Cystatin C-Based Equation to Estimate GFR without the Inclusion of Race and Sex.

BACKGROUND: The accuracy of estimation of kidney function with the use of routine metabolic tests, such as measurement of the serum creatinine level, has been controversial. The European Kidney Function Consortium (EKFC) developed a creatinine-based equation (EKFC eGFRcr) to estimate the glomerular filtration rate (GFR) with a rescaled serum creatinine level (i.e., the serum creatinine level is divided by the median serum creatinine level among healthy persons to control for variation related to differences in age, sex, or race). Whether a cystatin C-based EKFC equation would increase the accuracy of estimated GFR is unknown. METHODS: We used data from patients in Sweden to estimate the rescaling factor for the cystatin C level in adults. We then replaced rescaled serum creatinine in the EKFC eGFRcr equation with rescaled cystatin C, and we validated the resulting EKFC eGFRcys equation in cohorts of White patients and Black patients in Europe, the United States, and Africa, according to measured GFR, levels of serum creatinine and cystatin C, age, and sex. RESULTS: On the basis of data from 227,643 patients in Sweden, the rescaling factor for cystatin C was estimated at 0.83 for men and women younger than 50 years of age and 0.83 + 0.005 × (age - 50) for those 50 years of age or older. The EKFC eGFRcys equation was unbiased, had accuracy that was similar to that of the EKFC eGFRcr equation in both White patients and Black patients (11,231 patients from Europe, 1093 from the United States, and 508 from Africa), and was more accurate than the Chronic Kidney Disease Epidemiology Collaboration eGFRcys equation recommended by Kidney Disease: Improving Global Outcomes. The arithmetic mean of EKFC eGFRcr and EKFC eGFRcys further improved the accuracy of estimated GFR over estimates from either biomarker equation alone. CONCLUSIONS: The EKFC eGFRcys equation had the same mathematical form as the EKFC eGFRcr equation, but it had a scaling factor for cystatin C that did not differ according to race or sex. In cohorts from Europe, the United States, and Africa, this equation improved the accuracy of GFR assessment over that of commonly used equations. (Funded by the Swedish Research Council.).

Performance of creatinine-based equations to estimate glomerular filtration rate in White and Black populations in Europe, Brazil and Africa.

BACKGROUND: A new Chronic Kidney Disease Epidemiology Collaboration equation without the race variable has been recently proposed (CKD-EPIAS). This equation has neither been validated outside USA nor compared with the new European Kidney Function Consortium (EKFC) and Lund-Malmö Revised (LMREV) equations, developed in European cohorts. METHODS: Standardized creatinine and measured glomerular filtration rate (GFR) from the European EKFC cohorts (n = 13 856 including 6031 individuals in the external validation cohort), from France (n = 4429, including 964 Black Europeans), from Brazil (n = 100) and from Africa (n = 508) were used to test the performances of the equations. A matched analysis between White Europeans and Black Africans or Black Europeans was performed. RESULTS: In White Europeans (n = 9496), both the EKFC and LMREV equations outperformed CKD-EPIAS (bias of -0.6 and -3.2, respectively versus 5.0 mL/min/1.73 m², and accuracy within 30% of 86.9 and 87.4, respectively, versus 80.9%). In Black Europeans and Black Africans, the best performance was observed with the EKFC equation using a specific Q-value (= concentration of serum creatinine in healthy males and females). These results were confirmed in matched analyses, which showed that serum creatinine concentrations were different in White Europeans, Black Europeans and Black Africans for the same measured GFR, age, sex and body mass index. Creatinine differences were more relevant in males. CONCLUSION: In a European and African cohort, the performances of CKD-EPIAS remain suboptimal. The EKFC equation, using usual or dedicated population-specific Q-values, presents the best performance in the whole age range in the European and African populations included in this study.

Ineffectiveness of Intermittent Hemodialysis in a Critically Ill COVID-19 Patient: A Case of Persistent Heparin-Induced Hyperkalemia.

Heparin is widely used in the intensive care unit despite the risk of bleeding it can cause. Although it is rarely reported, hyperkalemia is one of the side effects associated with heparin therapy (unfractionated or fractionated heparin). It would be secondary to hypoaldosteronism by blocking the biosynthesis of aldosterone in the adrenal gland and often appears in context of prolonged heparin therapy or inappropriate renin production in elderly, diabetic, and kidney insufficiency patients. We report a case of persistent hyperkalemia in a diabetic COVID-19 patient treated with curative heparin in the context of severe COVID-19.

Prevalence, Location, and Determinants of Valvular Calcifications in Congolese Patients on Chronic Hemodialysis: A Multicenter Cross-Sectional Study.

Valvular calcifications (VCs) are one of the major cardiovascular complications in patients on chronic hemodialysis (HD) due to its prevalence and predictive morbidity and mortality. The current study assessed the prevalence, location, and risk factors of VC among chronic HD Congolese patients in Kinshasa. This observational study involved three HD centers in Kinshasa between March and August 2016. Consecutive consenting adults on maintenance HD for at least six months were recruited. VCs were defined as a luminous echo on one or more cusps of the aortic or mitral valve. Risk factors of VC were determined by multivariate analysis. Sixty patients (mean age: 52.5 ± 15.9 years) were enrolled. The mean serum calcium and phosphorus were7.9 ± 1.3 mg/dL and 5.7 ± 1.7 mg/dL, respectively. VCs were encountered in 38% of the whole group in aortic and mitral valvular location in 64% and 23%, respectively. Hypertension, age >60 years, tobacco use, and hyperphosphatemia were independently associated with VC. Despite a young age of patients, VCs were a common finding and associated with both traditional and chronic kidney disease-specific risk factors.

First Case of COVID-19-Associated Collapsing Glomerulopathy in Sub-Saharan Africa.

Although the lungs remain the main target of SARS-CoV-2, other organs, such as kidneys, can be affected, which has a negative impact on the outcomes of COVID-19 patients. Although previous studies of kidney disease in COVID-19 reported mainly SARS-CoV-2-induced tubular and interstitial injury, there is growing evidence coming out of Africa of glomerular involvement, especially collapsing glomerulopathy seen particularly in people of African descent. We report a case of collapsing glomerulopathy revealed by acute kidney injury and a new onset of full blown nephrotic syndrome in a black Congolese patient coinfected with COVID-19 and malaria.

Cost estimate of chronic hemodialysis in Kinshasa, the Democratic Republic of the Congo: A prospective study in two centers.

BACKGROUND: The number of patients on dialysis has significantly increased worldwide. However, prospective studies estimating the cost of hemodialysis (HD) in sub-Saharan Africa remain scarce. The present study aimed to evaluate the direct cost of treating end stage renal disease. Determinants of additional direct cost were also assessed. METHODS: This study is an analytical, prospective study of cost performed at two HD centers in Kinshasa for a period of 3 months among HD patients enrolled consecutively. The cost analyzed includes only expenditures: consultation, HD session, drugs, comorbidities, laboratory tests, and imaging. Transportation, patient hospitalization, and indirect costs are not taken into account. The determinants of the additional direct cost of HD are identified by multivariate logistic regression analysis. P < 0.05 is the level of statistical significance. FINDINGS: The average quarterly direct cost of chronic HD in United States Dollars (US$) is $7070 (~US$28,280 annual cost) at a rate of US$287 per patient per HD session. This cost includes the HD session (US$237) and medicine (US$33) costs, which account for 82.5% and 11.3% of the direct costs, respectively. The presence of at least 4 comorbidities (OR adjusted 4.3, 95% CI [1.23-14.95], P = 0.022) and infection (adjusted OR 4.56, 95% CI [1.05-19.85], P = 0.043) emerged as independent determinants of additional direct cost. CONCLUSION: The direct cost of HD is very high in Kinshasa, where more than 80% of Congolese people live on less than US$1.25 a day.

G1 is the major APOL1 risk allele for hypertension-attributed nephropathy in Central Africa.

BACKGROUND: Sub-Saharan Africans exhibit a higher frequency of chronic kidney disease (CKD) than other populations. In this study, we sought to determine the frequency of apolipoprotein L1 (APOL1) genotypes in hypertension-attributed CKD in Kinshasa, Democratic Republic of the Congo. METHODS: We performed a case-control study identifying 162 subjects: 79 with hypertension-attributed CKD and 83 controls living in Kinshasa who were genotyped for APOL1 risk variants between July 2013 and November 2016. We selected control subjects from the general population and matched them with the cases according to age. Logistic regression analysis was used to examine the relationship between APOL1 high-risk genotypes and CKD. RESULTS: The frequencies of the APOL1 G1 and G2 alleles were 19.1 and 7.1%, respectively. The number of individuals with the G1 and G2 risk alleles was significantly higher in the CKD group (12.7%) than in the control group (2.4%), particularly in individuals with end-stage kidney disease (14.3%). Subjects carrying two risk alleles was strongly and independently associated with hypertension-attributed nephropathy, with an adjusted odds ratio of 7.7 (95% confidence interval 1.5-39.7; P = 0.014). The high-risk APOL1 genotypes were G1/G1 and G1/G2, whereas G2/G2 was not found in the study population. CONCLUSIONS: The results of this study demonstrate the association of high-risk APOL1 genotypes with kidney disease in Kinshasa. The absence of G2/G2 may be consistent with powerful selective sweeps induced by Trypanosoma brucei gambiense infection. In contrast, the presence of APOL1 G2/G2 among individuals of African ancestry in the USA may indicate relaxation of natural selection in a trypanosome-free environment.

Performance of creatinine- or cystatin C-based equations to estimate glomerular filtration rate in sub-Saharan African populations.

Glomerular filtration rate (GFR) is the best index for kidney function; however, the applicability of GFR estimating equations in sub-Saharan African populations remains unclear. In a cross-sectional study of adults living in Kinshasa, Democratic Republic of Congo (n=210) and Abidjan, Ivory Coast (n=284), we evaluated the performance of creatinine and cystatin C-based equations using plasma clearance of iohexol as the reference standard. The race coefficient did not improve the performance of creatinine-based GFR estimates; in fact, both the Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology (CKD-EPI) equations performed better without the race coefficient in participants with GFR ≥60 mL/min/1.73m2. The CKD-EPI and Full Age Spectrum (FAS) equations were unbiased and had similar precision (SD of 17.9 versus 19 mL/min/1.73 m2) and accuracy within 30% (P30, 86.7% versus 87.4%) in participants with GFR ≥60 mL/min/1.73m2. Both equations performed poorly in the subgroup with measured GFR < 60 mL/min/1.73m2 (n=80), but the FAS equation had smaller bias (-4.8 mL/min/1.73m2 versus -7.7 mL/min/1.73m2 for CKD-EPI) and higher P30 (56.3% versus 31.3% for CKD-EPI). The corresponding equations including cystatin C alone or in combination with creatinine had similar performance. In a sub-Saharan African population, adjustment for race did not improve the performance of GFR estimating equations. The creatinine-based FAS and CKD-EPI equations performed reasonably well and were comparable when GFR was ≥ 60 mL/min/1.73m2. Cystatin C did not improve performance. The FAS equation may be preferable when GFR is < 60 mL/min/1.73m2, but this should be confirmed in larger studies.

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.

Performance of glomerular filtration rate estimation equations in Congolese healthy adults: The inopportunity of the ethnic correction.

CONTEXT AND OBJECTIVE: In the estimation of glomerular filtration rate (GFR), ethnicity is an important determinant. However, all existing equations have been built solely from Caucasian and Afro-American populations and they are potentially inaccurate for estimating GFR in African populations. We therefore evaluated the performance of different estimated GFR (eGFR) equations in predicting measured GFR (mGFR). METHODS: In a cross-sectional study, 93 healthy adults were randomly selected in the general population of Kinshasa, Democratic Republic of the Congo, between June 2015 and April 2016. We compared mGFR by plasma clearance of iohexol with eGFR obtained with the Modified Diet in Renal Disease (MDRD) equation with and without ethnic factor, the Chronic Kidney Disease Epidemiology (CKD-EPI) serum creatinine (SCr)-based equation, with and without ethnic factor, the cystatin C-based CKD-EPI equation (CKD-EPI SCys) and with the combined equation (CKD-EPI SCrCys) with and without ethnic factor. The performance of the equations was studied by calculating bias, precision and accuracy within 30% (P30) of mGFR. RESULTS: There were 48 women and 45 men. Their mean age was 45.0±15.7 years and the average body surface area was 1.68±0.16m2. Mean mGFR was 92.0±17.2 mL/min/1.73m2 (range of 57 to 141 mL/min/1.73m2). Mean eGFRs with the different equations were 105.5±30.1 and 87.2±24.8 mL/min/1.73m2 for MDRD with and without ethnic factor, respectively; 108.8±24.1 and 94.3x20.9 mL/min/1.73m2 for CKD-EPI SCr with and without ethnic factor, respectively, 93.5±18.6 mL/min/1.73m2 for CKD-EPI SCys; 93.5±18.0 and 101±19.6 mL/min/ 1.73m2 for CKD-EPI SCrCys with and without ethnic factor, respectively. All equations slightly overestimated mGFR except MDRD without ethnic factor which underestimated by -3.8±23.0 mL/min /1.73m2. Both CKD-EPI SCr and MDRD with ethnic factors highly overestimated mGFR with a bias of 17.9±19.2 and 14.5±27.1 mL/min/1.73m2, respectively. There was a trend for better P30 for MDRD and CKD-EPI SCr without than with the ethnic factor [86.0% versus 79.6% for MDRD (p = 0.21) and 81.7% versus 73.1% for the CKD-EPI SCr equations (p = 0.057)]. CKD-EPI SCrCys and CKD-EPI SCys were more effective than creatinine-based equations. CONCLUSION: In the Congolese healthy population, MDRD and CKD-EPI equations without ethnic factors had better performance than the same equations with ethnic factor. The equations using Cys C (alone or combined with SCr) performed better than the creatinine-based equations.

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.

Chronic kidney disease among high school students of Kinshasa.

BACKGROUND: Chronic kidney disease (CKD) is a major worldwide health problem. However, its burden among adolescents and young adults is unknown, especially in sub-Saharan Africa. The aim of this study was to investigate its prevalence in the school environment. The concordance of usual formulas used to estimate renal function was also assessed. METHODS: In an epidemiological cross sectional study, a random sample of 524 pupils (263 boys, mean age of 18.7 ± 1.4 years) from school environment of Kinshasa were studied. Recorded parameters of interest were anthropometric, proteinuria, serum creatinine and estimated glomerular filtration rate (eGFR) according to the Schwartz formula using uncalibrated creatinine levels from one random measurement. CKD was defined as the presence of kidney damage (daily proteinuria ≥ 300 mg) and/or reduced kidney function (eGFR < 60 ml/min/1.73 m2). Concordances between eGFR according to Schwartz, Cockcroft-Gault (C-G) indexed for BSA and modification of diet in renal disease (MDRD) study equations were computed using the kappa coefficient. RESULTS: The prevalence of CKD by the Schwartz formula was 1.5%. By stage, 0.8% had CKD stage 1 (proteinuria with normal eGFR) and 0.8% had CKD stage 3 (eGFR, 30 to 59 ml/min/1.73 m2). The prevalence of proteinuria ≥ 300 mg/day was 1% (one case had 2.7g/day). Agreement between eGFR according to Schwartz formula and the MDRD formula was excellent (kappa: 88.8%). Although correlations between all formulas were excellent (0.99; 0.87, and 0.89), agreement was poor between eGFR according to Schwartz and C-G indexed BSA equation (kappa: 52.7%) and, poorer with C-G unadjusted for BSA (kappa: 26.9%). CONCLUSION: In the large African city of Kinshasa, 2% of high school students have CKD. This high prevalence rate emphasizes the need for appropriate detection and prevention measures in this vulnerable young age population group.

Prevalence of low estimated glomerular filtration rate, proteinuria, and associated risk factors among HIV-infected black patients using Cockroft-Gault and modification of diet in renal disease study equations.

OBJECTIVE: To evaluate the prevalence of low estimated glomerular filtration rate (eGFR), proteinuria, and associated risk factors among HIV-infected black patients at primary health care. METHODS: A cross-sectional screening involving consecutive HIV-infected patients 18 years and older was done. Eighty-eight percent of patients were receiving highly active antiretroviral therapy (94% on first-line regimen: zidovudine + lamivudine + nevirapine). Simplified Modification of Diet in Renal Disease Study and Cockroft-Gault (CG) equations were used to estimate glomerular filtration rate and creatinine clearance, respectively. Determinants of dipstick proteinuria and low kidney function (<60 mL·min(-1)·1.73 m(-2)) were assessed using multivariate logistic regression analysis. RESULTS: Three hundred HIV-infected (231 females) patients were screened. Their mean age, duration of HIV, and CD4(+) count were 43 ± 9 years, 33 ± 27 months, and 397 ± 224 cells per cubic millimeter, respectively. The prevalence of low eGFR according to Modification of Diet in Renal Disease Study and CG equations was 3% and 10%, respectively. Proteinuria was observed in 20.5% of patients. Only CD4(+) cell count ≤200 cells per cubic millimeter emerged as a strong determinant of low CG creatinine clearance [adjusted odds ratio (OR) 3.03; 95% confidence interval (CI): 1.099 to 8.352], whereas age ≥45 years (adjusted OR 3.69; 95% CI: 1.756 to 7.787), familial history of diabetes mellitus (adjusted OR 2.20; 95% CI: 1.067 to 4.543), and hypertension (adjusted OR 3.07; 95% CI: 1.278 to 7.787) were significantly associated with proteinuria. CONCLUSIONS: Low eGFR and proteinuria are prevalent among these HIV-infected persons. Immunodeficiency emerged as one of the strongest determinants of renal impairment. This finding emphasizes the importance of highly active antiretroviral therapy in tackling the burden of chronic kidney disease in African HIV population.

Screening for proteinuria and chronic kidney disease risk factors in Kinshasa: a World Kidney Day 2007 study.

BACKGROUND: Although screening programs for chronic kidney disease (CKD) may be of great value, these programs are not yet implemented in the Democratic Republic of Congo. This study focused on proteinuria and examined its prevalence in terms of the number needed to screen for the different risk factors of CKD. Such knowledge would guide the utility of population screening to prevent end-stage renal disease. METHODS: A cross-sectional survey was conducted in Kinshasa on the Second World Kidney Day. A sample of 3,018 subjects was interviewed and the following measurements were performed: blood pressure, body mass index, glycemia and urine protein. Logistic regression analysis was used to identify determinants of proteinuria. RESULTS: The prevalence of proteinuria was 17.1% (95% CI 15.8-18.6). Other CKD risk factors identified were: hypertension, diabetes mellitus, obesity and metabolic syndrome. To identify 1 case of proteinuria, one would need to screen 4 persons with diabetes, 5 persons with hypertension, 4 subjects having metabolic syndrome, 5 persons aged >or=72 years and 9 persons without any of the conditions mentioned above. Age, overweight and diabetes were the strongest factors associated with proteinuria. CONCLUSIONS: This study indicates that proteinuria and traditional risk factors for CKD are very prevalent in Kinshasa. Realistic policies to stem these conditions should be a public health priority.