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.

Pregnancy-Associated Acute Kidney Injury in Low-Resource Settings: Progress Over the Last Decade.

Despite immense global effort, the maternal mortality rate in low-resource settings remains unacceptably high. Globally, this reflects the grave inequalities in access to health and reproductive services. Pregnancy-associated acute kidney injury (PRAKI) is an independent risk factor for mortality. The reported incidence of PRAKI in low- and middle-income countries is higher than that of high-income countries (4%-26% versus 1%-2.8%, respectively). Hypertensive disorders are now the leading cause of PRAKI in many regions, followed by hemorrhage and sepsis. PRAKI in low-resource settings carries a high mortality for both mother and child. Outcome studies suggest that PRAKI is associated with residual kidney dysfunction and may lead to dialysis dependence. This can be a death sentence in many regions with limited kidney replacement therapy. This review will summarize data on PRAKI on the African, Latin American, and Asian continents over the past decade. It will include the progress in published data, mortality, and treatment interventions and provide recommendations for the next decade.

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.

Trends in the epidemiology of childhood nephrotic syndrome in Africa: A systematic review.

Background: Childhood nephrotic syndrome, if left untreated, leads to progressive kidney disease or death. We quantified the prevalence of steroid-sensitive nephrotic syndrome, steroid-resistant nephrotic syndrome, and histological types as the epidemiology of nephrotic syndrome in Africa remains unknown, yet impacts outcomes. Methods: We searched MEDLINE, Embase, African Journals Online, and WHO Global Health Library for articles in any language reporting on childhood nephrotic syndrome in Africa from January 1, 1946 to July 1, 2020. Primary outcomes included steroid response, biopsy defined minimal change disease, and focal segmental glomerulosclerosis (FSGS) by both pooled and individual proportions across regions and overall. Findings: There were 81 papers from 17 countries included. Majority of 8131 children were steroid-sensitive (64% [95% CI: 63-66%]) and the remaining were steroid-resistant (34% [95% CI: 33-35%]). Of children biopsied, pathological findings were 38% [95% CI: 36-40%] minimal change, 24% [95% CI: 22-25%] FSGS, and 38% [95% CI: 36-40%] secondary causes of nephrotic syndrome. Interpretation: Few African countries reported on the prevalence of childhood nephrotic syndrome. Steroid-sensitive disease is more common than steroid-resistant disease although prevalence of steroid-resistant nephrotic syndrome is higher than reported globally. Pathology findings suggest minimal change and secondary causes are common. Scarcity of data in Africa prevents appropriate healthcare resource allocation to diagnose and treat this treatable childhood kidney disease to prevent poor health outcomes. Funding: Funding was provided by the Canadian Institute for Health Research (CIHR) and the National Institute of Health (NIH) for the H3 Africa Kidney Disease Research Network. This research was undertaken, in part, from the Canada Research Chairs program.

CKD and Pregnancy Outcomes in Africa: A Narrative Review.

Chronic kidney disease (CKD) is associated with adverse maternal and fetal outcomes and is reported to affect up to 3% of women of reproductive age in high-income countries, but estimated prevalence may be as much as 50% higher in low and middle-income countries (LMICs). All pregnancy complications occur much more frequently in women in LMICs compared with those in high-income countries. Given the anticipated high prevalence of CKD in women of reproductive age and high rates of maternal and fetal adverse events in Africa, we sought to explore the association between CKD and pregnancy outcomes in this setting through a narrative review of the literature. This review demonstrates the paucity of data in this area and highlights the systemic barriers that exist in many African countries that prevent robust management of noncommunicable diseases such as CKD during a woman's reproductive life. This evidence gap highlights the need for further research, starting by sampling normal ranges of serum creatinine concentrations in pregnant and nonpregnant women of reproductive age in the diverse populations of Africa, estimating prevalence of CKD, and understanding associated pregnancy outcomes. Research should then focus on pragmatic interventions that may improve outcomes for women and their infants.

Spectrum and Clinical Characteristics of Renal Diseases in Ghanaian Adults: A 13-Year Retrospective Study.

BACKGROUND: Renal diseases over the years have become one of the leading causes of morbidity and mortality worldwide. In this study, we assessed the spectrum and clinical characteristics of Ghanaians with renal diseases at the nephrology unit of Komfo Anokye Teaching Hospital (KATH), Kumasi. METHODS: This was a retrospective hospital-based study conducted at Komfo Anokye Teaching Hospital (KATH) from the years 2005 to 2017. A non-randomized sampling approach was used to include 1426 participants who were diagnosed with AKI, CKD, ESRD, and nephrotic syndrome at the nephrology unit of KATH during the years under review. All the 1426 patients were eligible for the study. Demographic characteristics as well as clinical data such as the kind of renal disease presentation, causes of the renal disease, and the treatment options were also obtained from their records. RESULTS: Overall, 1009 of the total participants had CKD (70.76%), 295 participants had ESRD (20.69%), 72 participants had AKI (5.05%), and 50 participants had nephrotic syndrome (3.51%). Furthermore, 69 (23.4%) participants with ESRD were on dialysis whiles 6 (8.3) and 17 (1.7) participants with only AKI and CKD superimposed AKI, respectively, were on dialysis. 226 (76.6%) participants with ESRD were on conservative therapy. Hypertension emerged as the major cause of renal disease presentation (53.93%) with bilateral leg edema (13.46%) being the major complaint. There was a significant association between CKD and age (p ≤ 0.001). Nephrotic syndrome also showed a significant association with age (p ≤ 0.001). CONCLUSION: This study revealed that patients at the nephrology unit of KATH, Ghana, are mainly adults between ages 46-55. The clinical pattern of renal diseases is dominated by CKD and ESRD. We conclude that hypertension, chronic glomerulonephritis, diabetic nephropathy, and sepsis are the most common causes of renal diseases. The commonest clinical presentations are bilateral leg edema, palpitations, headache, breathlessness, dizziness, and vomiting. Early diagnosis and management of these conditions may prevent or delay the progress to end-stage renal disease.

Global case studies for chronic kidney disease/end-stage kidney disease care.

The prevalence of chronic kidney disease and its risk factors is increasing worldwide, and the rapid rise in global need for end-stage kidney disease care is a major challenge for health systems, particularly in low- and middle-income countries. Countries are responding to the challenge of end-stage kidney disease in different ways, with variable provision of the components of a kidney care strategy, including effective prevention, detection, conservative care, kidney transplantation, and an appropriate mix of dialysis modalities. This collection of case studies is from 15 countries from around the world and offers valuable learning examples from a variety of contexts. The variability in approaches may be explained by country differences in burden of disease, available human or financial resources, income status, and cost structures. In addition, cultural considerations, political context, and competing interests from other stakeholders must be considered. Although the approaches taken have often varied substantially, a common theme is the potential benefits of multistakeholder engagement aimed at improving the availability and scope of integrated kidney care.

Hearing impairment among chronic kidney disease patients on haemodialysis at a tertiary hospital in Ghana.

BACKGROUND: Chronic kidney disease is a major public health challenge, globally. Inadequate excretion of metabolic waste products by the kidneys results in circulation of these toxic materials in the body. This can cause damage to tissues and organ systems including the auditory system which can lead to hearing loss. AIM: The study was aimed at determining the prevalence, degrees and types of hearing impairment among Chronic kidney disease patients on haemodialysis in Ghana. METHODS: A case-control study involving 50 Chronic Kidney disease patients and 50 age and gender-matched control group was carried out at the Korle Bu Teaching Hospital (KBTH). A structured questionnaire was administered to obtain basic socio-demographic data and case history of the participants. Audiological assessment was performed using a test battery comprising otoscopy, tympanometry and pure tone audiometry in a soundproof booth. RESULTS: Higher hearing thresholds were recorded across all the frequencies tested among the case group than the control group (p < 0.05) in both ears. Only sensorineural hearing loss was identified among the cases. The prevalence of hearing loss was 32% among the case group and 12% among the control group. No significant association was observed between hearing loss and duration of Chronic kidney disease (p = 0.16), gender of Chronic kidney disease patient and hearing loss (p = 0.88), and duration of Chronic kidney disease and degree of hearing loss (p=0.31). CONCLUSION: Our study showed that Chronic Kidney disease patients on haemodialysis are at higher risk of experiencing hearing loss. FUNDING: None declared.

Factors associated with acute kidney injury recovery in a tertiary hospital in Ghana: a prospective study.

INTRODUCTION: Acute kidney injury (AKI) is a challenging problem in developing countries due to late presentation of its victims to health care facilities. Data on the pattern of AKI, its outcome and factors associated with its recovery is scanty in developing countries therefore impeding AKI management. Aim: to study AKI recovery rate and its associated factors. METHODS: An observational study conducted from September 2013 to June 2014 at Korle-Bu Teaching Hospital (KBTH). Participants were adults, admitted with AKI at KBTH. Kidney Disease: Improving Global Outcomes (KDIGO) criteria was used to diagnose and stage AKI. RESULTS: Mean age (SD) of the participants was 41.9 (± 19.2) years. About a third of the patients (34.6%) were less than 29 years with 30-39 years and 40-60 years constituting 23.0% and 23.6% respectively. Females were in the majority (56.0%). AKI stages I, II and III accounted for 11.0%, 6.8% and 70.7% respectively. Majority, 82.2% of the patients recovered their kidney function. Stage III AKI was significantly associated with decreasing odds of recovery [OR = 0.4, 95%CI = 0.4-2.6, p = 0.002]. In addition, normal blood sodium was associated with recovery from AKI [OR, 95%CI = 2.3, (1.1-5.3), p = 0.043]. Almost half (45.5%) presented with fever whereas 32.5% and 22.5% presented with peripheral oedema and pulmonary oedema respectively. CONCLUSION: The study demonstrated high kidney function recovery following AKI. Dominant clinical features were fever, peripheral and pulmonary oedema. Advanced stage was associated with poor recovery whereas normal serum sodium level improves kidney function recovery.

Outcomes in adults and children with end-stage kidney disease requiring dialysis in sub-Saharan Africa: a systematic review.

BACKGROUND: The burden of end-stage kidney disease (ESKD) in sub-Saharan Africa is unknown but is probably high. Access to dialysis for ESKD is limited by insufficient infrastructure and catastrophic out-of-pocket costs. Most patients remain undiagnosed, untreated, and die. We did a systematic literature review to assess outcomes of patients who reach dialysis and the quality of dialysis received. METHODS: We searched PubMed, African Journals Online, WHO Global Health Library, and Web of Science for articles in English or French from sub-Saharan Africa reporting dialysis outcomes in patients with ESKD published between Jan 1, 1990, and Dec 22, 2015. No studies were excluded to best represent the current situation in sub-Saharan Africa. Outcomes of interest included access to dialysis, mortality, duration of dialysis, and markers of dialysis quality in patients with ESKD. Data were analysed descriptively and reported using narrative synthesis. FINDINGS: Studies were all of medium to low quality. We identified 4339 studies, 68 of which met inclusion criteria, comprising 24 456 adults and 809 children. In the pooled analysis, 390 (96%) of 406 adults and 133 (95%) of 140 children who could not access dialysis died or were presumed to have died. Among those dialysed, 2747 (88%) of 3122 adults in incident ESKD cohorts, 496 (16%) of 3197 adults in prevalent ESKD cohorts, and 107 (36%) of 294 children with ESKD died or were presumed to have died. 2508 (84%) of 2990 adults in incident ESKD cohorts discontinued dialysis compared with 64 (5%) of 1364 adults in prevalent ESKD cohorts. 41 (1%) of 4483 adults in incident ESKD cohorts, 2280 (19%) of 12 125 adults in prevalent ESKD cohorts, and 71 (19%) of 381 children with ESKD received transplants. 16 studies reported on management of anaemia, 17 on dialysis frequency, eight on dialysis accuracy, and 22 on vascular access for dialysis INTERPRETATION: Most patients with ESKD starting dialysis in sub-Saharan Africa discontinue treatment and die. Further work is needed to develop equitable and sustainable strategies to manage individuals with ESKD in sub-Saharan Africa. FUNDING: None.

Urinary Lysosomal Enzyme Activities and Albuminuria in Ghanaian Patients with Type 2 Diabetes Mellitus.

Renal tubular lysosomal enzyme activities like alanine aminopeptidase (AAP) and N-acetyl-ß-D-glucosaminidase (NAG) have been shown to increase in patients developing diabetic nephropathy and nephrosclerosis. This study aimed to determine the activities of N-acetyl-ß-D-glucosaminidase and alanine aminopeptidase and albumin concentration in urine samples of patients with type 2 diabetes. One hundred and thirty (65 type 2 diabetic and 65 nondiabetic) subjects participated in this study. Blood samples were drawn for measurements of fasting blood glucose, albumin (Alb), lipids, and creatinine (Cr). Early morning spot urine samples were also collected for activities of alanine aminopeptidase (AAP), N-acetyl-ß-D-glucosaminidase (NAG), and concentration of albumin (U-Alb) and creatinine (U-Cr). Both NAG/Cr and AAP/Cr were significantly increased in diabetic subjects compared to controls (p < 0.001). There was positive correlation between NAG/Cr and Alb/Cr (r = 0.49, p < 0.001) and between NAG/Cr and serum creatinine (r = 0.441, p < 0.001). A negative correlation was found between NAG/Cr and eGFR (r = -0.432, p < 0.05). 9.3% and 12% of diabetics with normoalbuminuria had elevated levels of AAP/Cr and NAG/Cr, respectively. We conclude that measuring the urinary enzymes activities (NAG/Cr and AAP/Cr) could be useful as a biomarker of early renal involvement in diabetic complications.

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.

Outcomes of acute kidney injury in children and adults in sub-Saharan Africa: a systematic review.

BACKGROUND: Access to diagnosis and dialysis for acute kidney injury can be life-saving, but can be prohibitively expensive in low-income settings. The burden of acute kidney injury in sub-Saharan Africa is presumably high but remains unknown. We did a systematic review to assess outcomes of acute kidney injury in sub-Saharan Africa and identify barriers to care. METHODS: We searched PubMed, African Journals Online, WHO Global Health Library, and Web of Science for articles published between Jan 1, 1990, and Nov 30, 2014. We scored studies, and all were of medium-to-low quality. We made a pragmatic decision to include all studies to best reflect reality, and did a descriptive analysis of extracted data. This study is registered with PROSPERO, number CRD42015015690. FINDINGS: We identified 3881 records, of which 41 met inclusion criteria, including 1403 adult patients and 1937 paediatric patients. Acute kidney injury in sub-Saharan Africa is severe, with 1042 (66%) of 1572 children and 178 (70%) 253 of adults needing dialysis in studies reporting dialysis need. Only 666 (64%) of 1042 children (across 11 studies) and 58 (33%) of 178 adults (across four studies) received dialysis when needed. Overall mortality was 34% in children and 32% in adults, but rose to 73% in children and 86% in adults when dialysis was needed but not received. Major barriers to access to care were out-of-pocket costs, erratic hospital resources, late presentation, and female sex. INTERPRETATION: Patients in these studies are those with resources to access care. In view of overall study quality, data interpretation should be cautious, but high mortality and poor access to dialysis are concerning. The global scarcity of resources among patients and health centres highlights the need for a health-system-wide approach to prevention and management of acute kidney injury in sub-Saharan Africa. FUNDING: None.

Human Heredity and Health (H3) in Africa Kidney Disease Research Network: A Focus on Methods in Sub-Saharan Africa.

CKD affects an estimated 14% of adults in sub-Saharan Africa, but very little research has been done on the cause, progression, and prevention of CKD there. As part of the Human Heredity and Health in Africa (H3Africa) Consortium, the H3Africa Kidney Disease Research Network was established to study prevalent forms of kidney disease in sub-Saharan Africa and increase the capacity for genetics and genomics research. The study is performing comprehensive phenotypic characterization and analyzing environmental and genetic factors from nine clinical centers in four African countries (Ghana, Nigeria, Ethiopia, and Kenya) over a 5-year period. Approximately 4000 participants with specified kidney disease diagnoses and 4000 control participants will be enrolled in the four African countries. In addition, approximately 50 families with hereditary glomerular disease will be enrolled. The study includes both pediatric and adult participants age <1 to 74 years across a broad spectrum of kidney diseases secondary to hypertension-attributed nephropathy, diabetes, HIV infection, sickle cell disease, biopsy-proven glomerular disease, and CKD of unknown origin. Clinical and demographic data with biospecimens are collected to assess clinical, biochemical, and genetic markers of kidney disease. As of March 2015, a total of 3499 patients and controls have been recruited and 1897 had complete entry data for analysis. Slightly more than half (50.2%) of the cohort is female. Initial quality control of clinical data collection and of biosample and DNA analysis is satisfactory, demonstrating that a clinical research infrastructure can be successfully established in Africa. This study will provide clinical, biochemical, and genotypic data that will greatly increase the understanding of CKD in sub-Saharan Africa.