Prevalence and Factors Associated with Chronic Kidney Disease among Patients Admitted to Medical Ward in a Tertiary Hospital, Northern Ethiopia, a Cross Sectional Study

doi:10.21203/rs.3.rs-1596427/v1

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Prevalence and Factors Associated with Chronic Kidney Disease among Patients Admitted to Medical Ward in a Tertiary Hospital, Northern Ethiopia, a Cross Sectional Study

https://doi.org/10.21203/rs.3.rs-1596427/v1

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Background: Chronic Kidney Disease is being recognized as a global public health problem. It is a major non-communicable disease with the global prevalence varying between 10.5% and 13.1%. Diabetes and hypertension appear to be the leading causes of chronic kidney disease worldwide. The aim of this study is to determine the prevalence and its associated factors of chronic kidney disease among patients admitted to medical ward in a tertiary hospital, Northern Ethiopia.

Methodology: An institution based cross-sectional study was undertaken using systematic random sampling technique to select study participants from October 20, 2017 to March 20, 2018 G.C. Data from 450 patients was collected using a pre-tested questionnaire designed to meet the study objective. After describing variables, logistic regression was conducted to identify independent associated factors of chronic kidney disease. Statistical significance was declared at P < 0.05.

Result: Of the 450 patients, 260 (57.8%) were males and more than half (54.2%) were between ages of 25 to 40 years. The prevalence of chronic kidney disease among patients admitted to medical ward was 17.3% (95% CI 13 - 29.9) and 14.4% (95 % CI 6.2 - 12.3) by Cockcroft Gault and MDRD equations, respectively and majority (61.5%) of them were stage 5. Hypertension (AOR = 7.8 95% CI 4.1, 14.9), history of recurrent urinary tract infection (AOR = 3.5 95% CI 1.1, 7.3) and history of using nephrotoxic drugs (AOR = 3.4 95% CI 2, 9.3) were significantly associated with chronic kidney disease.

Conclusion: The prevalence of chronic kidney disease among adult patients admitted to medical ward in tertiary hospital, Northern Ethiopia was high and majority of patients were stage 5. Hypertension, use of nephrotoxic agents and recurrent urinary tract infections were significantly associated. Knowing these risk factors will be very important for early detection of kidney disease and slowing progression. Since once end stage renal disease established, treatments are expensive, lifelong, resource intensive and scarce, especially in our country.

Chronic Kidney Disease

Hypertension

Nephrotoxic Agents

Recurrent Urinary Tract Infection

Chronic Kidney Disease (CKD) is defined as the presence of markers of kidney damage for more than 3 months. These markers include structural or functional abnormalities of the kidney, pathological abnormalities or other kidney damages, including abnormalities in the composition of blood or urine, abnormalities in imaging tests, presence of Glomerular Filtration Rate(GFR) less than 60 ml/min/1.73 m² (1). The presence of kidney disease is usually evaluated by GFR, an important marker of kidney function, and using indicators of kidney damage like proteinuria, abnormal urinary sediment, abnormal imaging studies and presence of kidney transplant (2).

CKD is a continually growing problem worldwide with estimated prevalence of ranging 10.5 -13.1% and has a risk-multiplier effect on major non-communicable diseases, including cardiovascular diseases. Because of this CKD has become a major health problem globally, especially, in developing countries with substantial effect in Sub-Saharan Africa (1, 3).The disease epidemiology is markedly different from other regions. Although middle-aged and elderly populations are predominantly affected in developed countries; in sub-Saharan Africa, CKD mainly affects economically productive young society between the ages of 20 to 50 years. Furthermore, it may not be associated with major risk factors like Hypertension, diabetes and smoking (4, 5). Hence determining magnitude and associated factors of CKD will be paramount important in our set up.

In addition to GFR, proteinuria has a significant role in assessing risk of CKD; especially, important since patients with stage 1 - 2 CKD and proteinuria have worse outcomes than people with stage 3 and no proteinuria. Furthermore, the risk of development of ESRD and cardiovascular mortality is accurately predicted by proteinuria measurements than by GFR (6 - 8).

CKD is generally unrecognized in the early stages, as there are no particular symptoms. They could have nonspecific symptoms generally unwell feelings and decrease in appetite or indistinguishable symptoms like pallor, fatigue, gastrointestinal disorders like hiccups, nausea and vomiting or with symptoms of heart failure (8). There is high prevalence of asymptomatic CKD among study populations (9, 10). Usually, CKD is diagnosed during the evaluation of patients who have high blood pressure, diabetes and those who have family history. However, developing countries are highly affected with CKD that cannot be explained by diabetes or hypertension (3); around 43% of people with CKD do not have diabetes or hypertension (11). Indeed in some places such as Sri Lanka and Nicaragua, the conventional risk factors were not associated with the disease prevalence (12, 13). But, in Ethiopia there is scarcity of data on prevalence and factors associated with CKD, the only report that we have is from Southern Ethiopia done only in diabetes patients. In this study we aim to describe the prevalence and factors associated with CKD in patients admitted to medical ward in tertiary hospital, Northern Ethiopia.

An institution-based cross-sectional study was conducted at Ayder Comprehensive Specialized Hospital (ACSH) which is located in Mekelle, Tigray regional state, Northern Ethiopia. This hospital provides referral service to a 9 million population in its catchment areas of Tigray, Afar, and Northern Amhara Regional States. The hospital has a total of 500 inpatient beds and 108 beds are assigned to the medical ward for medical cases admission, with an average of 250 - 300 admissions monthly (14). The study was conducted from October 20, 2017 - March 20, 2018 G.C.

Source and Study Population

The source population for this study was all admitted patients to Ayder comprehensive specialized hospital, whereas the study population of this study was patients attending their medical care in medical ward ACSH during the study period.

Sample size Determination and Sampling Technique

The sample size was calculated by using a single population proportion formula with assumptions; p = 50% (as there was no previous study in Ethiopia on similar study population), 95% level of confidence and 5% margin of error. Then sample size became 384. After adding 10% non-response rate, the minimum calculated sample was 424. Computer generated
simple random sampling technique was used to select the study participants.

Eligibility Criteria
Patients above 18 years of age admitted to medical ward of ACSH were included after excluding patients who had clear risk for acute kidney injury and/or diagnosed with acute kidney injury.

Study Variable

Dependent Variable: Chronic Kidney Disease Status

Independent Variables: Age, Gender, Occupation, Income, Educational Status, Resident Area, Hypertension, Diabetes, Family history of CKD, History of smoking, Body Mass Index (BMI), Exposures to nephrotoxins (like NSAIDS, radio contrast media and others).

Data Collection

Total of 982 patients were admitted to medical ward during the study periods, from those 572 patients were enrolled by using systematic random sampling technique to collect data through partially close-ended questionnaires, interview and document analysis. The questionnaire was designed to collect data related to socio demographic characteristic, history and physical examination, associated factors and investigation results like renal function test. The study groups were sequentially included, after excluding those with feature of acute kidney injury such us recent rise in creatinine, sepsis, critically ill and shock patients as can be seen in Fig 1.

Figure 1: Data collection procedure flow chart

Physical Examinations and Data Collection Procedures

Height was measured using portable stadio-meter and weight was determined using a weight scale; patient were dressed but without shoe by trained nurses. BMI was calculated as weight (in kilograms) divided by height in m². As per the WHO criteria, BMI was classified as normal/underweight BMI < 25kg/m², overweight: BMI 25 - 29.9 kg/m² and obese: BMI ≥ 30kg/m² (15).

We identified coexisting illness using patient medication chart, laboratory results and self-report method. Participants were considered to have diabetes mellitus if previously they had been recognized by the doctor as having DM, two fasting glucose values of ≥ 126 mg/dl using fingertip blood (Accu-trend glucometer) or they reported taking anti diabetic drug. Blood pressure was measured two times using a calibrated sphygmomanometer at the heart level. Hypertension was defined as systolic BP ≥ 140mmHg or diastolic BP ≥ 90mmHg or use of medication for hypertension.

Sample Collection Procedure and Laboratory Analysis

A random urine sample of MSU (midstream urine) had been collected from each patient using a clean catch technique and sterile container. Urinary excretion of protein and sugar was detected using urinary strips‘ACCU - ANSWER^R’. Serum creatinine was measured by alkaline picrate method (Jaffe kinetic assay). For estimated glomerular filtration rate (eGFR) determination, the abbreviated equations from the Modification of Diet in Renal Disease (MDRD) study and Cockcroft-Gault was used. Equation from the MDRD study: estimated GFR (ml/min per 1.73 m²) = 1.86 × (SCr) - 1.154 × (age) - 0.203, multiply by 0.742 for women and by 1.21 for African ancestry and Cockcroft-Gault equation: Ccr (ml/ min) = (140 - age) × Weight (Kg)/72 × SCr (mg/dl) × 0.85 if female.

Staging of kidney function was based on the national kidney foundation disease outcome quality initiative (NKF-KDOQI) classification (7). An eGFR < 60ml/min was used to define CKD. KDIGO guideline recommended to use albumin-to-creatinine ratio (ACR) more than 30mg/g to define CKD but such test was not available in the study area (5). Those with newly detected high creatinine and having patient with difficulty to differentiate acute kidney injury and chronic kidney disease were advised to start further work up and appointed at least after 3 months for follow-up investigation and treatment at the hospital and it was revised from Smart Care using their identification number.

Data Quality Control

Training was given for data collectors and supervisors about the aim of study, data collection procedures and ethical issues. Validity was checked by doing pretest on 30 patients at Mekelle hospital (out of the study area), based on this data collection tool was modified.

Data Analysis

Data entry and analysis were performed using Statistical Package for Social Science (SPSS) version 23. Categorical variables were described using frequencies and percentages. Continuous variables were also described using an appropriate combination of measure of central tendency and measure of dispersion. Odds ratio with its 95% confidence interval and p-value were calculated by running logistic regression to identify factor associated with CKD. Variables with a p-value < 0.05 during bivariate analysis were selected for multivariable analysis. Statistical significance was declared at p value < 0.05.

Total numbers of patients admitted to medical ward within the study period were 982, of which 572 patients were screened. Then, the data of 450 patients was analyzed as depicted in Fig 1. The mean and Standard Deviation (SD) of the age of the study participants was 45 ± 18 years and more than half (54.2%) of them were between 25 to 54 years of age. Table 1 shows that from the study, 260 (57.8 %) participants were males, with male to female ratio of 1.4:1. About 20.9% of the participants were not engaged in any formal education, and more than half of the participants were not employed in any work and live in rural area.

Table 1

Socio demographic characteristics of the study participants admitted to medical ward of ACSH, Northern Ethiopia, October 2017 to March 2018 (N = 450)

Characteristics		Frequency(N = 450)	Percentage	95% Confidence Interval
Characteristics		Frequency(N = 450)	Percentage	Lower	Upper
Sex
	Male	260	57.8	53.6	61.8
	Female	190	42.2	38.2	46.4
Age in years
	18-24 Years old	67	14.9	12.7	16.3
	25-54 Years old	244	54.2	53.2	57.8
	55-64 Years old	55	12.2	10.1	13.4
	65+ Years old	84	18.7	17.5	19.5
Residence (n = 450)
	Rural	269	59.8	55.4	63.9
	Urban	181	42.2	36.1	44.6
Educational Status
Higher education		68	15.5	12	18.4
Secondary school		131	29.1	24.9	33.3
Primary school		65	14.4	11.1	18.0
Able to read and write		92	20.4	16.9	24.2
Unable to read & write		94	20.9	17.3	24.2
Occupational Status
Farmer		165	36.7	32	41.1
Merchant		90	20	16.6	23.5
Government employee		74	16.4	13.3	19.8
House wife		31	6.9	4.7	9.3
Others		90	20	16.3	24

Clinical and Laboratory Related Characteristics

In the present study, it has been revealed that the prevalence of diabetes and hypertension was 9.1% (95% CI 6.7, 11.6) and 18.2% (95% CI 14.7, 21.8), respectively (Table 2). Around one third of the patients had history of use nephrotoxic drugs and recurrent urinary tract infection. More than half of the patients have already small shrunken kidney size at presentation, showing most of them came with advanced kidney disease.

Table 2

Clinical and laboratory related characteristics of the study participants admitted to medical ward of ACSH, North Ethiopia, October 2017 to March 2018 (N = 450)

Characteristics	Frequency (N = 450)	Percentage	95% Confidence Interval
Characteristics	Frequency (N = 450)	Percentage	Lower	Upper

Clinical characteristics
History of recurrent UTI	130	28.9	25	33.1
Family history of kidney disease	10	2.2	0.9	3.8
Diabetes mellitus	41	9.1	6.7	11.6
duration of DM (<5 years)	35	86.9	85.8	88.1
Hypertension	82	18.2	14.7	21.8
duration of HTN(>5years)	24	5.3	3.3	7.6
Obesity (BMI >30kg/m²)	6	1.3	0.8	1.6
History of nephrotoxic drug use	83	18.4	15.1	22.2
Laboratory Values
Anemia (HGB < 12mg/dl)	214	47.6	45.8	50.2
HBV infection	16	3.6	2.8	6.3
HCV infection	14	3.1	2.2	5.8
HIV infection	32	7.1	4.7	9.3
Urine dipstick proteinuria	110	24.4	20.9	28.4
Abdominal Ultrasound Findings
Small shrunken kidney	60	13.3	10.4	16.2
Enlarged kidney	14	3.1	1.8	4.9
Normal sized kidney	344	76.4	72.4	80.4
Poly cystic kidney	18	4	2.2	5.7
Obstructive Uropathy	10	2.2	1.1	3.8
Others*	4	0.9	0.1	1.8

The prevalence of CKD was 17% (CI 95% 13 - 29.9) and 14.4% (CI 95% 6.2 - 12.3) by Cockcroft Gault and MDRD equations respectively. Fig 2, demonstrates the prevalence of CKD classified by stages as per Cockcroft Gault equation according to national kidney foundation classification, there were 48 patients (61.5%) stage 5, 12.8% stage 1 and 15.3% stage 4 CKD patients.

In the multivariate analysis which can be shown in Table 2, patients with current hypertension were 7.8 times more likely to develop CKD than those with blood pressure < 140mmHg(AOR = 7.8 95% CI (4.1, 14.9), patients with history of recurrent UTI were 3.5 times more likely to develop CKD than patients without history (AOR = 3.5, 95% CI (1.1, 7.3). Patients with history of using nephrotoxic drugs were 3.4 times at risk of developing CKD than those who had no similar history (AOR = 3.4, 95% CI (2,9.3).

Table 3

Bivariate and multivariable analysis of factors associated with CKD among patients admitted to medical ward, ACSH, Northern Ethiopia, October 2017 to March 2018

Variable	Response	CKD		COR (95% CI)	P-value	AOR (95%CI)	P-value
Variable	Response	Yes	No	COR (95% CI)	P-value	AOR (95%CI)	P-value
Age	> 65 Years	14	70	1.1 (0.5 ,1.9)	0.84
Age	< 65 years	64	302	1	0.84	1
Gender	Male	52	208	0.63 (0.38, 1)	0.08
Gender	Female	26	164	1	0.08	1
Smoking status	Yes	19	40	2.6 (1.4 ,4.9)	0.02	1.8 (0.83,4.2)	0.129
Smoking status	No	59	332	1	0.02	1	0.129
History of exposures to nephrotoxic drugs	Yes	9	74	1.9 (0.9 , 3.9)	0.048	3.4 (2, 9.3)	0.001
History of exposures to nephrotoxic drugs	No	69	298	1	0.048	1	0.001
HIV infection	Yes	20	107	0.8 (0.5 , 1.49)	0.578	0.58 (0.4,1.4)	0.80
HIV infection	No	58	265	1	0.578	1	0.80
History of recurrent UTI	Yes	53	77	8.1 (4.7, 13.9)	0.000	3.5 (1.1 ,7.3)	0.01
History of recurrent UTI	No	25	295	1	0.000	1	0.01
Family history of CKD	Yes	2	3	7.6 (2.1 ,27.8)	0.02	1.2 (1.0 , 6.3)	0.161
Family history of CKD	No	76	368	1	0.02	1	0.161
Other chronic medical illness	yes	30	185	0.6 (0.3 ,1.0)	0.07	1.3 (1.3 ,9.6)	0.14
Other chronic medical illness	No	48	187		0.07	1
BMI	> 30	3	3	4.9 (0.9 ,24.8)	0.054	2.1 (0.2 ,16)	0.44
BMI	< 30	75	369	1	0.054	1
Systolic BP	≥ 140	47	59	8 (4.7, 13.6)	0.000	7.88 (4.1 ,14.9)	0.017
Systolic BP	< 140	31	313	1	0.000	1	0.017
Fasting blood sugar	≥ 126	13	28	2.4 (1.2 ,4.9)	0.013	0.69 (2.2,10.7)	0.24
Fasting blood sugar	< 126	65	344	1	0.013	1	0.24

COR: crude odds ratio, AOR: adjusted odds ratio, CI: confidence interval, DM: diabetes mellitus, N number, 1: references, CKD: chronic kidney disease

In this study majority of the patients were males accounting for about 57.8 % of the patients. More than half of patients were between 25 - 54 years of age. This is similar to a study done in Uganda where 51.3% of patients were males and with median age of 39 years (16) . Similarly, according to the study in sub-Saharan Africa, CKD mainly affects economically productive young society between the ages of 20 and 50; and was not associated with major risk factors like Hypertension (HTN), diabetes and smoking (17, 18), this might be due to most nontraditional risk factors like infectious cause are highly prevalent.

Prevalence of CKD based on eGFR from this study was 17.3% (95% CI 13 - 29.9) among hospitalized patients to medical ward. This is similar to the study done in Uganda that found 18% among hospitalized patients (16). The participants in the Uganda study were critically ill and hence the slight increase in total number of renal dysfunction cases. In a few in-patient studies in Africa, renal dysfunction ranged from 17% to almost 30% in HIV positive patients (19). The difference is that the African studies recruited patients with surgical and obstetric conditions as well. In a population based cohort study in Germany in 2012 the prevalence of CKD in community dwelling elderly and study done in a rural region of Haiti from patients that visit the outpatient’s department showed prevalence of 24% and 27%, respectively (20, 21). This is slightly higher than our study that is because they might have included elderly patients and used ACR to calculate proteinuria. Furthermore, the study didn’t use ACR categories to diagnose CKD which can underestimate the prevalence. But, another study done in Switzerland and United States showed lower prevalence, that is, 13.8 and 10%, respectively (22, 23). The reasons for the differences in the above mentioned studies and this study might be due to, the above results have conducted population based study with distributed risks and partly, might be due to our hospital being only referral hospital where patient’s with complication requiring renal replacement therapy are also admitted.

Majority of patients in this study present with stage 5 CKD (ESRD) in contrast to other studies where the prevalence of CKD stage 3 to 5 in the adult US population according to the third National Health and Nutrition Examination Survey (NHANES 3) was only 4.7% (23) and similarly in Swiss; stage 4 and 5 was only 4.5% (20). The reason why patients present in ESRD in this study might be because of the absence of screening of patients with known risk factors for CKD. To some extent, it can also be due our hospital is the only center with RRT for patient presenting with complication. This is consistent with many of African countries study like, Uganda and Botswana (16, 24).

Worldwide hypertension is recognized as one of the leading causes of CKD (25). This study revealed that patients with systolic hypertension were 3 times more likely to develop CKD than the non-hypertensive patients. Studies done in Uganda, Haiti and DRC also found correlation between hypertension and CKD (5, 16, 20). The use of nephrotoxic agents has been associated with CKD as demonstrated in Burundi (26). Similarly, in the present study the association of nephrotoxic drugs with CKD was 3.4 times than non-users. However, in Uganda, it was not found to be associated, this can be due to they have only assessed NSAID use unlike this study that include other nephrotoxic agent including contrast media (16).

While diabetes in most studies is mentioned as an independent predictor for CKD, in this study the prevalence of diabetes in the participants was 9.1% (95% CI 6.4 - 12.0); however in the multivariate regression model it was not significantly associated with CKD. A probable explanation for this might be the recent development of diabetes in the study participants. This is similar to study done in Haiti and Iran (20, 27). Infectious disease are known risk factors of CKD, but HIV infection was not associated with CKD in this study which is inconsistent with many African studies like Zambia and Botswana(16, 24) This can be explained by the high prevalence of HIV in non CKD patients leading to distribution of risk factors.

Limitation of the Study

The study population were admitted patients, which are at higher risk for development of CKD and does not represent the general population. Urinary Albumin-to-Creatinine ratio was not assessed, hence there is a possible underestimation of the prevalence of patients with proteinuria in this study especially stage 1 and 2 CKD. As this is a cross-sectional study design makes it may be impossible to infer a causal relationship between CKD and the risk factors.

In conclusion, we found a high prevalence of CKD among adult patients admitted to medical ward of Ayder Hospital and majority of them were CKD stage 5 (ESRD). In this study, significant association was demonstrated between CKD and elevated systolic blood pressure, history of using nephrotoxic drugs and history of recurrent urinary tract infection which are easily preventable by advocating importance of screening and incorporating in community health education about use of nephrotoxic drugs.

Recommendation

The study recommends further investigations at community level to find out the point prevalence of CKD and its associated factors so that a preventive strategy especially for the preventable associated factors or for an entire defensive framework could be implemented or designed to reduce the expansion of the disease. These data have to be noted by the health authorities in the country to integrate CKD in public health planning with the aim to develop adapted preventive strategies and give health education to the community about the importance of screening modalities in high risk patients and especially regarding the use of nephrotoxic drugs.

ACSH: Ayder Comprehensive Specialized Hospital; AKI: Acute Kidney Injury; BMI: Body Mass Index; BP: Blood Pressure; CKD: Chronic Kidney Disease; DM: Diabetes Mellitus; ESRD: End Stage Renal Disease; GFR: Glomerular Filtration Rate; HIV: Human Immunodeficiency Virus; MDRD: Modification of Diet in Renal Disease; UTI: Urinary Tract Infection; NSAID: Non-Steroidal Anti-Inflammatory Drugs; SPSS: Statistical Package for Social Science

Ethical Approval and Consent to Participant

Ethical clearance waived from Mekelle University, College of Health Sciences, and Institutional Review Board (IRB) with ethical clearance number ERC: 1405/2018. The permission was received from the medical director of the hospital before the commencement of the study and informed written consent was also obtained from all eligible participants. The study adhered to relevant national and international guidelines and regulations.

Consent for Publication

Not applicable for this manuscript

Availability of Data and Materials

The data set generated and analyzed during this study is available and can be shared from the corresponding author upon on reasonable request.

Computing Interest

The authors declare that they have no computing interest.

Funding

No specific funding was received

Author’s Contribution
MKW selected the topic, planned the study protocol, oversaw the study, entered the data, and reviewed the literature. MKW, MGW, EB and MG conducted the analysis and interpreted the results. MKW and EB drafted the final manuscript. All the author(s) reviewed and approved the final manuscript.

Acknowledgment

We sincerely thank, to Mekelle University, College of Health Sciences, for giving us the opportunity to do this research work and support in selecting this topic. We would also like to thank the data collectors and study participants for their participation.

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No competing interests reported.

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Prevalence and Factors Associated with Chronic Kidney Disease among Patients Admitted to Medical Ward in a Tertiary Hospital, Northern Ethiopia, a Cross Sectional Study

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Abstract

Figures

Background

Methods

Source and Study Population

Sample size Determination and Sampling Technique

Study Variable

Data Collection

Physical Examinations and Data Collection Procedures

Sample Collection Procedure and Laboratory Analysis

Data Quality Control

Data Analysis

Results

Clinical and Laboratory Related Characteristics

Discussion

Limitation of the Study

Conclusion

Recommendation

Abbreviations

Declarations

Ethical Approval and Consent to Participant

Consent for Publication

Availability of Data and Materials

Computing Interest

Funding

Acknowledgment

References

Additional Declarations

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