Chronic kidney disease and the global public health agenda: an international consensus.

Early detection is a key strategy to prevent kidney disease, its progression and related complications, but numerous studies show that awareness of kidney disease at the population level is low. Therefore, increasing knowledge and implementing sustainable solutions for early detection of kidney disease are public health priorities. Economic and epidemiological data underscore why kidney disease should be placed on the global public health agenda - kidney disease prevalence is increasing globally and it is now the seventh leading risk factor for mortality worldwide. Moreover, demographic trends, the obesity epidemic and the sequelae of climate change are all likely to increase kidney disease prevalence further, with serious implications for survival, quality of life and health care spending worldwide. Importantly, the burden of kidney disease is highest among historically disadvantaged populations that often have limited access to optimal kidney disease therapies, which greatly contributes to current socioeconomic disparities in health outcomes. This joint statement from the International Society of Nephrology, European Renal Association and American Society of Nephrology, supported by three other regional nephrology societies, advocates for the inclusion of kidney disease in the current WHO statement on major non-communicable disease drivers of premature mortality.

Rationale and Design of the Diet, CKD, and Apolipoprotein L1 Study in Low-Income and Middle-Income Countries.

Introduction: Diet, chronic kidney disease (CKD), and Apolipoprotein L1 (APOL1) (DCA) Study is examining the role of dietary factors in CKD progression and APOL1 nephropathy. We describe enrollment and retention efforts and highlight facilitators and barriers to enrollment and operational challenges, as well as accommodations made in the study protocol. Methods: The DCA study is enrolling participants in 7 centers in West Africa. Participants who consented were invited to complete dietary recalls and 24-hour urine collections in year 1. We conducted focus groups and semistructured interviews among study personnel to identify facilitators and barriers to enrollment as well as retention and operational challenges in the execution of the study protocol. We analyzed emerging themes using content analyses. Results: A total of 712 participants were enrolled in 18 months with 1256 24-hour urine and 1260 dietary recalls. Barriers to enrollment were the following: (i) a lack of understanding of research, (ii) the burden of research visits, and (iii) incorporating cultural and traditional nuances when designing research protocols. Factors facilitating enrollment were the following: (i) designing convenient research visits, (ii) building rapport and increased communication between the research team and participants, and (iii) cultural sensitivity - adapting research protocols for the populations involved. Offering home visits, providing free dietary counseling, reducing the volume of study blood collection, and reducing the frequency of visits were some changes made in the study protocol that increased participant satisfaction. Conclusion: Adopting a participant-centered approach with accommodations in the protocol for cultural adaptability and incorporating participant feedback is vital for carrying out research in low-income and middle-income regions.

Cardiovascular Risk Factor Burden and Association With CKD in Ghana and Nigeria.

Introduction: Cardiovascular disease is the leading cause of morbidity and mortality in patients with chronic kidney disease (CKD); however, the burden of cardiovascular risk factors in patients with CKD in Africa is not well characterized. We determined the prevalence of selected cardiovascular risk factors, and association with CKD in the Human Heredity for Health in Africa Kidney Disease Research Network study. Methods: We recruited patients with and without CKD in Ghana and Nigeria. CKD was defined as estimated glomerular filtration rate of <60 ml/min per 1.73 m2 and/or albuminuria as albumin-to-creatinine ratio <3.0 mg/mmol (<30 mg/g) for ≥3 months. We assessed self-reported (physician-diagnosis and/or use of medication) hypertension, diabetes, and elevated cholesterol; and self-reported smoking as cardiovascular risk factors. Association between the risk factors and CKD was determined by multivariate logistic regression. Results: We enrolled 8396 participants (cases with CKD, 3956), with 56% females. The mean age (45.5 ± 15.1 years) did not differ between patients and control group. The prevalence of hypertension (59%), diabetes (20%), and elevated cholesterol (9.9%), was higher in CKD patients than in the control participants (P < 0.001). Prevalence of risk factors was higher in Ghana than in Nigeria. Hypertension (adjusted odds ratio [aOR] = 1.69 [1.43-2.01, P < 0.001]), elevated cholesterol (aOR = 2.0 [1.39-2.86, P < 0.001]), age >50 years, and body mass index (BMI) <18.5 kg/m2 were independently associated with CKD. The association of diabetes and smoking with CKD was modified by other risk factors. Conclusion: Cardiovascular risk factors are prevalent in middle-aged adult patients with CKD in Ghana and Nigeria, with higher proportions in Ghana than in Nigeria. Hypertension, elevated cholesterol, and underweight were independently associated with CKD.

APOL1 genotype associated risk for preeclampsia in African populations: Rationale and protocol design for studies in women of African ancestry in resource limited settings.

BACKGROUND: Women of African ancestry are highly predisposed to preeclampsia which continues to be a major cause of maternal death in Africa. Common variants in the APOL1 gene are potent risk factor for a spectrum of kidney disease. Recent studies have shown that APOL1 risk variants contribute to the risk of preeclampsia. The aim of the study is to understand the contribution of APOL1 risk variants to the development of preeclampsia in pregnant women in Ghana. METHODS: The study is a case-control design which started recruitment in 2019 at the Korle Bu Teaching Hospital in Ghana. The study will recruit pregnant women with a target recruitment of 700 cases of preeclampsia and 700 normotensives. Clinical and demographic data of mother- baby dyad, with biospecimens including cord blood and placenta will be collected to assess clinical, biochemical and genetic markers of preeclampsia. The study protocol was approved by Korle Bu Teaching Hospital Institutional Review Board (Reference number: KBTH-IRB/000108/2018) on October 11, 2018. PRELIMINARY RESULTS: As of December 2021, a total of 773 mother-baby pairs had been recruited and majority of them had complete entry of data for analysis. The participants are made up of 384 preeclampsia cases and 389 normotensive mother-baby dyad. The mean age of participants is 30.69 ± 0.32 years for cases and 29.95 ± 0.32 for controls. Majority (85%) of the participants are between 20-30years. At booking, majority of cases had normal blood pressure compared to the time of diagnosis where 85% had a systolic BP greater than 140mmHg and a corresponding 82% had diastolic pressure greater than 90mmHg. CONCLUSION: Our study will ultimately provide clinical, biochemical and genotypic data for risk stratification of preeclampsia and careful monitoring during pregnancy to improve clinical management and outcomes.

Transplant: The Success of Renal Transplant Programs.

In the absence of malignancy or other severe comorbidity, kidney transplantation offers better survival rates and quality of life than dialysis. Despite this survival advantage, many lower- and upper-middle-income countries do not offer adequate kidney transplant services. This is particularly troubling because end-stage kidney disease often is more common in these countries than in high-income countries and overall is less costly in the life of a patient. We describe the contrasting levels of provision of kidney transplantation in Mexico, India, Nigeria, Ghana, and Zimbabwe, and kidney transplant services for children in Africa.

Urine-Based Detection of Biomarkers Indicative of Chronic Kidney Disease in a Patient Cohort from Ghana.

Chronic kidney disease (CKD) is a global health burden with a continuously increasing prevalence associated with an increasing incidence of diabetes and hypertension in aging populations. CKD is characterized by low glomerular filtration rate (GFR) and other renal impairments including proteinuria, thus implying that multiple factors may contribute to the etiology this disease. While there are indications of ethnic differences, it is hard to disentangle these from confounding social factors. Usually, CKD is detected in later stages of the disease when irreversible renal damage has already occurred, thus suggesting a need for early non-invasive diagnostic markers. In this study, we explored the urine secretome of a CKD patient cohort from Ghana with 40 gender-matched patients and 40 gender-matched healthy controls employing a kidney injury and a more general cytokine assay. We identified panels of kidney-specific cytokine markers, which were also gender-specific, and a panel of gender-independent cytokine markers. The gender-specific markers are IL10 and MME for male and CLU, RETN, AGER, EGFR and VEGFA for female. The gender-independent cytokine markers were APOA1, ANGPT2, C5, CFD, GH1, ICAM1, IGFBP2, IL8, KLK4, MMP9 and SPP1 (up-regulated) and FLT3LG, CSF1, PDGFA, RETN and VEGFA (down-regulated). APOA1-the major component of HDL particles-was up-regulated in Ghanaian CKD patients and its co-occurrence with APOL1 in a subpopulation of HDL particles may point to specific CKD-predisposing APOL1 haplotypes in patients of African descent-this, however, needs further investigation. The identified panels, though preliminary, lay down the foundation for the development of robust CKD-diagnostic assays.

HIV Viremia Is Associated With APOL1 Variants and Reduced JC-Viruria.

Variants in the Apolipoprotein L1 (APOL1) gene (G1-rs60910145, rs73885319, G2-rs71785313) are common in Africans and in individuals of recent African ancestry and are associated with an increased risk of non-diabetic chronic kidney disease (CKD) and in particular of HIV associated nephropathy (HIVAN). In light of the significantly increased risk of HIVAN in carriers of two APOL1 risk alleles, a role in HIV infectivity has been postulated in the mechanism of APOL1 associated kidney disease. Herein, we aim to explore the association between HIV viremia and APOL1 genotype. In addition, we investigated interaction between BK and JC viruria, CKD and HIV viremia. A total of 199 persons living with HIV/AIDS (comprising 82 CKD cases and 117 controls) from among the participants in the ongoing Human Heredity and Health in Africa (H3Africa) Kidney Disease Research Network case control study have been recruited. The two APOL1 renal risk alleles (RRA) genotypes were associated with a higher risk of CKD (OR 12.6, 95% CI 3.89-40.8, p < 0.0001). Even a single APOL1 RRA was associated with CKD risk (OR 4.42, 95% CI 1.49-13.15, p = 0.007). The 2 APOL1 RRA genotypes were associated with an increased probability of having HIV viremia (OR 2.37 95% CI 1.0-5.63, p = 0.05). HIV viremia was associated with increased CKD risk (OR 7.45, 95% CI 1.66-33.35, P = 0.009) and with a significant reduction of JC virus urine shedding (OR 0.35, 95% CI 0.12-0.98, p = 0.046). In contrast to prior studies, JC viruria was not associated with CKD but was restricted in patients with HIV viremia, regardless of CKD status. These findings suggest a role of APOL1 variants in HIV infectivity and emphasize that JC viruria can serve as biomarker for innate immune system activation.

H3Africa partnerships to empower clinical research sites to generate high-quality biological samples.

BACKGROUND: The Institute of Human Virology Nigeria (IHVN) - Human Heredity and Health in Africa (H3Africa) Biorepository (I-HAB) seeks to provide high-quality biospecimens for research. This depends on the ability of clinical research sites (CRS) - who provide biospecimens - to operate according to well-established industry standards. Yet, standards are often neglected at CRSs located in Africa. Here, I-HAB reports on its four-pronged approach to empower CRSs to prepare high-quality biospecimens for research. OBJECTIVES: I-HAB sought (1) to assess a four-pronged approach to improve biobanking practices and sample quality among CRSs, and (2) to build human capacity. METHODS: I-HAB partnered with two H3Africa principal investigators located in Nigeria and Ghana from August 2013 through to May 2017 to debut its four-pronged approach (needs assessment, training and mentorship, pilot, and continuous quality improvement) to empower CRSs to attain high-quality biospecimens. RESULTS: Close collaborations were instrumental in establishing mutually beneficial and lasting relationships. Improvements during the 12 months of engagement with CRSs involved personnel, procedural, and supply upgrades. In total, 51 staff were trained in over 20 topics. During the pilot, CRSs extracted 50 DNA biospecimens from whole blood and performed quality control. The CRSs shipped extracted DNA to I-HAB and I-HAB that comparatively analysed the DNA. Remediation was achieved via recommendations, training, and mentorship. Preanalytical, analytical and post-analytical processes, standard operating procedures, and workflows were systematically developed. CONCLUSION: Partnerships between I-HAB and H3Africa CRSs enabled research sites to produce high-quality biospecimens through needs assessment, training and mentorship, pilot, and continuous monitoring and improvement.

Regional Patterns and Association Between Obesity and Hypertension in Africa: Evidence From the H3Africa CHAIR Study.

Hypertension and obesity are the most important modifiable risk factors for cardiovascular diseases, but their association is not well characterized in Africa. We investigated regional patterns and association of obesity with hypertension among 30 044 continental Africans. We harmonized data on hypertension (defined as previous diagnosis/use of antihypertensive drugs or blood pressure [BP]≥140/90 mmHg/BP≥130/80 mmHg) and obesity from 30 044 individuals in the Cardiovascular H3Africa Innovation Resource across 13 African countries. We analyzed data from population-based controls and the Entire Harmonized Dataset. Age-adjusted and crude proportions of hypertension were compared regionally, across sex, and between hypertension definitions. Logit generalized estimating equation was used to determine the independent association of obesity with hypertension (P value <5%). Participants were 56% women; with mean age 48.5±12.0 years. Crude proportions of hypertension (at BP≥140/90 mmHg) were 47.9% (95% CI, 47.4-48.5) for Entire Harmonized Dataset and 42.0% (41.1-42.7) for population-based controls and were significantly higher for the 130/80 mm Hg threshold at 59.3% (58.7-59.9) in population-based controls. The age-adjusted proportion of hypertension at BP≥140/90 mmHg was the highest among men (33.8% [32.1-35.6]), in western Africa (34.7% [33.3-36.2]), and in obese individuals (43.6%; 40.3-47.2). Obesity was independently associated with hypertension in population-based controls (adjusted odds ratio, 2.5 [2.3-2.7]) and odds of hypertension in obesity increased with increasing age from 2.0 (1.7-2.3) in younger age to 8.8 (7.4-10.3) in older age. Hypertension is common across multiple countries in Africa with 11.9% to 51.7% having BP≥140/90 mmHg and 39.5% to 69.4% with BP≥130/80 mmHg. Obese Africans were more than twice as likely to be hypertensive and the odds increased with increasing age.

Cross-sectional study of association between psychosocial stressors with chronic kidney disease among migrant and non-migrant Ghanaians living in Europe and Ghana: the RODAM study.

OBJECTIVES: The association between psychosocial stressors (PS) and chronic kidney disease (CKD) among sub-Saharan African (SSA) populations is unknown. We examined the association between PS and CKD prevalence among rural and urban Ghanaians and Ghanaian migrants living in three European cities. We also assessed if the influence of PS on CKD is partially mediated by primary risk factors (hypertension and diabetes) of CKD. DESIGN: A multi-centred cross sectional data from the Research on Obesity and Diabetes among African Migrants study. SETTING: Rural and urban Ghana and three European cities (Amsterdam, Berlin and London). PARTICIPANTS: A random sample of 5659 adults (Europe 3167, rural Ghana 1043 and urban Ghana 1449) aged 25-70 years. EXPLANATORY MEASURES: PS defined by negative life events, perceived discrimination, perceived stress at work/home and depressive symptoms. Three CKD outcomes were considered using the 2012 Kidney Disease: Improving Global Outcomes severity of CKD classification. Comparisons between PS and CKD outcomes were made using logistic regression analyses across all sites. RESULTS: We observed higher proportion of negative life events (68.7%) and perceived permanent stress (15.9%) among Ghanaians living in Ghana than Ghanaians living in Europe. Depressive symptoms (7.5%) and perceived discrimination (29.7%) were more common among Ghanaians living in Europe than Ghanaians living in Ghana. No significant association was observed between any of the PS constructs and CKD outcomes across sites except for positive association between stress at work/home and albuminuria (2.81, 95% CI 1.46 to 5.40) and CKD risk (2.78, 95% CI 1.43 to 5.43) among Ghanaians living in Berlin. CONCLUSION: Our study found a positive association between stress at work/home and albuminuria and CKD risk. There was no convincing evidence of associations between the other PS constructs and the prevalence of CKD risk. Further studies are needed to identify potential factors driving the high prevalence of CKD among these populations.

Cross-sectional study of association between socioeconomic indicators and chronic kidney disease in rural-urban Ghana: the RODAM study.

OBJECTIVES: Studies from high-income countries suggest higher prevalence of chronic kidney disease (CKD) among individuals in low socioeconomic groups. However, some studies from low/middle-income countries show the reverse pattern among those in high socioeconomic groups. It is unknown which pattern applies to individuals living in rural and urban Ghana. We assessed the association between socioeconomic status (SES) indicators and CKD in rural and urban Ghana and to what extent the higher SES of people in urban areas of Ghana could account for differences in CKD between rural and urban populations. SETTING: The study was conducted in Ghana (Ashanti region). We used baseline data from a multicentre Research on Obesity and Diabetes among African Migrants (RODAM) study. PARTICIPANTS: The sample consisted of 2492 adults (Rural Ghana, 1043, Urban Ghana, 1449) aged 25-70 years living in Ghana. EXPOSURE: Educational level, occupational level and wealth index. OUTCOME: Three CKD outcomes were considered using the 2012 Kidney Disease: Improving Global Outcomes severity of CKD classification: albuminuria, reduced glomerular filtration rate and high to very high CKD risk based on the combination of these two. RESULTS: All three SES indicators were not associated with CKD in both rural and urban Ghana after age and sex adjustment except for rural Ghana where high wealth index was significantly associated with higher odds of reduced estimated glomerular filtration rate (eGFR) (adjusted OR, 2.38; 95% CI 1.03 to 5.47). The higher rate of CKD observed in urban Ghana was not explained by the higher SES of that population. CONCLUSION: SES indicators were not associated with prevalence of CKD except for wealth index and reduced eGFR in rural Ghana. Consequently, the higher SES of urban Ghana did not account for the increased rate of CKD among urban dwellers suggesting the need to identify other factors that may be driving this.

20 year trends in renal disease mortality in Ghana: A review of autopsies.

AIM: Data on the changing levels in renal morbidity and mortality are scant globally. We sought to assess trends in renal disease mortality and attributable causes over a 20 year period in Ghana. METHODS: A retrospective analysis of 20 year autopsy records of the Pathology Departments of leading teaching hospitals in Ghana, (Korle-Bu Teaching Hospital (KBTH) in Accra and Komfo Anokye Teaching Hospital (KATH) in Kumasi) from January 1994 to December 2013. Data comprising autopsies from in-patients, community cases and coroners' cases were used. We defined primary cause of death as death directly due to renal disease and secondary cause of death as death in which renal disease was a comorbid or contributing factor. RESULTS: Over the period, there were a total of 94 309 deaths, of which 5608 were attributed to renal disease (5.9/100). Mortality rate remained fairly the same from 1994 to 2009 (5.0%), but doubled from 2010 to 2013 (10.8%). Similar trends were observed among males and females during the same period. However, males had slightly higher mortality rates (6.6%; 95% CI: 46.1%-6.8%) compared to females (5.6%; 95% CI: 5.4%-5.8%; P = 0.271). The major leading attributable causes of renal disease death include end stage renal disease 45.0% and acute pyelonephritis accounting for 20.9% of the cases. Hypertensive heart disease accounted for 30.0% of all secondary cause of death while congestive heart disease and septicaemia accounted for 13.0% and 12.0%, respectively. CONCLUSIONS: We observed marked increase in the renal disease mortality rate during the last few years predominantly driven by chronic and infectious related renal diseases as a main cause, and hypertensive heart disease and congestive heart failure as the main secondary causes. Measures geared towards prevention, treatment and managing such conditions may impact on the reduction of renal disease mortality rate among Ghanaian populations.

Chronic kidney disease burden among African migrants in three European countries and in urban and rural Ghana: the RODAM cross-sectional study.

Background: Chronic kidney disease (CKD) is a major burden among sub-Saharan African (SSA) populations. However, differences in CKD prevalence between rural and urban settings in Africa, and upon migration to Europe are unknown. We therefore assessed the differences in CKD prevalence among homogenous SSA population (Ghanaians) residing in rural and urban Ghana and in three European cities, and whether conventional risk factors of CKD explained the observed differences. Furthermore, we assessed whether the prevalence of CKD varied among individuals with hypertension and diabetes compared with individuals without these conditions. Methods: For this analysis, data from Research on Obesity & Diabetes among African Migrants (RODAM), a multi-centre cross-sectional study, were used. The study included a random sample of 5607 adult Ghanaians living in Europe (1465 Amsterdam, 577 Berlin, 1041 London) and Ghana (1445 urban and 1079 rural) aged 25-70 years. CKD status was defined according to severity of kidney disease using the combination of glomerular filtration rate (G1-G5) and albuminuria (A1-A3) levels as defined by the 2012 Kidney Disease: Improving Global Outcomes severity classification. Comparisons among sites were made using logistic regression analysis. Results: CKD prevalence was lower in Ghanaians living in Europe (10.1%) compared with their compatriots living in Ghana (13.3%) even after adjustment for age, sex and conventional risk factors of CKD [adjusted odds ratio (OR) = 0.70, 95% confidence interval (CI) 0.56-0.88, P = 0.002]. CKD prevalence was markedly lower among Ghanaian migrants with hypertension (adjusted OR = 0.54, 0.44-0.76, P = 0.001) and diabetes (adjusted OR = 0.37, 0.22-0.62, P = 0.001) compared with non-migrant Ghanaians with hypertension and diabetes. No significant differences in CKD prevalence was observed among non-migrant Ghanaians and migrant Ghanaians with no hypertension and diabetes. Among Ghanaian residents in Europe, the odds of CKD were lower in Amsterdam than in Berlin, while among Ghanaian residents in Ghana, the odds of CKD were lower in rural Ghana (adjusted OR = 0.68, 95% CI 0.53-0.88, P = 0.004) than in urban Ghana, but these difference were explained by conventional risk factors. Conclusion: Our study shows important differences in CKD prevalence among Ghanaians living in Europe compared with those living in Ghana, independent of conventional risk factors, with marked differences among those with hypertension and diabetes. Further research is needed to identify factors that might explain the observed difference across sites to implement interventions to reduce the high burden of CKD, especially in rural and urban Ghana.

Relationship between educational and occupational levels, and Chronic Kidney Disease in a multi-ethnic sample- The HELIUS study.

BACKGROUND: Ethnic minority groups in high-income countries are disproportionately affected by Chronic Kidney Disease (CKD) for reasons that are unclear. We assessed the association of educational and occupational levels with CKD in a multi-ethnic population. Furthermore, we assessed to what extent ethnic inequalities in the prevalence of CKD were accounted for by educational and occupational levels. METHODS: Cross-sectional analysis of baseline data from the Healthy Life in an Urban Setting (HELIUS) study of 21,433 adults (4,525 Dutch, 3,027 South-Asian Surinamese, 4,105 African Surinamese, 2,314 Ghanaians, 3,579 Turks, and 3,883 Moroccans) aged 18 to 70 years living in Amsterdam, the Netherlands. Three CKD outcomes were considered using the 2012 KDIGO (Kidney Disease: Improving Global Outcomes) severity of CKD classification. Comparisons between educational and occupational levels were made using logistic regression analyses. RESULTS: After adjustment for sex and age, low-level and middle-level education were significantly associated with higher odds of high to very high-risk of CKD in Dutch (Odds Ratio (OR) 2.10, 95% C.I., 1.37-2.95; OR 1.55, 95% C.I., 1.03-2.34). Among ethnic minority groups, low-level education was significantly associated with higher odds of high to very-high-risk CKD but only in South-Asian Surinamese (OR 1.58, 95% C.I., 1.06-2.34). Similar results were found for the occupational level in relation to CKD risk. CONCLUSION: The lower educational and occupational levels of ethnic minority groups partly accounted for the observed ethnic inequalities in CKD. Reducing CKD risk in ethnic minority populations with low educational and occupational levels may help to reduce ethnic inequalities in CKD and its related complications.