Management Outcome and Associated Factors among Patients with Chronic Kidney Disease at Selected Tertiary Hospitals in Ethiopia: A Multi Center Prospective Observational Study

Abstract

Aim: With an exponential rise in incidence and death over time, chronic kidney disease has become a major hazard to the world. Patients with chronic renal disease who were dependent on dialysis were dying at a rising rate in Ethiopia. The study’s objectives were to ascertain the management outcomes and associated factors for patients with chronic renal disease at selected Ethiopian tertiary hospitals.

Methods: A prospective observational study was carried out in a few Ethiopian tertiary hospitals from June 30, 2022 to March 30, 2023 among patients with chronic kidney disease who were not reliant on dialysis. Consecutively, 170 study participants were enrolled. Data abstraction, interviewer-administered surveys, and phone follow-up formats were used to gather data. Versions 4.6.0 and 25 of the Statistical Packages for Social Science were utilized for data entry and statistical analysis, respectively. Cox regression analysis, both bivariate and multivariate, was used to find the factors that predicted the death from chronic renal disease. A statistically significant p-value was one that was ≤ 0.05.

Result: Over 649.266 person-months, 170 patients were followed. Of these patients, 120(70.6%) were male and the mean (± SD) age of the patients was 45.19 ± 13.86 years. Overall, 71 (41.8%) were died with an estimated 109 deaths per 1000 person-months. The mean survival time was 116.9 days (95% CI:105.3-128.5). Hypertension (90%), anemia (95.8%), and edema (99.4%) were the most frequently prevalent comorbidity and complications. Severe anemia at admission [AHR=3.3, 95% CI,(1.39-7.8)], systolic blood pressure > 159 mmHg [AHR= 4.65, 95%CI(2.07-10.42)], modified Charleston comorbidity index score ≥ 5 [AHR=5.00, 95% CI(2.60-9.64)], and uremic encephalopathy [AHR=2.58, 95% CI,(1.45-4.5)] were predictors of chronic kidney disease patients’ mortality.

Conclusion: Among patients with chronic renal disease, the overall mortality rate was high. Hypertension, anemia, and edema were the common comorbidity and complications. Severe anemia, systolic blood pressure > 159 mmHg, modified Charleston comorbidity index ≥ 5, and uremic encephalopathy were predictors of mortality. As a result, patients with chronic renal disease would likely have a lower death rate if these factors were specifically managed.

Keywords

• Chronic Kidney disease
• All-cause mortality
• Multimorbidity
• Tertiary hospital.

Citation

Garedow AW, Tesfaye GT, Tefera GM, Yizengaw MA (2024) Management Outcome and Associated Factors among Patients with Chronic Kidney Disease at Selected Tertiary Hospitals in Ethiopia: A Multi-Center Prospective Observational Study. J Nephrol Kidney Dis 5(1): 17.

Introduction

Chronic kidney disease, is irreparable structural or functional kidney damage (estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 or albuminuria ≥30 mg per 24 hours) for more than 3 months and classified into five stages based on eGFR, albumin creatinine ratio and blood pressure [1-3]. Over the past few decades, chronic kidney diseases become more common. It has become a global public health issue because of the rapid growth of common risk factors such race, gender, age, and family history, smoking, obesity, diabetes, and hypertension, resulting in a heavier burden that developing countries are unprepared to address [4]. In addition, there are other risk factors for chronic kidney disease (CKD) such as heavy metal exposure, excessive drinking, smoking, painkiller use, cancer, hyperlipidemia, metabolic syndrome, HIV infection, hepatitis C virus infection, and a , and a history of cardiovascular disease (CVD) [5].

The effectiveness of CKD treatment can be affected by potential consequences of the disease, such as fluid retention, hyperkalemia, high blood pressure, anemia, heart disease, weak bones, erectile dysfunction, infection, complications during pregnancy, and end-stage renal disease [6,7]. It is possible to use albuminuria and continuously elevated blood
creatinine as predictive and diagnostic markers. When a false-positive reduction in estimated eGFR from serum creatinine is suspected, serum cystatin C is a potential biomarker [8]. A patient has chronic kidney disease (CKD) if their eGFR is less than 60 mL/min/1.73 m2 or if they exhibit kidney disease markers (proteinuria, hematuria, and radiological abnormalities) that have persisted for more than three months [9]. A different technique for diagnosing the kidneys is ultrasound imaging.
It can verify the existence of cysts, small kidneys, cortical thinning, and other conditions [10].

Early CKD detection and prevention remain the best strategies for managing the disease in settings with limited resources. It is necessary
to strengthen primary, secondary, and tertiary prevention strategies, emphasizing raising awareness and performing routine tests for diabetes, hypertension, and albuminuria [11]. Reducing CV risk factors, managing albuminuria, and steering clear of possible nephrotoxins are all essential components of optimal CKD care [12]. Use insulin for diabetic treatment, erythropoietin for anemia and antiplatelet medication for coronary artery disease (CAD), and atorvastatin for dyslipidemia [13]. Diabetes, proteinuria, and a lower age are risk factors for end-stage renal disease (ESRD). Younger patients with CKD had much higher relative mortality risks [14]. Patients with CKD who are younger have significantly greater relative mortality risks [14]. Creatinine doubling, renal death and allcause mortality are among the outcomes of CKD [15].

CKD was occurs in 7–34.3% of the world’s population [16,17]. In 2020, there were more than 700 million cases of CKD worldwide [18]. A research that covered ten Asian nations found that 65.6 million persons with CKD had advanced CKD, out of 434.3 million adults with CKD [7,16]. The prevalence of CKD in Africa varied by region with values ranging from 3.7 to 69.5% [19-21], similarly, research carried out in many tertiary hospitals in Ethiopia found that the prevalence of CKD was 7.4% in the general population, 14.3% -18.22%, 22.1%, and 26% in patients with diabetes, hypertension, and hypertension combined [22-26]. Globally, chronic kidney disease is becoming an important threat that increases morbidity and mortality. A 2020 Global Burden of Disease report [27], predicted that 1.2 million deaths were directly caused by lower glomerular filtration rates. Between 1990 and 2017, the all-age mortality rate from CKD increased by 41.5% [28,29].

According to a population-based prospective cohort research performed out in Taiwan, around 39% of CKD patients deceased from all causes before reaching the age of 65 [30]. Studies conducted across African nations indicate that the all-cause death rate for patients with chronic kidney disease (CKD) ranged from 32.56% to 39% [31,32]. The all-cause mortality of patients with chronic kidney disease (CKD) ranges from 17% to 35.1%, according to retrospective studies done in a few Ethiopian dialysis units [33,34]. The Chronic Renal Insufficiency Cohort (CRIC) data show that 35.0 hospitalizations per 100 person-years are caused primarily by CKD [35]. According to a multicenter cohort research conducted in Japan, the hospitalization rate of patients with chronic kidney disease (CKD) was 17.1 times greater than that of age and sexmatched controls. All-cause hospitalization increased with CKD stage and with the presence of diabetes [36].

A nationally representative cross-sectional study of primary care in Scotland concluded that 98.2% of persons with chronic kidney disease (CKD) had one or more comorbidities [37]. Only 4% of patients in a different prospective cohort study with stage 3 CKD were found to have no comorbidities, 26% to have one, 29% to have two, and 40% to have more than two. The overall incidence of hypertension was 88%, followed by “painful condition” (30%), anemia (24%), ischemic heart disease (23%), diabetes (17%), and thyroid problems (12%) [38]. Anemia (64.5%), hypertension (45%), chronic glomerulonephritis (24%) and diabetes (20%) were the most common comorbidities and complications, according to a hospital-based cross-sectional study conducted in Ethiopia [39]. Regarding CKD patients, another cross-sectional study conducted in Ethiopia revealed that around 85.33% had anemia varying in severity [40].

Countries with low or middle incomes are insufficiently prepared tohandle the catastrophic effects of chronic kidney disease (CKD), especially when the disease is advanced. Common risk factors are increasing at a rapid rate, especially in developing nations, which will lead to deeper and more significant burdens than these countries have the capacity to handle [41]. Patients with CKD need to be watched for complications and treated if one is found, as these diseases have the potential to determine the outcomes of therapy [42]. Although the abundance of evidence regarding the global burden of CKD in terms of mortality and morbidity, few studies have been conducted in Africa, especially in Ethiopia. The majority of the studies that are currently available were retrospectively or cross-sectional during short time periods [31,32]. The currently available prospective observational studies had small sample sizes and were short-term in scope. Dialysis-dependent CKD patients were the only ones included in previous studies on the effects of CKD treatment and related factor [33,34]. Studies done on CKD patients who are hospitalized have limitations as well. Therefore, the aim of this study was to identify the management outcomes and related factors for patients with chronic kidney disease (CKD) at certain Ethiopian tertiary hospitals.

Methods and Material

Study design, period and settings

The Prospective observational study was conducted among nondialysis dependent chronic kidney disease patients admitted at Jimma University Medical Center (JUMC), St. Paul’s Hospital (St.PH) and Menelik II comprehensive specialized and Referral Hospital (MCSRH) from June 30, 2022 to March 30, 2023.

JUMC is one of the oldest public hospitals in the country with a bed capacity of 800. Geographically, it is located in the city of Jimma, 352 km southwest of Addis Ababa. Currently it is the only teaching and referral hospital in the southwestern part of the country providing health services for patients come from the catchment population of about 15 million people.

One of the service departments offering service 365 days a year is the renal clinic. It has six licensed nurses and one full-time nephrologist. For both CKD and AKI patients, there were two hemodialysis machines available to provide dialysis treatments. On average, 18–21 people follow dialysis service and dialyzed twice per week.

St.PH is another public hospital founded in 1969 with the help of the German Evangelical Church and run under FMoH. The hospital has about 350 beds serving about 300,000 patients on average annually. It has a catchment population of more than 5 million. It is an academic center for SPHMMC, where different Specialty and sub-specialty medical education is being provided. It is providing sub-specialty certificate in Nephrology and it has both kidney transplant and dialysis services. It has seven fulltime Nephrologists, 32 nurses, and 18 hemodialysis machines available to provide dialysis treatments. About 45–50 people receive dialysis twice to three times per week on average.

MCSRH is one of the public health care facilities run under Addis Ababa City Administration Health Bureau. It has 203-bed capacity and one of the first Ethiopian hospitals established in 1902 E.C. It serves the city community and other referral cases from different corners of Ethiopia. In addition to its already well-known services in forensic, pathology, and optometry, MCSRH offers a variety of services.

Since May 2022, MCSRH has started to provide large scale kidney transplant and dialysis with public-private partnership under the auspices of the Addis Ababa Health Bureau, and YeAb Medical Center. Accordingly, it’s providing transplant and dialysis services having one full-timer Nephrologist, 18 nurses and 32 dialysis machine which can dialyze up to 90 patients per day.

Population

All CKD patients admitted and managed at JUMC, St.PH and MCSRH during the study period were the source of population. The study population were, all non- dialysis dependent CKD patients who fulfilled the inclusion criteria. The Inclusion criteria were CKD patients aged ≥ 18 years and admitted to the hospitals’ internal medicine ward at the time of data collection, CKD patients who provided their consent to participate in the study, CKD patients on treatment except RRT .CKD Patients having in-complete medical records, with confirmed cognitive disorder, unwilling to participate CKD patients admitted to intensive care unit and pregnant women were excluded. Dependent variable was CKD Treatment outcomes (alive and death); independent variables include Sociodemographic characteristics (Sex, age, marital status, educational
status, income status, and residency), duration of CKD illness, history of hospitalization due to CKD, History and current status of smoking and drinking, physical activity, diet issue, admission, on averagely during hospitalization and at discharge stage of CKD, laboratory investigations (renal function test, CBC, urine analysis, electrolyte tests, FBS and lipid profiles), CKD comorbidities, modified Charleston comorbidity index, CKD complications, and number of complications., Duration of hospitalization, number & types of medications used during hospitalization.

Sample size and Sampling technique /Sampling procedures

The sample size was calculated using simple population proportion formula by considering p=0.5 (estimated 50% death of CKD patients due to lack published data on non-dialysis dependent hospitalized CKD patient’s mortality in Ethiopia) and d (sampling error) = 5% and using 95% confidence level, the final sample sizes was 176. Consecutive sampling technique was used to include participants until the required sampling size was obtained. Based on the settings estimated monthly
admission, the total sample size was distributed proportionally. Accordingly; 0.4*176; 69, 0.31*176; 56, and 0.29*176; 51 samples were allocated to JUMC, St.PH and MCSRH, respectively.

Based on the minimum requirements settled (having fully functional dialysis center, recruiting full time nephrologist and
providing uninterrupted service for the past 3 months before data collection initiation) to select the study settings. Accordingly, Jimma University Medical Center, Felege-hiyot teaching hospital, Haromaya University teaching hospital, Gondar University teaching hospital, Hawassa University teaching hospital, St. Paul’s Hospital, Tikur Anbessa Specialized hospital, Emperor Zewditu Memorial hospital and Menelik II comprehensive specialized and Referral Hospital were nominated to be the study settings. From these study settings, Jimma University Medical Center, St. Paul’s Hospital, and Menelik II comprehensive specialized and Referral Hospital were selected by lottery method to be the study area
for this study.

Data collection instrument and procedures

Non-dialysis dependent CKD patients who admitted to internal medicine wards were approached for the study. After written informed consent has been acquired, study participants were recruited. Structured data collecting instrument, which included questionnaire and data abstraction formats, were developed by researching different literatures for important variables to this study and used to extract all necessary information [32,34,37,38,42-54]. The structured questionnaire was
translated to vernacular languages; Amharic and Afan Oromo and then back to English. An interview with self-administered questionnaire was undertaken to collect information such as socio-demographics and self-reported non-pharmacologic management of CKD. The sociodemographic characteristics included age, gender, educational and marital status, occupation, residence, history of hospitalization event related to CKD, and the length of CKD sickness. Self-reported nonpharmacologic management of CKD factors were diet and physical activity plan, history and current status of smoking and drinking habit. Data abstraction formats were employed to collect most recent preadmission and throughout hospitalization laboratory investigations, imaging results, and other clinical follow-up data required for the study. Estimated glomerular filtration rate (eGFR) was estimated by the CKDEPI creatinine equation [55]. Types and amount comorbid medical illnesses and most probable CKD related sequelae were acquired from medical charts and the patients or their attendants. Types and number of medications prescribed, duration of hospital stay and CKD treatment outcome in hospital were also abstracted. The modified Charleston Comorbidity Index (mCCI) for hospitalized patients was used to weigh and categorize their comorbidity [56]. Phone-call format was used to follow the conditions (how they were doing, how they adhered to their appointment, their post referral management) of the patients discharged or referred alive from the study settings. The phone call was conducted for one to three times per patient depending on their length of hospital stay and occurrence of primary outcome [57]. The first call was conditional; if the patients’ length of hospital stay was around two months, they called twice only. If they discharged with in less than one month of hospital stay, they called three times every two months starting from the first date of admission. Patients who continued receiving chronic RRT had following at their respective dialysis facility. Data were acquired by following the patients for six days to six months with trained data collectors (nurses and pharmacists), through interviews, following the patient in the ward and reviewing their chart and phone-calling the patients or their family or close relative or friend. The outcome of treatments was measured based on the records of attending physician, observing the patients’ status, laboratory results, imaging results, treatment provided, the data provided by the patients or their family or their close relatives or close friends.

Outcome measurement and validation

The primary outcome of this study was all cause mortality of admitted CKD patients while on follow-up as confirmed by attending ward physician’s death summary or information given by family member or close relatives or friends. The secondary outcomes of this study were length of hospital stay; defined by the date the patient admitted to the hospitals
to the date they left the hospital due to death or discharge or referred, started renal replacement therapy; defined by the date machine support initiated due to complete termination of kidney function, complicated as explained by the presence of clinical (confirmed by attending physician diagnosis recorded on the patient chart) and laboratory results (serum potassium for hyperkalemia, calcium, phosphorus, PTH, bicarbonate for metabolic acidosis, albumin, CBC for infection and anemia, Proteinuria and hematuria for AKI, Scr. for creatinine clearance.) and imaging results (Ultrasound, ECG, MRI, dual energy X-ray absorptiometry (DXA) and EEG) that indicate the development of new complications with in the period of follow up and progression in stage of CKD as defined by a decrease in eGFR from baseline by ≥ 25% [58]. Comorbidity and complications; the patient’s self-reported medical history, the drugs they took, the results of the clinical assessment, the lab results, and the imaging data were used to determine the patient’s comorbidity and complications. Following a comparison of the available information with the reference values, these medical issues were confirmed.

Data quality management

Training was given to the data collectors (three BSc. Nurses) and supervisor (one Clinical Pharmacist) to familiarize them with the data collection instruments and on how to collect the necessary data from patient medical charts, and how to conduct patient interview on face to face and on phone call. Subsequent support was provided by the principal investigator as needed. Pre-test was conducted on nine patients at Zewditu memorial hospital for completeness of variables one week
before the actual data collection started. Based on the results obtained from pre-test, amendments were made on the assessment tools and way of assessment. The principal investigator and appointed supervisor were closely supervised the data collection on a daily basis. At the end of each data collection days, the principal investigator or the supervisor was checked the completeness of filled questionnaire and recorded information to ensure its quality.

Data analysis and interpretation

The collected data were checked for completeness and coded. Data were entered into Epidata version 4.6.0. and exported to Statistical Packages for Social Science (SPSS) version 25 for statistical analysis. Descriptive statistical analysis such as frequency and percentages for categorical variables; means and standard deviations for continuous variables, were performed to describe the study variables. Kaplan Meier survival curve was used to indicate the survival time of the patients. Cox regression was performed to identify the association between the independent and dependent variables. Before Cox regression, the multi-collinearity test was done to know the interaction of independent variables, and the adequacy of cell distribution was checked by using the chi-square (ꭓ2) test. Bivariate cox-regression was performed to select candidate variables for multivariate cox-regression analysis. Variables having a p-value <0.25 were selected for multivariate cox-regression analysis. And multivariate cox-regression was performed to identify independent predictors of mortality. Finally, variables having p-value <0.05 were considered statistically significant. Hazard Ratios (HR) and 95% CI were used to identify the strength of the association.

Ethical consideration

The study was conducted in accordance with the principles of the Declaration of Helsinki and the International Council on Harmonization Guidelines for Good Clinical Practice. This study was conducted after ethical clearance was obtained from Jimma University’s Institute of Health Sciences’ Research Ethical Review Board (Ref. No; IHRPG1/12/6/22), Institutional Review Board of St. Paul’s Hospital Millennium Medical College (Ref. No; PM23/149) and Addis Ababa City Administration
Health Bureau (Ref. No; A/A/ 1249/227). An official letter of support was submitted to the hospitals’ heads of department of internal medicine ward. Written informed consent was gained from the study participants after they understood the purpose of study and its benefit. Participants were assured about the confidentiality of their information in the study by excluding any of personal identifier in the data collection form. Participants were informed about the right to withdraw at any point of the follow up and interview.

Operational definitions and definition of terms

Chronic Kidney Disease: an abnormalities of kidney structure or function, present for >3 months, with implications for health and CKD is classified based on cause, GFR category, and albuminuria category (CGA). Stage I; Normal or high (≥90), Stage II; mildly decreased (60-89), Stage III; moderately decreased (30-59), Stage IV; Severely decreased (15-29),
Stage V; Kidney failure (<15) ml/min/1.73m2. Persistent albuminuria categories are A1; normal to mildly increased (<30), A2; Moderately increased (30-300), A3; Severely increased (>300) mg/g [59]. 

Treatment outcome in Hospital: treatment outcome was explained as improved; decreased in stage, stable; no decrease or increase in stage of CKD throughout the hospitalization, progressed in stage = increased in stage CKD, developed to ESRD, died, and complicated due to CKD .

Treatment outcome after discharged: Alive/ died

Cardiovascular disease: Coronary artery disease, cardiomyopathy, valvular heart disease, myocardial infarction, congestive heart failure, cerebrovascular disease, atrial fibrillation, peripheral arterial disease [60].

Hyperkalemia; serum potassium concentration greater than 5.5 mEq [61].
Hypertension; Clinic /Office systolic BP >130/80mm Hg [62,63].

Edema: presence of peripheral edema during presentation as diagnosis or patient on recent diuretic medications for fluid overload indication during the study period [6].

Comorbidity: self-reported doctor-diagnosed condition, diseasespecific medication or blood results, and treatment burden as number of ongoing medications [5].

Complications: Medical problem reported by patients, diagnosed by clinicians, indicated by investigations or medication provided following CKD illness [64].

Multimorbidity: Presentation of at least two types of medical problem simultaneously.
Advance stage of CKD: Stage of CKD beyond stage three.
End Stage Renal Failure: Stage five (eGFR < 15 ml/mn/1.73m2) [65].

Results

Patient flow chart

The response rate of participants was (170/178) (95.5%). Greater proportion the patients were included from JUMC. About 71 CKD patients’ death were recorded throughout follow-up period (Figure 1).

Figure 1: Patient flow chart of patients admitted at selected tertiary Hospitals in Ethiopia, June 2022 to March 2023

Demographic and clinical characteristics of patients

Of 170 CKD patients included in this study, 120(70.6%) were males. The mean (± SD) age of the CKD patients was 45.19 ± 13.86 years. About 84.1% of CKD patients’ age were <60 years. Out of total, almost two-third (78.8%) of them married. About one-third (37.6%) were farmers. About one-third (28.8%) of the participant cannot read and write (Table 1).

Table 1: Socio-demographic characteristics of CKD patients admitted at selected tertiary Hospitals in Ethiopia, June 2022 to March 2023, (N=170).

Others; NGO employee, Retired

The mean (± SD) systolic blood pressure (SBP) was 158.17 ±26.39, 151.40 ± 23.25 and 144.13 ± 21.28 mmHg at admission, averagely during hospitalization and at discharge respectively. Majority (86.2%) of patients on average had SBP of ≥130 mmHg. The mean (± SD) of diastolic blood pressure (DBP) was 91.35±13.51, 86.96 ±11.5 and 83.81 ±9.66 mmHg at admission, on average during hospitalization and at discharge respectively. About more than three quarter (83.2 %) of the participants had DBP of 80-110 mmHg throughout hospitalization period. More than half (51.8%) of study participants had grade three edema at the beginning of study. About 60.6%) of the patients had grade one edema on discharge.

The participants stayed in hospital for mean (± SD) of 17.22 ± 7.57 days. More than half (60.6%) of the study participants had stayed in hospital for more than two weeks. About 70.6% patients had less than two years duration of CKD illness. Majority, 92.3% and 90%, of the patients had infection and hypertension respectively. About one-third (33.5%) of the patients had five or greater score of modified Charleston comorbidity index. Majority (92.4%) the patients had history of hospitalization event due to CKD. Almost all, 169(99.4%) of this study participants had at least one comorbidity. The mean (± SD) of comorbidity across the patients was 2.79± 0.95. The mean (± SD) duration of follow-up was 114.6±77.9 days
(Table 2).

Table 2: Clinical characteristics and comorbidities among CKD Patients admitted at selected tertiary Hospitals in Ethiopia, June 2022 to March 2023, (N=170).

Others; Bronchial asthma, Bicytopenia, Colonic CA, SLE, paraplegia, Solitary Kidney, hemorrhoid, hypertensive heart disease, diabetic rethinopathy. TNC; total number of comorbidity, CPN; chronic pyelonephritis, SLE; systemic lupus erythematous

Laboratory findings of chronic kidney disease Patients

Of 170 CKD patients, about 115(67.8%), had stage five (<15ml/mn/1.73 m2), CKD during hospitalization. The mean (± SD) of eGFR was 11.43 ±9.1, 11.95±10.6 and 13.64 ±11.57 ml/min/1.73m2 at admission, on average during hospitalization and at discharge respectively. About the quarter (25%) of the study participants were in stage four (15-29 ml/ min/1.73m2) CKD. In general, almost all (99%) of the study participants had stage three and above CKD. The mean (±SD), of serum creatinine
was 8.1±5), 8.5±5.5) and 8.1±5.8) mg/dl at admission, on average during hospitalization and at discharge respectively. Over half (51.8%) of the study participants had > 5.5 serum potassium. The mean (±SD), of serum potassium was 5.37±1.04, 5.36± 0.98) and 5.00± 0.98 at admission, on average during hospitalization and at discharge respectively. Majority (75.3%), of the study participants had moderate to severe anemia having mean (±SD), serum hemoglobin 8.38± 2.30, 8.22 ± 1.77 and 8.42 ± 1.72 at admission, on average during hospitalization and at discharge respectively. Majority (87%) of the study participants had grade one to two proteinuria on urine dipstick at the beginning of the study. About 71.8% became free of proteinuria on discharge. Around 79.5% of the patients had grade two and above hematuria at baseline. Majority (79.4%) of them became negative at discharge from hospitals. Of total patients with urine investigation, 27.7% had bacteria in their urine. Among 70% of the participants, white blood cell was high on urine analysis at beginning of the study. Protein excretion rate on a 24-hour urine sample collection was 300 mg/24 hours in 34.7% of research participants (Table 3).

Table 3: Laboratory findings of CKD Patients admitted at selected tertiary Hospitals in Ethiopia, June 2022 to March 2023, (N=170).

Non-Pharmacologic management profile of chronic kidney disease patients

Out of total, majority (92.9%), of the patients had a dietary plan with the clinicians or any health care providers. More than three quarter (84.1%), of the participants had adhered to their dietary plan. Regarding intense moderate exercise, around 69 of all CKD patients had a history of intense moderate exercise which was <3 days per week and 30% had <150 minutes per week of intense moderate exercise. Regarding to smoking and drinking habit status, 27.6% and 34.7% were previous smoker and drunker respectively (Table 4).

Table 4: Self-reported non-pharmacologic management approaches for the CKD patients admitted at selected tertiary Hospitals in Ethiopia, June 2022 to March 2023, (N=170).

Pharmacologic management profile of chronic kidney disease patients

Fifty (29.4%) and 2 (1.2%) of the total CKD patients took ACEIs and ARBs, respectively. Of the BBs, 34 (20%) of the CKD patients received metoprolol prescriptions. 119 (or 70%) of the total CKD patients took calcium channel blockers (CCBs). Furosemide was used to manage the majority (97.7%) of the patients while they were in the hospital. After insulin (38.8%), metformin was the second most commonly prescribed anti-diabetic drug (19.4%). Prior to furosemide, antibiotics were the second (94.1%), most frequently recommended medicine for the hospitalized CKD patients. More than half of study participants (61.8%) and (68.2%) used ranitidine and iron supplements, respectively. Approximately 65 (38.2%) of the study subjects received more than ten different prescriptions while they were in the hospital (Table 5).

Table 5: Medications used among chronic kidney disease patients admitted at selected tertiary Hospitals in Ethiopia, June 2022 to March 2023, (N=170).

Others; Calcium supplement, PRBC, ESA, Salbutamol Puff, labetalol, Omeprazole, pantoprazole, prednisolone, table salt, UFH; warfarin ACEI/ARBs: Angiotensin converting enzyme inhibitors/Angiotensin receptor blockers, TNM; total number of medications

Complications of CKD patients: Nearly all (169; 99.4%) of the total CKD patients experienced edema. The majority of the patients, 163 (95.8%), 161 (94.7%), and 152 (89.4%) experienced anemia, acute renal injury, and reduced urine output respectively. The mean (± SD), of complications across the patients was 9.35± 1.5 (Table 6).

Table 6: Chronic kidney disease complications among CKD patients admitted at selected tertiary Hospitals in Ethiopia, June 2022 to March 2023, (N=170).

Others: hyperparathyroidism, hypernatremia, Upper GI bleeding

CVD; Cardiovascular disease, AKI; Acute kidney injury, DM; Diabetic mellitus, CPN; chronic pyelonephritis, UG; Uremic gastropathy, Ischemic heart disease, CCI; Charleston comorbidity index

Management of CKD patients’ comorbidities and complications: From the 65 of CKD patients with both DM and HTN, 61(93.9%) patients took Non-ACEIs based regimen with Insulin and 23 (35.4%), were prescribed with ACEIs based regimen+ insulin. Iron preparations 105 (64.4%), was commonly used for the treatment of CKD patients with anemia. This study also revealed that furosemide 165 (97%), was commonly prescribed for the management of CKD patients with edema and regular insulin 115 (94.2%), and calcium gluconate 72(59.0%), were taken in the CKD patients who had hyperkalemia as complication. About half 28(48.3%), of the CKD patients with CVD had treated by BBs (Table 7).

Table 7: Medication regimens for the management of chronic kidney disease comorbidities and complications among chronic kidney disease patients admitted at selected tertiary Hospitals in Ethiopia, June 2022 to March 2023, (N=170).

DM; Diabetes mellitus, ACEI; angiotensin converting enzyme inhibitors, MTF; Metformin, ASA; acetyl salicylic acid, BBs; beta blockers, HTN; hypertension, CVD; cardiovascular disease, ESA; Erythropoiesis stimulating agents, PRBC; packed red blood cells

Treatment outcome of chronic kidney patients: Over the course of 649.266 person-months of follow-up, 71 (41.8%) patients’ death were recorded. According to estimates, there were 109 deaths per 1000 person- months at the end of the follow-up. From the total number of deaths, about half (47.9%), was occurred in hospital. 99 (58.2%), patients were survivors, of whom 42(24.7%), were on chronic renal replacement therapy. The mean (±SD), of decline in eGFR for the patients progress in stage of CKD was 13.0 ± 8.5 ml/ mn/ 1.73m2. The mean (±SD), percent of reduction from baseline eGFR was 49 ± 18.2% (Table 8).

Table 8: Treatment outcome of CKD Patients admitted at selected tertiary Hospitals in Ethiopia, June 2022 to March 2023, (N=170).

DU; Dialysis Units, TO; Treatment Outcome, RRT; renal replacement therapy, *; included in other groups

Survival time of CKD patients: The mean survival time of CKD patients was 116.9 days (95% CI: 105.3- 128.5). About 60% of the patients were survived at first half of the follow-up period. Of total who were alive at third month, about 90.1% were stayed survived at end of study (Figure 2).

Predictors of Chronic Kidney disease mortality: On bivariate cox regression; Serum potassium on average during
hospitalization and at discharge, hemoglobin less than 7 mg/dl throughout hospitalization, systolic blood pressure >159 mmHG on discharge, presence of ischemic heart disease, modified CCI, total number of comorbidity, presence of Hyperkalemia, CVD, Wasting, Encephalopathy, Uremic Gastropathy, vomiting, using intranasal oxygen and not prescribing amlodipine as management and using ≥ 10 types of medications were candidate for multivariate cox-regression at a p-value <0.25. By a multivariate cox proportional hazard regression modeling, variables with p- value < 0.05 were considered as the predictors of CKD patients’ mortality. Accordingly, admission hemoglobin < 7 mg/dl [AHR=3.3, 95%CI, (1.39-7.8) P=0.006], systolic blood pressure at discharge >159 mmHg [AHR= 4.65, 95%CI (2.07-10.42), P=0.000], having modified CCI weights greater than or equal to five [AHR= 5.00, 95%CI (2.60-9.64), P=0.000], having Encephalopathy [AHR= 2.58 , 95%CI (1.45-4.56), P=0.001], and having nausea and vomiting [AHR= 1.68, 95%CI (1.01- 2.80), P= 0.046] remained significantly associated with CKD mortality (Table 9).

Table 9: Bivariate and multivariate Cox Regression of risk factor analysis for mortality of CKD patients admitted at selected tertiary Hospitals in Ethiopia, June 2022 to March 2023.

Discussion

This was the pioneer study assessing the treatment outcomes and associated factors among admitted non-dialysis dependent chronic kidney disease patients at selected tertiary Hospitals in Ethiopia. Over a period of 649.266 person-months, 170 patients were followed and 71 (41.8%), patients were passed away. The mean survival time of CKD patients was 116.9 days (95% CI: 105.3-128.5. The most commonly prevalent comorbidities were infection (92.3%), and hypertension (90%). About one-third (33.5%), of the patients had five or greater weight of mCCI.

The most common CKD related complications were edema (99.4%), anemia (95.4%), AKI (94.7%). The mean (± SD), of complications across the patients was 9.35± 1.5.

Severe anemia at admission [AHR= 3.3, 95%CI, (1.39-7.8) P=0.006], systolic blood pressure at discharge greater than 159 mmHg [AHR= 4.65, 95%CI (2.07-10.42), P=0.000], having modified CCI weights greater than or equal to five [AHR= 5.00, 95%CI (2.60-9.64), P=0.000], and having Encephalopathy [AHR= 2.58 , 95%CI (1.45-4.56), P=0.001] were the factors significantly associated with CKD patients’ mortality.

The mortality rate in the current study was in line with the previous research done in Tanzania [31], and Ethiopia [34], despite it is lower than the studies conducted in Korea and in Pakistan [46,66], as well as in Canada [67], and Girona; Spain [68]. The difference can be explained by the fact that this study was conducted among a smaller sample size over
a shorter period of time. However, this result is higher than the studies done in the USA [65], Spain [58], patients from 11 European countries [69], and Ethiopia [33]. The fact that this study included hospitalized, non-dialysis dependent CKD patients may account for the discrepancy. Most study participants had advanced CKD, which is distinguished by a heavy burden of comorbidities and complications.

The proportion of patients with infection (92.3%), was higher than the study conducted in Ethiopia [33], and Nepal [70]. The elevated infection risks, like edema and severe proteinuria, could account for this discrepancy. The prevalence of hypertension (90%) was consistent with earlier research conducted at the University of Southampton [64], Nigerian Tertiary Kidney Care Hospital [49], and Tikur Anbessa Specialized Hospital [71]. However, it was higher than studies conducted
in India [72], Ghana [53], Ethiopia [39,40]. The plausible explanation could be the proportion of stages of CKD patients in this study was higher for advanced stage group. In addition, the participants of this study had high load of comorbidity and complication which also challenge the management of hypertension.

The multimorbidity in this study (94.1%) was higher than the studies conducted in Nigeria [49,73], and Taiwan [74]. The most likely reason could be the higher proportion advanced stage CKD in this study. The participants with at least five score of mCCI (33.5%), was lower than the study conducted in Singapore [75]. The gap may be caused by a different lifestyle and longer life expectancies of previous study. All of CKD patients experienced at least five secondary complications. This was in line with the Singaporean study [76].

The prevalence of anemia in this study (95.8%), was in line with the earlier study carried out in Nepal [77]. In contrast to the studies done in Ethiopia [40], and Ghana [53], this study result was higher. The strong impact of uremic syndrome of this study can be used to explain the differences. This research’s edema prevalence (99.4%) was consistent with the study done in Ghana [53], but higher than the studies done in the UK [78], Malaysia [47], and Nigeria [79]. The high prevalence of
proteinuria and bedridden could be the likely explanation for the variance.

Evidence on the quantifiable prevalence of AKI on CKD among CKD patients is limited. However, data suggests that AKI and CKD work together to advance each other in a bidirectional manner [80]. The prevalence of uremic encephalopathy (45.3%) is in agreement with the study done in Tanzania [31], but, lower than the earlier studies carried out in Korea [81], and at Ayder Comprehensive Specialized Hospital [82]. The discrepancy can be explained by study facilities’ competence in identifying the problem.

The hazard of mortality among CKD patients with the admission Hg. less than seven mg/dl was increased by a 3.3 when compared with those who had Hg. level greater than ten mg/dl. This was in line with the study conducted among Japanese [83]. However, this result was lower than the study conducted in Indonesia [84]. The discrepancy could be due to the
previous study was conducted among ESRD patients on dialysis which may had blood loss during the procedure and used different method. The current result is higher than the researches done in Denmark [85], and Italy [86]. The possible discrepancy may be caused by the study design; this study focused on anemia among hospitalized CKD patients, whereas
earlier investigations focused on new-onset anemia among patients with CKD.

The hazard of mortality in CKD patients with systolic blood pressure at discharge greater than 159 mmHg was found to be increased by 4.65 times when compared with those with less than 130 mmHg. This result was higher than earlier research done in USA [87]. The variance may be related to an earlier study that was done among CKD patients in pre-ESRD stages and whose results were presented based on sub-group analysis.

Comparing CKD patients with mCCI score of five or greater to those with mCCI weights of less than five, the risk of mortality increased by 5 times. This was higher than the study conducted in the USA [88]. The most likely explanation is that whereas the majority of research participants in this one had a significant burden of complications and co-morbidities and were therefore ineligible for dialysis, the earlier study participants were candidates for hemodialysis.

Uremic encephalopathy was observed to increase the risk of death in CKD patients by 2.58 times compared to those without it. This result is higher than the previous study conducted in Peru [89]. Most of this study’s participants were not on hemodialysis, which is the main treatment for the problem. However, the previous study participants were dialysis dependent, can be the most plausible justification.

The hazard of mortality among CKD patients presented with vomiting was increased by a 1.68-fold when compared with those without it. This outcome was lower than the study conducted in Tanzania [31]. The most plausible explanation is that the current study was conducted among admitted CKD patients where perhaps such a problem was already addressed or the outcome was known, whereas the prior study was undertaken among CKD patients with acute complications in emergency departments.

Conclusion

The rate of all-cause mortality was higher among CKD patients. Severe anemia, higher SBp, higher score of mCCI, Uremic encephalopathy and vomiting were among the indicators substantially linked to CKD patients’ mortality. The majority of the study’s participants had more comorbid CKD problems than average. Among the most common comorbidities were infections, hypertension, and diabetes. CCBs, insulin, and antibiotics made up the majority of the recommended drugs. The most prevalent CKD complications among patients were anemia, edema, reduced urine output, and hyperkalemia.

Acknowledgment

We would like to thank Jimma University, data collectors and all study participants.

Funding

This research was funded by Jimma University Institute of Health. The funding body had no any role in the design of the study, data collection, and analysis, interpretation of data and in writing the manuscript.

Authors’ Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Availability of Data and Materials

Readers who will require data and materials of the current study can communicate and get from the corresponding author with a reasonable request.

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