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

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: Elevated plasma PCSK9 level is an independent major predictor of incident CV events and all-cause mortality in black African HD patients.

Circulating Proprotein Convertase Subtilisin/Kexin Type 9 Levels Predict Future Cardiovascular Event Risks in Hemodialyzed Black African Patients.

CONTEXT AND OBJECTIVE: Cardiovascular diseases are the leading cause of mortality in patients. In this context, proprotein convertase subtilisin/kexin type 9 (PCSK9) appears to be the new biomarker identified as interfering in lipid homeostasis. This study aimed to investigate the association between PCSK9, dyslipidemia, and future risk of cardiovascular events in a population of black Africans. METHODS: A cross-sectional study was conducted between August 2016 and July 2020 in six hemodialysis centers in the city of Kinshasa, Democratic Republic of the Congo. Serum PCSK9 was measured by ELISA; lipid levels of 251 chronic kidney disease grade 5 (CKD G5) hemodialysis patients and the Framingham predictive instrument were used for predicting cardiac events. RESULTS: Total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c), and triglycerides (TG) were significantly increased in the tertile with the highest PCSK9. By contrast, high-density lipoprotein cholesterol (HDL-c) was significantly decreased in the same tertile. A strong positive and significant correlation was found between PCSK9 and TC, TG, and LDL-c. Negative and significant correlation was observed between PCSK9 and HDL-c. The levels of PCSK9, smoking, overweight, and atherogenic dyslipidemia were associated with future risks for cardiovascular events in univariate analysis. After adjustment, all these variables persisted as independent determinants of future risk for cardiovascular events. The probability of having a cardiovascular event in this population was independently associated with PCSK9 levels. Compared to the patients in the lowest PCSK9 tertile, patients with PCSK9 levels in the middle (aOR 5.9, 95% CI 2.06-17.3, P<0.001) and highest tertiles (aOR 8.9, 95% CI 3.02-25.08, P<0.001) presented a greater risk of cardiac event. CONCLUSION: Increased PCSK9 serum levels are associated with higher levels of TC, LDL-c, and TG and lower levels of HDL-c in black African hemodialysis patients. Serum PCSK9 levels in these patients predict increased risk of cardiovascular events, independent of traditional potential confounders.

Prognostic Significance of Abnormal Ankle-Brachial Index Among Long-term Hemodialysis Patients in Kinshasa, the Democratic Republic of the Congo.

OBJECTIVE: Early identification of atherosclerosis using a non-invasive tool like ankle-brachial index (ABI) could help reduce the risk for cardiovascular disease among long-term hemodialysis patients. The study objective was to assess the frequency and impact of abnormal ABI as a marker of subclinical peripheral artery disease (PAD) in chronic hemodialysis patients. METHODS: This was a historic cohort study of kidney failure patients on long-term hemodialysis for at least 6 months. The ABI, measured with two oscillometric blood pressure devices simultaneously, was used to assess subclinical atherosclerosis of low limb extremities. Abnormal ABI was defined as ABI <0.9 or >1.3 (PAD present). Survival was defined as time to death. Independent factors associated with abnormal ABI were assessed using multiple logistic regression analysis. Kaplan-Meier method (log-rank test) was used to compare cumulative survival between the two groups; a P value <0.05 was statistically significant. RESULTS: Abnormal ABI was noted in 50.6% (n=43) of the 85 kidney failure patients included in the study; 42.4% (n=36) had a low ABI, and 8.2% (n=7) had a high ABI. Factors associated with PAD present were cholesterol (adjusted odds ratio [AOR], 1.02; 95% confidence interval [CI], 1.01-1.04; P=0.019), inflammation (AOR, 9.44; 95% CI, 2.30-18.77; P=0.002), phosphocalcic product (AOR, 6.25; 95% CI, 1.19-12.87; P=0.031), and cardiac arrhythmias (AOR, 3.78; 95% CI, 1.55-7.81, P=0.009). Cumulative survival was worse among patients with PAD present (log-rank; P=0.032). CONCLUSION: The presence of PAD was a common finding in the present study, and associated with both traditional and emerging cardiovascular risk factors as well as a worse survival rate than patients without PAD.

Prevalence and factors associated with pulmonary arterial hypertension on maintenance hemodialysis patients in Kinshasa, Democratic Republic of Congo: a cross-sectional study.

BACKGROUND: Although cardiovascular diseases in particular Pulmonary Arterial Hypertension (PAH) is associated with, high morbid-mortality in chronic hemodialysis, but its magnitude remains paradoxically unknown in sub-Saharan Africa. The aim of this study was to evaluate the prevalence of PAH and associated factors in chronic hemodialysis in Sub-Saharan African population. METHOD: In a cross-sectional study, patients treated with HD for at least 6 months in 4 hemodialysis centers were examined. PAH was defined as estimated systolic pulmonary arterial pressure (sPAP) ≥ 35 mmHg using transthoracic Doppler echocardiography performed 24 h after the HD session. RESULTS: Eighty-five HD patients were included; their average age was 52.6 ± 15.9 years. Fifty-seven patients (67.1%) were male. Mean duration of HD was 13.3 ± 11 months. With reference to vascular access, 12 (14.1%), 29 (34.1%) and 44 (51.8%) patients had AVF, tunneled cuff and temporary catheter, respectively. The underlying cause of ESRD was diabetes in 30 patients (35.3%). The prevalence of PAH was 29.4%. Patients with PAH had more hyponatremia (11 (44%) vs 10 (16.7%), p = 0.010). In multivariate analysis, unsecured healthcare funding (aOR 4, 95% CI [1.18-6.018]), arrhythmia (aOR 3, 95% CI [1.29-7.34]), vascular access change (aOR 4, 95% CI [1.18-7.51]) and diastolic dysfunction (aOR 5, 95% CI [1.35-9.57] were independently associated with PAH. CONCLUSION: One third of hemodialysis patients exhibit PAH, which is independently associated with low socioeconomic status (unsecured funding, vascular access change) and cardiovascular complications (arrhythmia, diastolic dysfunction).

Factors associated with residual urine volume preservation in patients undergoing hemodialysis for end-stage kidney disease in Kinshasa.

BACKGROUND: Decreased residual urine volume (RUV) is associated with higher mortality in hemodialysis (HD). However, few studies have examined RUV in patients on HD in Sub-Saharan Africa. The aim of this study was to identify predictors of RUV among incident hemodialysis patients in Kinshasa. METHODS: This historical cohort study enrolled 250 patients with ESRD undergoing hemodialysis between January 2007 and July 2013 in two hemodialysis centers in Kinshasa. RUV were collected over 24 h at the initiation of HD and 6 and 12 months later during the interdialytic period. We compared the baseline characteristics of the patients according to their initial RUV (≤ 500 ml/day vs >  500 ml/day) using Student's t, Mann-Whitney U and Chi2 tests. Linear mixed-effects models were used to search for predictors of decreased RUV by adding potentially predictive baseline covariates of the evolution of RUV to the effect of time: age, sex, diabetes mellitus, hypertension, diastolic blood pressure, diuretics, angiotensin conversion enzyme inhibitors (ACEI), angiotensin receptor blockers, hypovolemia, chronic tubulointerstitial nephropathy, left ventricular hypertrophy and initial hemodialysis characteristic. A value of p < 0.05 was considered the threshold of statistical significance. RESULTS: The majority of hemodialysis patients were male (68.8%, sex ratio 2.2), with a mean age of 52.5 ± 12.3 years. The population's RUV decreased with time, but with a slight deceleration. The mean RUV values were 680 ± 537 ml/day, 558 ± 442 ml/day and 499 ± 475 ml/day, respectively, at the initiation of HD and at 6 and 12 months later. The use of ACEI at the initiation of HD (beta coefficient 219.5, p < 0.001) and the presence of chronic tubulointerstitial nephropathy (beta coefficient 291.8, p = 0.007) were significantly associated with RUV preservation over time. In contrast, the presence of left ventricular hypertrophy at the initiation of HD was significantly associated with decreased RUV over time (beta coefficient - 133.9, p = 0.029). CONCLUSIONS: Among incident hemodialysis patients, the use of ACEI, the presence of chronic tubulointerstitial nephropathy and reduced left ventricular hypertrophy are associated with greater RUV preservation in the first year of dialysis.

Glomerular hyperfiltration is strongly correlated with age in Congolese children with sickle cell anaemia.

AIM: Glomerular hyperfiltration is an early marker of sickle cell nephropathy and can lead to microalbuminuria and renal failure. Our aim was to identify the associated risk factors, as these could be of preventative importance. METHODS: We recruited 150 children with sickle cell anaemia (SCA), aged two to 18 years and living in Kinshasa, the Democratic Republic of Congo. Hyperfiltration and microalbuminuria were defined as an estimated glomerular filtration rate of less than 140 mL/min/1.73 m² and an albumin creatinine ratio of between 30 and 299 mg/g, respectively. Independent determinants of hyperfiltration were assessed using logistic regression analysis. RESULTS: Glomerular hyperfiltration was observed in 60 (40%) children, who were significantly older (10.2 ± 4.1 versus 7.9 ± 4.3 years, p = 0.001) and had a lower body mass index level (14.7 ± 2.3 versus 15.0 ± 2.3 kg/m2 ) than the 60% without. A higher proportion had microalbuminuria (25.0 versus 13.3%), but the difference was not statistically significant (p>0.05). Increased age and decreased body mass index were the main independent factors associated with glomerular hyperfiltration in the multivariate analysis. A quarter (25%) of the 60 children with SCA with glomerular hyperfiltration had microalbuminuria. CONCLUSION: Glomerular hyperfiltration was a common finding in this study and was significantly associated with age.

Congolese children with sickle cell trait may exhibit glomerular hyperfiltration: A case control study.

BACKGROUND: The prevalence of sickle cell trait is extremely high in sub-Saharan Africa. Recent studies have reported the impact of sickle cell carriers on renal function. However, data on renal abnormalities in children with sickle cell trait in this part of the world are unknown. In this report, we assess the glomerular function of children with sickle cell trait (SCT). METHODS: A case control study was conducted to assess the glomerular function in 43 Congolese children with sickle cell trait (Hb-AS) matched for age to 65 children with sickle cell anemia in steady state (Hb-SS) and 67 normal controls (Hb-AA). RESULTS: There was a significant difference in the blood pressure levels between the Hb-AS group vs Hb-SS group (P<.05). The estimated glomerular filtration rate (eGFR) corrected for body surface area was increased in Hb-AS group compared to Hb-AA group, but there was no significant difference between the two groups (P=.48). At the same time, the eGFR was decreased, but no significantly so, in the Hb-AS group compared to the Hb-SS group (P=.19). The proportion of children with Hb-AS (16.3%) who had hyperfiltration was higher compared to the proportion (6.1%) found in the Hb-AA group, but lower compared to the proportion found in the Hb-SS group (30%). However, in both situations, the difference was not statistically significant. No case of proteinuria was detected in children with Hb-AS. CONCLUSION: It appears that at least one of six children with SCT had hyperfiltration. The findings could form a basis for further studies on this renal physiology among SCT individuals in Africa.

Impact of residual urine volume decline on the survival of chronic hemodialysis patients in Kinshasa.

BACKGROUND: Despite the multiple benefits of maintaining residual urine volume (RUV) in hemodialysis (HD), there is limited data from Sub-Saharan Africa. The aim of this study was to assess the impact of RUV decline on the survival of HD patients. METHODS: In a retrospective cohort study, 250 consecutive chronic HD patients (mean age 52.5 years; 68.8% male, median HD duration 6 months) from two hospitals in the city of Kinshasa were studied, between January 2007 and July 2013. The primary outcome was lost RUV. Preserved or lost RUV was defined as decline RUV < 25 (median decline) or ≥ 25 ml/day/month, respectively. The second endpoint was survival (time-to death). Survival curves were built using the Kaplan-Meier methods. We used Log-rank test to compare survival curves. Predictors of mortality were assessed by Cox proportional hazards regression models. RESULTS: The cumulative incidence of patients with RUV decline was 52, 4%. The median (IQR) decline in RUV was 25 (20.8-33.3) ml/day/month in the population studied, 56.7 (43.3-116.7) in patients deceased versus 12.9 (8.3-16.7) in survivor patients (p < 0.001). Overall mortality was 78 per 1000 patient years (17 per 1000 in preserved vs 61 per 1000 lost RUV). Forty six patients (18.4%) died from withdrawal of HD due to financial constraints. The Median survival was 17 months in the whole group while, a significant difference was shown between lost (10 months, n = 119) vs preserved RUV group (30 months, n = 131; p = 0001). Multivariate Cox proportional hazards models showed that, decreased RUV (adjusted HR 5.35, 95% CI [2.73-10.51], p < 0.001), financial status (aHR 2.23, [1.11-4.46], p = 0.024), hypervolemia (a HR 2.00, [1.17-3.40], p = 0.011), lacking ACEI (aHR 2.48, [1.40-4.40], p = 0.002) or beta blocker use (aHR 4.04, [1.42-11.54], p = 0.009), central venous catheter (aHR 6.26, [1.71-22.95], p = 0.006), serum albumin (aHR 0.93, [0.89-0.96], p < 0.001) and hemoglobin (aHR 0.73, [0.63-0.84], p < 0.001) had emerged as the independent predictors of all-cause mortality. CONCLUSION: More than half of HD patients in this cohort study experienced fast RUV decline which contributed substantially to increase mortality, highlighting the need for its prevention and management.

[Predictors of physical incapacity degree to chronic hemodialysis patients in Kinshasa : Key role of the residual diuresis]. / Prédicteurs du degré d'incapacité physique chez les hémodialysés de Kinshasa : rôle primordial de la diurèse résiduelle.

OBJECTIVE: Identifying predictors of physical incapacity degree in patients on chronic hemodialysis in Kinshasa. METHODS: Bicentric analytical study, between January 2007 and July 2013. Degree of physical handicap was evaluated at 6months of hemodialysis based on the scale of Rosser. Logistic regression sought the predictors of no or light physical incapacity (Rosser<3) vs. moderate to maximum (Rosser≥3). P was set at 0.05. RESULTS: One hundred twenty-seven patients (127) patients received at least 6months of hemodialysis (53.3±11years; 73.2 % male), 79 (62.2 %) had no or light incapacity and 48 (37.8 %) moderate to maximum. Predictors of lower physical incapacity in univaried analysis were: secured funding, high socioeconomic level, lack of diabetes mellitus, high body weight, normal systolic and diastolic blood pressure, residual diuresis 3months later, hemoglobin and hematocrit, low comorbidity, arteriovenous fistula, erythropoietin, at least 12hours of hemodialysis per week and lack of intradialytic complications. After logistic regression, a high residual diuresis 3months of hemodialysis has proved an independent predictor of lower physical Incapacity (aOR 0.998; P=0.024) next to the lack of diabetes mellitus (aOR 0.239; P=0.024), good control of systolic (aOR 0.958; P=0.013) and diastolic (aOR 1.089; P=0.003) blood pressure and the use of erythropoietin (aOR 5.687; P=0.004). CONCLUSION: Preserving residual diuresis is associated with lower physical incapacity and must be integrated in the management in hemodialysis.

Prevalence of microalbuminuria and diagnostic value of dipstick proteinuria in outpatients from HIV clinics in Bukavu, the Democratic Republic of Congo.

BACKGROUND: Microalbuminuria is a marker of early kidney disease and high cardiovascular risk in various populations, including HIV positive patients. However, the diagnostic value of qualitative (dipstick) proteinuria and the burden of microalbuminuria in HIV positive patients living in sub-Saharan Africa are relatively unclear. METHODS: In a cross-sectional study, 235 HIV- positive outpatients were screened for proteinuria in 3 HIV-clinics in Bukavu. A spot urine sample from each subject was tested both by a dipstick and albumin-creatinine-ratio (ACR) assay. The performance of dipstick proteinuria exceeding 1+ was compared with that of microalbuminuria (≥ 30 mg/g creatinine). RESULTS: The prevalence of microalbuminuria and dipstick proteinuria ≥ (1+), ≥ (2+) and ≥ (3+) was 11%, 41%, 3.5% and 0.7%, respectively.Compared to microalbuminuria, the dipstick (proteinuria of 1+ or greater) had an overall sensitivity of 60% and a specificity of 61%. The positive predictive value was 15.4% and the negative predictive value 92.8%. CONCLUSION: Proteinuria is highly prevalent in HIV positive patients. The limited sensitivity and specificity of the dipstick to detect significant microalbuminuria make it unattractive as a screening tool in HIV positive patients.

Renal function in children suffering from sickle cell disease: challenge of early detection in highly resource-scarce settings.

BACKGROUND: The prevalence of Sickle cell disease is extremely high in Democratic Republic of Congo. Despite this high prevalence of the disease, data on renal abnormalities in children are rare. METHOD: The study proposed to assess blood pressure, glomerular function, urea and uric acid levels in 65 steady state Congolese children with homozygous sickle cell disease and 67 normal controls. RESULTS: In Hb-SS group, blood pressure level tended to be lower than Hb-AA groups but there was no statistically significant difference (p>0.05) between the two groups. The absolute values for GFR corrected for BSA were significantly higher in Hb-SS group compared to Hb-AA group (130.5±34.1 ml/min/1.73 m2 vs 113.7±24.5 ml/min/1.73 m2; p = 0.004). Children with Hb-SS were more likely to hyperfiltrate (30.8% of subjects) than children with Hb-AA (6.1% of subjects). Proteinuria was found in 4 (6.2%) children with Hb-SS. Uric acid level was significantly increased in children with Hb-SS compared to corresponding values in control group (4.4±1.3 mg/dl vs 3.5±1.1 mg/dl; p<0.001). Urea level was significantly decreased compared to corresponding values in Hb-AA group (15.3±8.3 mg/dl vs 22.9±10.1 mg/dl; p<0.001). CONCLUSION: Hyperfiltration, low creatinine, lower urea and high uric acid are more common in children with sickle cell disease than in normal controls.

[Acute renal failure and severe malaria in Congolese children living in Kinshasa, Democratic Republic of Congo]. / Insuffisance rénale aiguë dans les formes graves du paludisme chez les enfants vivant à Kinshasa.

BACKGROUND: Data on acute renal failure in complicated malaria in children in the Democratic Republic of Congo are sparse. The objective of this study was to document the profile of acute renal failure in severe malaria in admitted patients in pediatric hospitals from Kinshasa. METHODS: A prospective cohort study was conducted from January 2008 to December 2008 in children admitted in emergency units of five hospitals in Kinshasa for severe malaria. RESULTS: In our series, 378 children with severe malaria were included. There were 226 boys and 152 girls (sex ratio 1.49). One hundred and ninety four (194) of these patients were under 5 years old. Acute renal failure was observed in 89 children (23.6%) and 87 of them had blackwater fever (BWF). This form of severe malaria was predominant in children older than 5 years. Quinine was the commonest antimalarial drug involved in the genesis of BWF. Dialysis was indicated in 23 children (24.0%) and was effective (acute peritoneal dialysis) in 21 patients. The death rate in children with ARF was 12.6% (n=87). Recovery of renal function was obtained by conservative treatment in the remained group. CONCLUSION: This study confirmed the emergence of BWF in seemed protected autochthon children older than 5 years. BWF remained the leading cause of acute renal failure in complicated malaria among Congolese children in Kinshasa.

[Prevalence of proteinuria and its association with HIV/AIDS in Congolese children living in Kinshasa, Democratic Republic of Congo]. / Prévalence de la protéinurie et son association avec le VIH/sida chez l'enfant à Kinshasa, Congo.

CONTEXT: In Sub-Saharian Africa, the extent of the HIV-related kidney diseases is less known. Even so, that region is supposed to be the epicentre of such complications. This study aimed to determine the prevalence of proteinuria in Congolese children living in Kinshasa and to study its association with the HIV infection. METHODS: By a cross-sectional and multicentric study (in six hospitals of Kinshasa), 194 children were consecutively recruited from August 2008 to February 2009. Among these, 101 naives HIV-infected children and 93 HIV-uninfected children like a control group. Proteinuria was assessed using urine dipstick completed by the 24-hour proteinuria assessment (Esbach method). Determinants of proteinuria were assessed by logistic regression. RESULTS: The median age of all children recruited was 84 months (9-221 months). Concerning the HIV-infected children, the median age was 76 months (9-221 months) with a male/female ratio of 1/1. The prevalence of proteinuria in this group was in order to 23.8%. HIV infected children have seven times more probability to present proteinuria than non infected children (OR 6.9; IC 95%: 2.3-20.8; P<0.001). Important immunosuppression was the main determinant of proteinuria (OR 10.4; IC 95%: 3.34-32.48; P<0.001). CONCLUSION: Proteinuria is common in Congolese children. The HIV infection rises significantly the probability to present proteinuria in children of this study, more so among those with important immunosuppression. This raises the question about the ideal time to initiate HAART in order to reduce the prevalence of kidney injury and to provide the best outcome.