Factors associated with acute kidney injury (AKI) and mortality in COVID-19 patients in a Sub-Saharan African intensive care unit: a single-center prospective study.

INTRODUCTION: Acute kidney injury (AKI) is a complication of severe coronavirus disease 2019 (COVID-19). Kidney damage associated with COVID-19 could take specific features due to environmental and socio-cultural factors. This study evaluates the incidence of AKI, the associated factors, and mortality in COVID-19 patients in a Sub-Saharan African intensive care unit. METHODS: In a prospective cohort study conducted in the intensive care unit (ICU) of the Centre Médical de Kinshasa (CMK), consecutive patients admitted for COVID-19 were screened for the presence of AKI between 27 March, 2020 and 27 January 2022. AKI was defined according to Kidney Disease Improving Global Outcomes (KDIGO) guidelines. The primary outcome was occurrence of AKI. The secondary outcome was 48 days' mortality and recovery of the renal function at intensive care unit (ICU) discharge. Survival (time-to death) curves were built using the Kaplan Meier methods. Multivariate analyses were performed by logistic regression to identify factors associated with AKI and Cox regression to explore the association between AKI and in-hospital mortality. The significance level of the p-value was set at 0.05. RESULTS: The median(IQR) sequential organ failure assessment score (SOFA) score and mean age of patients (215) including in our cohort were respectively 3(2-4) and 58.9 ± 14.9 years. The incidence of AKI was 28.4% with stages 1, 2, or 3 AKI accounted for 39.3%, 11.5%, and 49.2%, respectively. Hemodialysis was required in 16 out 215 (7.4%) patients. Dyspnea (adjusted odds ratio (aOR):2.27 [1.1--4.57] p = 0.021), SOFA ≥5 (aOR:3.11[1.29-7.53] p = 0.012), AST/ALT ratio (aOR: 1.53 [1.09-1.79] p = 0.015), N/L ratio (aOR:2.09 [1.09-3.20] p = 0.016), mechanical ventilation (aOR: 3.20 [1.66-10.51] p = 0.005) and Amikacin (aOR: 2.91 [1.37-6.18] p = 0.006) were the main factors associated with AKI. Patients with AKI had a mortality rate of 52.5% and 67.2% of the survivors did not recover kidney function at the end of hospitalization. Adjusted Cox regression analysis revealed that COVID-19-associated AKI was independently associated with in-hospital death (HR:2.96 [1.93-4.65] p = 0.013) compared to non-AKI patients. CONCLUSIONS: AKI was present in three out of ten COVID-19 patients. The most significant factors associated with AKI were dyspnea, SOFA ≥ 5, AST/ALT and N/L ratio, mechanical ventilation and Amikacin. AKI has been associated with an almost threefold increase in overall mortality and seven out of ten survivors did not recover kidney function after AKI.

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.

Reverse epidemiology of elevated blood pressure among chronic hemodialysis black patients with stroke: a historical cohort study.

BACKGROUND: Stroke is the third leading cause of cardiovascular mortality in dialysis patients. The objective of this study was to assess the extent of stroke in chronic hemodialysis patients. METHODS: Historical cohort of patients enrolled in two hemodialysis (HD) centers from January 1, 2010 to December 31, 2011, including 191 patients (mean age 52 years, 68% men). Incidence curves and survival time analysis between the first day of HD and the end of the study were described by the Kaplan-Meier method. Independent stroke predictors were identified by multiple logistic regression analysis. P < 0.05 defined the level of statistical significance. RESULTS: 12 incident stroke were recorded during the study period, with 1622.1 person-months (PM), a stroke incidence rate of 7.4 cases per 1000 PM (95% CI = 7.35-7.44) at the point date. The incidence of stroke at 6 months, 12 months and 24 months was 9.8%, 11.9% and 13%, respectively. Only the absence of arterial hypertension (RR = 5.7, 95% CI: 1.52-21.42) emerged as an independent determinant of stroke. CONCLUSION: The high incidence of stroke in Kinshasa HD centers is partially explained by reverse epidemiology. Efforts must be made to understand this phenomenon in order to reduce its impact.

Albuminuria, serum antioxidant enzyme levels and markers of hemolysis and inflammation in steady state children with sickle cell anemia.

BACKGROUND: Oxidative stress is thought to be involved in the pathogenesis of microalbuminuria in Sickle cell anemia (SCA). Antioxidant enzymes such as glutathione peroxidase (GPx) and Cu-Zn superoxide dismutase (SOD) may play an important protective role. This study aimed to evaluate the association between albuminuria and these two antioxidant enzymes. METHODS: We consecutively recruited Steady state children aged between 2 and 18 years old with established diagnosis of homozygous SCA in two hospitals of Kinshasa/DR Congo. The relationship between Urinary Albumin Creatinine Ratio (UACR) and other variables of interest (age, systolic blood pressure, diastolic blood pressure, plasma GPx and Cu-Zn SOD, free plasmatic hemoglobin, LDH, indirect bilirubin, white blood cells (WBC), percentage of fetal hemoglobin, serum iron, ferritin, CRP) was analyzed by Bivariate correlation (Pearson's correlation coefficient). Microalbuminuria was defined by urine albumin/creatinine ratio between 30 and 299 mg/g. RESULTS: Seventy Steady state Black African children with SCA (56% boys; average age 9.9 ± 4.3 years; 53% receiving hydroxyurea) were selected. Prevalence of microalbuminuria was 11.8%. LDH (r = 0.260; p = 0.033) and WBC count (r = 0.264; p = 0.033) were positively correlated with UACR whereas GPx (- 0.328; p = 0.007) and Cu-Zn SOD (- 0.210; p = 0.091) were negatively correlated with UACR. CONCLUSIONS: Albuminuria is associated with decreased antioxidant capacity and increased levels of markers of hemolysis and inflammation. Therefore, strategies targeting the reduction of sickling and subsequent hemolysis, oxidative stress and inflammation could help preventing or at least delaying the progression of kidney disease in SCA children.

25 [OH] Vitamin D and Intact Parathyroid Hormone in Congolese Hemodialysis Patients: Evaluation of KDIGO Targets.

Background: Data on 25 [OH] vitamin D and intact parathyroid hormone [iPTH] in hemodialysis patients are very limited in sub-Saharan African countries. The present study aimed to assess the magnitude of hypovitaminosis D, and to evaluate the achievement of iPTH KDIGO 2017 targets among chronic hemodialysis patients followed in Kinshasa. Methods: We conducted a multicenter cross-sectional study in 6 hospitals in Kinshasa. All patients followed on hemodialysis for more than 3 months were included. Hypovitaminosis D was defined as <30 ng/mL (insufficiency = 20-29 ng/mL; deficiency if <20 ng/mL) and the targets for iPTH values were based on the 2017 KDIGO guidelines. The determinants for hypovitaminosis D were evaluated by logistic regression. Results: 251 patients [mean age 56 ± 14 years, 72.5% men, 63% hypertensive, 31% diabetic, 100% supplemented with native 25 [OH] vitamin D + CaCO3 were included. Hypovitaminosis D was found in 79.7% (deficiency 47.4%) and was associated with the male gender aOR 2.7 [1.4-5.2], p = 0.004, the low-permeability dialyzer 2.2 [1.1-4.2], p = 0.025 and anemia 3.9 [1.2-12.7], p = 0.022. Only 40% of patients with 25 [OH] vitamin D deficiency had iPTH according to KDIGO targets vs 6% of patients with severe hyperparathyroidism (iPTH > 600 pg/mL), 45% with levels between 16 and 150 pg/mL and 9% a iPTH ≤ 15 pg/mL. Conclusion: Despite a sunny environment, a large proportion of Congolese hemodialysis patients have hypovitaminosis D, in particular a deficiency. Among them, less than half have target iPTH values. These results show the benefit of regular monitoring of these parameters in order to optimize treatment.

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.

Albuminuria status and patterns of dyslipidemia among type 2 diabetes black patients managed at a tertiary health-care hospital: A Post hoc analysis.

Cardiovascular disease (CVD) risk in type 2 diabetes mellitus (T2DM) increases with the development of albuminuria and is related in part to dyslipidemia. The present analysis assessed lipid profile and patterns of dyslipidemia in T2DM patients according to albuminuria status. This was a post hoc analysis of data from 181 T2DM patients seen at a tertiary health-care hospital and enrolled in a cross-sectional study of albuminuria status. Abnormal albuminuria was defined as microalbuminuria [albumin to creatinine ratio (ACR) 30-299.9 mg/g] or macro-albuminuria (ACR ≥300 mg/g). Atherogenic dyslipidemia was defined as triglycerides (TGs) ≥150 mg/dL and/or high-density lipoprotein-cholesterol (HDL-c) <40 mg/dL in men and <50 mg/dL in women using international consensus criteria. High levels of total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-c), HDL-c, non-HDL-c, TG, and low level of HDL-c were defined according to 2012 American Association of Clinical Endocrinologists' guidelines. Comparisons between T2DM patients with and without abnormal albuminuria were done using Chi-square test, Student's t-test, or two-sample t-test with equal variance and Mann-Whitney test as appropriate. P< 0.05 defined the level of statistical significance. Of the 181 T2DM patients, 93 (51%) had abnormal albuminuria with 32% and 19% having microalbuminuria and macro-albuminuria, respectively. Average TC, HDL-c, HDL-c, non-HDL-c, and TG levels were 171 ± 41, 111 ± 36, 38 ± 16, 133 ± 38, and 98 (45-234) mg/dL, respectively. These values were significantly lower for TC (P = 0.047), LDL-c (P = 0.030), and non-HDL-c (P = 0.05) in comparison with patients with normal albuminuria. Low HDL-c (64.5%) and high TG (9.7%) were, respectively, the most and less frequent patterns of isolated dyslipidemia in patients with abnormal albuminuria. Atherogenic dyslipidemia with mainly low HDL-c levels is common in T2DM patients with abnormal albuminuria and could contribute to CVD and renal disease progression.