hansen Krogh D, et al. Regi stro Argentino de Diálisis Crónica. SAN - INCUCAI 2018. Sociedad Argentina de Nefrología e Instituto Nacional Central Único Coordinador de Ablación e Implante. Bue nos Aires, Argentina; 2019. In: In: http://san.org.ar/2015/docs/registros/2019/2018_VERSION_COMPLETA.pdf ); accessed June 2020. [ Links ]

5. Young EW, Albert JM, Satayathum S, et al. Predictors and consequences of altered mineral metabolism: the dialysis outcomes and practice patterns study. Kidney Int 2005; 67: 1179-87. [ Links ]

6. Slinin Y, Foley RN, Collins AJ. Calcium, phosphorus, parathyroid hormone, and cardiovascular disease in hemodialysis patients: the USRDS waves 1, 3, and 4 study. J Am Soc Nephrol 2005; 16: 1788-93. [ Links ]

7. Tentori F, Blayney MJ, Albert JM, Gillespie BW, Kerr PG, Bommer J. Mortality risk for dialysis patients with differ ent levels of serum calcium, phosphorus, and PTH: the Dialysis Outcomes and Practice Patterns Study (DOPPS). Am J Kidney Dis 2008; 52: 519-30. [ Links ]

8. Blacher J, Guerin AP, Pannier B, Marchais SJ, London GM. Arterial calcifications, arterial stiffness, and cardiovascular risk in end-stage renal disease. Hypertension 2001; 38: 938-42. [ Links ]

9. London GM, Guérin AP, Marchais SJ, Métivier F, Pannier B, Adda H. Arterial media calcification in end-stage renal disease: impact on all-cause and cardiovascular mortality. Nephrol Dial Transplant 2003; 18: 1731-40. [ Links ]

10. Bruzzone ME, Giammona AM, Touceda L, et al. Calcifica ciones valvulares y vasculares en hemodiálisis crónica. Nephrol Dial Transplant 2014; 34: 183-90. [ Links ]

11. Moe SM, O Neill KD, Reslerova M, Fineberg N, Persohn S, Meyer CA. Natural history of vascular calcification in dialysis and transplant patient. Nephrol Dial Transplant 2004; 19: 2387-93. [ Links ]

12. Goodman WG, Goldin J, Kuizon BD, Yoon C, Gales B, Sider D. Coronary-artery calcification in young adults with end-stage renal disease who are undergoing dialysis. N Engl J Med 2000; 342: 1478-83. [ Links ]

13. Jablonski K, Chonchol M. Vascular calcification in end stage renal disease. Hemodial Int 2013; 17: S17-21. [ Links ]

14. Gutiérrez OM, Mannstadt M, Isakova T, et al. Fibroblast growth factor 23 and mortality among patients undergoing hemodialysis. N Engl J Med 2008; 359: 584-92. [ Links ]

15. Ketteler M, Bongartz P, Westenfeld R, et al. Association of low fetuin- A (AHSG) concentration in serum with cardiovascular mortality in patients on dialysis: a cross-sectional study. The Lancet 2003; 361: 827-33. [ Links ]

16. Hermans M, Brandenburg V, Ketteler M, et al. Association of serum fetuin-A levels with mortality in dialysis patient. Kidney Int 2007; 72: 202-7. [ Links ]

17. Wang AY, Woo J, Lam CW, et al. Associations of serum fetuin-A with malnutrition, inflammation, atherosclerosis and valvular calcification syndrome and outcome in peri toneal dialysis patient. Nephrol Dial Transplant 2005; 20: 1676-85. [ Links ]

18. Adragao T, Pires A, Lucas C, et al. A simple vascular calci fication score predicts cardiovascular risk in haemodialisis patients. Nephrol Dial Transplant 2004; 19: 1480-8. [ Links ]

19. Kauppila LI, Polak JF, Cupples LA, Hannan MT, Kiel DP, Wilson PW. New indices to classify location, severity and progression of calcific lesions in the abdominal aorta: a 25- year follow-up study. Atherosclerosis 1997; 132: 245-50. [ Links ]

20. Youden WJ. Index for rating diagnostic tests. Cancer 1950; 3: 32-5. [ Links ]

21. Scialla JJ, Xie H, Rahman M, et al. Fibroblast growth factor-23 and cardiovascular events in CKD. J Am Soc Nephrol 2014; 25: 349-60. [ Links ]

22. Mehta R, Cai X, Lee J, et al. Association of fibroblast growth factor 23 with atrial fibrillation in chronic kidney disease, from the chronic renal insufficiency cohort study. JAMA Cardiol 2016; 1: 548-56. [ Links ]

23. Chen HY1, Chiu YL, Hsu SP, Pai MF, Yang JY, Peng YS. Fetuin A/nutritional status predicts cardiovascular outcomes and survival in hemodialysis patients. Am J Nephrol 2014; 40: 233-41. [ Links ]

24. Rosa-Diez G., Bratti G, Filannino G, et al. Prevalencia de factores asociados a calcificaciones vasculares en paci entes con enfermedad renal crónica en diálisis. Medicina (B Aires) 2017; 77: 207-13. [ Links ]

25. Niu Q, Hong Y, Lee CH, Men C, Zhao H, Zuo L. Abdominal aortic calcification can predict all-cause mortality and CV events in dialysis patients: A systematic review and meta-analysis. PLoS one 2018; 13: e0204526. [ Links ]

26. Hong D, Wu S, Pu L, et al. Abdominal aortic calcification is not superior over other vascular calcification in predict ing mortality in haemodialysis patients a retrospective observational study. BMC nephrol 2013; 14: 120-9. [ Links ]

27. Mazzaferro S, Tartaglione L, Rotondi S, Bover J, Goldsmith D, Pasquali M. News on biomarkers in CKD-MBD. Semin Nephrol 2014; 34: 598-611. [ Links ]

28. Bellasi A, Raggi P. Vascular imaging in chronic kidney disease. Curr Opin Nephrol Hypertens 2012; 21: 382-8. [ Links ]

29. Torregrosa JV, Bover J, Cannata Andía J, et al. Recomen daciones de la Sociedad Española de Nefrología para el manejo de las alteraciones del metabolismo óseo-mineral en los pacientes con enfermedad renal crónica (SEN-MM). Nefrologia 2011; 31: 3-32. [ Links ]

30. Sociedad Argentina de Nefrología. Segundo consenso de metabolismo óseo-mineral 2017. 1ra ed. Buenos Aires: Journal, 2018, p 26. In: In: http://san.org.ar/2015/docs/con sensos/B94_Consenso_SAN2.pdf ); accessed June 2020. [ Links ]

31. Kidney disease: improving global outcomes (KDIGO) CKD-MBD update work group. KDIGO 2017 clinical practice guideline update for the diagnosis, evaluation, preven tion, and treatment of chronic kidney disease-mineral and bone disorder (CKD-MBD). Kidney Int suppl 2017; 7: 1-59. [ Links ]

32. Bover J, Górriz JL, Ureña-Torres P, et al. Detección de las calcificaciones cardiovasculares: ¿una herramienta útil para el nefrólogo?. Nefrología 2016; 36: 587-96. [ Links ]

Received: July 13, 2020; Accepted: October 05, 2020

*Postal address: Pehuén Fernández, Hospital Privado Universitario de Córdoba, Naciones Unidas 346, Barrio Parque Vélez Sarsfield, 5016 Córdoba, Argentina e-mail: pehuenfernandez@hotmail.com

Creative Commons License This is an open-access article distributed under the terms of the Creative Commons Attribution License