Evolution of nephrotic-associated focal segmental glomerulosclerosis and relation to the glomerular tip lesio11See Editorial by Haas,P. 1188.

Evolution of nephrotic-associated focal segmental glomerulosclerosis and relation to the glomerular tip lesion.BackgroundSeveral entities or variants within focal segmental glomerulosclerosis (FSGS) have been described, but their changes with time and interrelationships are undetermined.MethodsChanges with time were studied in two series of segmental sclerosing lesions in the nephrotic syndrome, one of 22 specimens from ten patients in a trial, the other of 176 specimens from 121 consecutive patients.ResultsThe earliest lesions were probably all at the tubular origin, equivalent to the tip variant of FSGS. In some patients, lesions remained at this site, but progression to renal failure was accompanied by morphologic progression, with development of lesions at various sites, equivalent to FSGS, not otherwise specified (NOS). Progression was more likely if there were large lesions, abnormal mesangium, and extensive acute tubular damage. Patients with lesions at the tubular origin at presentation had a shorter duration of symptoms and less chronic renal damage than those with multiple lesions, were more likely to have a complete response of the nephrotic syndrome, and were less likely to progress to renal failure. Recurrent nephrotic syndrome occurred in 12 of 14 allografts at risk, and was usually accompanied by lesions at the tubular origin, then multiple lesions.ConclusionAt least some patients with FSGS (NOS) have evolved from the tip variant. The tip variant has been considered a distinct entity. Another interpretation is that it includes two conditions, one an early form of classic FSGS, and the other closely related to minimal change nephropathy (MCN), equivalent to the glomerular tip lesion as originally defined

The Ghana Renal Registry – a first annual report

There are few data on the treatment of kidney disease in sub-Saharan Africa and no formal reports of kidney replacement therapy (KRT) in Ghana. We report data from the newly established Ghana Renal Registry on the prevalence, causes, and modality of treatment of kidney disease in Ghana. Using the web-based data capture system of the African Renal Registry, data were obtained for patients who had KRT in Ghana between January and December 2017. A total of 201 patients started KRT, giving an incidence rate of 6.9 per million population (pmp). There were 687 patients on KRT, a prevalence rate of 23.6 pmp. The median age of prevalent patients was 45.5 years and 63.6% were male. Hypertensive kidney disease was the most common primary kidney disease, reported in 39.9%. The overwhelming majority of patients (96.2%) were treated with haemodialysis, 3.5% had a kidney transplant, and only two were on continuous ambulatory peritoneal dialysis. The incidence and prevalence of KRTtreated kidney failure in Ghana is low, and the patients are younger than those on KRT in high- and upper-middleincome countries. The major cause of kidney failure is hypertensive kidney disease and the vast majority of the patients are treated with haemodialysis

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

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.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.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.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

Copy number of FCGR3B, which is associated with systemic lupus erythematosus, correlates with protein expression and immune complex uptake.

Copy number (CN) variation (CNV) has been shown to be common in regions of the genome coding for immune-related genes, and thus impacts upon polygenic autoimmunity. Low CN of FCGR3B has recently been associated with systemic lupus erythematosus (SLE). FcgammaRIIIb is a glycosylphosphatidylinositol-linked, low affinity receptor for IgG found predominantly on human neutrophils. We present novel data demonstrating that both in a family with FcgammaRIIIb-deficiency and in the normal population, FCGR3B CNV correlates with protein expression, with neutrophil uptake of and adherence to immune complexes, and with soluble serum FcgammaRIIIb. Reduced FcgammaRIIIb expression is thus likely to contribute to the impaired clearance of immune complexes, which is a feature of SLE, explaining the association between low FCGR3B CNV and SLE that we have confirmed in a Caucasian population. In contrast, antineutrophil cytoplasmic antibody-associated systemic vasculitis (AASV), a disease not associated with immune complex deposition, is associated with high FCGR3B CN. Thus, we define a role for FCGR3B CNV in immune complex clearance, a function that may explain why low FCGR3B CNV is associated with SLE, but not AASV. This is the first report of an association between disease-related gene CNV and variation in protein expression and function that may contribute to autoimmune disease susceptibility

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

High-depth African genomes inform human migration and health

The African continent is regarded as the cradle of modern humans and African genomes contain more genetic variation than those from any other continent, yet only a fraction of the genetic diversity among African individuals has been surveyed1. Here we performed whole-genome sequencing analyses of 426 individuals—comprising 50 ethnolinguistic groups, including previously unsampled populations—to explore the breadth of genomic diversity across Africa. We uncovered more than 3 million previously undescribed variants, most of which were found among individuals from newly sampled ethnolinguistic groups, as well as 62 previously unreported loci that are under strong selection, which were predominantly found in genes that are involved in viral immunity, DNA repair and metabolism. We observed complex patterns of ancestral admixture and putative-damaging and novel variation, both within and between populations, alongside evidence that Zambia was a likely intermediate site along the routes of expansion of Bantu-speaking populations. Pathogenic variants in genes that are currently characterized as medically relevant were uncommon—but in other genes, variants denoted as ‘likely pathogenic’ in the ClinVar database were commonly observed. Collectively, these findings refine our current understanding of continental migration, identify gene flow and the response to human disease as strong drivers of genome-level population variation, and underscore the scientific imperative for a broader characterization of the genomic diversity of African individuals to understand human ancestry and improve health

High-depth African genomes inform human migration and health

The African continent is regarded as the cradle of modern humans and African genomes contain more genetic variation than those from any other continent, yet only a fraction of the genetic diversity among African individuals has been surveyed1. Here we performed whole-genome sequencing analyses of 426 individuals—comprising 50 ethnolinguistic groups, including previously unsampled populations—to explore the breadth of genomic diversity across Africa. We uncovered more than 3 million previously undescribed variants, most of which were found among individuals from newly sampled ethnolinguistic groups, as well as 62 previously unreported loci that are under strong selection, which were predominantly found in genes that are involved in viral immunity, DNA repair and metabolism. We observed complex patterns of ancestral admixture and putative-damaging and novel variation, both within and between populations, alongside evidence that Zambia was a likely intermediate site along the routes of expansion of Bantu-speaking populations. Pathogenic variants in genes that are currently characterized as medically relevant were uncommon—but in other genes, variants denoted as ‘likely pathogenic’ in the ClinVar database were commonly observed. Collectively, these findings refine our current understanding of continental migration, identify gene flow and the response to human disease as strong drivers of genome-level population variation, and underscore the scientific imperative for a broader characterization of the genomic diversity of African individuals to understand human ancestry and improve health