Human Immunodeficiency Virus Nephropathy in Central Africa: The Value of Renal Ultrasound

Introduction: HIV-Associated Nephropathy may shorten the life expectancy of affected patients. Its early detection is beneficial for the indication of treatment and hence prevention of progression to the end-stage of renal failure. The final diagnosis requires renal biopsy which may be difficult in some African area; clinical and ultrasound criteria may be helpful. The aim of this study was twofold: to characterize renal sonographic changes in HIV-positive patients with HIV associated Nephropathy and to investigate the correlation between renal sonographic changes and histological lesions in central Africa.Methods: A prospective and multi-center study conducted from January 2013 to July 2015 included, for renal ultrasound evaluation of the length, thickness and echogenicity, forty two of the 334 biologically confirmed HIV-positive patients who presented with significant proteinuria suggestive of HIV associated Nephropathy. And transcutaneous renal biopsy with histopathology has been performed in 16 patients of them. Statistical analyzes were used.Results: There were 100 men and 234 women; proteinuria was positive in 42 patients, (12.6%). The average length of the kidneys was 111 ± 8 mm (normal), with 10% of patients with pathological values (5% with kidneys of reduced size and 5%, increased size). The kidneys had an average thickness of 44 ± 5 mm (normal), with 21% of patients presenting an increase in renal thickness. Quantitative echogenicity was calculated at 1.492 ± 0.793 (normal), with 79% of patients with increased quantitative echogenicity. Of the 16 patients biopsied, all had tubulo-interstitial lesions, and 75% of them associated with glomerular lesions. In simple correlation analysis, tubular dilatation was positively and significantly related to quantitative echogenicity (r = 0.67, p < 0.01) and to renal parenchyma thickness (r = 0.67; 0.85, p ? 0.05). The relationship between the other parameters studied did not reach statistical significance. In multiple linear regression, glomerular hyalinosis, glomerular proliferation, tubular dilatation, tubular atrophy, interstitial fibrosis, and interstitial inflammation emerged as the main determinants of quantitative echogenicity; however, the relationship was statistically significant only for tubular dilatation (? = 0.305, p = 0.034).Conclusion: The present study showed the characteristic of renal change and the relation with histology found in central Africans patients

APOL1 C-Terminal Variants May Trigger Kidney Disease through Interference with APOL3 Control of Actomyosin

The C-terminal variants G1 and G2 of apolipoprotein L1 (APOL1) confer human resistance to the sleeping sickness parasite Trypanosoma rhodesiense, but they also increase the risk of kidney disease. APOL1 and APOL3 are death-promoting proteins that are partially associated with the endoplasmic reticulum and Golgi membranes. We report that in podocytes, either APOL1 C-terminal helix truncation (APOL1Δ) or APOL3 deletion (APOL3KO) induces similar actomyosin reorganization linked to the inhibition of phosphatidylinositol-4-phosphate [PI(4)P] synthesis by the Golgi PI(4)-kinase IIIB (PI4KB). Both APOL1 and APOL3 can form K+ channels, but only APOL3 exhibits Ca2+-dependent binding of high affinity to neuronal calcium sensor-1 (NCS-1), promoting NCS-1-PI4KB interaction and stimulating PI4KB activity. Alteration of the APOL1 C-terminal helix triggers APOL1 unfolding and increased binding to APOL3, affecting APOL3-NCS-1 interaction. Since the podocytes of G1 and G2 patients exhibit an APOL1Δ or APOL3KO-like phenotype, APOL1 C-terminal variants may induce kidney disease by preventing APOL3 from activating PI4KB, with consecutive actomyosin reorganization of podocytes.info:eu-repo/semantics/publishe

APOL1-associated kidney disease in pediatric population in the Democratic Republic of Congo

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Clinical and genetic factors are associated with kidney complications in African children with sickle cell anaemia

Clinical and genetic factors have been reported as influencing the development of sickle cell nephropathy (SCN). However, such data remain limited in the paediatric population. In this cross-sectional study, we enrolled 361 sickle cell disease children from the Democratic Republic of Congo. Participants were genotyped for the beta (beta)-globin gene, apolipoprotein L1 (APOL1) risk variants, and haem oxygenase-1 (HMOX1) GT-dinucleotide repeats. As markers of kidney damage, albuminuria, hyperfiltration and decreased estimated glomerular filtration with creatinine (eGFRcr) were measured. An association of independent clinical and genetic factors with these markers of kidney damage were assessed via regression analysis. Genetic sequencing confirmed sickle cell anaemia in 326 participants. Albuminuria, hyperfiltration and decreased eGFRcr were present in 65 (20%), 52 (16%) and 18 (5 center dot 5%) patients, respectively. Regression analysis revealed frequent blood transfusions, indirect bilirubin and male gender as clinical predictors of SCN. APOL1 high-risk genotype (G1/G1, G2/G2 and G1/G2) was significantly associated with albuminuria (P = 0 center dot 04) and hyperfiltration (P = 0 center dot 001). HMOX1 GT-dinucleotide long repeats were significantly associated with lower eGFRcr. The study revealed a high burden of kidney damage among Congolese children and provided evidence of the possible role of APOL1 and HMOX1 in making children more susceptible to kidney complications

Proprotein Convertase Subtilisin/Kexin 9 level is independently associated with 10-year cardiovascular risk in blood donors in Kinshasa: A cross-sectional study based on Framingham predictive equation

Context and objective: Proprotein Convertase Subtilisin Kexin type 9 (PCSK9) plays an important role in lipid homeostasis. The present study aimed&nbsp; to determine whether PCSK9 is a potential cardiovascular risk (CVR) factor among apparently healthy people. Methods:&nbsp; A cross-sectional&nbsp; study was conducted between August 2016 and July 2020 in the City of Kinshasa, Democratic Republic of the Congo. Volunteer and regular blood&nbsp; donors from the Catholic medical network (Bureau Diocésain des OEuvres Médicales [BDOM]/Kinshasa) were enrolled in this study. Serum PCSK9&nbsp; and lipid levels were measured by ELISA and enzymatic colorimetric method, respectively. Framingham’s predictive equation was used for predicting&nbsp; cardiac events. Pearson's correlation coefficients (r) were calculated to assess the association between the different lipid fractions and&nbsp; PCSK-9. The search for the determinants of 10 year-risk of a high cardiovascular event was carried out using the cultivariate binary logistic&nbsp; regression model. Results: Of 296 subjects included in the present study, 264 (89.1 %) had low and 32 (10.8 %) high CVR. Age ≥ 50 years (aOR 5), low HDL-c (aOR 5),&nbsp; high LDL-c (aOR 6), hypertriglyceridemia (aOR 4), and belonging to the 3rd tertile of PCSK9 ((aOR 4.4) emerged as independent determinants of high&nbsp; CVR. Conclusion: High plasma levels of PCSK9 are associated with high CVR in apparently healthy people. Prospective studies in the general population&nbsp; to confirm this Framingham cardiovascular prediction are needed.&nbsp; &nbsp; French title: Le taux de Proprotein Convertase Subtilisin/Kexin 9 est indépendamment associé au risque cardiovasculaire à 10 ans chez les donneurs de sang à Kinshasa : Etude transversale basée sur Contexte et objectif: La Proprotéine Convertase Subtilisine Kexin type 9 (PCSK9) est importante dans l'homéostasie des lipides. Cette étude visait à&nbsp; établir le rôle potentiel de PCSK9 comme facteur de risque cardiovasculaire (RCV). Méthodes. L’enquête transversale couvrant la période d’août 2016 à juillet 2020 a été conduite dans la ville de Kinshasa (RD Congo), sur des donneurs de sang volontaires et réguliers au sein du réseau médical catholique (BDOM). La technique Elisa a permis l’analyse de PCSK9 sérique et le taux des lipides était dosé par la méthode enzymatique colorimétrique. L'équation de prédiction des événements CV a recourru à la méthode Framingham. La corrélation entre le taux des lipides sériques et le PCSK-9 a été faite à l’aide de corrélation linéraire de Pearson. La régression logistique binaire multivariée a déterminé le niveau du risque futur&nbsp; des événements CV. Résultats: 264/296 sujets (89,1 %) avaient un RCV faible, 32 (10,8 %) un RCV élevé. Les principaux déterminants du RCV étaient :&nbsp; âge ≥ 50 ans (ORa 5), taux bas de HDL-c (ORa 4), taux élevé de LDL-c (ORa 6) et/ou de triglycéride (ORa 4) et l'appartenance au 3ème tertile de PCSK9 (ORa 4). Conclusion: Le taux plasmatique élevé de PCSK9 constitue un facteur de risque un RCV élevé dans cette population en bonne santé apparente. L’extension de l’étude dans la &nbsp; pulation générale est nécessaire pour la validation de ces résultats. &nbsp; &nbsp; &nbsp

Circulating Proprotein Convertase Subtilisin/Kexin type 9 level independently predicts incident cardiovascular events and all-cause mortality in hemodialysis black Africans patients.

Cardiovascular (CV) disease is the leading cause of mortality in patients with end-stage kidney disease (ESKD). The aim of the present study was to determine whether Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9) could be an independent predictor of CV events and all-cause mortality in black African haemodialysis patients. We carried out a prospective cohort study of all consecutive hemodialysis (HD) patients between August 2016 and July 2020, admitted in six hemodialysis centers of Kinshasa, Democratic Republic of Congo. Independent determinants of plasma PCSK-9 measured by ELISA were sought using multiple linear regression analysis. Kaplan-Meier's method described the incidence of CV events while competitive and proportional risk models looked for independent risk factors for death at the .05 significance level. Out of 207 HD patients, 91 (43.9%) died; 116 (56.1%) have survived. PCSK9 level was significantly higher in deceased patients compared to survivors: 28.0 (24.0-31.0) ng/l vs 9.6 (8.6-11.6) ng/ml (p <  0.001). Patients with plasma PCSK9 levels in tertile 3 had a higher incidence of CV events and mortality compared to patients with plasma PCSK9 levels in tertile 2 or tertile 1 (p <  0.001). Tertile 3 negatively influence survival rates (26.6%) compared to tertile 2 (54.7%) and tertile 1 (85.3%). Patients in tertile 3 and tertile 2 had a 4-fold higher risk of death than patients in tertile 1. After adjustment for all parameters, competitive risk analysis showed that mortality was 2 times higher in patients with stroke. Similarly, serum albumin < 3.5 g/dL or PCSK9 in tertile 3 were respectively associated with 2 or 6 times higher rates of deaths. Elevated plasma PCSK9 level is an independent major predictor of incident CV events and all-cause mortality in black African HD patients

APOL1 C-Terminal Variants May Trigger Kidney Disease through Interference with APOL3 Control of Actomyosin

The C-terminal variants G1 and G2 of apolipoprotein L1 (APOL1) confer human resistance to the sleeping sickness parasite Trypanosoma rhodesiense, but they also increase the risk of kidney disease. APOL1 and APOL3 are death-promoting proteins that are partially associated with the endoplasmic reticulum and Golgi membranes. We report that in podocytes, either APOL1 C-terminal helix truncation (APOL1Δ) or APOL3 deletion (APOL3KO) induces similar actomyosin reorganization linked to the inhibition of phosphatidylinositol-4-phosphate [PI(4)P] synthesis by the Golgi PI(4)-kinase IIIB (PI4KB). Both APOL1 and APOL3 can form K+ channels, but only APOL3 exhibits Ca2+-dependent binding of high affinity to neuronal calcium sensor-1 (NCS-1), promoting NCS-1-PI4KB interaction and stimulating PI4KB activity. Alteration of the APOL1 C-terminal helix triggers APOL1 unfolding and increased binding to APOL3, affecting APOL3-NCS-1 interaction. Since the podocytes of G1 and G2 patients exhibit an APOL1Δ or APOL3KO-like phenotype, APOL1 C-terminal variants may induce kidney disease by preventing APOL3 from activating PI4KB, with consecutive actomyosin reorganization of podocytes.status: publishe