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Anemia in chronic kidney disease in a Hospital in the Northwest region to the State of Rio Grande do Sul

Abstracts

Introduction:

Chronic kidney disease (CKD) has been identified in an increasing number of patients and among its consequences is the anemia.

Objective:

To verify the occurrence of anemia in patients with CKD undergoing hemodialysis at a Hospital in the South Region, Brazil, as well as their kidney profile and iron profile.

Methods:

It was performed a retrospective, descriptive and analytical study. It was analyzed 45 patient records with results from the beginning of the hemodialysis treatment until nine months later.

Results:

Over 50.0% of the patients had hypertension and diabetes and 68.8% were male. The anemia was present in 97.8% of the patients and treated with erythropoietin and/or iron. In the evaluated period occurred increase in median hemoglobin levels (p < 0.001), hematocrit (p < 0.001), ferritin, creatinine (p < 0.001) and urea under (p = 0.039). The transferrin saturation was low in 35.6% of the patients after about one year under hemodialysis treatment. There was correlation between creatinine and urea, both rising.

Conclusion:

After the Introduction of treatment for anemia occurred increased plasma levels of hemoglobin and clinical improvement, even though not having a complete normalization of these levels.

anemia; creatinine; erythropoietin; renal insufficiency, chronic; urea


Introdução:

A doença renal crônica (DRC) tem sido identificada em um número crescente de pacientes e, dentre suas consequências, encontra-se a anemia.

Objetivo:

Verificar a ocorrência de anemia em pacientes com DRC que realizavam hemodiálise em um hospital da Região Sul, Brasil, bem como seu perfil laboratorial renal e de ferro.

Métodos:

Realizou-se estudo retrospectivo descritivo analítico. Foram analisados 45 prontuários com resultados de exames desde o início do tratamento hemodialítico até nove meses após.

Resultados:

Mais de 50,0% dos pacientes apresentava hipertensão arterial e diabetes e 68,8% era do gênero masculino. A anemia esteve presente em 97,8% dos pacientes e foi tratada com eritropoetina e/ou ferro. No período avaliado, ocorreu aumento nas medianas dos níveis de hemoglobina (p < 0,001), hematócrito (p < 0,001), ferritina, creatinina (p < 0,001) e ureia pré (p = 0,039). A saturação de transferrina estava baixa em 35,6% dos pacientes após aproximadamente um ano de tratamento hemodialítico. Houve correlação entre creatinina e ureia, ambas elevando-se.

Conclusão:

Após a Introdução de tratamento para anemia, ocorreu aumento dos níveis plasmáticos de hemoglobina e melhora do quadro, ainda que sem normalização completa desses níveis.

anemia; creatinina; eritropoetina; insuficiência renal crônica; ureia


Introduction

Chronic kidney disease (CKD) is a major public health problem.1Bastos MG, Bregman R, Kirsztajn GM. Doença renal crônica: frequente e grave, mas também prevenível e tratável. Rev Assoc Med Bras 2010;56:248-53. DOI: http://dx.doi.org/10.1590/S0104-42302010000200028
http://dx.doi.org/10.1590/S0104-42302010...
A census carried out in Brazilian dialysis units registered with the Brazilian Society of Nephrology, reported an increasing trend in the number of dialysis patients in the last decade, and the number estimated in January 2011 was 91,314 patients. The prevalence rate of dialysis in 2011 was 475 patients/million of the population, and there are 26,680 estimated patients who will started treatment in 2011, with an incidence rate of 149 patients/million of the population, and hemodialysis was the initial treatment mode in 90.6% of the cases.2Sesso RCC, Lopes AA, Thomé FS, Lugon JR, Watanabe Y, Santos DR. Diálise crônica no Brasil - Relatório do Censo Brasileiro de Diálise, 2011. J Bras Nefrol 2012;34:272-7. DOI: http://dx.doi.org/10.5935/0101-2800.20120009
http://dx.doi.org/10.5935/0101-2800.2012...
Progressive loss of kidney function results in clinical manifestations, of which anemia is common in CKD patients.3Canziani MEF, Bastos MG, Bregman R, Pecoits-Filho R, Tomiyama C, Draibe SA, et al. Deficiência de ferro e anemia na doença renal crônica. J Bras Nefrol 2006;28:86-90.

Racki S, Maleta I. Role of renal anemia in progression of chronic kidney disease. Acta Med Croatica 2009;63:33-7.

Abensur H. Deficiência de ferro na doença renal crônica. Rev Bras Hematol Hemoter 2010;32:95-8. DOI: http://dx.doi.org/10.1590/S1516-84842010005000047
http://dx.doi.org/10.1590/S1516-84842010...
-6Fishbane S, Nissenson AR. Anemia management in chronic kidney disease. Kidney Int Suppl 2010:S3-9. PMID: 20671741 DOI: http://dx.doi.org/10.1038/ki.2010.188
http://dx.doi.org/10.1038/ki.2010.188...

The prevalence and severity of anemia are related to the kidney disease stage,7Abensur H. Anemia da doença renal crônica. J Bras Nefrol 2004;26:26-8.,8Kohagura K, Tomiyama N, Kinjo K, Takishita S, Iseki K. Prevalence of anemia according to stage of chronic kidney disease in a large screening cohort of Japanese. Clin Exp Nephrol 2009;13:614-20. DOI: http://dx.doi.org/10.1007/s10157-009-0197-z
http://dx.doi.org/10.1007/s10157-009-019...
and the relative deficiency/reduction in erythropoietin (EPO) production is the main cause,1Bastos MG, Bregman R, Kirsztajn GM. Doença renal crônica: frequente e grave, mas também prevenível e tratável. Rev Assoc Med Bras 2010;56:248-53. DOI: http://dx.doi.org/10.1590/S0104-42302010000200028
http://dx.doi.org/10.1590/S0104-42302010...
,3Canziani MEF, Bastos MG, Bregman R, Pecoits-Filho R, Tomiyama C, Draibe SA, et al. Deficiência de ferro e anemia na doença renal crônica. J Bras Nefrol 2006;28:86-90. because the kidneys produce this hormone that stimulates red blood cell production and when the patient develops CKD, he/she does not produce it in sufficient amounts.9National Kidney Foundation. Anemia and Chronic Kidney Disease. 33th ed. New York: National Kidney Foundation; 2006-2007. In addition of EPO deficiency, other situations may contribute to the occurrence of anemia in CKD, such as iron, folic acid and vitamin B12 deficiency; blood loss; hemolysis, hyperparathyroidism and inflammation, and these should be investigated before the Introduction of EPO replacement therapy - the most common being iron deficiency (52.0%).7Abensur H. Anemia da doença renal crônica. J Bras Nefrol 2004;26:26-8.,1010 Abensur H, Bastos MG, Canziani MEF. Aspectos Atuais da Anemia na Doença Renal Crônica. J Bras Nefrol 2006;28:104-7.

Anemia causes fatigue, reduced exercise capacity, reduced libido and cognitive function, which ultimately have a negative impact on their quality of life,1Bastos MG, Bregman R, Kirsztajn GM. Doença renal crônica: frequente e grave, mas também prevenível e tratável. Rev Assoc Med Bras 2010;56:248-53. DOI: http://dx.doi.org/10.1590/S0104-42302010000200028
http://dx.doi.org/10.1590/S0104-42302010...
,1111 Valderrábano F, Jofre R, López-Gómez JM. Quality of life in end-stage renal disease patients. Am J Kidney Dis 2001;38:443-64. PMID: 11532675 DOI: http://dx.doi.org/10.1053/ajkd.2001.26824
http://dx.doi.org/10.1053/ajkd.2001.2682...
in addition to being related to heart failure, 1212 Besarab A, Soman S. Anemia management in chronic heart failure: lessons learnt from chronic kidney disease. Kidney Blood Press Res 2005;28:363-71. DOI: http://dx.doi.org/10.1159/000090191
http://dx.doi.org/10.1159/000090191...
,1313 Virani SA, Khosla A, Levin A. Chronic kidney disease, heart failure and anemia. Can J Cardiol 2008;24:22B-4B. DOI: http://dx.doi.org/10.1016/S0828-282X(08)71026-2
http://dx.doi.org/10.1016/S0828-282X(08)...
cardiovascular diseases are the leading causes of mortality in CKD.5Abensur H. Deficiência de ferro na doença renal crônica. Rev Bras Hematol Hemoter 2010;32:95-8. DOI: http://dx.doi.org/10.1590/S1516-84842010005000047
http://dx.doi.org/10.1590/S1516-84842010...
Thus, RBC indices, serum iron, transferrin and ferritin saturation, among others, are tests that may be part of the clinical investigation and monitoring of patients with CKD.7Abensur H. Anemia da doença renal crônica. J Bras Nefrol 2004;26:26-8.

In chronic kidney failure (CKF), there is also impairment in the excretion of toxic non-volatile solutes, with consequent increase in the plasma concentrations of all catabolites derived mainly from protein metabolism, characterized by increased urea and creatinine.1414 Ajzen H, Schor N. Guia de medicina ambulatorial e hospitalar de nefrologia. 2ª ed. São Paulo: Manole; 2005. Creatinine dosage can be used as an aid in kidney function diagnosis, it is most useful and a more sensitive and specific indicator then urea;1515 Pereira AB, Santos BFC. Avaliação da Função Renal. In: Ajzen H, Schor N. Guia de medicina ambulatorial e hospitalar de nefrologia. 2ª. ed. São Paulo: Manole; 2005. p.19-37. however, other markers of renal function and renal damage have been investigated and may be introduced in clinical practice to assist in the diagnosis, monitoring, analysis and prognosis of kidney disease progression.1616 Sodré FL, Costa JCB, Lima JCC. Avaliação da função e da lesão renal: um desafio laboratorial. J Bras Patol Med Lab 2007;43:329-37.

Whereas anemia is one of the main consequences of CKD and, when found, requires proper treatment and monitoring, checking the tests results can characterize the hematologic changes, iron behavior dynamics, as well as urea and creatinine concentrations and their possible relations with anemia in CKF patients on hemodialysis. Thus, this study aimed at checking the occurrence of anemia in patients with CKD who underwent hemodialysis in a hospital in the northwestern region of Rio Grande do Sul, as well as the kidney and iron profiles of these patients.

Methods

Study design, sample and variables

This is a retrospective descriptive analytic study. The information was obtained from medical records of patients with CKD who were undergoing treatment in the hemodialysis ward of a hospital in the northwestern region of Rio Grande do Sul - RS, Brazil. The charts of all patients on hemodialysis were studied, and we included in the study those who had at least four routine examinations, which are quarterly held on the site. There were 105 patients on hemodialysis, of which 45 had the least number of tests required for inclusion in the study.

We studied the results from the hemoglobin, hematocrit, ferritin, serum iron, transferrin saturation, creatinine and pre-and post-hemodialysis urea tests. Anemia was defined as cases in which the hemoglobin level was < 13 g/dL for men and < 12 g/dL for women.1717 World Health Organization. Iron Deficiency Anaemia Assessment, Prevention and Control: a guide for programme managers; 2001. For the other tests we used adapted reference values from the Brazilian Association of Hematology and Hemotherapy1818 Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular [Internet]. 2012 [cited 2012 Oct 10]. Available from: http://www.abhh.org.br/pt-br/
http://www.abhh.org.br/pt-br/...
and the Brazilian Society of Nephrology.1919 Sociedade Brasileira de Nefrologia [Internet] 2012. [cited 2013 Oct. 06]. Available from: http://www.sbn.org.br/
http://www.sbn.org.br/...
We recorded the results from the first examination after the patients started on hemodialysis and three subsequent ones. This research project was approved by the Research Ethics Committee o Unijuí, under protocol # 143.971/2012.

Statistical analysis

The data was processed using the PASW Data Editor Statistics (version 18.0, Chicago, IL, USA) statistical package. The descriptive analysis is presented as mean ± standard deviation, relative and absolute frequency. For quantitative variables, we performed the Kolmogorov-Smirnov normality test, in which we used the parametric comparisons of independent means, we also used the Student t test and the nonparametric U (Mann Whitney test). In the analysis of the paired parametric variables we used the Student t-test; and the nonparametric Wilcoxon test for the non-parametric ones. Non-parametric variables were expressed as median and interquartile range (IQR). In the qualitative variables, we used the Pearson chi-square test and the Fisher's Exact test. In the correlations, we used Spearman's and Pearson's tests, depending on the normality of the variables. A p-value < 0.05 was considered significant.

Results

The study included 45 patients with median age of 61 years, ranging between 49 and 71 years, and 2 months of time elapsed between hemodialysis treatment onset and the completion of the first test (TTTHRPE), ranging between 1-3 months; there were no statistical differences between genders. Among hemodialysis patients, 68.8% (31/45) were males and 44.0% were aged 60-79 years. Among women, 42.0% were aged 60-79 years. Table 1 shows the sample profile.

Table 1
Profile of patients under dialysis in a hospital in the northwestern portion of rio Grande do Sul state, Brazil

Among CKD-predisposing factors, 12 (38.7%) men had systemic hypertension (SH); three (09.8%) had diabetes mellitus (DM); five (16.1%) hypertension and DM; there was no information for six (19.3%) and five men had other predisposing factors (16.1%). Among women, five (35.7%) had hypertension; one (07.1%) DM; two (14.3%) hypertension and DM; there was no information for two (14.3%); and four (28.6%) had other predisposing factors.

The results of tests performed at baseline and after nine months (first and fourth tests) showed that there was a statistically significant increase in median hemoglobin levels (p < 0.001, p = 0.015 Men, Fem p = 0.013), hematocrit (p < 0.001 Men p = 0.007; Women p = 0.013), creatinine, and urea pre (creatinine p < 0.001 Men p < 0.001, p = 0.030 Women, urea pre: p = 0.039, p = Men. 0.009, p = 0.634 Fem), except the urea pre women (Table 2).

Table 2
Comparison of sequential tests, after starting hemodialysis, in patients from a hospital in the northwestern portion of rio Grande do Sul state, Brazil

Among the 14 women, 13 (92.9%) had used EPO and iron at some time during treatment with hemodialysis and one (07.1%) used iron only; among men, 22 (71.0%) used EPO and iron, three (09.7%) used EPO only; one (03.2%) iron only; and for five (16.1%) we had no information on the use of these. The initially prescribed EPO doses ranged between 2000-4000 IU, also with variable dosing - according to medical criteria. Iron supplementation when in injectable form was performed using iron hydroxide saccharate III 100 mg (variable dosing according to medical criteria) and, when per os, the iron salt used was ferrous sulfate at an initial dose of 300 mg.

Table 3 shows that in the first test, hemoglobin was statistically correlated with TTTHRPE (r = 0.379 - Regular, p = 0.01); age (r = 0.307 - Regular, p = 0.04), hemoglobin in the fourth test (r -0.385 - Regular, p < 0.001) and hematocrit (r = -0.901 - very strong, p < 0.001).

Table 3
Correlation between hemodialysis patient variables from a hospital in the northwestern portion of Rio Grande do Sul state, Brazil

The amounts of urea in the first test were correlated with age (inversely), creatinine, urea pre in the fourth test and urea post, similarly to what happened with creatinine (Table 3).

In the correlation analysis between patients with hemoglobin concentration below normal (in the first and fourth tests) and patients with low, normal and high transferrin saturation (the first and fourth tests); low, normal and high iron; high creatinine and low normal and high ferritin; there was a significant linear correlation between low hemoglobin and normal ferritin in the first test (r = 0.397 - Regular, p = 0.054).

Anemia was present in 44 patients (97.8%) in the first test after the start of hemodialysis and after nine months of treatment, 41 (91.1%) had the same. On Table 4, we see hemoglobin variations stratified by gender.

Table 4
Hemoglobin variables comparison in the first and fourth test, classified by gender, from patients of a hospital in the northwestern portion of Rio Grande do Sul state, Brazil

Table 5 shows the distribution of patients according to the results of the hematological, iron and kidney tests.

Table 5
Comparison of hematological variables, kidney and iron laboratorial profiles from the first and fourth tests of hemodialysis patients from a hospital in the northwestern portion of Rio Grande do Sul state, Brazil

Discussion

A slightly higher percentage of patients on hemodialysis were male (68.8%), as observed in the study by Sesso et al.2020 Sesso R, Lopes AA, Thomé FS, Bevilacqua JL, Romão Jr JE, Lugon JR. Relatório do Censo Brasileiro de Diálise. J Bras Nefrol 2008;30:233-8. and Ammirati et al.,2121 Ammirati AL, Watanabe R, Aoqui C, Draibe SA, Carvalho AB, Abensur H, et al. Variações nos níveis de hemoglobina de pacientes em hemodiálise tratados com eritropoietina: uma experiência brasileira. Rev Assoc Med Bras 2010;56:209-13. DOI: http://dx.doi.org/10.1590/S0104-42302010000200021
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who reported 57.0% and 56.6%, respectively. It is possible that the higher number of men is due to the fact that, generally, women are more concerned about health care, following more strictly the treatment of hypertension and DM; which prevents or prolongs the time to effect the consequences, CKF among them. Gutierrez et al.2222 Gutierrez DMD, Minayo MCS, Oliveira KNLC (In Memoriam). Homens e cuidados de saúde em famílias empobrecidas na Amazônia. Saúde Soc São Paulo 2012;21:871-83. reported that the action of men in taking care of themselves often occurs indirectly, happening on a chain of relationship and influences where professionals teach the women, and they teach their male companions, and we can say that women are still considered as the basis for health care.

Hypertensive and diabetics, and patients with a family history of CKD are more likely to develop CKD,2323 Romão Junior JE. Doença renal crônica: definição, epidemiologia e classificação. J Bras Nefrol 2004;26:1-3. and this study shows that more than half of the patients had predisposing factors such as hypertension, diabetes mellitus, or both. In the study led by Ammirati et al.2121 Ammirati AL, Watanabe R, Aoqui C, Draibe SA, Carvalho AB, Abensur H, et al. Variações nos níveis de hemoglobina de pacientes em hemodiálise tratados com eritropoietina: uma experiência brasileira. Rev Assoc Med Bras 2010;56:209-13. DOI: http://dx.doi.org/10.1590/S0104-42302010000200021
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Most of the patients had arterial hypertension and diabetes mellitus. Thus, we highlight the importance of controlling these factors, to delay and/or prevent its progression to CKF and its consequences, whereas patients with the aforementioned chronic diseases are in the risk group, which ultimately facilitate kidney injury.2323 Romão Junior JE. Doença renal crônica: definição, epidemiologia e classificação. J Bras Nefrol 2004;26:1-3.

Most had anemia shortly after the start of hemodialysis (97.8%), which reinforces that this is common in patients with CKD. In a study held in Iran, Afshar et al.2424 Afshar R, Sanavi S, Salimi J, Ahmadzadeh M. Hematological profile of chronic kidney disease (CKD) patients in Iran, in pre-dialysis stages and after initiation of hemodialysis. Saudi J Kidney Dis Transpl 2010;21:368-71. found that, among patients with CKD who underwent hemodialysis, 85.0% had anemia, which is the same percentage found in another study involving patients from a kidney clinic in Santa Catarina.2525 Draczevski L, Teixeira ML. Avaliação do perfil bioquímico e parâmetros hematológicos em pacientes submetidos à hemodiálise. Rev Saud Pesq. 2011;4:15-22. In the study led by Pedruzi et al.,2626 Pedruzzi LM, Leal VO, Barros AF, Lobo JC, Mafra D. Fatores relacionados à força de preensão manual de pacientes submetidos à hemodiálise: ênfase na anemia. J Braz Soc Food Nutr 2012;37:22-33. 62.0% of hemodialysis patients had anemia, but these were on hemodialysis for more than 6 months. The higher percentage found in our study is probably due to the fact that this has been described for the first examination after initiation of treatment with hemodialysis.

In any event, after a period of approximately 12 months on hemodialysis, 91.1% of patients still had anemia. The significant increase in median hemoglobin concentration (p < 0.001) over time on hemodialysis (Table 2), as well as the increased number of patients in the groups with a higher concentration of stratified hemoglobin (Table 4), shows a reduction in anemia severity, even if this had still remained, and it is related to the Introduction of EPO and/or iron use during hemodialysis, as well as increasing hematocrit. It is noteworthy that in our study, when patients began hemodialysis they were mostly with anemia but without treatment (EPO and/or iron). When starting EPO and/or iron replacement, there is an expected increase in hemoglobin concentration and hematocrit.

The administration of EPO improves clinical outcome and the patient's quality of life is essential in controlling anemia.2727 Romão Junior JE, Bastos MC. Uso de medicamentos estimuladores da eritropoiese. J Bras Nefrol 2007;29:12-6. Before its use, it is necessary to ensure that the patient has adequate iron stock to achieve and maintain planned hemoglobin levels. Iron supplementation maximizes hemoglobin levels, since this metal is essential for the treatment of anemia2727 Romão Junior JE, Bastos MC. Uso de medicamentos estimuladores da eritropoiese. J Bras Nefrol 2007;29:12-6.,2828 Abensur H, Castro MCM. Reposição de ferro no Tratamento da anemia. J Bras Nefrol 2007;29:9-11. and its reduction in CKD patients caused by chronic blood loss, and the possible functional deficiency of the metal can lead to iron-deficiency anemia.5Abensur H. Deficiência de ferro na doença renal crônica. Rev Bras Hematol Hemoter 2010;32:95-8. DOI: http://dx.doi.org/10.1590/S1516-84842010005000047
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Clinical improvement is due to EPO; iron supplementation is closely related to the loss also by hemodialysis, but helps reduce anemia.

According to Bregman & Pecoits-Filho,2929 Bregman R, Pecoits-Filho R. Faixa ideal de hemoglobina. J Bras Nefrol 2007;29:17-8. the ideal hemoglobin range in CKD patients should be between 11 to 12 g/dL, and shall not be less than 11 g/dL, and higher values are not associated with better survival, there is even greater tendency for mortality. On first examination, 95.6% of patients had hemoglobin levels below 11 g/dL, dropping to 77.8% of patients having this level in the fourth test. There was an increase in the number of patients with hemoglobin levels between 11 and 12 g dL from the first (4.4%) to the fourth examination (13.3%); however, no woman maintained hemoglobin levels within this range - considered adequate (Table 4). Ammirati et al.2121 Ammirati AL, Watanabe R, Aoqui C, Draibe SA, Carvalho AB, Abensur H, et al. Variações nos níveis de hemoglobina de pacientes em hemodiálise tratados com eritropoietina: uma experiência brasileira. Rev Assoc Med Bras 2010;56:209-13. DOI: http://dx.doi.org/10.1590/S0104-42302010000200021
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found that maintaining hemoglobin levels within a target range is difficult, since most of the patients in their study had high amplitude fluctuations. For these authors, the proportion of patients with hemoglobin within the target in each month during the study period ranged from 42.0% to 61.0%, averaging 50.0%, values that were higher than those found in our study.

The positive correlation between low hemoglobin and normal ferritin (the first test) allows us to report that anemia in CKD occurs, initially and overall, with normal ferritin levels. It is noteworthy that, generally, in chronic disease anemia serum ferritin is normal or high,3030 Hoffbrand AV, Pettit JE, Moss PAH. Fundamentos em Hematologia. 4ª ed. Porto Alegre: Artmed; 2004. as it was observed in the present study. CKD is considered an inflammatory condition that leads to elevated serum levels of several inflammation markers,1010 Abensur H, Bastos MG, Canziani MEF. Aspectos Atuais da Anemia na Doença Renal Crônica. J Bras Nefrol 2006;28:104-7. ferritin among them, even in the lack of iron.3131 Failace R. Hemograma: manual de interpretação. 5ª ed. Porto Alegre: Artmed; 2009. In the first test (Table 5), ferritin was normal (53,3%) or high (46.7%), and in the fourth test, 2.2% had low ferritin, 35.6% normal and 62.2% had high ferritin; these results can be expected in an inflammatory situation. Only one patient showed a decrease in serum ferritin between the first and the fourth tests, probably by secondary iron deficiency, since this patient had transferrin saturation (fourth test) below 20.0%.

Due to elevated ferritin by inflammation, transferrin is saturated, since it functionally evaluates iron available for erythropoiesis, and in patients with more advanced CKD stages, transferrin saturation index below 20.0% has a sensitivity of about 80.0% in identifying cases of absolute iron deficiency anemia.3232 Bevilacqua JL, Canziani MEF. Monitorização dos parâmetros hematimétricos. J Bras Nefrol 2007;29:7-8.,3333 Ribeiro-Alves MA, Gordan PA. Diagnóstico de anemia em pacientes portadores de doença renal crônica. J Bras Nefrol 2007;29:4-6. Some patients had elevation of serum iron and transferrin saturation values above the reference, probably due to treatment with oral iron and/or injectable and/or with EPO, which may have resulted in a metal overload for these patients.

In 33.3% of patients, transferrin saturation was below 20% in the first test, rising to 35.6% in the fourth test. Possibly, these were patients with secondary iron deficiency, since iron depletion is a complication of hemodialysis, due to the process itself and the repeated phlebotomies carried out for the tests, with a loss of about 100 mg iron/month.3131 Failace R. Hemograma: manual de interpretação. 5ª ed. Porto Alegre: Artmed; 2009.

In addition, this iron deficiency may have been due to increased hepcidin because of inflammatory mediators acting on the liver, stimulating its production.3131 Failace R. Hemograma: manual de interpretação. 5ª ed. Porto Alegre: Artmed; 2009. This peptide blocks the duodenal absorption of iron, providing a situation of absolute iron deficiency, characterized by absence of iron in the patient's deposits (high serum ferritin levels and reduced transferrin saturation). Hepcidin is also active in the reticuloendothelial system, preventing the mobilization of iron deposits contained in macrophages, causing a state of functional iron deficiency, characterized by no utilization of the iron present in the deposits (high serum ferritin and low transferrin saturation).5Abensur H. Deficiência de ferro na doença renal crônica. Rev Bras Hematol Hemoter 2010;32:95-8. DOI: http://dx.doi.org/10.1590/S1516-84842010005000047
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,1010 Abensur H, Bastos MG, Canziani MEF. Aspectos Atuais da Anemia na Doença Renal Crônica. J Bras Nefrol 2006;28:104-7. In a multicenter cross-sectional study involving patients with CKD in pre-dialysis stage from the states of SP, RJ, MG and PR, the authors3Canziani MEF, Bastos MG, Bregman R, Pecoits-Filho R, Tomiyama C, Draibe SA, et al. Deficiência de ferro e anemia na doença renal crônica. J Bras Nefrol 2006;28:86-90. found transferrin saturation below 20% in 21.0% of patients and ferritin < 100 ng/ml in 53.0%; thus, it can be assumed that iron deficiency occurs in some patients during progressive loss of renal function, but related to increased hepcidin due to the inflammatory response, which could explain the low iron concentration in the first test after hemodialysis onset in our study.

Regarding kidney function, there was a significant increase in median concentrations of creatinine and urea pre within the study period (Table 2). On the first test, creatinine and urea were elevated (100.0% in both), and only a few patients reached urea values considered normal after hemodialysis (15.5%), which also occurred in general in the fourth test (Table 5). In the study led by Draczevski & Teixeira,2525 Draczevski L, Teixeira ML. Avaliação do perfil bioquímico e parâmetros hematológicos em pacientes submetidos à hemodiálise. Rev Saud Pesq. 2011;4:15-22. 50.0% of patients reached values of urea post within the reference range. Despite the difference with our study, urea values of all patients were reduced, even if they did not reach reference values, and demonstrate that hemodialysis fulfilled its function, but without statistical significance.

Creatinine values remained above those considered normal reference in all tests. The increase of two kidney markers from the first to the fourth tests, assessed by two markers, reflects the buildup of normally removed substances in part by glomerular filtration, which could be related to kidney damage. However, these markers suffer interference from many factors and may be also increased, among others, due to higher protein intake (urea) and increased muscle mass (creatinine).1616 Sodré FL, Costa JCB, Lima JCC. Avaliação da função e da lesão renal: um desafio laboratorial. J Bras Patol Med Lab 2007;43:329-37. Since malnutrition is a marker of poor prognosis in CKD patients, and the low calorie-protein intake is a major cause of malnutrition,3434 Bastos MG. Avaliação do estado nutricional. J Bras Nefrol 2004;26:42-3. the raise in urea concentration may be considered a positive factor, since it may reflect an improvement in caloric and protein intake. Creatinine increase may reflect an improvement in nutritional status, such as increased muscle mass, and in a study, serum creatinine correlated positively with mental component subscale in assessing the quality of life of patients who underwent hemodialysis, which also describes that the creatinine level may be associated with better quality of life.3535 Guerrero VG, Alvarado OS, Espina MC. Qualidade de vida de pessoas em hemodiálise crônica: relação com variáveis sociodemográficas, médico-clínicas e de laboratório. Rev. Latino-Am Enfermagem 2012;20 [09 telas].

Serum creatinine is used as an index of renal function, but it is not a very sensitive method, because its concentration is affected by factors other than glomerular filtration, such as individuals with reduced muscle mass, after excessive intake of cooked meat, malnutrition and certain medications that can interfere with tubular secretion of creatinine or the laboratory technique.3434 Bastos MG. Avaliação do estado nutricional. J Bras Nefrol 2004;26:42-3. Still, creatinine is used as a non-isolated marker and one of the ways to monitor kidney function development is to follow through on its serum dosage. With respect to urea, it is not exclusively excreted by the kidneys, and it is considered a weak predictor of glomerular filtration, since a high percentage of it returns to the same plasma by passive diffusion, in addition to diet and the rate of hepatic production interfering and altering plasma values. It is used in joint determination with serum creatinine.1616 Sodré FL, Costa JCB, Lima JCC. Avaliação da função e da lesão renal: um desafio laboratorial. J Bras Patol Med Lab 2007;43:329-37.

As one can see, there was a joint increase of serum creatinine and urea concentrations, because there was a correlation between creatinine and urea (pre and post), and creatinine between the first and the fourth tests; urea in the first and fourth tests and urea post in the first and fourth tests (Table 3), showing a progressive increase from the first to the fourth tests.

The main cause of anemia in CKD patients is a deficiency in EPO production by injury to kidney peritubular cells and its prevalence increases with decreased in kidney function.5Abensur H. Deficiência de ferro na doença renal crônica. Rev Bras Hematol Hemoter 2010;32:95-8. DOI: http://dx.doi.org/10.1590/S1516-84842010005000047
http://dx.doi.org/10.1590/S1516-84842010...
,3131 Failace R. Hemograma: manual de interpretação. 5ª ed. Porto Alegre: Artmed; 2009. Accordingly, kidney injury is linked to anemia, but there was no correlation between low hemoglobin concentration and high concentrations of urea or creatinine (Table 3).

The results of this study have limitations such as the small number of patients, the relatively short follow-up period, the reference ranges considered, as well as the Methods used to obtain the results, which were not investigated. In addition, kidney function was evaluated from urea and creatinine results, even with new markers being introduced, but which are not part of routine laboratorial practice.

Conclusions

By analyzing some hematological and biochemical parameters, we found that most patients on hemodialysis developed anemia due to CKF; however, after starting anemia treatment, there were increased concentrations of hemoglobin, reducing its severity, although few patients reached levels considered adequate.

As a consequence of hemodialysis and CKD - having inflammatory characteristics, there was a reduction in the concentrations of iron and/or in the functional impairment of such metal and increasing concentration of kidney markers, which may reflect increased protein intake and better nutritional status, with possible muscle mass increase; but there was no relationship between this increase and anemia. Anemia treatment with EPO is required. As iron deficiency may be present, iron supplementation is essential when needed, since replacement of EPO alone is not enough when there is inadequate iron supply.

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Publication Dates

  • Publication in this collection
    Jul-Sep 2014

History

  • Received
    09 Mar 2013
  • Accepted
    19 Nov 2013
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