Study design and setting
This was a prospective study conducted among adult patients admitted on the medical wards of Masaka RRH. This is the largest government hospital in Masaka district, which is located in south central Uganda. The hospital provides both preventive and curative services to over two million people. This hospital has 330 bed capacity with the medical wards using up over 21% of the hospital beds. Medical wards admit patients with various medical conditions including but not limited to anemia, liver cirrhosis, heart failure, malaria, diabetes mellitus and hypertensive disorders. The hospital has no specialized nephrology clinic. However, it runs a daily general medical outpatient clinic, hypertension and diabetes mellitus clinics at least once a week.
Study population and procedures
All adult patients admitted to the medical wards of Masaka RRH between September 2020 and November 2020 were consecutively screened for eligibility to join the study. Patients were enrolled if: 1) were aged 18 years and above; 2) were admitted on medical wards for at least 24 h; 3) provided written informed consent. Patients were excluded if they had no phone contacts to allow follow-up. Details are shown by study patient flow chart in Fig. 1.
A detailed questionnaire was administered to all enrolled patients by study personnel. The questionnaire captured information on demographics and risk factors for kidney disease. A venous blood sample and a midstream spot urine sample were collected from all patients using aseptic techniques. Approximately 4mls of venous blood was drawn from each patient into a syringe then placed into a red top vacutainer to assess for serum creatinine. The eGFR were calculated using the chronic kidney disease-Epidemiology collaboration (CKD-EPI) 2021 equation which was used for identifying the patients with kidney disease in the field for sub-sequent follow-up. Given that CKD-EPI 2021 equation has not been validated in Africa, at analysis, eGFR has also been estimated using two additional creatinine-based equations: a) Full Age Spectrum (FAS) equation with specific Q values for African people and b) CKD EPI 2009 (without and with race factor) equation [8,9,10,11,12], however, findings from these estimates were not used for participant management. All patients were provided with a sterile urine container and educated briefly about provision of 20 mls of early morning mid-stream urine to assess for proteinuria.
Follow up phone call was conducted for all patients meeting the definition of kidney disease, 90-days following the baseline assessment. During the phone call, we established if patient was either still alive or had deceased but without establishing cause of death. Kidney disease was defined as proteinuria of ≥ 1 + and or kidney disease improving global outcome (KDIGO) eGFR criteria of < 60 mls/minute/1.73m2 [2]. Patients who were still alive were requested to return to the medical outpatient clinic for a repeat venous blood sample collection to measure the post 90-days serum creatinine and spot urine dipstick testing for proteinuria.
Outcome of interest as patients returned for clinic visit after 90 days was either CKD or no confirmed CKD. Clinical end point of the study was: 1) no confirmed CKD, 2) developed CKD. Lost to follow up (LTFU) was defined as going 2 months without attending a scheduled study visit. Chronic kidney disease was defined as ≥ 90 days of KDIGO eGFR criteria of < 60mls /min /1.73m2 and or proteinuria of ≥ + 1. Interval censoring strategy was used to determine the study outcomes.
Prevalence of CKD was also compared between the KDIGO eGFR criteria of < 60 ml/min/1.73m2 and with the age-adapted eGFR threshold definitions for CKD [13].
Laboratory evaluations
The venous blood collected was centrifuged within one hour of collection to obtain serum. Sample analysis for serum creatinine was conducted at Masaka RRH laboratory using Jaffe method traceable to an isotope dilution mass spectrometry [14]. SCr was measured using COBAS machine (C311) manufactured by (Roche diagnostics, North America) with a standard calibration reference range of 66-106umol/L. Urine samples were tested within 30 min of collection for proteinuria using a 10-parameter dipstick (Urinspect strips) manufactured by Artron laboratories.
Data management and statistical analysis
All data was entered into Microsoft office excel database, then exported to STATA version 13 software package for analysis. Continuous and discrete variables were summarized into medians with interquartile ranges (IQR). Categorical variables were summarized into frequencies and percentages. Proportions and bivariate analysis were used to identify risk factors associated with kidney disease by deriving percentages, odds ratios (OR), confidence intervals (CI) and P value for the respective relationships. P-value of ≤ 0.05 was considered statistically significant.
The prevalence of kidney disease was calculated as total number of patients with proteinuria of ≥ 1 + and or decreased eGFR of < 60mls/min/1.73m2 as calculated by each eGFR equation divided by the total number of patients enrolled. Proportion of patients who developed chronic kidney disease was calculated as number of patients with ≥ 90 days of decreased eGFR of < 60mls/min/1.73m2 as calculated by each equation and or proteinuria divided by total number of patients with kidney disease at baseline.
Prevalence of kidney disease at baseline determined by age adapted eGFR threshold definition was calculated as number of patients having age adapted eGFR definition of CKD divided by total number of patients enrolled.
Proportion of patients who developed CKD was calculated as number of patients with age-adapted eGFR threshold definitions of CKD at ≥ 90 days divided by number of patients followed up having kidney disease by age-adapted eGFR threshold definition of CKD at baseline screening.