Survival of hemodialysis patients at a university hospital

Introdução: A doença renal crônica (DRC) apresenta altas taxas de morbidade e mortalidade, especialmente na população em diálise. Objetivo: Determinar a taxa de sobrevida; caracterizar o perfil epidemiológico e clínico; identificar as comorbidades e as variáveis associadas à sobrevida dos pacientes submetidos à hemodiálise. Métodos: Trata-se de um estudo de natureza descritiva e longitudinal constituído por 162 pacientes submetidos à hemodiálise, em um hospital universitário. As variáveis categóricas foram descritas por meio de frequências e porcentagem e as numéricas por meio de média ± desvio padrão. A análise por meio da regressão de Cox foi utilizada para estudar a influência de diversas variáveis clínicas e demográficas. Foram construídas as curvas de sobrevida das variáveis significantes com o método de Kaplan Meyer. Resultados: A idade média foi de 48,09 anos, a renda familiar mensal e o nível de instrução mostraram-se reduzidos na maior parte dos estudados. A hipertensão arterial mostrou-se a principal comorbidade associada à insuficiência renal crônica terminal, seguida pelo diabetes mellitus. Os fatores que comprometeram significativamente a sobrevida dos pacientes foram a idade avançada no início da terapia, a hemoglobina e a albumina. A taxa de sobrevida global foi de 84,71% e 63,32% em um e cinco anos, respectivamente. Conclusão: A taxa de sobrevida foi considerada baixa e mostrou-se decrescente ao longo dos anos, não representando melhorias apesar dos avanços tecnológicos, diagnósticos e terapêuticos. A idade avançada, a hipoalbuminemia e a anemia são fortes preditores de mortalidade. Resumo


IntroductIon
Chronic kidney disease (CKD) consists of kidney damage and/or slow, progressive and irreversible loss of renal function. 1It carries high morbidity and mortality. 2,3he number of patients with endstage kidney disease (ESRD) treated with renal replacement therapy (RRT) grows globally at a rate of approximately 7% per year.This rate exceeds the population growth rate. 4he three treatment modalities for patients with ESRD are hemodialysis (HD), peritoneal dialysis or kidney transplantation.HD is the most used in the majority of countries. 5etween the years of 2000 and 2006 in Brazil, the number of patients in dialysis grew at a rate of about 9% a year; and the Public Healthcare System (SUS) funded 89% of that treatment. 4ccording to the census data collected from dialysis units in Brazil, held in July 2010, the number of patients undergoing dialysis was 92,091; 90.6% in HD. 6 Epidemiological surveys estimate that there are over 2 million Brazilians having some degree of renal dysfunction and, of these, about 70% are unaware of the condition. 7he risk factors that most influence the mortality of dialysis patients are advanced age and diabetes mellitus as causes of chronic renal failure (CRF), and additional comorbidities to the kidney condition. 8zevedo et al., 9 published a study from Barbacena, Minas Gerais, in which they report that the main causes of death were cardiovascular disease, infections and neoplasms.The overall survival rate found was 86.2% and 60%, in one and five years, respectively.
In a meta-analysis, Mailloux & Henrich, cited by Azevedo et al., 9 reported that HD patient survival time depends on factors such as gender, age, dialysis adequacy ratio (Kt/V), hemoglobin (Hb), albumin, calcium x phosphorus product (CaxP) and parathyroid hormone (PTH), among others.
In the study by Barbosa et al., 10 held in Sao Paulo, high mortality rates were reported, and mortality by CKD was 10 to 20 times higher than in the general population.
The importance of determining survival for renal patients on HD favors the improvement of care, since it enables the early identification of patients at high risk, which improves their survival and quality of life.Besides contributing to the strategic planning of health actions -as evidence suggests that the increase in spending on HD is due to the increased survival of patients and not specifically to the growing demand for treatment. 11n São Luís, Maranhão, we did not find studies depicting data correlated with patient survival, we felt motivated to do this study, which aims to determine the survival rate, characterize the clinical and epidemiological profile and identify the comorbidities and the variables associated with survival of patients on hemodialysis.

Method
This is a descriptive cohort study.We carried out a retrospective and longitudinal study involving 162 CKD patients undergoing HD at the Nephrology Department of the Presidente Dutra University Hospital at the Federal University of Maranhão -UFMA.
The inclusion criteria were: having started treatment between January 2007 and December 2011; be chronically enrolled in a regular HD program for at least three months, undergoing three sessions per week for 4 hours.
We collected our data from the computerized registration system of the Hemodialysis Service (NEFRODATA-ACD, version 4.5.4.268); information pertaining to gender, age, race, education, family income, CKD cause, length of stay in treatment, comorbidity, destination, cause of death and the results from the following variables -Kt/V, albumin, calcium x phosphorus, Hb and PTH.The quality parameters used were: Kt/V > 1.2; Albumin > 3.5 g/dl; calcium x phosphorus < 55 mg 2 /DL 2 ; Hb ≥ 11 g/dl and PTH = 150-300 pg/ml.The data concerned the period from January 2007 to December 2012.
Categorical variables were described by frequencies and percentages, and the numerical variables by using the mean ± standard deviation.We used the Cox regression analysis to study the influence of various clinical and demographic variables on patient survival.Those variables with p-value < 0.10 were eligible for the multivariate model, a p value < 0.05 was considered statistically significant.
We used the Kaplan Meyer method to build the survival curves of the significant variables.Statistical analyzes were performed using the Data Analysis and Statistical Software (STATA), version 12.0.
This study was preceded by the approval from the Ethics Committee of the Federal University of Maranhão, protocol No. 123.351.

results
We assessed the medical records from 162 patients, of whom 72 (44.44%) were females and 90 (55.56%) were males.Their average age was 48.09 years, with a standard deviation (SD) of 19.88.
The sociodemographic and clinical characteristics of the patients studied upon dialysis onset, are presented on Table 1.
As to monthly family income and educational level, of the 162 patients, 83 (51.23%) received up to two minimum wages and 140 (86.42%)had up to 8 years of study.
Regarding comorbidities, hypertension and diabetes mellitus were the main causes of comorbidity that prevailed in patients starting dialysis in this study, and 60 (37.04%) patients had more than one associated disease.
Table 2 shows data on the survival of patients by year.Importantly, three patients died before reaching one year of study and the survival rate decreased over the years on hemodialysis.
Table 3 depicts the Cox regression univariate analysis results, analyzing the impact of clinical and demographical variables on patient survival.The variables that showed statistically significant influence on survival were: age when starting HD, serum albumin and Hb.Variables such as gender, skin color, educational level, income, diabetes mellitus, cardiovascular disease, Kt/V, calciumphosphorus product and PTH did not affect patient survival.
In the multivariate analysis (Table 4), the factors associated with patient survival were the same that were significant in the Cox univariate regression analysis.There was a significantly increased hazard ratio (HR) for each additional variables analyzed, the educational level factor had only marginally significant effect, with a higher survival rate from patients with more than eight years of schooling.The hypertension variable had no statistically significant influence on patient survival.

dIscussIon
As for the sociodemographic characteristics, it is noteworthy that the mean age was 48.09 years with SD = 19.88.This result represents a significant social data -as seen in other studies, because ESRD affects a population at full working age, causing spending in social areas due to early retirement, outpatient expenses and medications. 10onthly family income and educational level were reduced in most of the patients investigated, 83 (51.23%) received up to two minimum wages and 140 (80.42%)][14] Hypertension was found to be the major comorbidity associated with ESRD, being present in more than half (77.77%) of the patients analyzed, followed by diabetes mellitus (37.66%).Similar results were found in other studies. 10,15iabetic nephropathy (33.33%) was the main underlying disease in the study group, followed by chronic glomerulonephritis (22.22%) and hypertensive nephropathy (17.28%), contrary to results from some studies, 6,13,16 i.e. the study from Calado et al. 17 conducted in São Luís, in 2009.However, these results were partially similar to those found in Rio Grande do Sul in 2007, where the diabetic nephropathy was the most common cause (24%) of underlying disease in patients under hemodialysis. 18In this study, the factors that significantly compromised survival of HD patients were older age at treatment onset, Hb and serum albumin.Other variables, which in previous studies 10,19 had an association with patient survival, in this study were not associated with mortality, such as gender, skin color, schooling, income, high blood pressure, diabetes mellitus, cardiovascular diseases, Kt/V, calcium-phosphorus product and parathyroid hormone.
Several studies have suggested that DM is a predictor of mortality, especially due to cardiovascular causes arising from accelerated aterosclerosis. 20Similar results have been found in several studies, 18,[21][22][23] although this study did not prove such association.One of the limitations of our study, as well as in the study of Angelo et al., 20 is not to be able to include and evaluate all the variables needed to assess survival in diabetic patients, as the type of DM, smoking, BMI, physical exercise, dyslipidemia.Such information was not possible because of missing data in the records.
The overall mortality rate was 24.69%, with an overall survival of 84.71% and 63.32% in one and five years, respectively.This rate is similar to the one reported by Azevedo et al. 9 and Silva et al. 18 , in which they found 86.2% in a year and 60% in five years; 91% in one year and 64% in five years, respectively.Large studies show 89% survival rates at one year and 57% in five years, respectively, in the countries of the European Dialysis and Transplant Association. 24ccording to the census data from dialysis units in Brazil, 6 held in July 2010, the gross mortality rate (with the dialysis population on July 1 in the denominator) was 17.9% during the year.This rate was reduced to 14.9, when the denominator included patients at risk in the year (who were submitted to dialysis during the year).Studies reported by Dialysis Outcomes and Practice Patterns Study (DOPPS) 25 consistently showed a marked difference in gross mortality between countries, with mortality in the United States being one of the highest.In 2003, DOPPS reported gross mortality rates at one year being 6.6% in Japan, 15.6% in Europe and 21.7% in the United States.These results show that the overall mortality rate in this study -24.69%, is above the rates of the Brazilian record as well as those from Japan, Europe and the United States in the studies cited above.
This mortality rate has remained high despite technological advances; which may be explained by the greater severity and age of patients starting treatment, offsetting these data.
Age had a statistically significant impact on patient survival, with an increased HR for each year in the age of hemodialysis onset.This effect strengthens the evidence that mortality rates rise with increasing age.The survival rate was higher in patients who started HD with less than 60 years of age and has remained higher over the months when compared to the survival of patients with 61 years or more (Figure 1).Similar data was also found in other studies. 8egarding Hb, Cox regression univariate and multivariate analyses showed that it had a 52% 60% protection factor, respectively, at each increased level, reflecting the current knowledge that patients with higher levels of Hb have lower mortality. 9,26,27However, Hb was not statistically significant when categorized for the Kaplan Meyer method.
9][30] However, the Hb target range is still controversial in Nephrology, since most recent studies show that higher Hb targets can cause thrombolytic complications, uncontrolled hypertension and mortality. 28,31urrent recommendations suggest customized treatment for anemia, assigning more freedom to the Hb value for each patient -taking clinical status and risk factors into account, since some of them will benefit from higher levels of Hb, which will increase their quality of life and compensate for possible risks. 31,32lbumin averaged 3,82 g/dL ± 0.71 in the patients investigated.Similar results were found in a study in Castelo Branco -Portugal, 33 in which albumin had mean values above 3.5 g/dL.It is noteworthy that some authors consider that desirable serum albumin for hemodialysis patients should be ≥ 4.0 g/dL and lower values are strongly linked to mortality.
Survival was significantly higher for patients who had albumin values ≥ 3.5 g/dL (Figure 2), especially in the first year of hemodialysis treatment, confirming that hypoalbuminemia at hemodialysis onset is a strong predictor of mortality. 27,33,34he causes of mortality of patients in this study could not be identified due to impaired information in the records thereof.This is partly due to the fact that many deaths occur in the patient's own home or in other institutions.
This study has its own retrospective-related limitations: 27 cases were excluded due to lack of adequate information.We suggest greater concern for patient records and an active search for information about their deaths, when they do not happen in healthcare centers.This will help us identify the main causes of death of patients in HD and, therefore, seek the best results for their survival.
It is important to stress that several studies show that pre-dialysis nephrology monitoring and the type of vascular access directly influence mortality in the days of hospitalization and even total treatment cost.Thus, these factors represent another limitation to our study, because they were not associated to patient survival.

conclusIons
This study showed that ESKD in this population affects mostly males, of working age, with low income and low level of education, in addition to confirming that hypertension and diabetes mellitus represent the most prevalent causes of comorbidities in patients in hemodialysis onset.Moreover, advanced age upon treatment onset, Hb and serum albumin were directly related to survival, with a significantly higher risk for each year in age when starting HD and a significantly lower risk for every increase in Hb levels and albumin, confirming that advanced age, hypoalbuminemia and anemia are strong predictors of mortality.
Survival rate was considered low and decreased over the years, not showing improvements despite advances in technology, diagnosis and treatment.
These findings enable the early identification of patients at risk, enabling improvements and adjustments in the care of patients on hemodialysis and, therefore, improvements in the survival and quality of life of such patients.

tAble 1
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tAble 2
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