Distribution of the ACE Gene Polymorphisms in Type 2 Diabetes Mellitus Patients, Their Associations with Nephropathy Biomarkers and Metabolic Indicators at a Tertiary Hospital in Uganda.

Purpose: We aimed at determining the distribution of the ACE insertion/deletion gene polymorphisms among type 2 diabetic patients and their association with the nephropathy biomarkers and the metabolic indicators. Patients and Methods: Data were collected from 237 adult type 2 diabetes mellitus patients receiving healthcare at the diabetic clinic of Mbarara Regional Referral Hospital. Peripheral blood genomic DNA was amplified using a conventional PCR technique and analyzed for the ACE homozygous forms of the insertion (II), deletion (DD) and heterozygous insertion deletion (ID) genotypes as well as their respective allele counts. Biomarkers of nephropathy were analyzed on a Beckman coulter AU480 chemistry analyzer using system compatible reagents. Results: Majority of the participants were older persons (Median = 57, IQR = 49-64) and female 171 (72.2%). Most of them had the Deletion allele 198 (83.5%) and DD genotype 116 (48.9%). At multivariate logistic regression, the nephropathy biomarkers that is microalbuminuria, serum creatinine, urea, eGFR and electrolytes had no association with the ACE I/D alleles or genotypes (p > 0.05). On the other hand, selected metabolic indicators had a positive relationship. The insertion allele was associated with increasing glycated hemoglobin (OR = 1.082, p = 0.019) and decreasing serum glucose levels (OR = 0.891, p = 0.001). Deletion allele was associated with decreasing glycated hemoglobin (OR = 0.924, p = 0.047) and increasing serum glucose levels (OR = 1.208, p = 0.001). ACE II genotype was associated with decreasing serum glucose levels (OR = 0.873, p = 0.029). ACE DD genotype was associated with decreasing glycated hemoglobin (OR = 0.917, p = 0.010) and increasing serum glucose levels (OR = 1.132, p = 0.001). ACE ID genotype was associated with increasing glycated hemoglobin (OR = 1.077, p = 0.022), triglyceride levels (OR = 1.316, p = 0.031) and decreasing serum glucose levels (OR = 0.933, p = 0.038). Conclusion: The presence or absence of the ACE I/D alleles and genotypes affects the ultimate increase or decrease in the serum glucose, glycated hemoglobin and triglyceride levels. Although there was no significant association between the biomarkers of nephropathy and the ACE I/D alleles or genotypes, the above implicated metabolic indicators should be included in healthcare guidelines used when attending to type 2 diabetic patients.

The Future of Kidney Care in Low and Middle-Income Countries: Challenges, Triumphs and Opportunities.

Chronic kidney disease (CKD) affects about 850 million people worldwide and is projected to be the fifth leading cause of death by 2040. Individuals from low- and middle-income countries (LMICs) bear the bulk of CKD. They face challenges including lack of awareness among the general population as well as health care providers, unique risk factors such as genetic predispositions, infectious diseases and environmental toxins, limited availability and affordability of diagnostic tests, medications and limited access to kidney replacement therapies. The inadequate health system infrastructure, human resources, and financing mechanisms to support comprehensive and integrated kidney care worsens the situation. Overcoming these challenges needs concerted efforts towards early detection, intervention and multidisciplinary follow up, policy, collaboration, advocacy and financing. To achieve this, there is need for individual governments to include kidney health among the key health priorities and build capacity towards resilient health care systems. Integrating kidney care using the roadmaps of well-established management systems for other chronic diseases such as HIV has the potential to expedite the widespread adoption of kidney health. This article aims to provide an overview of the current state and future prospects of kidney care in LMICs, highlighting the main challenges, ongoing efforts, and opportunities for improvement. We present case studies of exemplary efforts from three continents of the world with the highest densities of LMICs and propose potential strategies for a sustainable solution.

Airway microbiome signature accurately discriminates Mycobacterium tuberculosis infection status.

Mycobacterium tuberculosis remains one of the deadliest infectious agents globally. Amidst efforts to control TB, long treatment duration, drug toxicity, and resistance underscore the need for novel therapeutic strategies. Despite advances in understanding the interplay between microbiome and disease in humans, the specific role of the microbiome in predicting disease susceptibility and discriminating infection status in tuberculosis still needs to be fully investigated. We investigated the impact of M.tb infection and M.tb-specific IFNγ immune responses on airway microbiome diversity by performing TB GeneXpert and QuantiFERON-GOLD assays during the follow-up phase of a longitudinal HIV-Lung Microbiome cohort of individuals recruited from two large independent cohorts in rural Uganda. M.tb rather than IFNγ immune response mainly drove a significant reduction in airway microbiome diversity. A microbiome signature comprising Streptococcus, Neisseria, Fusobacterium, Prevotella, Schaalia, Actinomyces, Cutibacterium, Brevibacillus, Microbacterium, and Beijerinckiacea accurately discriminated active TB from Latent TB and M.tb-uninfected individuals.

Higher prevalence of kidney function impairment among older people living with HIV in Uganda.

Background: People living with HIV (PLWH) are at risk of kidney function impairment due to HIV-related inflammation, antiretroviral therapy (ART), diabetes mellitus, and hypertension. Older persons may experience a higher burden of chronic kidney disease (CKD) as kidney function declines with increasing age. There is a paucity of data comparing the prevalence of kidney function impairment in older PLWH to that in HIV-uninfected people in sub-Saharan Africa. Methods: We conducted a cross-sectional study among people aged ≥ 60 years living with and without HIV in Kampala, Uganda who were matched 1:1 by community location. We collected data on sociodemographics, comorbidities, and HIV-related clinical characteristics. We defined kidney function impairment as an estimated glomerular filtration rate(eGFR) < 60mls/min/1.73m2 with or without proteinuria. We constructed multivariable logistic regression models to study associations between participant characteristics and kidney function impairment. Results: We enrolled 278 people (median age 66 years); 50% were PLWH, and 51.8% were female. Overall, the prevalence of kidney function impairment was 23.0% (95% CI:18.4%-28.4%); 33.1% (95% CI: 25.7%-41.4%) versus 12.9% (95% CI: 8.3%-19.7%) among people living with and without HIV (p-value < 0.01). The prevalence of proteinuria among PLWH versus people without HIV was 43.9% (95% CI:35.8%-52.3%) versus 19.4% (95% CI:13.6%-26.9%) p-value < 0.01. Living with HIV (OR = 3.89(95% CI: 2.04-7.41), p-value < 0.01), older age (OR = 1.13, (95% CI:1.07-1.20), p-value < 0.01), female sex (OR = 1.95, (95% CI:1.06-3.62), p-value = 0.03) and a prior diagnosis of hypertension (OR = 2.19(95% CI:1.02-4.67), p-value = 0.04) were significantly associated with kidney function impairment. Conclusions: HIV infection is strongly associated with kidney function impairment among older PLWH. Prioritizing routine measurements of kidney function and proteinuria in older PLWH will enable early detection and institution of measures to reduce the progression of kidney disease.

Capacity for the management of kidney failure in the International Society of Nephrology Africa region: report from the 2023 ISN Global Kidney Atlas (ISN-GKHA).

The burden of chronic kidney disease and associated risk of kidney failure are increasing in Africa. The management of people with chronic kidney disease is fraught with numerous challenges because of limitations in health systems and infrastructures for care delivery. From the third iteration of the International Society of Nephrology Global Kidney Health Atlas, we describe the status of kidney care in the ISN Africa region using the World Health Organization building blocks for health systems. We identified limited government health spending, which in turn led to increased out-of-pocket costs for people with kidney disease at the point of service delivery. The health care workforce across Africa was suboptimal and further challenged by the exodus of trained health care workers out of the continent. Medical products, technologies, and services for the management of people with nondialysis chronic kidney disease and for kidney replacement therapy were scarce due to limitations in health infrastructure, which was inequitably distributed. There were few kidney registries and advocacy groups championing kidney disease management in Africa compared with the rest of the world. Strategies for ensuring improved kidney care in Africa include focusing on chronic kidney disease prevention and early detection, improving the effectiveness of the available health care workforce (e.g., multidisciplinary teams, task substitution, and telemedicine), augmenting kidney care financing, providing quality, up-to-date health information data, and improving the accessibility, affordability, and delivery of quality treatment (kidney replacement therapy or conservative kidney management) for all people living with kidney failure.

Hypertension Related Co-Morbidities and Complications in Women of Sub-Saharan Africa: A Brief Review.

Hypertension is the leading cause of cardiovascular disease in women, and sub-Saharan African (SSA) countries have some of the highest rates of hypertension in the world. Expanding knowledge of causes, management, and awareness of hypertension and its co-morbidities worldwide is an effective strategy to mitigate its harms, decrease morbidities and mortality, and improve individual quality of life. Hypertensive disorders of pregnancy (HDPs) are a particularly important subset of hypertension, as pregnancy is a major stress test of the cardiovascular system and can be the first instance in which cardiovascular disease is clinically apparent. In SSA, women experience a higher incidence of HDP compared with other African regions. However, the region has yet to adopt treatment and preventative strategies for HDP. This delay stems from insufficient awareness, lack of clinical screening for hypertension, and lack of prevention programs. In this brief literature review, we will address the long-term consequences of hypertension and HDP in women. We evaluate the effects of uncontrolled hypertension in SSA by including research on heart disease, stroke, kidney disease, peripheral arterial disease, and HDP. Limitations exist in the number of studies from SSA; therefore, we will use data from countries across the globe, comparing and contrasting approaches in similar and dissimilar populations. Our review highlights an urgent need to prioritize public health, clinical, and bench research to discover cost-effective preventative and treatment strategies that will improve the lives of women living with hypertension in SSA.

Challenges to Implementation of Community Health Worker-Led Chronic Obstructive Pulmonary Disease (COPD) Screening and Referral in Rural Uganda: A Qualitative Study using the Implementation Outcomes Framework.

Background: Chronic obstructive pulmonary disease (COPD) is the third leading cause of death globally. The burden of COPD is expected to increase in low- and middle-income countries (LMICs). COPD screening and diagnostics tools are often inaccessible in rural settings of LMICs. To contribute to the growing body of evidence on the effectiveness of Community Health Worker (CHW) interventions, this study aims to understand the facilitators and barriers of implementing a CHW-led COPD screening and referral program in rural Uganda. Methods: This qualitative study was conducted from September to October 2022 to explore Community Members, CHWs, and Healthcare Providers (HCPs) perceptions on the challenges of CHW-delivered COPD programming in Nakaseke, rural Uganda. In total, we held eight individual in-depth interviews with CHWs, ten in-depth interviews with HCPs and six focus group discussions with 34 Community Members. Research assistants audio-recorded and transcribed interviews verbatim. The implementation outcomes framework guided the thematic analysis. Results: Implementation acceptability was constrained by a lack of COPD awareness, a lack of perceived utility in COPD screening as well as stigma around the diagnostic process. Limited spirometry adoption was also attributed to Community Member accessibility and willingness to participate in the COPD diagnostic referral process. The high patient volume and the complex, time-consuming diagnostic and referral process hindered successful implementation. To enhance program sustainability, all participants suggested increasing CHW support, medication access, decentralizing COPD care and upscaling follow-up of Community Members by CHWs. Conclusion: CHW-led interventions remain a potentially critical tool to alleviate barriers to treatment and self-management in settings where access to care is limited. While community-based interventions can create sustainable infrastructure to improve health outcomes, formative assessments of the potential barriers prior to intervention are required. Evidence-based, localized approaches and sustained funding are imperative to achieve this.

Self-care and healthcare seeking practices among patients with hypertension and diabetes in rural Uganda.

BACKGROUND: Implementing effective self-care practices for non-communicable diseases (NCD) prevents complications and morbidity. However, scanty evidence exists among patients in rural sub-Saharan Africa (SSA). We sought to describe and compare existing self-care practices among patients with hypertension (HTN) and diabetes (DM) in rural Uganda. METHODS: Between April and August 2019, we executed a cross-sectional investigation involving 385 adult patients diagnosed with HTN and/or DM. These participants were systematically randomly selected from three outpatient NCD clinics in the Nakaseke district. Data collection was facilitated using a structured survey that inquired about participants' healthcare-seeking patterns, access to self-care services, education on self-care, medication compliance, and overall health-related quality of life. We utilized Chi-square tests and logistic regression analyses to discern disparities in self-care practices, education, and healthcare-seeking actions based on the patient's conditions. RESULTS: Of the 385 participants, 39.2% had only DM, 36.9% had only HTN, and 23.9% had both conditions (HTN/DM). Participants with DM or both conditions reported more clinic visits in the past year than those with only HTN (P = 0.005). Similarly, most DM-only and HTN/DM participants monitored their weight monthly, unlike those with only HTN (P<0.0001). Participants with DM or HTN/DM were more frequently educated about their health condition(s), dietary habits, and weight management than those with only HTN. Specifically, education about their conditions yielded adjusted odds ratios (aOR) of 5.57 for DM-only and 4.12 for HTN/DM. Similarly, for diet, aORs were 2.77 (DM-only) and 4.21 (HTN/DM), and for weight management, aORs were 3.62 (DM-only) and 4.02 (HTN/DM). Medication adherence was notably higher in DM-only participants (aOR = 2.19). Challenges in self-care were significantly more reported by women (aOR = 2.07) and those above 65 years (aOR = 5.91), regardless of their specific condition(s). CONCLUSION: Compared to rural Ugandans with HTN-only, participants with DM had greater utilization of healthcare services, exposure to self-care education, and adherence to medicine and self-monitoring behaviors. These findings should inform ongoing efforts to improve and integrate NCD service delivery in rural SSA.

Design Research to Embed mHealth into a Community-Led Blood Pressure Management System in Uganda: Protocol for a Mixed Methods Study.

BACKGROUND: Uncontrolled hypertension is a leading risk factor for cardiovascular diseases. In Uganda, such diseases account for approximately 10% of all deaths, with 1 in 5 adults having hypertension (>90% of the hypertensive cases are uncontrolled). Although basic health care in the country is available free of cost at government facilities, regularly accessing medication to control hypertension is difficult because supply chain challenges impede availability. Clients therefore frequently suspend treatment or buy medication individually at private facilities or pharmacies (incurring significant costs). In recent years, mobile health (mHealth) interventions have shown increasing potential in addressing health system challenges in sub-Saharan Africa, but the acceptability, feasibility, and uptake conditions of mobile money approaches to chronic disease management remain understudied. OBJECTIVE: This study aims to design and pilot-test a mobile money-based intervention to increase the availability of antihypertensive medication and lower clients' out-of-pocket payments. We will build on existing local approaches and assess the acceptability, feasibility, and uptake of the designed intervention. Furthermore, rather than entering the study setting with a ready-made intervention, this research will place emphasis on gathering applied ethnographic insights early, which can then inform the parameters of the intervention prototype and concurrent trial. METHODS: We will conduct a mixed methods study following a human-centered design approach. We will begin by conducting extensive qualitative research with a range of stakeholders (clients; health care providers; religious, cultural, and community leaders; academics; and policy makers at district and national levels) on their perceptions of hypertension management, money-saving systems, and mobile money in the context of health care. Our results will inform the design, iterative adaptation, and implementation of an mHealth-facilitated pooled financing intervention prototype. At study conclusion, the finalized prototype will be evaluated quantitatively via a randomized controlled trial. RESULTS: As of August 2023, qualitative data collection, which started in November 2022, is ongoing, with data analysis of the first qualitative interviews underway to inform platform and implementation design. Recruitment for the quantitative part of this study began in August 2023. CONCLUSIONS: Our results aim to inform the ongoing discourse on novel and sustainable pathways to facilitate access to medication for the management of hypertension in resource-constrained settings. TRIAL REGISTRATION: German registry of clinical trials DRKS00030922; https://drks.de/search/en/trial/DRKS00030922. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/46614.

Dietary intake, body composition and micronutrient profile of patients on maintenance hemodialysis attending Kiruddu National Referral Hospital, Uganda: A cross sectional study.

Patients on maintenance hemodialysis are at a great risk for altered nutritional status, characterized by protein energy wasting and micronutrient deficiency due to medication interactions and dietary restrictions. This study determined the dietary intake, micronutrient profile and body composition of patients on maintenance hemodialysis at Kiruddu National referral hospital (KNRH), Uganda. A cross sectional study was done among adult CKD patients on maintenance hemodialysis therapy at KNRH. Data concerning patients' demographics, clinical history and dietary intake was obtained using interactive and quantitative food frequency questionnaires. Body composition was obtained using the TANITA BC-351, Japan weighing Bathroom scale and anthropometric measurements using standard methods and procedures. Serum micronutrient profile assessment was done using the COBAS Auto analyzer. Data analysis was done using the SPSS software version 20. T-test was used to make comparisons and logistic regression analysis was done to check for any correlations. A P-value of < 0.05 was considered statistically significant. Among the 63 hemodialysis patients, 38% were female, with a median duration of hemodialysis of 12 months and the overall age range of patients was 31-40 years. Majority (92.1%) of the patients had hypertension. Carbohydrates like maize flour were highly consumed, in addition to eggs among the proteins on the daily basis. Fruits and vegetables were not highly consumed. Regarding body composition; 75% of the study participants had normal Body mass Index (BMI), the mean muscle mass was 51.94±8.68, body fat was 15.25±7.35, bone mass was 2.77±0.46 and body water was 62.04±9.06. Patients had deranged micronutrient levels especially for Vitamin D, Potassium and phosphorus. In conclusion, hemodialysis patients at KNRH, have altered nutritional status as evidenced by altered body weight for some patients and deranged micronutrient levels. We recommend that hemodialysis patients should be regularly assessed for nutritional status, appropriately treated and educated about their nutritional status.

Meta-analysis of African ancestry genome-wide association studies identified novel locus and validates multiple loci associated with kidney function.

Despite recent efforts to increase diversity in genome-wide association studies (GWASs), most loci currently associated with kidney function are still limited to European ancestry due to the underlying sample selection bias in available GWASs. We set out to identify susceptibility loci associated with estimated glomerular filtration rate (eGFRcrea) in 80027 individuals of African-ancestry from the UK Biobank (UKBB), Million Veteran Program (MVP), and Chronic Kidney Disease genetics (CKDGen) consortia.We identified 8 lead SNPs, 7 of which were previously associated with eGFR in other populations. We identified one novel variant, rs77408001 which is an intronic variant mapped to the ELN gene. We validated three previously reported loci at GATM-SPATA5L1, SLC15A5 and AGPAT3. Fine-mapping analysis identified variants rs77121243 and rs201602445 as having a 99.9% posterior probability of being causal. Our results warrant designing bigger studies within individuals of African ancestry to gain new insights into the pathogenesis of Chronic Kidney Disease (CKD), and identify genomic variants unique to this ancestry that may influence renal function and disease.

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).

Glycocalyx-Sodium Interaction in Vascular Endothelium.

The glycocalyx generally covers almost all cellular surfaces, where it participates in mediating cell-surface interactions with the extracellular matrix as well as with intracellular signaling molecules. The endothelial glycocalyx that covers the luminal surface mediates the interactions of endothelial cells with materials flowing in the circulating blood, including blood cells. Cardiovascular diseases (CVD) remain a major cause of morbidity and mortality around the world. The cardiovascular risk factors start by causing endothelial cell dysfunction associated with destruction or irregular maintenance of the glycocalyx, which may culminate into a full-blown cardiovascular disease. The endothelial glycocalyx plays a crucial role in shielding the cell from excessive exposure and absorption of excessive salt, which can potentially cause damage to the endothelial cells and underlying tissues of the blood vessels. So, in this mini review/commentary, we delineate and provide a concise summary of the various components of the glycocalyx, their interaction with salt, and subsequent involvement in the cardiovascular disease process. We also highlight the major components of the glycocalyx that could be used as disease biomarkers or as drug targets in the management of cardiovascular diseases.

Self-paced online learning to improve knowledge competencies for hypertension among medical students in Uganda: A pre-post study.

The growing burden of hypertension (HT) is projected to reach 1.56 billion globally by 2025 and is an increasing public health concern, even for low- and middle-income countries (LMIC) like Uganda, where the prevalence of HT is 31.5%. The objective of this study was to test the effectiveness of a freely available HT online course on knowledge competencies for medical students in Uganda. The online course was developed by a multidisciplinary team at Johns Hopkins University to address HT control in resource-constrained healthcare settings. Students in the 3rd, 4th, and 5th years of medical school were randomly selected to participate in the online course. Pre and post knowledge tests were administered using an online survey system. Of the 201 invited students, 121 (60.2%) completed the study. Significant improvements in mean knowledge scores were evident following the online course completion for Module 1, Fundamentals of HT (21.9±2.5 to 23.7±2.5, p<0.001), and Module 2, Basics of HT Management (14.9±3.3 to 18.5±4.3, p<0.001). No statistically significant differences were evident by gender or school year. Students who took a shorter duration to complete the course had significantly higher mean score improvement between pre- and post-test (mean score improvement 7.0 if <4 weeks, 3.6 if 4-8 weeks, and 3.7 if >8 weeks, p<0.003). Students recognized information on blood pressure measurement (32.2%) and HT management (22.3%) as the most important concept addressed in the course. A self-paced online course, complementing medical school training, improved knowledge on HT burden and management in Uganda.

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.