Risk Factors of Chronic Kidney Disease Among Patients Attending at Dessie Comprehensive Specialized Hospital, Dessie, Amhara Region, Northeastern Ethiopia: Unmatched Case–Control Study

Study Setting, Design and Period

The study was conducted in Dessie Comprehensive Specialized Hospital, Dessie town, Amhara region, Northeast Ethiopia. A Hospital-based unmatched Case-control study was conducted during the study period from May 10 to July 15, 2022.

Sample Size Determination and Sampling Procedure

Sample Size Determination: The sample size was calculated by considering the following assumption; 95% confidence level 80% power, 34.3% proportion of hypertension in previous study [25], adjusted odds ratio of 2.39, 10% non- response rate, and 2:1 controls to case ratio. Using unmatched case-control in Epi info version 7.2.2.6 software Stat Calc. Based on the above assumptions the estimated optimal sample size used for this study was 234 (156 controls and 78 cases).

Sampling Technique and Procedure: All cases with confirmed CKD disease by urologist and full-filling case selection criteria as indicated from their medical record and at the time of data collection were included in the study until total sample size was obtained. Primarily, patients with CKD in the hospital were small in number, thus all the available cases were considered to be included in the study. Controls were selected by a systematic random sampling method to get the required sample of controls. The average estimated total urological cases without including CKD in the total study period using average weekly urological patient flows of May 2022 was 333 and Kth interval from N/n = 333/156=2.13~ 2. Controls were selected by every 2 intervals and the first study subject of control was determined daily and selected by lottery method using medical record number of patients. On daily base control were selected proportionally for cases based on control to case ratio until the required numbers of cases were obtained.

Study Variables

• Dependent Variable: Chronic Kidney Diseases (Yes/No)
• Independent variable: Socio-demographic characters like age of patients, sex, place of residence, educational level, occupation, and income
• Comorbidities like diabetes mellitus, hypertension ,CVD , HIV/AIDS, kidney stone, recurrent urinary tract infection, family history of chronic kidney diseases, history of burn, anemia
• Behavioral and lifestyle factors like Smoking, Alcohol drinking Chat chewing, physical exercise, consumption of unhealthy drinks and diet, Consumption of over the counter medications.

Operational Definitions

Chronic kidney disease (CKD): is defined as structural/ functional abnormalities of the kidney or decreased GFR <60 ml/min/1.73m2 for more than 3 months [17]. According to Kidney Foundation Disease Outcomes Quality Initiative (KDOQI) CKD is divided into five stages of kidney damage, from mild kidney dysfunction to complete failure [7]. Generally, a person with stage 1(GFR > 90 ml/min/1.73 m2) considered to be normal, stage 2 (GFR between 60-89 ml/ min/1.73 m2) which is mild, additionally CKD is considered as having moderate to severe kidney damage. Stage 3 is further broken up into two levels of kidney damage: 3A) a level of GFR between 45 to 59 ml/min/1.73 m2, and 3B) a level of GFR between 30 and 44 ml/min/1.73 m2. In addition, GFR for stage 4 is 15–29 ml/min/1.73 m2 [7, 8] later, it leads to end-stage renal disease (ESRD).

End-stage renal disease (ESRD): kidney failure is defined as a GFR<15 mL/min/1.73 m² or very high albuminuria (>300 mg albumin/24 h) [12, 13]. ESRD is irreversible and fatal unless treated by dialysis or kidney transplant [3, 4, 5]. Indicating that the kidney has stopped working permanently.

Glomerular Filtration Rate (GFR): is a measure of how well kidneys are cleaning blood-taking out extra water and waste. Specifically, it estimates how much blood passes through the glomeruli each minute [26]. It is central to the diagnosis and management of Chronic Kidney Disease and accepted as the best overall measure of kidney function.

GFR can be calculated from standardized serum Creatinine and estimating equations, such as the Modification of Diet in Renal Disease (MDRD), Study equation CKD-EPI or the Cockcroft-Gault formula [27]. The severity of kidney disease can be classified into five stages according to the level of GFR which is given as: According to Kidney Foundation Disease Outcomes Quality Initiative (KDOQI).

The CKD-EPI equation, expressed as a single equation, is: GFR = 141 * min(Scr/κ,1)α * max(Scr/κ, 1)-1.209 * 0.993Age * 1.018 [if female] * 1.159 [if black] Scr is serum creatinine (mg/ dL), κ is 0.7 for females and 0.9 for males, α is -0.329 for females and -0.411 for males, min indicates the minimum of Scr/κ or 1, and max indicates the maximum of Scr/κ or 1. Diabetic Mellitus: defined as random blood sager >200mg/ dl or FBS> 126mg/dl and/or self-reported on anti- hyperglycemic medication [28]. Hypertension:  defined as a systolic (SBP) ≥140 mmHg and/or diastolic blood pressure of (DBP) ≥90 mmHg or self- reported on anti-hypertension drugs [28]. Renal replacement therapy:  a therapy that replaces the normal blood-filtering functions of kidneys are used when the kidneys are not working well [29]. Hemodialysis: a type of treatment that filters the blood through a machine. It Removes harmful waste and extra fluids the body no longer needs. Also, hemodialysis helps Control blood pressure, balance potassium, sodium, calcium, and bicarbonate [30]. Over-the-counter medicine (OTC): defined as nonprescription medicine, that can buy without a prescription including NSAID and some other commonly used drugs and herbal medications to treat aches and pains [31]. Ever chat chewer: defined as a respondent whoever chewed chat during his lifetime [32]. Sufficient salt intake: individuals who take no more than 6g of salt a day (2.4g sodium) which is equivalent to one teaspoon [33]. Sufficient fat intake: individuals who take up to 35% of the calories from fat that is equivalent to 97 gram in 2500calories diet [33]. Sufficient sugar intake: individual who consume no more than 150 discretionary calories of sugar this is equivalent to 38 g or 9 teaspoons (tsp) of sugar per day for men and no more than 100 discretionary calories of sugar equivalent to 25 g or 6 tsp of sugar per day for women [34]. Significant alcohol intake: individuals who take more than 2 standard drinks of alcohol for males and more than 1 per day for females. E.g. 1 standard drink=1 standard bottle of regular beer and the net alcohol content of a standard drink is approximately 10g of ethanol [35]. Sufficient physical exercise: Adults doing at least 150–300 min of moderate-intensity aerobic physical activity per week [33].

Ever smoker: A person who has ever been a cigarette smoker or cigar smoker [34]. Underground water: Are sources of water found beneath the land surface it includes springs and wells [36].

Data Collection Tools and Procedures

Data were collected using semi-structured interviewer- administered questionnaire with supportive of medical records review to address all important variables using their medical record numbers when they return to outpatient department for checkup. The questionnaire was adapted from different literature and guidelines developed for a similar purpose by a different author.

Two data collectors and one supervisor were recruited and trained on how to collect data and check the completeness of data and training was given by the principal investigator for one day. There were continuous supervision by the principal investigator and trained supervisor.

Data Quality Control

The questionnaires were originally prepared in English and it was translated to local language (Amharic) for the purpose of data collection and then translated back to English by language experts to ensure its correctness and consistency. Two weeks before commencements of the study, the semi- structured interviewer-administered questionnaires was pre-tested among 5% (4 cases and 8 controls) a total of 12 samples in Kombolcha general Hospital by their local languages to prevent information leakage for the purpose of checking whether questions is clear or not, then after necessary corrections was done for unclear questions based on the pretesting findings. Internal consistency of the data was checked using Cronbach’s alpha with value of 0.75.

Data Management and Statistical Analysis

After the data were checked for completeness and consistency, coded and entered into Epi data version 4.6 software. Finally, the data were exported to and analyzed by STATA version 14 software. Descriptive statistics like frequencies and percentages were calculated to see the distribution of the variable.

To find out risk factors of CKD, first bivariable logistic regression was conducted and variables having a P-value of < 0.2 were entered in multivariable logistic regression analysis to control the possible confounders. Finally, variables in the multivariable logistic regression analysis having a P-value of <0.05 and the corresponding AOR with 95% confidence level was declared as a statistically significantly associated variables with CKD. To check co-linearity between risk factors, tolerance and variance inflation factor (VIF) were used. The Hosmer–Lemeshow test for the model was checked to assess whether the necessary assumptions for the application of multiple logistic regression are fulfilled or not.

Ethical Consideration

Ethical clearance was obtained from Institutional Research Ethical Review Committee (IRERC) of Wollo University, College of Medicine and Health sciences ethically approved the study with a letter reference number (CMHS/345/2022 on the date of 23/04/20222). The procedure and purposes of the study were explained to Dessie’s comprehensive specialized hospital. A letter of support was then obtained from Dessie comprehensive specialized hospital with a letter reference number (DCSH- 2/742/2022 on the date of 03/05/2022). Then permission and support letters were written to the medical ward department. Clients were asked for their consent verbally to confirm their willingness to participate in the study. Before enrolling any of the eligible study participants, the purpose, benefits, and confidential nature of the study were described and discussed with each participant. Confidentiality was ensured by omitting the names of the respondents from the questionnaire. Only those that consented and proved their willingness to take part in the study were enrolled in the study. The importance of medical check-ups, early detection, prompt medical management, nutrition relevance to CKD, and lifestyle modifications were provided by the data collectors during the data collection period.

Socio-Demographic Characteristics

A total of 234 study participants (78 cases and 156 controls) were enrolled into the study making the response rate of 99% and 100% respectively. Of which, 26(33.33%) of the cases and 70(44.87%) of the controls were females. The mean age of cases and controls was 52(±14SD) and 47(±17SD) respectively. Twenty-six (33.33%) of the cases and 37 (23.72%) of the controls were above 60 years of age. Forty-two (53.85%) of case and 89 (57.05 %) of controls were live in rural area .Eighteen (23.08 %) of the cases and 28 (17.95 %) of the controls were unable to read and write. Four (5.13%) of the cases and 29(18.59%) of the controls had tertiary and above educational level. In regarding to occupational status 37 (47.44 %) of cases and 58 (37.18%) of controls were self-employed, while 5 (6.41%) of cases and 20(12.82%) of controls were governmental workers. The mean monthly household income in ETB for cases and controls were 2588 and 3490 with standard deviation of ± 2243 and ± 2605 respectively See Table 1 for detail.

Key: Average monthly income in Ethiopian Birr. Table 1: Socio-demographic characteristics of study participants who were attending at Dessie Comprehensive Specialized Hospital, Ethiopia, 2022.

Comorbidity Related Variables

Among the study participants, 65(83.33%) of cases and 49(31.41%) of controls had anemia. The mean hemoglobin level of participants among cases and controls was 10.2(±2.5SD) and 13.6(±2SD) respectively. The mean creatinine level of study participants among cases and controls was 3.26 and 0 .88 with a standard deviation of ± 2.1and ±0.5 respectively.

About 52 (66.67%) of cases and 44 (28.21%) of controls had hypertension. Among the participants, 25(48.08%) cases and 21(47.73%) controls had hypertension of fewer than five year duration. Thirty-two (41.03%) of the cases and 24(15.38%) of controls had diabetes mellitus, of which

14 (43.75%) of the case and 14(58.33%) of controls had diabetes mellitus less than five years duration.

About Fifth-nine (75.64%) of cases and 73(46.79%) of controls had cardio-respiratory diseases. Forty-two (53.85%) of cases and 95(60.90%) of controls had a history of burn. More than one-tenth (15.38) of cases and 26(16.67%) of controls live with HIV/AIDS.

Roughly 64(82.05%) of the cases and 78(82.05%) of controls had a history of kidney stones. similarly, this study revealed that about twenty-five (32.05%) of cases and 32(20.51%) of controls had a family history of kidney disease See Table 2 for details.

Among 78 cases who participated in this study, 32(13.67%) were in stage 3B (30-44) or had a moderate decrease in glomerular filtration rates. About 21(8.8%) of cases were on stage 4 or had a severe decrease in GFR. Ten Glomerular filtration rates (CKD-EPI) $$ \mathrm {法} = \mathrm {法} + \mathrm {法} $$

80 $$ \mathrm {d} = \frac {1}{2} \mathrm {d} _ {1} + \frac {1}{2} \mathrm {d} _ {2} $$

66.6667 $$ \mathrm {C O} _ {2} + \mathrm {H} _ {2} \mathrm {O} = \mathrm {H C O} _ {3} + \mathrm {H} _ {2} \mathrm {O} $$

$$ \mathrm {C O} _ {2} + \mathrm {H} _ {2} \mathrm {O} = \mathrm {H C O} _ {3} ^ {-} + \mathrm {H} ^ {+} $$ $$ \mathrm {型} = \mathrm {型} $$ $$ \mathrm {C O} _ {2} + \mathrm {H} _ {2} \mathrm {O} = \mathrm {H C O} _ {3} ^ {-} + \mathrm {H} ^ {+} $$ $$ \mathrm {d} = \frac {1}{2} \mathrm {d} _ {1} + \frac {1}{2} \mathrm {d} _ {2} $$ $$ \mathrm {C O} _ {2} + \mathrm {H} _ {2} \mathrm {O} = \mathrm {H C O} _ {3} + \mathrm {H} _ {2} \mathrm {O} $$ $$ \mathrm {C O} _ {2} + \mathrm {H} _ {2} \mathrm {O} = \mathrm {H C O} _ {3} ^ {-} + \mathrm {H} ^ {+} $$ $$ \mathrm {C O} _ {2} + \mathrm {H} _ {2} \mathrm {O} = \mathrm {H C O} _ {3} ^ {-} + \mathrm {H} ^ {+} $$ $$ \square $$ $$ \| $$ $$ \square $$ $$ \mathrm {法} = \mathrm {法} $$ $$ - 1 $$ $$ \mathrm {C O} _ {2} + \mathrm {H} _ {2} \mathrm {O} = \mathrm {H C O} _ {3} + \mathrm {H} _ {2} \mathrm {O} $$ Figure 1: Distribution of CKD by CKD-EPI Stage Classification.

Life Style And Behavioral Factors

Among interviewed study participants, 26(33.33 %) of cases and 20(12.82 %) of controls had a history of cigarette smoking. About 42(53.85%) of cases and 72(46.15%) of controls had a history of chat chewing. Seventy-five (96.15%) (4.27%) of cases were on stage 3A (45-59) or had a mild to moderate decrease in GFR. About 15(6.4%) of cases reached on end stages of renal diseases (ESRD) or had GFR < 15 with or without dialysis See Figure 1 for detail.

$$ \mathrm {型} = \mathrm {型} $$

$$ - 1 $$ $$ \mathrm {B} = \mathrm {B} _ {1} + \mathrm {B} _ {2} + \dots + \mathrm {B} _ {n} $$ of cases and 111(71.15 %) of controls consumed high in salt foods, whereas 74(94.87%) of cases and 104(66.67%) of controls consumed high in fat foods. About 37 (47.44%) of cases and 58 (37.18%) of controls had a history of alcohol drinking. About 70(89.74%) of cases and 89(57.05%) of controls used Non-steroid Anti-inflammatory drugs as a means of controlling pain. Fifty-two (66.67%) of cases and 65(41.67%) of controls consumed or used herbal drugs s as a means of medication See Table 3 for detail.

Factors Associated with Chronic Kidney Disease

Chi-square assumption was tested for further analysis and to determine determinants of Chronic Kidney Disease (CKD). Bivariable and multivariable logistic regression analysis were conducted. In bivariable analysis variables with p value <0.2 were selected for multivariable analysis and using average standard error those variables with average standard error of 2.0 and above were not analyzed in the final model (like Educational status, salt, fat, caffeinated drinks, NSAID drug usage and anemia) finally 14 variables from 29 variables (Sex of the participants, Age, hypertensions status, diabetes- mellitus, cardio-respiratory diseases, …. Herbal medication usage history) were analyzed in multivariable analysis .The Hosmer–Lemeshow goodness of fit test for final model were conducted for multiple logistic regression (p-value = 0.3595) the model was good since p-value was >0.05 and the odds ratios were adjusted for all other variables keeping constant in the final models and Significant was declared using 95% CI with chronic kidney disease.

After keeping the other variables constant the odds of developing CKD among males was 2.54 [AOR; 2.54, 95%CI (1.125- 5.754)] times higher than females. Similarly, the odds of developing CKD were 5.33 [AOR; 5.33, 95%CI (2.107- 13.489)] times higher for patients who had hypertension compared to those who had not. Furthermore, the odd of developing CKD among patients who had diabetes- mellitus was 3.64 [AOR; 3.64, 95%CI (1.530- 8.671)] times higher compared to their counterparts. Patients with kidney stones were 3.91 times odds of developing CKD compared to those without kidney stones [AOR; 3.91, 95%CI (1.492-10.257)]. This study also confirmed that the use of underground water was a positive factor of CKD development [AOR; 2.63, 95%CI (1.108- 6.262] See Table 4 for detail.

Note: Statistically significant at *P<0.05, **P<0.01. Table 4: Multivariable binary logistic regression on risk factors of CKD among patients attending at Dessie Comprehensive Specialized Hospital, Dessie, Amhara region, North-east Ethiopia, 2022.

Ethics Approval and Consent to Participate

Ethical clearance letter was gained from the ethical committee of Department of public health, Wollo University. Before delivering the questionnaire, written consent was obtained from every participant. No names and possible identifying issues written on the questionnaire to secure the data confidential.