Urinary tract infection in patients with chronic kidney disease under conservative treatment

Abstract

ABSTRACT Objectives: to assess the prevalence and associated risk factors for urinary tract infection in patients with chronic kidney disease under conservative treatment and identify the microorganisms isolated in the urine of these patients and the staging of chronic kidney disease. INTRODUCTION Nowadays, there is an increase in the life expectancy of the world population, with an increase in the prevalence and incidence of chronic diseases, such as hypertension (HP) and Diabetes Mellitus (DM), which are the main causes of chronic kidney disease (CKD), especially in the elderly(1). According to the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines, CKD should be classified according to its cause and category of glomerular filtration rate (GFR) and albuminuria, which are factors that enable the identification of the risk of adverse outcomes, such as progressive CKD, end-stage renal disease, acute kidney injury, all-cause mortality and cardiovascular mortality. With it, through nutritional intervention and strict control of blood pressure and blood glucose, when performed by a multidisciplinary team, there is improvement in clinical parameters and, consequently, renal replacement therapy (RRT) is postponed and the survival of chronic renal individuals is increased.

Headnote

ABSTRACT

Objectives: to assess the prevalence and associated risk factors for urinary tract infection in patients with chronic kidney disease under conservative treatment and identify the microorganisms isolated in the urine of these patients and the staging of chronic kidney disease. Methods: a cross-sectional, analytical study carried out at the Conservative Treatment Outpatient Clinic of a university hospital in the city of Sâo Paulo. Results: the prevalence of urinary tract infection is 22%. The risk factors Diabetes Mellitus, hypertension, heart disease, neoplasms and thyroid and autoimmune diseases stand out in the infected group (p < 0.001). Most of the microorganisms found in urine cultures (87.9%) were Gram-negative, being Escherichia coli (50.70%), followed by Klebsiella pneumoniae (23.1%) and Enterococcus spp. (9.7%). Conclusions: the findings of this investigation reveal the intrinsic association between risk factors and microorganisms for the development of urinary tract infection.

Descriptors: Chronic Kidney Disease; Conservative Treatment; Urinary Tract; Bacteria; Urine.

RESUMO

Objetivos: avaliar a prevalência e os fatores de risco associados para infecção do trato urinário em pacientes com doença renal crônica em tratamento conservador e identificar os microrganismos isolados na urina desses pacientes e o estadiamento da doença renal crônica . Métodos: estudo transversal, analítico, realizado no Ambulatório de Tratamento Conservador de um hospital universitário da cidade de São Paulo. Resultados: a prevalência de infecção do trato urinário é de 22%. Destacam-se no grupo com infecção os fatores de risco Diabetes Mellitus, hipertensão arterial sistêmica, doença cardíaca, neoplasias e doenças da tireoide e autoimunes (p<0,001). Em sua maioria (87,9%), os microrganismos encontrados nas uroculturas foram Gram-negativos, sendo Escherichia coli (50,70%), seguida de Klebsiella pneumoniae (23,1%) e Enterococcus spp. (9,7%). Conclusões: os achados desta investigação revelam a intrínseca associação entre os fatores de risco e os microrganismos para o desenvolvimento da infecção do trato urinário.

Descritores: Doença Renal Crônica; Tratamento Conservador; Trato Urinário; Bactéria; Urina.

RESUMEN

Objetivos: evaluar la prevalencia y los factores de riesgo asociados de infección del tracto urinario en pacientes con enfermedad renal crónica en tratamiento conservador e identificar los microorganismos aislados en la orina de estos pacientes y la estadificación de la enfermedad renal crónica. Métodos: estudio transversal, analítico, realizado en el Ambulatorio de Tratamiento Conservador de un hospital universitario de la ciudad de Sâo Paulo. Resultados: la prevalencia de infección del tracto urinario es del 22%. Los factores de riesgo de diabetes mellitus, hipertensión arterial sistémica, cardiopatías, neoplasias y enfermedades tiroideas y autoinmunes destacan en el grupo con infección (p <0,001). La mayoría de los microorganismos encontrados en los urocultivos (87,9%) fueron Gram negativos, siendo Escherichia coli (50,70%), seguida de Klebsiella pneumoniae (23,1%) y Enterococcus spp. (9,7%). Conclusiones: los hallazgos de esta investigación revelan la asociación intrínseca entre factores de riesgo y microorganismos para el desarrollo de infección del tracto urinario.

Descriptores: Lesión Renal; Tratamiento Conservador; Sistema Urinario; Bacterias; Orina.

INTRODUCTION

Nowadays, there is an increase in the life expectancy of the world population, with an increase in the prevalence and incidence of chronic diseases, such as hypertension (HP) and Diabetes Mellitus (DM), which are the main causes of chronic kidney disease (CKD), especially in the elderly(1).

Chronic non-communicable diseases are responsible for about 60% of the causes of death worldwide, affecting about 35 million people a year. Cardiovascular disease (CVD) has the greatest epidemiological impact, accounting for about 30% of all deaths worldwide. CVD has progressively increased, due to the accumulation of traditional risk factors, such as HP and DM, as well as aging and increased life expectancy, resulting from the demographic transition observed in recent decades. HP, DM and CVD are strongly related to the loss of kidney function, which can lead to end-stage renal disease(2-3).

CKD is defined as the presence of structural or functional abnormalities of the kidneys for more than three months, with health implications. According to the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines, CKD should be classified according to its cause and category of glomerular filtration rate (GFR) and albuminuria, which are factors that enable the identification of the risk of adverse outcomes, such as progressive CKD, end-stage renal disease, acute kidney injury, all-cause mortality and cardiovascular mortality.

The GFR can be estimated from the serum creatinine dosage, associated with other parameters such as age, sex, race and body size(4).

CKD treatment varies according to patients' underlying disease, the stage of the disease, the speed of decrease in the GFR, the complications and comorbidities, particularly cardiovascular ones. The progression of CKD can be delayed in the stages prior to the terminal phase. This pre- or non-dialysis treatment is known as conservative. With it, through nutritional intervention and strict control of blood pressure and blood glucose, when performed by a multidisciplinary team, there is improvement in clinical parameters and, consequently, renal replacement therapy (RRT) is postponed and the survival of chronic renal individuals is increased. However, when it progresses to more advanced stages, passing to terminal CKD, RRT is necessary, which replaces renal function through hemodialysis, peritoneal dialysis or renal transplantation(5).

Expressive loss of renal function can cause uremic syndrome, which affects practically all organs and systems. Uremia involves more than just a failure of renal excretion, compromising several metabolic and endocrine functions performed by the kidneys. Chronic renal patients, uremic or not, are considered immunocompromised, and the infection is an important cause of death in patients with CKD, in whom the cellular immune function is depressed®. Furthermore, CKD is a risk factor for the decrease in vitamin D levels, which also favors the appearance of infectious diseases®.

CKD is an important risk factor for the development of healthcare-associated infections (HAI), which are associated with high rates of mortality and morbidity, with urinary tract infections (UTIs) and pneumonia being the ones with the highest incidence in patients with CKD. Worldwide, annually, UTIs affect 150 million people, accounting for 34,343 admissions to Intensive Care Units. In Brazil, UTIs are among the most common infections, accounting for a large part of care in primary care and emergency services(8-9).

Among the risk factors for the development of UTI are female gender, admission to intensive care, sexual activity, use of barrier contraceptives, vaginal infection, trauma and manipulation, DM, obesity, genetic susceptibility and anatomical abnormalities. UTIs are characterized by conditions ranging from the asymptomatic presence of bacteria in the urine to severe kidney infection, which can result in sepsis, and can be of hospital origin or acquired in the community™.

Bacteria responsible for UTI can be Gram-positive or Gram-negative, the latter being the ones with the highest incidence. Escherichia coli is the microorganism causing most infections in all situations and age groups, accounting for 74.4% of UTIs in outpatients and 47% of infections in hospitalized patients. In addition to E. coli, they cause UTI, in variable frequency: Gram-negative Klebsiella spp., Pseudomonas aeruginosa, Proteus spp., Streptococcus agalactiae and Staphylococcus saprophyticus(vl). Considering that the progression of CKD may be directly related to recurrent infectious focus, studies that address UTIs and the identification of risk factors for impaired renal function are necessary for management and care of the population undergoing conservative treatment for CKD(12).

OBJECTIVES

To assess the prevalence and associated risk factors for UTI in patients with CKD under conservative treatment and identify the microorganisms isolated in the urine of these patients and the staging of CKD.

METHODS

Ethical aspects

This study was previously approved by the Institutional Review Board of the Universidade Federal de Såo Paulo, in compliance with standard 466 of the Brazilian National Health Council (Conselho Nacional de Saúde)(13).

Study design, period, and place

This is an epidemiological study, with a cross-sectional, analytical design, guided by the checklist of the STrengthening the Reporting of Observational Studies in Epidemiology (STROBE)(14). It was carried out between February 2017 and March 2020.

This study was carried out at the Conservative Treatment Outpatient Clinic of the Hospital do Rim e Hipertensåo, Fundaçâo Oswaldo Ramos, Sâo Paulo, Brazil. It is an institution that is a world reference in interprofessional care, teaching and research aimed at patients undergoing conservative and dialysis treatment and in the pre- and post-transplant periods. This study was carried out at the Conservative Treatment Outpatient Clinic, which predominantly assists adults and elderly (mostly aged 50 or over), male, whose main causes are CKD, HP and DM. Regarding the staging of CKD, most patients seen are in stages 3, 4 and 5 of CKD, and due to the high demand and demand for the service, patients in stages 1 and 2 are advised to seek the primary health network®.

Patients referred for conservative outpatient treatment have tests that can make specialist assessment doubtful, who considers the results of tests performed within a period of up to three months; for safety, new tests are requested to confirm or update these results, where patients waited a period of one week up to 36 months of waiting. Many of those who, in fact, should have already started treatment are still in the diagnostic confirmation phase(15).

Population and sample

To compose the sample of this study, the records of urine cultures collected from February 2010 to February 2018 were searched, totaling 1,555 exams, and, of these, 343 had a positive result for some microorganism. Considering a confidence level of 95%, margin of error of 5%, the first positive urine culture of each patient and excluding duplicate results, the infected group (GI) was composed of 134 individuals and the non-infected group (NIG) for 81, totaling 215 individuals.

The selected participants were submitted to the following inclusion criteria: medical records of patients treated at the Conservative Treatment Outpatient Clinic with prevalence of stages 3b, 4 and 5 of CKD and people aged > 18 years who had a urine culture collected in the period from February 2010 to February 2018. Participants whose medical records were not found during data collection were excluded from the sample.

Study protocol

For data collection, we used a structured instrument composed of sociodemographic (age, sex, race, education and origin) and clinical variables (presence of DM, SAH, heart disease; patients with cancer, thyroid and autoimmune diseases; clearance of creatinine and CKD staging and classification), in cases of positive urine culture (type of microorganism and antibiogram), in addition to the infection outcome (stay in the Conservative Treatment Outpatient Clinic, death and dialysis). The outcome variable considered in both groups was the presence or absence of infection and risk factors(16).

The presence of microorganisms in the urine was considered an episode of urinary tract infection. Thus, UTI episodes were identified considering the current recommendations regarding HAIs used in Brazil. Confirmation of the infection episode was performed by recording physicians' clinical assessment and diagnosis in the medical record and the result of the first positive urine culture for any microorganism(17).

Analysis of results, and statistics

For statistical analysis, the chi-square test was performed to compare categorical variables between IG and NIG, and the Mann-Whitney test for continuous variables. To verify the risk factors between IG and NIG, the logistic regression model was used and, after this analysis, multiple regression was performed. Through the forward method, the factors that best explained the occurrence of infection were selected. For all analyses, a significance level of 5% was used (p-value < 0.05).

RESULTS

A total of 215 participants were analyzed, 134 participants with positive urine culture and 81 with negative urine culture, being allocated to IG and NIG. The main risk factors in GI are DM, HP, heart disease, neoplasms and thyroid and autoimmune diseases (p< 0.001). Additionally, E. coli (50.7%), Klebsiella pneumoniae (23.1%) and Enterococcusspp. (9.7%) were observed as frequent microorganisms. The outcomes of patients who had UTI. Most of them (76.1%) remained in conservative outpatient treatment.

Regarding the IG's sociodemographic characteristics, the mean age was 72.4 (±14.2) years. The majority were female (69.4%), white (63.6%), with elementary education (82.4%) and from Sâo Paulo (61.1%). In the NIG, the mean age was 53.3 (±16.3); most were male (45.2%), white (36.4%), with high school (70%) and from Sâo Paulo (38.9%). Regarding comorbidities, in the IG, most patients had HP (67.6%), DM (71.4%) or other comorbidities (85.2%). The mean Body Mass Index (BMI) of 28.2 (±5.4) was also observed. In the GSI, most patients had HP (32.4%), with a mean BMI of 23.9 (3.85) (Table 1).

Table 2 presents multiple logistic regression analysis to verify which variables best explain the occurrence or not of UTI in people with CKD undergoing conservative treatment.

Table 3 shows the microorganisms found in urine culture of IG participants and the sensitivity profile. The most frequent were E. coli (50.7%), K.pneumoniae (23.1%) and Enterococcus spp. (9.7%), being E. coli and K. pneumoniae, mostly resistant.

Table 4 presents the occurrence of UTI according to staging/ glomerular filtration rate in patients with CKD under conservative treatment. In this sample, UTI was more frequent in patients at stage 4 (37.4%), followed by CKD 5 (32%).

DISCUSSION

Kidney disease is a global public health problem, affecting more than 750 million people worldwide. The impact of kidney disease varies substantially worldwide, as does its detection and treatment, due to limited or inconsistent data collection and surveillance practices™. UTIs are one of the main problems in patients with CKD, both in conservative treatment and in RRT, directly influencing morbidity and mortality rates(19).

Infection is a clinical condition caused by pathological microorganisms that, as a result of the pathophysiology of CKD, can have a negative impact on the health status of this population, contributing to the increase in morbidity and mortality™.

CKD is prevalent in the general adult population. In the United States, it is estimated to be present in 13.1% of adults. In Brazil, data are uncertain, but population studies estimate that 3 to 6 million people have CKD(20-21).

The world population has been growing rapidly in recent years. In the next two decades, it is estimated that the number of elderly people will exceed 30 million people, which will correspond to 13% of the world population. The increase in the number of elderly people is accompanied by an increase in chronic diseases, including HP and DM, the main risk factors for CKD, which explains the age profile found in this study, corroborating the majority of the population of chronic kidney patients(22-23).

Women are often more susceptible to UTI because of their anatomy. The existence of a wetter environment also predisposes to the growth of microorganisms, as well as old age and local climacteric changes. In this study, female patients were 1.87 times more likely to have UTI when compared to male patients, which can be explained by the presence of comorbidities and low immunity in this population00'2®.

In IG patients, elementary school was the most prevalent in relation to high school and higher education. For those who attended elementary school, 10.92 times more likely to have a UTI were shown, compared to those with secondary education, and 13.26 times more likely, when compared to those with higher education. This data highlights the negative impact that lower levels of education have on health(25).

In this investigation, it was observed that the main risk factors for UTI in chronic kidney patients under conservative treatment were HP, DM, heart disease, neoplasms and thyroid and autoimmune diseases. In this context, several studies have linked these comorbidities with decreased renal function. HP is considered the primary cause of the development of CKD, being characterized by structural changes in the renal parenchyma, with repercussions on renal hemodynamics. It is associated with a lifestyle based on a diet high in fat, salt and carbohydrates. Additionally, DM can be configured as an adjunct to HP, potentiating kidney damage and accelerating the progression of CKD. Diabetic nephropathy is therefore the clinical condition found in most chronic kidney patients. Some studies have revealed that chronic hyperglycemia is significant for the development of fibrosis in the glomerular basement membrane and, consequently, for the decrease in the glomerular filtration rate(2-3A26).

According to the US annual report of renal system data, older age, DM, HP, CVD and higher BMI are associated with CKD(27). In developing countries, the prevalence and incidence rates are lower, a fact that can be explained by underreporting and the delay in diagnosis. Moreover, racial and environmental aspects can influence the number of cases(28).

A study carried out in Brazil in 2014, with the objective of verifying the prevalence of CKD and the factors associated with it in 1,016 elderly people, showed that age, DM, metabolic syndrome, inadequate self-assessment of health, HP and obesity were associated with CKD(29).

When the presence of UTI was associated with comorbidities, in this study, hypertensive individuals were 4.17 times more likely to have UTI than non-hypertensive individuals, diabetics, 1.99 times more likely compared to non-diabetics and those with disease heart disease, 2.11 times more likely than those without heart disease.

Patients with other antecedents, such as neoplasms and thyroid and autoimmune diseases, had 48.66 times more chances of UTI in this study compared to those without other antecedents.

The pathophysiology of HP, DM, heart disease, some neoplasms and autoimmune diseases may involve cellular mechanisms for the release of inflammatory and oxidative substances that contribute to immunomodulation imbalance, resulting in systemic susceptibility to infection. In this sense, chronic kidney patients under conservative treatment have these conditions exacerbated in favor of overlapping of these comorbidities(30). Thus, the data presented in this investigation showed that the UTI was significant and that the microorganisms highlighted as the most opportunistic were prevalent and triggered unpleasant systemic repercussions.

Similar to the data demonstrated in this investigation, BeraldoMassoli et al. revealed that the most common microorganisms found in UTI were enteric Gram-negative, especially E. coli, followed by Klebsiella, Proteus and Pseudomonas'31'.In a study carried out by D'Addazio and Moraes, the predominant bacteria were Escherichia coli, Klebsiella, Proteus, Pseudomonas and Citrobacter'32'1.

E. coli is predominant in urinary infections in patients with CKD, as it is associated with azotemia, urinary flow and decreased urinary concentration. It is prevalent in UTIs, in patients with CKD, affecting women over 65 years, with 41% resistance to ciprofloxacin and more severe in the presence of comorbidities(33).

Carbapenemase-producing K. pneumoniae (CPK) stands out as an important microorganism in HAI. It has great dissemination capacity and limited therapeutic options. The microorganisms found in this study are consistent with those mentioned in the literature, as they stand out as cause of infection in the community'34'.

Outpatients have also shown resistance to antimicrobials, as evidenced in this study in outpatients under conservative treatment'11'. The resistance presented by microorganisms, both in the community and in the hospital environment, is a serious issue, which can lead the patient to sepsis and even death and, thus, cause irreparable damage to patients and their family'10'.

In this study, most participants were classified in stages 3, 4 and 5 of CKD, i.e., with moderate to severe decline in renal function or end-stage CKD. The diagnosis was made through serum creatinine dosage and, after calculation of creatinine clearance by Cockcroft-Gault, patients were identified in the staging'30'.

CKD has an important impact on the morbidity and mortality of patients, and conservative treatment is essential to delay the progression of renal dysfunction and reduce the occurrence of complications'35'. UTI can contribute to the progression of kidney disease and loss of function. In this study, patients remained in outpatient conservative treatment, need for RRT and death in IG. This scenario can impact patients' quality of life. CKD prevention, treatment and control is a challenge for the State and health institutions'36'.

In the study carried out by Oliveira et al., it was identified that there is a compromise in the quality of life of patients with CKD, in the physical and emotional domains. Higher hospitalization rates lead to worse quality of life'37'.

In summary, the present study glimpsed the main risk factors for UTI and the most frequent microorganisms as well as the staging of CKD in chronic renal patients undergoing conservative treatment.

Study limitations

This study had as limitations the fact that it was carried out in a single center, which may not reflect the reality of other locations. Data were obtained from medical records, often making it difficult to obtain the information. The sample of the non-infected group is small and may not reflect the characteristics of the entire population with CKD. However, the study was carried out in a world reference service for the care of patients with CKD under conservative treatment.

Contributions to nursing

The present study contributes to a multidisciplinary clinical practice, aiming to control modifiable risk factors causing HAI, propose the creation of CKD progression monitoring protocols, and institute educational hygiene actions in the elderly for UTI prevention as a role for nurses working in the Conservative Treatment Outpatient Clinic. Given these findings, more research is needed in the outpatient setting, especially with patients under conservative treatment.

CONCLUSIONS

The present investigation demonstrated UTI in chronic kidney patients under conservative treatment associated with risk factors of advanced age, DM, HP, heart disease, BMI and the presence of other antecedents (neoplasms of different systems, thyroid diseases and autoimmune diseases). Most patients in this study population were in stages 3, 4 and 5 of CKD and UTI was more frequent in patients in stages 4 and 5, and the main microorganisms found in urine cultures were E. coli and K. pneumoniae with high resistance profile.

Sidebar

How to cite this article:

Coutinho GMM, Silva EC, Campanharo CRV, Belasco AGS, Fonseca CD, Barbosa DA. Urinary tract infection in patients with chronic kidney disease under conservative treatment. Rev Bras Enferm. 2022;75(3):e20210065. https://doi.org/10.1590/0034-7167-2021-0065

Corresponding author:

Graciana Maria de Moraes Coutinho

E-mail: [email protected]

EDITOR IN CHIEF: Antonio José de Almeida Filho

ASSOCIATE EDITOR: Priscilla Valladares Broca

Submission: 03-18-2021 Approval: 08-27-2021

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