Estimated glomerular filtration rate: applicability of creatinine-based equations in African children.

BACKGROUND: The Schwartz equation is the most widely used serum creatinine (SCr)-based formula to estimate the glomerular filtration rate (GFR) in children of European descent, but whether this applies to African children is unclear. METHODS: In a cross-sectional study, 513 apparently healthy African children aged 6 to 16 years were randomly recruited in school area of Kinshasa, the Democratic Republic of Congo (DRC). SCr was measured using calibrated enzymatic method. SCr was normalized using Q-values designed for European descent children, due to the absence of Q-values for African children. Commonly used eGFR equations were applied in this population. RESULTS: Normalization of SCr using Q-values for European descent children was effective in this cohort. The majority of African children (93.4%) have normalized SCr (SCr/Q) values within the reference interval (0.67-1.33) of children of European descent. The bedside-Schwartz equation was associated with significant age and sex dependency. However, the FAS-Age formula showed no sex and age dependency. The new CKiDU25 equation did not show a significant sex dependency. The recently introduced EKFC and LMR18 equations also showed no age and sex dependency, although the distribution of eGFR-values was not symmetrical. On the other hand, the FAS-Height and the Schwartz-Lyon equations showed significant sex dependency but no age dependency. CONCLUSIONS: The reference interval for SCr designed for European descent children can be applied to African children. Of all the equations studied, FAS-Age performed best and is most suitable because no height measurements are required. Establishment of specific Q-values for the widespread Jaffe-measured creatinine in Africa can further broaden applicability.

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 (ß)-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 (5·5%) 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 = 0·04) and hyperfiltration (P = 0·001). 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.

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.

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.

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.

Inequalities in access to pediatric ESRD care: a global health challenge.

The increasing attention paid to chronic kidney disease (CKD) as a major cause of mortality and disability, as well as the advances in management of CKD in children, have created a growing demand for pediatric renal replacement therapy (RRT) worldwide. A study by Koch Nogueira and colleagues of children on the transplant waiting list showed large disparities in access to pediatric kidney transplantation between regions in Brazil. This finding raises a wider question about inequalities in access to CKD care in children. Here we review the available data on the global burden of end-stage renal disease in children, the need for pediatric RRT, and its actual provision worldwide. We focus on inequalities in access to renal care for children that currently exist between and within countries. Reduction in worldwide inequalities in access to RRT in children remains a challenge, which requires greater awareness and effective interventions and policies.

High rate of sickle cell anaemia in Sub-Saharan Africa underlines the need to screen all children with severe anaemia for the disease.

AIM: Neonatal screening for sickle cell anaemia is not common practice in the Democratic Republic of Congo, and we determined the prevalence in children with unknown electrophoresis of haemoglobin and anaemia. METHODS: A cross-sectional study was conducted in four hospitals in the country's capital Kinshasa. RESULTS: We screened 807 patients with anaemia (Hb < 6 g/dL) for sickle cell disease. The overall mean age at presentation was 42.7 months ± 29.7 months, and most patients (76.3%) were less than five years of age, with a peak incidence at seven to 36 months of age (45%). The median age at the first transfusion was 29 months (range 4-159 months). Of these 807 children, 36 (4.5%) were homozygous for haemoglobin S disease and 45 (5.6%) were heterozygotes. The proportion of patients with homozygous sickle cell anaemia was slightly higher in children with a medical history of hand foot syndrome, in children who had received more than three transfusions and in children up to 36 months of age at their first transfusion. CONCLUSION: The high prevalence of sickle cell anaemia in children in Sub-Saharan Africa underlines the need for neonatal screening or, if that is not possible, screening of all children with severe anaemia to identify patients with the disease and provide early management.

Pediatric non-Hodgkin lymphomas: first report from Central Africa.

BACKGROUND: Information on presentation and outcome of pediatric non-Hodgkin's lymphoma is limited from Africa. The demographic characteristics, distribution of different subtypes were noted and compared with published reports from other parts of the world. METHODS: The study was conducted in Kinshasa, the Democratic Republic of Congo between January 2002 and December 2012. RESULTS: A total of 63 cases of pediatric non-Hodgkin's lymphoma were retrospectively analyzed. This cohort represents the largest series of pediatric non-Hodgkin's lymphoma presented from sub-Saharan Africa. Median age was 8.7±3.6 years. There were 43 (68.3%) males. A mean of 82 ± 59 days passed from detection of the first sign to referral to oncology unit. Morphology distribution showed that 42 cases (66.7%) had a diagnosis of Burkitt lymphoma, 16 cases (25.4%) had diffuse large B-cell lymphoma and 5 cases (7.9%) had NHL-not otherwise specified. The majority of patients (82.5%) had advanced stage (stage III and IV). Immunohistochemistry findings were available for 32 biopsy samples. All (100%) cases were B-cell non-Hodgkin's lymphoma and immunohistochemistry had identified 18 (56.3%) cases of Burkitt lymphoma. In our cohort, 22 of 32 cases expressed positive bcl-2 and 12 (37.5%) were found to be positive for bcl-6. Thirty-one (96.7%) cases were positive for high Ki-67 antigen expression. Assuming that cases lost to follow-up worsened and died, the mortality would be 98.4%. CONCLUSION: In comparison to western data, we observed higher proportion of B-cell non-Hodgkin's lymphoma, Burkitt Lymphoma and patients with bcl-2 expression.

The challenges of caring for children with nephrotic syndrome in a tertiary institution in the Democratic Republic of Congo.

AIM: The care of children with resistant nephrotic syndrome (NS) in the Democratic Republic of Congo is compromised by resource deficiencies that range from inadequate healthcare budgets, to scarce laboratory facilities and inconsistent drug supplies. The aim of this study was to describe the clinical profile and management of children with nephrotic syndrome in Kinshasa, the country's capital and its largest city. METHODS: We retrospectively reviewed the medical records of 62 patients with a diagnosis of NS, who were seen in the Paediatric Nephrology Unit at the University Hospital of Kinshasa between January 1983 and January 2008. RESULTS: Of the 62 children diagnosed with nephrotic syndrome, 33 were boys and 29 were girls, giving a male to female ratio of 1.14:1. Their median age at initial presentation was 7.5 years (range: 1.5-13 years) with a peak incidence at six to nine years of age (38.7%). No cases of plasmodium malariae were isolated in our series. Sixteen (25.8%) of the children had resistant corticoid nephrotic syndrome and six of the children (9.7%) died. CONCLUSION: Age, the prevalence of steroid-resistant NS and the mortality rate in our series were higher than those reported in Asian and Western countries.

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.

Acute Crises and Complications of Sickle Cell Anemia Among Patients Attending a Pediatric Tertiary Unit in Kinshasa, Democratic Republic Of Congo.

In the Democratic Republic of Congo, the incidence of sickle cell anemia (SCA) is estimated to affect 30,000 to 40,000 neonates per year. However, there is paucity of data on acute clinical manifestations in sickle cell children. In these circumstances, it is difficult to develop a health care policy for an adequate management of sickle cell patients. This was a seven years' retrospective study of children admitted with acute sickle cell crisis in the Department of Pediatrics in University Hospital of Kinshasa, Kinshasa, the Democratic Republic of Congo. A total of 108 patients were identified as having SCA. There were 56 (51%) girls and 52 (49%) boys. Median age was 10.5 years (range 1-24 years). No child was diagnosed by neonatal screening. The median age of diagnosis of sickle cell anemia was 90 months (range: 8-250 months). The median age at the first transfusion was 36 months (range 4-168). In this series, 61 (56.5%) patients were eligible for hydroxyurea. However, this treatment was only performed in 4 (6.6%) of them. Pain episodes, acute anemic crisis and severe infection represent respectively 38.2%, 34.3% and 21.9% of events. Altered sensorium and focal deficit were encountered occasionally and represented 3.4% of acute events. Acute renal manifestations, cholelithiasis and priapism were rarely reported, in this cohort. In Kinshasa, the care of patients suffering from sickle cell anemia is characterized by the delayed diagnosis and low detection of organ complications compared to reports of Western countries. This situation is due to resources deficiencies.

Nephrotic Syndrome in a Child Suffering from Tetralogy of Fallot: A Rare Association.

Nephrotic syndrome is an uncommon complication of tetralogy of Fallot and has been rarely reported in pediatric population. We describe a 4-year-old female Congolese child who was referred for investigation for persistent dyspnea, edema, and cyanosis and nephrotic range proteinuria. Our patient presented with a tetralogy of Fallot and nephrotic syndrome. Conclusion. This case reminds us that children with tetralogy of Fallot may develop nephrotic proteinuria.

Malaria, clinical features and acute crisis in children suffering from sickle cell disease in resource-limited settings: a retrospective description of 90 cases.

BACKGROUND: The prevalence of sickle cell disease (SCD) is extremely high in the Democratic Republic of Congo (DRC). Despite the high prevalence of this disease in our midst, there has been no report on the clinical features in the sickle cell pediatric population suffering from malaria in our midst. METHODS: A retrospective survey of records from the Department of Paediatrics of the University Hospital of Kinshasa, Kinshasa, Democratic Republic of Congo, was done for the period 1998­2008. For the 10 years studied, 108 children with SCD were reviewed and the data of those who developed malaria during admission were retrieved and analyzed. RESULTS: Of the 90 homozygous sickle cell children with malaria, fever, pallor, and jaundice were the commonly-found symptoms. Lethargy, severe anemia, respiratory distress, splenomegaly, hepatomegaly,digestive disorders, and prostration were common in children under 5 years, with significant difference (P, 0.05) to the older children. Transfusion because of to severe anemia was found necessary in 54.4% of cases. No case of cerebral malaria was found. Blackwater fever was a rare event. Hand­foot syndrome was present in 12.8% of patients, exclusively in those less than 5 years old. Pain crisis was associated in 46 cases (51.1%). Pain crisis was particularly present in SCD children less than 5 years of age (74.5% vs 25.6%, P , 0.001). No death was observed in this series. CONCLUSION: We conclude that the acute crisis related to SCD is more common in children less than 5 years of age. High risk of a requirement for blood transfusion was found in young children. Anti-malarial prophylaxis is advocated in Kinshasa.

[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.