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.

Community-acquired acute kidney injury in adults in Africa.

AIMS: We review recent published data on demographics, causes, diagnoses, treatment, and outcome of acute kidney injury (AKI) in Africa. METHODS: A review of the incidence, etiology, diagnoses, and treatment of AKI in adults in Africa from studies published between the years 2000 and 2015. RESULTS: The incidence of AKI in hospitalized patients in Africa ranges from 0.3 to 1.9% in adults. Between 70 and 90% of cases of AKI are community acquired. Most patients with AKI are young with a weighted mean age of 41.3 standard deviation (SD) 9.3 years, and a male to female ratio of 1.2 : 1.0. Medical causes account for between 65 and 80% of causes of AKI. This is followed by obstetric causes in 5 - 27% of cases and surgical causes in 2 - 24% of cases. In the reported studies, between 17 and 94% of patients who needed dialysis received this. The mortality of AKI in adults in Africa ranged from 11.5 to 43.5%. CONCLUSIONS: Most reported cases of AKI in Africa originate in the community. The low incidence of hospital-acquired AKI is likely to be due to under ascertainment. Most patients with AKI in Africa are young and have a single precipitating cause. Prominent among these are infection, pregnancy complications and nephrotoxins. Early treatment can improve clinical outcomes.

Immunosuppression for progressive membranous nephropathy: a UK randomised controlled trial.

BACKGROUND: Membranous nephropathy leads to end-stage renal disease in more than 20% of patients. Although immunosuppressive therapy benefits some patients, trial evidence for the subset of patients with declining renal function is not available. We aimed to assess whether immunosuppression preserves renal function in patients with idiopathic membranous nephropathy with declining renal function. METHODS: This randomised controlled trial was undertaken in 37 renal units across the UK. We recruited patients (18-75 years) with biopsy-proven idiopathic membranous nephropathy, a plasma creatinine concentration of less than 300 µmol/L, and at least a 20% decline in excretory renal function measured in the 2 years before study entry, based on at least three measurements over a period of 3 months or longer. Patients were randomly assigned (1:1:1) by a random number table to receive supportive treatment only, supportive treatment plus 6 months of alternating cycles of prednisolone and chlorambucil, or supportive treatment plus 12 months of ciclosporin. The primary outcome was a further 20% decline in renal function from baseline, analysed by intention to treat. The trial is registered as an International Standard Randomised Controlled Trial, number 99959692. FINDINGS: We randomly assigned 108 patients, 33 of whom received prednisolone and chlorambucil, 37 ciclosporin, and 38 supportive therapy alone. Two patients (one who received ciclosporin and one who received supportive therapy) were ineligible, so were not included in the intention-to-treat analysis, and 45 patients deviated from protocol before study end, mostly as a result of minor dose adjustments. Follow up was until primary endpoint or for minimum of 3 years if primary endpoint was not reached. Risk of further 20% decline in renal function was significantly lower in the prednisolone and chlorambucil group than in the supportive care group (19 [58%] of 33 patients reached endpoint vs 31 [84%] of 37, hazard ratio [HR] 0·44 [95% CI 0·24-0·78]; p=0·0042); risk did not differ between the ciclosporin (29 [81%] of 36) and supportive treatment only groups (HR 1·17 [0·70-1·95]; p=0·54), but did differ significantly across all three groups (p=0·003). Serious adverse events were frequent in all three groups but were higher in the prednisolone and chlorambucil group than in the supportive care only group (56 events vs 24 events; p=0·048). INTERPRETATION: For the subset of patients with idiopathic membranous nephropathy and deteriorating excretory renal function, 6 months' therapy with prednisolone and chlorambucil is the treatment approach best supported by our evidence. Ciclosporin should be avoided in this subset. FUNDING: Medical Research Council, Novartis, Renal Association, Kidney Research UK.

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.

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.

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.

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.

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.

Prevalence of chronic kidney disease in hypertensive patients in Ghana.

Chronic kidney disease (CKD) is common in tropical Africa although there are few data on the prevalence of this disorder. Therefore we initiated a multicenter screening study to identify the prevalence and staging of CKD in 712 patients with known hypertension in four polyclinics in Accra, Ghana. We measured estimated glomerular filtration rate by the six-variable modification of diet in renal disease equation and proteinuria by the protein/creatinine ratio. All the subjects studied were Ghanaian. Of the 712 patients studied, the median age was 59 years (range 19-90 years) and 560 (78.7%) of the patients were female. The mean duration of hypertension was 4 years (range 0.1-50). The overall prevalence of CKD was 46.9% (95% CI: 43.2-50.7%); 19.1% had CKD stages 1-2 and 27.8% had CKD stages 3-5. There was no difference in age between patients with or without CKD (p = 0.12). The overall prevalence of proteinuria was 28.9% (95% CI: 25.6-32.4%); 14.7% of subjects had preexisting diabetes mellitus and their prevalence of CKD (55%; 95% CI: 42.4-62.2) did not differ from those without diabetes (46%; 95% CI: 41.9-50.0, p = 0.133). CKD is common in hypertensive patients in Ghana, with a prevalence of 46.9%. This provides justification for the inclusion of this group in CKD screening programs in Ghana.

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.

Prediction of ESRD in pauci-immune necrotizing glomerulonephritis: quantitative histomorphometric assessment and serum creatinine.

BACKGROUND: Clinical and pathologic features that predict outcome have important potential application in patients with pauci-immune necrotizing glomerulonephritis (usually antineutrophil cytoplasmic antibody-associated vasculitis). This study examines the predictive value of simple quantitative renal histologic measurements in a large cohort with extended follow-up. STUDY DESIGN: Cohort study. SETTING & PARTICIPANTS: 390 consecutive patients with pauci-immune necrotizing glomerulonephritis at a single hospital (1983-2002); 90 patients underwent repeated kidney biopsy during follow-up. PREDICTORS: Age and serum creatinine concentration at biopsy, antineutrophil cytoplasmic antibody specificity, percentage of normal glomeruli, percentage of glomeruli with active lesions, and index of chronic damage (quantitative measurement of established cortical damage) in the initial kidney biopsy for all patients. The same factors were assessed in both biopsy specimens for patients undergoing an additional biopsy. OUTCOMES & MEASUREMENTS: End-stage renal disease and patient survival. RESULTS: Mortality at 1 and 5 years was 23% and 40%, respectively: standardized mortality ratio, 4.74 (95% CI, 3.62-6.32). End-stage renal disease was reached by 14% and 18% at 1 and 5 years, respectively. In multivariable analysis, serum creatinine level at biopsy and percentage of normal glomeruli in the initial biopsy specimen were the best predictors of kidney survival. C Statistics were 0.80 for creatinine level alone and 0.83 for creatinine level with normal glomeruli. In patients undergoing an additional biopsy, rapid progression in the index of chronic damage and serum creatinine level at the second biopsy were associated with kidney survival in multivariable analysis. LIMITATIONS: Retrospective analysis. External validity of the index of chronic damage requires further assessment. Selection bias may influence repeated biopsy analyses. CONCLUSIONS: Serum creatinine level at biopsy best predicts kidney survival in patients with pauci-immune necrotizing glomerulonephritis overall.

Prevention and transplantation in chronic kidney disease: what is achievable in emerging countries? Meeting report: Bamako meeting December 4-6, 2008.

Experts from all continents discussed the present and future of nephrology and transplantation medicine in emerging countries during a 3-day conference, supported by the World Health Organization, the International Society of Nephrology, the Transplantation Society-Global Alliance for Transplantation and the Ministry of Health of the Republic of Mali. This conference was held in Bamako, Mali on December 4-6, 2008, and focused on prevention and treatment of chronic kidney disease in emerging countries. Apart from delivering high-quality medical and scientific knowledge, the meeting was mainly a call to action for emerging countries to start chronic kidney disease prevention and screening programs, develop end-stage renal disease registries and start or further elaborate transplantation programs. International as well as regional collaborations need to be stimulated and strengthened in order to allow emerging countries to acquire the information, technology, experience and skills necessary to achieve these ambitious goals.

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.