Genome-wide association analysis of cystatin-C kidney function in continental Africa.

BACKGROUND: Chronic kidney disease is becoming more prevalent in Africa, and its genetic determinants are poorly understood. Creatinine-based estimated glomerular filtration rate (eGFR) is commonly used to estimate kidney function, modelling the excretion of the endogenous biomarker (creatinine). However, eGFR based on creatinine has been shown to inadequately detect individuals with low kidney function in Sub-Saharan Africa, with eGFR based on cystatin-C (eGFRcys) exhibiting significantly superior performance. Therefore, we opted to conduct a GWAS for eGFRcys. METHODS: Using the Uganda Genomic Resource, we performed a genome-wide association study (GWAS) of eGFRcys in 5877 Ugandans and evaluated replication in independent studies. Subsequently, putative causal variants were screened through Bayesian fine-mapping. Functional annotation of the GWAS loci was performed using Functional Mapping and Annotation (FUMA). FINDINGS: Three independent lead single nucleotide polymorphisms (SNPs) (P-value <5 × 10-8 (based on likelihood ratio test (LRT))) were identified; rs59288815 (ANK3), rs4277141 (OR51B5) and rs911119 (CST3). From fine-mapping, rs59288815 and rs911119 each had a posterior probability of causality of >99%. The rs911119 SNP maps to the cystatin C gene and has been previously associated with eGFRcys among Europeans. With gene-set enrichment analyses of the olfactory receptor family 51 overlapping genes, we identified an association with the G-alpha-S signalling events. INTERPRETATION: Our study found two previously unreported associated SNPs for eGFRcys in continental Africans (rs59288815 and rs4277141) and validated a previously well-established SNP (rs911119) for eGFRcys. The identified gene-set enrichment for the G-protein signalling pathways relates to the capacity of the kidney to readily adapt to an ever-changing environment. Additional GWASs are required to represent the diverse regions in Africa. FUNDING: Wellcome (220740/Z/20/Z).

Cross-sectional validation of the COPD Assessment Test (CAT) among chronic obstructive pulmonary disease patients in rural Uganda.

Measuring quality of life is a key component in the management of Chronic Obstructive Pulmonary Disease (COPD). The COPD assessment test (CAT), an easy to administer and shorter instrument than the standard Saint George's respiratory questionnaire (SGRQ), could be an alternative tool for measuring the quality of life of COPD patients in rural Uganda. A cross-sectional study was conducted between June and August 2022, consecutively recruiting 113 COPD patients aged > 40 years from the Low-Dose Theophylline for the management of Biomass-associated COPD (LODOT-BCOPD) study. Upon obtaining consent, participants answered an interviewer administered social demographic, CAT and SGRQ questionnaire. Internal consistency for both SGRQ and CAT was determined using Cronbach's alpha coefficient and values > 0.7 were considered acceptable while correlations were determined using Spearman's rank correlation. Limits of Agreement were visualised using Bland Altman and pair plots. Of the 113 participants, 51 (45.1%) were female. The mean age was 64 ± 12 years, 19 (16.8%) had history of smoking while majority (112 (99.1%)) reported use of firewood for cooking. There was a strong correlation of 0.791 (p < 0.001) between the CAT and SGRQ total scores with a high internal consistency of CAT, Cronbach's alpha coefficient of 0.924 (0.901-0.946). The agreement between the absolute CAT scores and the SGRQ scores was good with a mean difference of -0.932 (95% Confidence Interval: -33.49-31.62). In summary, CAT has an acceptable validity and can be used as an alternative to the SGRQ to assess the quality of life of COPD patients in rural Uganda.

HIV and Associated TB: A Lethal Association for Kidney Health?

Human immunodeficiency virus (HIV) and tuberculosis (TB) are the leading infectious causes of death globally. The combined brunt of these diseases is experienced mainly in low-income and lower-middle-income countries. HIV/TB have devastating effects on the kidneys, leading to accelerated decline of kidney function as well as mortality. Managing the triad of TB/HIV and kidney disease is challenging. We discuss the epidemiology of HIV/TB coinfection and the kidney and the key mechanisms of kidney disease including genetic susceptibility. The clinical presentation and pathology, as well as the challenges of diagnosing CKD in these patients, also are discussed. The strategies to prevent and manage HIV/TB-related kidney disease such as proper assessment, avoiding nephrotoxic regimens, drug dose adjustments, kidney function monitoring, avoidance of drug-drug interactions, and other interventions are explored. We also briefly discuss the complexities around HIV/TB patients on dialysis and kidney transplantation. HIV/TB coinfection presents an increased risk for kidney-related morbidity and mortality; patients with this triad need to be given special consideration for future research and management.

Measurement of kidney function in Malawi, South Africa, and Uganda: a multicentre cohort study.

BACKGROUND: The burden of kidney disease in many African countries is unknown. Equations used to estimate kidney function from serum creatinine have limited regional validation. We sought to determine the most accurate way to measure kidney function and thus estimate the prevalence of impaired kidney function in African populations. METHODS: We measured serum creatinine, cystatin C, and glomerular filtration rate (GFR) using the slope-intercept method for iohexol plasma clearance (mGFR) in population cohorts from Malawi, Uganda, and South Africa. We compared performance of creatinine and cystatin C-based estimating equations to mGFR, modelled and validated a new creatinine-based equation, and developed a multiple imputation model trained on the mGFR sample using age, sex, and creatinine as the variables to predict the population prevalence of impaired kidney function in west, east, and southern Africa. FINDINGS: Of 3025 people who underwent measured GFR testing (Malawi n=1020, South Africa n=986, and Uganda n=1019), we analysed data for 2578 participants who had complete data and adequate quality measurements. Among 2578 included participants, creatinine-based equations overestimated kidney function compared with mGFR, worsened by use of ethnicity coefficients. The greatest bias occurred at low kidney function, such that the proportion with GFR of less than 60 mL/min per 1·73 m2 either directly measured or estimated by cystatin C was more than double that estimated from creatinine. A new creatinine-based equation did not outperform existing equations, and no equation, including the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) 2021 race-neutral equation, estimated GFR within plus or minus 30% of mGFR for 75% or more of the participants. Using a model to impute kidney function based on mGFR, the estimated prevalence of impaired kidney function was more than two-times higher than creatinine-based estimates in populations across six countries in Africa. INTERPRETATION: Estimating GFR using serum creatinine substantially underestimates the individual and population-level burden of impaired kidney function in Africa with implications for understanding disease progression and complications, clinical care, and service provision. Scalable and affordable ways to accurately identify impaired kidney function in Africa are urgently needed. FUNDING: The GSK Africa Non-Communicable Disease Open Lab. TRANSLATIONS: For the Luganda, Chichewa and Xitsonga translations of the abstract see Supplementary Materials section.

Neutrophil gelatinase-associated lipocalin is elevated in children with acute kidney injury and sickle cell anemia, and predicts mortality.

Urine neutrophil gelatinase-associated lipocalin (NGAL) is a biomarker of acute kidney injury that has been adapted to a urine dipstick test. However, there is limited data on its use in low-and-middle-income countries where diagnosis of acute kidney injury remains a challenge. To study this, we prospectively enrolled 250 children with sickle cell anemia aged two to 18 years encompassing 185 children hospitalized with a vaso-occlusive pain crisis and a reference group of 65 children attending the sickle cell clinic for routine care follow up. Kidney injury was defined using serial creatinine measures and a modified-Kidney Disease Improving Global Outcome definition for sickle cell anemia. Urine NGAL was measured using the NGAL dipstick and a laboratory reference. The mean age of children enrolled was 8.9 years and 42.8% were female. Among hospitalized children, 36.2% had kidney injury and 3.2% died. Measured urine NGAL levels by the dipstick were strongly correlated with the standard enzyme-linked immunosorbent assay for urine NGAL (hospitalized children, 0.71; routine care reference, 0.88). NGAL levels were elevated in kidney injury and significantly increased across injury stages. Hospitalized children with a high-risk dipstick test (300ng/mL and more) had a 2.47-fold relative risk of kidney injury (95% confidence interval 1.68 to 3.61) and 7.28 increased risk of death (95% confidence interval 1.10 to 26.81) adjusting for age and sex. Thus, urine NGAL levels were found to be significantly elevated in children with sickle cell anemia and acute kidney injury and may predict mortality.

Association of impaired kidney function with mortality in rural Uganda: results of a general population cohort study.

OBJECTIVE: To determine the association between baseline kidney function and subsequent all-cause mortality. DESIGN AND SETTING: A general population-based cohort study from rural Uganda. PARTICIPANTS: People aged 18 years and above with measured baseline estimated glomerular filtration rate (eGFR), recruited from survey rounds in 2011-2012 or 2014-2015 and followed up to March 2019. OUTCOME MEASURE: The primary outcome was all-cause mortality, identified through reports from community health workers and verified by verbal autopsy. The association between baseline eGFR category and mortality was determined using multivariable Cox regression. RESULTS: Of 5812 participants in both rounds, we included 5678 (97.7%) participants with kidney function and mortality data; the median age was 36 years (IQR 24-50), 60.7% were female, 10.3% were hypertensive, 9.8% were HIV-positive and 1.5% were diabetic. During a median follow-up of 5.0 years (IQR 3.7-6.0) there were 140 deaths. In age-adjusted and sex-adjusted analyses, eGFR <45 mL/min/1.73 m2 at baseline was associated with a 5.97 (95% CI 2.55 to 13.98) increased risk of mortality compared with those with baseline eGFR >90 mL/min/1.73 m2. After inclusion of additional confounders (HIV, body mass index, diabetes, hypertension, alcohol and smoking status) into the model, eGFR <45 mL/min/1.73 m2 at baseline remained strongly associated with mortality (HR 6.12, 95% CI 2.27 to 16.45), although the sample size fell to 3102. Test for trend showed strong evidence (p<0.001) that the rate of mortality increased progressively as the category of baseline kidney function decreased. When very high eGFR was included as a separate category in age-adjusted and sex-adjusted analyses, baseline eGFR ≥120 mL/min/1.73 m2 was associated with increased risk of mortality (HR 2.68, 95% CI 1.47 to 4.87) compared with the reference category of 90-119 mL/min/1.73 m2. CONCLUSION: In a prospective cohort in rural Uganda we found that impaired baseline kidney function was associated with subsequently increased total mortality. Improved understanding of the determinants of kidney disease and its progression is needed in order to inform interventions for prevention and treatment.

Acute kidney injury in hospitalized children with sickle cell anemia.

BACKGROUND: Children with sickle cell anemia (SCA) are at increased risk of acute kidney injury (AKI) that may lead to death or chronic kidney disease. This study evaluated AKI prevalence and risk factors in children with SCA hospitalized with a vaso-occlusive crisis (VOC) in a low-resource setting. Further, we evaluated whether modifications to the Kidney Disease: Improving Global Outcomes (KDIGO) definition would influence clinical outcomes of AKI in children with SCA hospitalized with a VOC. METHODS: We prospectively enrolled 185 children from 2 - 18 years of age with SCA (Hemoglobin SS) hospitalized with a VOC at a tertiary hospital in Uganda. Kidney function was assessed on admission, 24-48 h of hospitalization, and day 7 or discharge. Creatinine was measured enzymatically using an isotype-dilution mass spectrometry traceable method. AKI was defined using the original-KDIGO definition as ≥ 1.5-fold change in creatinine within seven days or an absolute change of ≥ 0.3 mg/dl within 48 h. The SCA modified-KDIGO (sKDIGO) definition excluded children with a 1.5-fold change in creatinine from 0.2 mg/dL to 0.3 mg/dL. RESULTS: Using KDIGO, 90/185 (48.7%) children had AKI with 61/185 (33.0%) AKI cases present on admission, and 29/124 (23.4%) cases of incident AKI. Overall, 23 children with AKI had a 1.5-fold increase in creatinine from 0.2 mg/dL to 0.3 m/dL. Using the sKDIGO-definition, 67/185 (36.2%) children had AKI with 43/185 (23.2%) cases on admission, and 24/142 (16.9%) cases of incident AKI. The sKDIGO definition, but not the original-KDIGO definition, was associated with increased mortality (0.9% vs. 7.5%, p = 0.024). Using logistic regression, AKI risk factors included age (aOR, 1.10, 95% CI 1.10, 1.20), hypovolemia (aOR, 2.98, 95% CI 1.08, 8.23), tender hepatomegaly (aOR, 2.46, 95% CI 1.05, 5.81), and infection (aOR, 2.63, 95% CI 1.19, 5.81) (p < 0.05). CONCLUSION: These results demonstrate that AKI is a common complication in children with SCA admitted with VOC. The sKDIGO definition of AKI in children with SCA was a better predictor of clinical outcomes in children. There is need for promotion of targeted interventions to ensure early identification and treatment of AKI in children with SCA.

Mineral bone disorders and kidney disease in hospitalized children with sickle cell anemia.

Background: Mineral bone disorders (MBD) are common in sickle cell anemia (SCA). Frequent vaso-occlusive crises (VOC) further impact MBD in children with SCA. We evaluated the prevalence of markers of SCA-related MBD (sMBD) in hospitalized children and assessed the relationship between sMBD and individual mineral abnormalities with kidney disease. Methods: We prospectively recruited 185 children with SCA hospitalized with a VOC. Serum measures of mineral bone metabolism (calcium, phosphate, parathyroid hormone, 25-hydroxy vitamin D, FGF23, osteopontin) were measured at enrollment. The primary outcome was markers of sMBD defined as a composite of hypocalcemia, hyperphosphatemia, hyperparathyroidism, or deficiency in 25-OH vitamin D. Secondary outcomes included individual abnormalities in mineral metabolism. The Kidney Disease: Improving Global Outcomes (KDIGO) guidelines were used to define SCA-associated acute kidney injury (AKI). AKI was further assessed using urine NGAL as a marker of tubular injury. Acute kidney disease (AKD) was defined as a composite of AKI, an eGFR < 90 ml/min per 1.73 m2 using the Cystatin C GFR equation, or evidence of structural injury (positive biomarker test or albuminuria). Results: The mean age of children was 8.9 years and 41.6% were female. The prevalence of sMBD was 47.6%, with hypocalcemia the most frequent abnormality (29.9%, 55/184) followed by hyperphosphatemia (20.7%, 38/184), hyperparathyroidism (8.7%, 16/185), and vitamin D deficiency (5.4%, 10/185). There was no association between sMBD and sKDIGO-defined AKI using serial changes in creatinine or when incorporating biomarkers to define AKI. However, the presence of AKD was associated with a 2.01-fold increased odds of sMBD (95% CI 1.05 to 3.83) and was driven by a decrease in eGFR (OR, 2.90 95% CI: 1.59 to 5.29). When evaluating individual mineral abnormalities, hypocalcemia was associated with AKD and low eGFR while hyperparathyroidism was associated with low eGFR, AKI and structural injury. Vitamin D deficiency was associated with structural kidney injury. Vitamin D deficiency, hyperparathryoidism, and increases in FGF23 and osteopontin predicted mortality (p < 0.05 for all). Conclusion: MBD is common among children with SCA hospitalized with VOC. Biomarkers of kidney injury and bone health may help risk stratify children at risk of sMBD. Routine evaluation of sMBD in children with SCA may improve long-term bone health.

Effectiveness of low-dose theophylline for the management of biomass-associated COPD (LODOT-BCOPD): study protocol for a randomized controlled trial.

BACKGROUND: COPD is a leading cause of death globally, with the majority of morbidity and mortality occurring in low- and middle-income country (LMIC) settings. While tobacco-smoke exposure is the most important risk factor for COPD in high-income settings, household air pollution from biomass smoke combustion is a leading risk factor for COPD in LMICs. Despite the high burden of biomass smoke-related COPD, few studies have evaluated the efficacy of pharmacotherapy in this context. Currently recommended inhaler-based therapy for COPD is neither available nor affordable in most resource-limited settings. Low-dose theophylline is an oral, once-a-day therapy, long used in high-income countries (HICs), which has been proposed for the management of COPD in LMICs in the absence of inhaled steroids and/or bronchodilators. The Low-dose Theophylline for the Management of Biomass-Associated COPD (LODOT-BCOPD) trial investigates the clinical efficacy and cost-effectiveness of low-dose theophylline for the management of biomass-related COPD in a low-income setting. METHODS: LODOT-BCOPD is a randomized, double-blind, placebo-controlled trial to test the efficacy of low-dose theophylline in improving respiratory symptoms in 110 participants with moderate to severe COPD in Central Uganda. The inclusion criteria are as follows: (1) age 40 to 80 years, (2) full-time resident of the study area, (3) daily biomass exposure, (4) post-bronchodilator FEV1/FVC below the 5th percentile of the Global Lung Initiative mixed ethnic reference population, and (5) GOLD Grade B-D COPD. Participants will be randomly assigned to receive once daily low-dose theophylline (200 mg ER, Unicontin-E) or placebo for 52 weeks. All participants will receive education about self-management of COPD and rescue salbutamol inhalers. We will measure health status using the St. George's Respiratory Questionnaire (SGRQ) and quality of life using the EuroQol-5D (EQ-5D) at baseline and every 6 months. In addition, we will assess household air pollution levels, serum inflammatory biomarkers (fibrinogen, hs-CRP), and theophylline levels at baseline, 1 month, and 6 months. The primary outcome is change in SGRQ score at 12 months. Lastly, we will assess the cost-effectiveness of the intervention by calculating quality-adjusted life years (QALYs) from the EQ-5D. TRIAL REGISTRATION: ClinicalTrials.gov  NCT03984188 . Registered on June 12, 2019 TRIAL ACRONYM: Low-dose Theophylline for the Management of Biomass-Associated COPD (LODOT-BCOPD).

Prevalence of microalbuminuria and associated factors among HIV - infected ART naïve patients at Mulago hospital: a cross-sectional study in Uganda.

BACKGROUND: HIV infection affects multiple organs and the kidney is a common target making renal disease, one of the recognized complications. Microalbuminuria represents an early, important marker of kidney damage in several populations including HIV-infected antiretroviral therapy (ART) naïve patients. Early detection of microalbuminuria is critical to slowing down progression to chronic kidney disease (CKD) in HIV-infected patients, however, the burden of microalbuminuria in HIV-infected antiretroviral therapy (ART) naïve patients in Uganda is unclear. METHODS: A cross-sectional study was conducted in the Mulago Immune suppression syndrome (ISS) clinic among adult HIV - infected ART naïve outpatients. Data on patient demographics, medical history was collected. Physical examination was performed to assess body mass index (BMI) and hypertension. A single spot morning urine sample from each participant was analysed for microalbuminuria using spectrophotometry and colorimetry. Microalbuminuria was defined by a urine albumin creatinine ratio (UACR) 30-299 mg/g and macroalbuminuria by a UACR > 300 mg/g. To assess the factors associated with microalbuminuria, chi-square, Fisher's exact test, quantile regression and logistic regression were used. RESULTS: A total of 185 adult participants were consecutively enrolled with median age and CD4+ counts of 33(IQR = 28-40) years and 428 (IQR = 145-689) cells/µL respectively. The prevalence of microalbuminuria was 18.9% (95% CI, 14-25%). None of the participants had macroalbuminuria. CD4+ count <350cells/µL was associated with increased risk of microalbuminuria (OR: 0.27, 95% CI: 0.12-0.59), P value = 0.001). Diabetes mellitus, hypertension, smoking, alcohol intake were not found to be significantly associated with microalbuminuria. CONCLUSION: Microalbuminuria was highly prevalent in adult HIV - infected ART naive patients especially those with low CD4+ count. There is need to study the effect of ART on microalbuminuria in adult HIV - infected patients.

Prevalence of chronic respiratory disease in urban and rural Uganda.

OBJECTIVE: To determine the prevalence of chronic respiratory diseases in urban and rural Uganda and to identify risk factors for these diseases. METHODS: The population-based, cross-sectional study included adults aged 35 years or older. All participants were evaluated by spirometry according to standard guidelines and completed questionnaires on respiratory symptoms, functional status and demographic characteristics. The presence of four chronic respiratory conditions was monitored: chronic obstructive pulmonary disease (COPD), asthma, chronic bronchitis and a restrictive spirometry pattern. FINDINGS: In total, 1502 participants (average age: 46.9 years) had acceptable, reproducible spirometry results: 837 (56%) in rural Nakaseke and 665 (44%) in urban Kampala. Overall, 46.5% (698/1502) were male. The age-adjusted prevalence of any chronic respiratory condition was 20.2%. The age-adjusted prevalence of COPD was significantly greater in rural than urban participants (6.1 versus 1.5%, respectively; P < 0.001), whereas asthma was significantly more prevalent in urban participants: 9.7% versus 4.4% in rural participants (P < 0.001). The age-adjusted prevalence of chronic bronchitis was similar in rural and urban participants (3.5 versus 2.2%, respectively; P = 0.62), as was that of a restrictive spirometry pattern (10.9 versus 9.4%; P = 0.82). For COPD, the population attributable risk was 51.5% for rural residence, 19.5% for tobacco smoking, 16.0% for a body mass index < 18.5 kg/m2 and 13.0% for a history of treatment for pulmonary tuberculosis. CONCLUSION: The prevalence of chronic respiratory disease was high in both rural and urban Uganda. Place of residence was the most important risk factor for COPD and asthma.

Trends of admissions and case fatality rates among medical in-patients at a tertiary hospital in Uganda; A four-year retrospective study.

BACKGROUND: Sub-Saharan Africa suffers from a dual burden of infectious and non-communicable diseases. There is limited data on causes and trends of admission and death among patients on the medical wards. Understanding the major drivers of morbidity and mortality would help inform health systems improvements. We determined the causes and trends of admission and mortality among patients admitted to Mulago Hospital, Kampala, Uganda. METHODS AND RESULTS: The medical record data base of patients admitted to Mulago Hospital adult medical wards from January 2011 to December 2014 were queried. A detailed history, physical examination and investigations were completed to confirm the diagnosis and identify comorbidities. Any histopathologic diagnoses were made by hematoxylin and eosin tissue staining. We identified the 10 commonest causes of hospitalization, and used Poisson regression to generate annual percentage change to describe the trends in causes of hospitalization. Survival was calculated from the date of admission to the date of death or date of discharge. Cox survival analysis was used to identify factors associate with in-hospital mortality. We used a statistical significance level of p<0.05. A total of 50,624 patients were hospitalized with a median age of 38 (range 13-122) years and 51.7% females. Majority of patients (72%) had an NCD condition as the primary reason for admission. Specific leading causes of morbidity were HIV/AIDS in 30% patients, hypertension in 14%, tuberculosis (TB) in 12%), non-TB pneumonia in11%) and heart failure in 9.3%. There was decline in the proportion of hospitalization due to malaria, TB and pneumonia with an annual percentage change (apc) of -20% to -6% (all p<0.03) with an increase in proportions of admissions due to chronic kidney disease, hypertension, stroke and cancer, with apc 13.4% to 24%(p<0.001). Overall, 8,637(17.1%) died during hospitalization with the highest case fatality rates from non-TB pneumonia (28.8%), TB (27.1%), stroke (26.8%), cancer (26.1%) and HIV/AIDS (25%). HIV-status, age above 50yrs and being male were associated with increased risk of death among patients with infections. CONCLUSION: Admissions and case fatality rates for both infectious and non-infectious diseases were high, with declining trends in infectious diseases and a rising trend in NCDs. Health care systems in sub-Saharan region need to prepare to deal with dual burden of disease.

Kidney disease in Uganda: a community based study.

BACKGROUND: Chronic kidney disease (CKD) is a major cause of morbidity and mortality in Sub-Saharan Africa (SSA). The majority of studies on CKD in SSA have been conducted among HIV-infected populations and mainly from large health facilities. We determined the prevalence of CKD and its predictors among populations in communities in central Uganda. METHODS: A cross-sectional study was conducted in Wakiso district using multi-stage sampling. Data was collected on age, sex, socio-economic status, history of alcohol intake, diabetes mellitus, hypertension and smoking. Measurement of blood pressure, weight and height to determine body mass index (BMI) and investigations including HIV testing, fasting blood sugar, creatinine and urinalysis were conducted. Logistic regression was used to estimate the strength of the association between variables and the presence of CKD estimated using the Cockcroft Gault formula. RESULTS: A total of 955 participants aged 18-87 years were enrolled into the study. The median age was 31 years (Interquartile range 24-42) and majority (67%) were female. Up to 21.4% (204/955) had abnormal renal function with CKD stage 1 in 6.2% (59/955), stage 2 in 12.7% (121/955), stage 3 in 2.4% (23/955), CKD stage 4 in 0% and CKD stage 5 in 0.1% (1/995). Female gender OR 1.8 (95% Confidence Interval [CI] 1.2-2.8), age >30 years OR 2.2(95% CI 1.2-3.8) and high social economic status OR 2.1 (95% CI 1.3-3.6) were associated with increased risk of CKD while BMI > 25Kg/m2 was protective against CKD OR 0.1 (95% CI 0.04-0.2). Traditional risk factors such as HIV-infection, diabetes mellitus, smoking and alcohol intake were not found to be significantly associated with CKD. CONCLUSION: We found a high prevalence of kidney disease in central Uganda. Interestingly the traditional risk factors associated with CKD previously documented, were not associated with CKD.

Determinants of Raised Blood Pressure in Urban Uganda: A Community-Based Case-Control Study.

OBJECTIVE: Rapid urbanization is changing the epidemiology of non-communicable diseases in sub-Saharan Africa. We aimed to identify the determinants of raised blood pressure in urban Uganda to highlight targets for preventive interventions. DESIGN: Case-control. SETTING: Three community-based sites in Kampala, the capital of Uganda. PARTICIPANTS: Participants were eligible to enroll if they were aged ≥18 years and not pregnant. METHODS: 450 cases with raised blood pressure were frequency matched by sex and age to 412 controls. Unconditional logistic regression was used to evaluate the association of socio-demographic, lifestyle, anthropometric, and laboratory variables with the outcome of raised blood pressure. Cases currently treated with antihypertensive medication and cases not treated with antihypertensive medication were analyzed separately. RESULTS: Significantly increased odds of raised blood pressure were associated with overweight body mass index (BMI) (25 kg/m2 ≤ BMI < 30 kg/m2), obese BMI (BMI ≥ 30 kg/m2) and hemoglobin A1c ≥ 6.5%. Significantly decreased odds of raised blood pressure were associated with moderate-to-vigorous work-related physical activity of >4 hours/week. No significant associations were found between raised blood pressure and marital status, education level, car or flush toilet ownership, dietary habits, alcohol consumption, smoking habits, moderate-to-vigorous leisure-related physical activity > 4 hours/week, waist-to-hip ratio, or total cholesterol levels. CONCLUSIONS: Targeted interventions are needed to address the key modifiable risk factors for raised blood pressure identified in this study, namely elevated BMI and regular physical activity, in order to reduce the burden of cardiovascular disease in urban Uganda.

The burden of hypertension in sub-Saharan Africa: a four-country cross sectional study.

BACKGROUND: Hypertension, the leading single cause of morbidity and mortality worldwide, is a growing public health problem in sub-Saharan Africa (SSA). Few studies have estimated and compared the burden of hypertension across different SSA populations. We conducted a cross-sectional analysis of blood pressure data collected through a cohort study in four SSA countries, to estimate the prevalence of pre-hypertension, the prevalence of hypertension, and to identify the factors associated with hypertension. METHODS: Participants were from five different population groups defined by occupation and degree of urbanization, including rural and peri-urban residents in Uganda, school teachers in South Africa and Tanzania, and nurses in Nigeria. We used a standardized questionnaire to collect data on demographic and behavioral characteristics, injuries, and history of diagnoses of chronic diseases and mental health. We also made physical measurements (weight, height and blood pressure), as well as biochemical measurements; which followed standardized protocols across the country sites. Modified Poison regression modelling was used to estimate prevalence ratios (PR) as measures of association between potential risk factors and hypertension. RESULTS: The overall age-standardized prevalence of hypertension among the 1216 participants was 25.9%. Prevalence was highest among nurses with an age-standardized prevalence (ASP) of 25.8%, followed by school teachers (ASP = 23.2%), peri-urban residents (ASP = 20.5%) and lowest among rural residents (ASP = 8.7%). Only 50.0% of participants with hypertension were aware of their raised blood pressure. The overall age-standardized prevalence of pre-hypertension was 21.0%. Factors found to be associated with hypertension were: population group, older age, higher body mass index, higher fasting plasma glucose level, lower level of education, and tobacco use. CONCLUSIONS: The prevalence of hypertension and pre-hypertension are high, and differ by population group defined by occupation and degree of urbanization. Only half of the populations with hypertension are aware of their hypertension, indicating a high burden of undiagnosed and un-controlled high blood pressure in these populations.

Cardiovascular risk factors among patients with chronic kidney disease attending a tertiary hospital in Uganda.

INTRODUCTION: Chronic kidney disease (CKD) is a risk factor for the development of cardiovascular disease, which is the primary cause of morbidity and mortality in patients with CKD. Local data about cardiovascular risk factors among CKD patients is generally scanty. OBJECTIVE: To determine the prevalence of the common cardiovascular risk factors among patients with CKD attending the nephrology out-patient clinic in Mulago national referral hospital in Uganda. METHODS: This was a cross-sectional study in which 217 patients with a mean age of 43 years were recruited over a period of nine months. Data on demographic characteristics, risk factors for cardiovascular disease, complete blood count, renal function tests/electrolytes, and lipid profiles were collected using a standardised questionnaire. RESULTS: One hundred and eleven (51.2%) of the participants were male. Hypertension was reported in 90% of participants while cigarette smoking was present in 11.5%. Twenty-two participants (10.2%) were obese and 16.1% were diabetic. A total of 71.9% had a haemoglobin concentration < 11 g/dl, with the prevalence of anaemia increasing with advancing renal failure (p < 0.001); 44.7% were hypocalcaemic and 39.2% had hyperphosphataemia. The prevalence of abnormal calcium and phosphate levels was found to increase with declining renal function (p = 0.004 for calcium and p < 0.001 for phosphate). CONCLUSION: This study demonstrated that both traditional and non-traditional cardiovascular risk factors occurred frequently in patients with CKD attending the nephrology out-patient clinic at Mulago Hospital.

Diagnostic accuracy of fine needle aspiration cytology in providing a diagnosis of cervical lymphadenopathy among HIV-infected patients.

BACKGROUND: Opportunistic infections and malignancies cause lymphadenopathy in HIV-infected patients. The use and accuracy of fine needle aspiration cytology in diagnosing of cervical lymphadenopathy among HIV-infected patients is not well studied in Uganda. OBJECTIVE: The aim of this study was to determine the diagnostic accuracy of fine needle aspiration cytology in providing a diagnosis of cervical lymphadenopathy among HIV-infected patients in Uganda. METHODS: We consecutively recruited adult HIV-infected patients with cervical lymphadenopathy admitted to Mulago Hospital medical wards. Clinical examination, fine needle aspiration and lymph node biopsy were performed. We estimated the sensitivity, specificity; negative and positive predictive values using histology as the gold standard. RESULTS: We enrolled 108 patients with a mean age of 33 years (range, 18-60), 59% were men and mean CD4 was 83(range, 22-375) cells/mm(3). The major causes of cervical lymphadenopathy were: tuberculosis (69.4%), Kaposi's sarcoma-KS (10.2%) and reactive adenitis (7.4%). Overall fine needle aspiration cytology accurately predicted the histological findings in 65 out of 73 cases (89%) and missed 7 cases (9.5%). With a sensitivity of 93.1%, specificity of 100%, positive predictive value of 100% and negative predictive value of 78.7% for tuberculosis and 80%; 98.4%;88.9% and 98.9% for KS respectively. No fine needle aspiration complications were noted. CONCLUSIONS: Fine needle aspiration cytology is safe and accurate in the diagnosis of tuberculosis and KS cervical lymphadenopathy among HIV-positive patients.

ACE-I/ARB therapy prior to contrast exposure: what should the clinician do?

Contrast-induced nephropathy (CIN) is now one of the three leading causes of acute kidney injury in the world. A lot is known about the risk factors of CIN, yet it remains a major cause of morbidity, end stage renal disease, prolonged hospital stay, and increased costs as well as a high mortality. Many patients undergoing contrast-based radiological investigations are treated with angiotensin converting inhibitors (ACE-Is) or angiotensin receptor blockers (ARBs) for their cardiac and renal benefits and their known mortality benefits. However, controversy exists among clinicians as to whether ACE-Is and ARBs should be continued or discontinued prior to contrast media exposure. In this paper we review the current evidence on ACE-I/ARB therapy for patients undergoing procedures involving use of contrast media and provide recommendations as to whether these drugs should be continued or held prior to contrast exposure.