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.

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.

Measured (and estimated) glomerular filtration rate: reference values in West Africa.

Background: Establishment of normal reference values for glomerular filtration rate (GFR) is mandatory in nephrology. However, no data are available for measured GFR (mGFR) in Africa. Methods: GFR was measured in 237 healthy adult subjects (103 women and 134 men, mean age 34 ± 10 years) by iohexol plasma clearance. Results: The mean mGFR was 103 ± 17 mL/min/1.73 m2 and the median value was 103 mL/min/1.73 m2 (2.5th and 97.5th percentiles are 76 and 137 mL/min/1.73 m2, respectively). No significant difference in mGFR results was observed in patients < 40 years of age, whereas a significant decline in mGFR was observed after 40 years of age. There was no significant difference between mGFR in men and women. Conclusions: Normal GFR values and descriptions of percentiles are now available for West Africa. As in Caucasians, no significant difference was observed between men and women. Moreover, the same age-associated decline in mGFR is also observed after 40 years of age, as in Caucasians.

Analytical and clinical evaluation of the new Fujirebio Lumipulse®G non-competitive assay for 25(OH)-vitamin D and three immunoassays for 25(OH)D in healthy subjects, osteoporotic patients, third trimester pregnant women, healthy African subjects, hemodialyzed and intensive care patients.

BACKGROUND: In this study, we provide a short analytical evaluation of the new Fujirebio Lumipulse®G non-competitive immunoassay for 25(OH)D. Clinical performance was compared with three commercial competitive automated immunoassays against a Vitamin D Standardization Program (VDSP)-traceable liquid chromatography-tandem mass spectrometry (LC-MS/MS) in six different clinically relevant populations. METHODS: Lumipulse®G 25(OH)D precision, measurement uncertainty, recovery, limit of quantification were assessed, as well as 25(OH)D2 and C3-epimer recovery. For method comparison, 250 serum samples obtained in healthy Caucasians and Africans, osteoporotic, hemodialyzed and intensive care patients and 3rd trimester pregnant women were analyzed by all methods. Correlation was studied using Passing-Bablok and Bland-Altman analysis. Concordance correlation coefficient (CCC) was calculated to evaluate agreement between immunoassays and the LC-MS/MS. RESULTS: The Lumipulse®G 25(OH)D assay presented interesting analytical features and showed excellent correlation to the LC-MS/MS results (y=1.00×-1.35 ng/mL), as obtained in healthy Caucasian individuals. In the other special populations, Lumipulse®G presented a concordance with LC-MS/MS which was generally higher than competitors, even if all methods significantly under-recovered 25(OH)D in hemodialyzed patients. Intra-assay CV ranged from 12.1% at 9.6 ng/mL to 2.1% at 103.7 ng/mL and inter-assay CV ranged from 16.2 to 3.7% at the same concentrations, respectively. Measurement uncertainty, with a probability of 95%, were respectively 33.1 and 7.6% at these concentrations. LOQ was found to be at 4.6 ng/mL. Mean (95% CI) 25(OH)D2 revovery was 77% (74-81) and no cross-reactivity was observed with C3-epimer. CONCLUSIONS: Fujirebio Lumipulse®G 25-OH Vitamin D Total assay is therefore considered suitable for assessment of vitamin D status in clinical routine.

Effect of a bis-thiazolium compound on the biosynthesis of Plasmodium falciparum phospholipids.

In the eukaryotic cell, phospholipids can be biosynthesized by two pathways, one from choline and the other one from ethanolamine. The functional effectiveness of each pathway depends on the type of the cell. Thiazolium designed-drugs have shown, under in vivo conditions, antiplasmodial and antimalarial activities with inhibition of the phospholipids biosynthesis. This study aimed to discover the pathways involved in the biosynthesis of phospholipids in Plasmodium and deduce the biochemical steps inhibited by T4, a bis-thiazolium bromide drug. We compared the uptake of radiolabeled precursors and their selective incorporation in the phospholipids of cultured Plasmodium-infected and -uninfected erythrocytes which revealed that phosphatidylcholine of Plasmodium is synthesized both from choline and ethanolamine (4.7 vs 1.9 nmol/10(10) cells x h(-1)). T4 has no effect on the biosynthesis of phosphatidylethanolamine but T4 inhibited, in a selective way, the in vitro uptake of choline. However no enzymes in the biosynthesis of phospholipids seem to be inhibited by T4 but rather an inhibition of choline entry into the parasite.

[Immune, inflammatory, and nutritional protein profile in children with iron deficiency in Côte d'Ivoire]. / Déficit en fer, profil protéique immunitaire, inflammatoire et nutritionnel chez l'enfant de Côte-d'Ivoire.

Throughout the world and particularly in sub-Saharan Africa, deficiencies in trace elements constitute a real public health problem because of the insufficient nutritional quality of food. These trace elements are necessary for many of the body's biochemical reactions. The role of microelements such as vitamin A and zinc has been established in the functioning of the immune system and secretion of inflammatory reaction proteins, but the role of iron in these functions remains to be elucidated. The sample consists of 186 children (3/4) 80 with an iron deficiency and 106 with normal iron status. They range in age from 5 to 15 years and all attend school in the department of Adzope. The study excluded all children with parasites that might affect blood iron, protein and other hematological indicators, in particular, Plasmodium falciparum, Giardia intestinalis, Trichomonas intestinalis, Ascaris lumbricoides, and Ancylostoma. Inflammatory, immune and nutritional proteins were measured by radial immunodiffusion (Mancini's method). Ferritin was measured by a specific immunoenzymatic assay. Hematological indicators were tested by an automatic blood cell counter. Nutritional status was estimated by the weight/height ratio (W/H). This analysis showed that iron deficiency was associated with reduced IgG levels (p < 0.05), although immunoglobulins A and M remained stable (p > 0.05. Iron deficiency was also associated with reduced levels of thyroxine-binding prealbumin (TBPA) and albumin (p < 0.05). Inflammatory proteins did not differ significantly between the two groups (p > 0.05). Furthermore, the prognostic inflammatory and nutritional index (PINI) did not show any inflammatory, vital or nutritional risk, because it was lower than or equal to 2. Finally, malnutrition was not observed in the iron-deficient children: the difference in the weight/height ratio (W/H = 96.58 +/- 2.4%) between the children with iron deficiency and those with normal iron status (98.7 +/- 4.3%) did not differ significantly. The reduced IgG associated with iron deficiency may be attributed to the role that iron plays in the proliferation and maturation of lymphocytes. Reduced iron levels would thus lead to slowing down the hematopoietic mechanism, resulting in a decrease in B lymphocyte production and thus inevitably a reduction in IgG synthesis. The reduction in albumin and TBPA associated with the iron deficiency but in the absence of any sign of malnutrition (W/H > 96%) or inflammatory risk (PINI < 2) in either study group shows that iron may play a dominant role during protein synthesis. Iron deficiency might limit the energy of cellular tissues, leading to a reduction in RNA activity (transcription and translation), which would in turn decrease ribosome activity in tissues and thus reduce amino acid synthesis in cells, resulting in the reduction observed in protein synthesis. The lack of difference between the study groups in inflammatory proteins, notably CRP and alpha1-GPA, indicates that iron deficiency does not appear to be related to an inflammatory process. This study of children without any apparent clinical signs of iron deficiency shows that such a deficiency may be associated with a disruption in protein production. The proteins concerned include IgG, TBPA and albumin. The public authorities should pay particular attention to improving children's diets, especially their micronutrient levels, including for iron, vitamin A and zinc.

Vitamin D, bone alkaline phosphatase and parathyroid hormone in healthy subjects and haemodialysed patients from West Africa: impact of reference ranges and parathyroid hormone generation assays on the KDIGO guidelines.

BACKGROUND: The Kidney Disease: Improving Global Outcomes (KDIGO) guidelines recommend targets based on multiples of the upper limit of normal (ULN) of parathyroid hormone (PTH) concentration. However, the ULN has not always been correctly established by manufacturers. While it is known that the ULN is supposed to be higher in African Americans than in Caucasians, it is largely unknown in Africans. METHODS: We established the ULN of PTH concentration in a population of 240 healthy Ivorians using second- and third-generation PTH assays before and after supplementation with 100 000 IU of cholecalferol. We measured the levels of PTH, bone alkaline phosphatase, 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D in 100 haemodialysed Ivorian patients. RESULTS: The prevalence of vitamin D deficiency in Ivory Coast is low. The ULN obtained using the third-generation PTH assay was similar to that obtained in Caucasians but was higher when PTH was measured using the second-generation PTH assay. According to the KDIGO guidelines, ∼20% of the haemodialysed patients were below twice the ULN and 30% were above nine times the ULN. Approximately 25% of the patients were even >12 times the ULN. We observed a discrepancy in the results between the two PTH assays (14%) that was relatively more important than what we observed from previous studies in Caucasians using the same strategy. CONCLUSIONS: We found a low prevalence of vitamin D deficiency in a tropical country like Ivory Coast. We also established the PTH reference range, which could prove useful for the follow-up of haemodialysed patients, particularly for the large number of patients suffering from secondary hyperparathyroidism who are at high risk of adverse bone events.

HPV seminal shedding among men seeking fertility evaluation in Abidjan, Ivory Coast.

BACKGROUND: Little is known about the semen shedding of human papillomaviruses (HPV) in African men. OBJECTIVES: To detect and identify HPV types in semen samples from men seeking fertility evaluation in Abidjan, Ivory Cost. STUDY DESIGN: Sixty-three semen samples were tested by PCR using consensus primers and HPV types were determined by PCR product sequencing or by line probe assay (LiPA) when sequencing was inconclusive. RESULTS: A total of 19 HPV isolates belonging to 11 HPV types were identified in semen samples from 18 (28.6%) men. Ten (55.5%) of the HPV-positive men shed oncogenic HPV types. An association of borderline significance (P=0.06) was observed between HPV semen shedding and a lower sperm count. CONCLUSION: HPV shedding in semen is common in African men. The relationship between HPV semen shedding and sperm quality merits to be further investigated.

Glomerular Filtration Rate in Healthy Living Potential Kidney Donors: A Meta-Analysis Supporting the Construction of the Full Age Spectrum Equation.

BACKGROUND: Normal kidney function or, more specifically, normal glomerular filtration rate (GFR) in men and women and its decline with age is still much debated today. The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation has gender (and race) multiplication factors, accounts for a decline that starts at very young age and assumes that the mean GFR is as high as 120-130 ml/min/1.73 m2 from a young age. The full age spectrum (FAS) estimated mean GFR is about 107 ml/min/1.73 m2 at a young age and remains constant until the age of 40 years and then starts to decline both in men and women. The aim of this research study was to give more insight into 'normal' GFR levels and the physiological decrease of kidney function with age and to use a meta-analysis to evaluate the mathematical construction of the FAS and the CKD-EPI equation. METHODS: We conducted a meta-analysis of published GFR measurements in healthy Caucasian living potential kidney donors (n = 5,482, 46.8% men). Only publications dating from 2000 were selected to avoid the possible influence of body surface area changes in the last decades on the indexed GFR, expressed in ml/min/1.73 m2. RESULTS: We found that the mean GFR ≈ 107 ml/min/1.73 m2 up to the age of 40 years, but renal decline begins beyond 40 years. No evidence could be found for any difference between men and women in the separate age groups. CONCLUSIONS: The current meta-analysis supports the mathematical form of the FAS equation, which matches the age/sex dependency of measured GFR for healthy potential living kidney donors.

[Inadequacy of the African-American ethnic factor to estimate glomerular filtration rate in an African general population: Results from Côte d'Ivoire]. / Inadéquation du facteur ethnique pour l'estimation du débit de filtration glomérulaire en population générale noire-africaine : résultats en Côte d'Ivoire.

Glomerular filtration rate (GFR) estimation is fundamental in clinical nephrology. It is usually estimated from equations based on serum creatinine. An ethnic factor is currently recommended for the black population for the two most used equations, i.e. the Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) and Modification of Diet in Renal Disease (MDRD) study equations. However, these factors were determined from African-American subjects. Therefore, their use in the African subject (non-American) remained questionable. To date, no data are available in West Africa for the adequacy of these ethnic coefficients, as compared with a measurement of GFR by a reference method. One hundred and twenty subjects of the general population, with no nephrologic history, were included in the study (60 women and 60 men). GFR was determined by a reference method, i.e. the plasma clearance of iohexol. The performance (bias, standard deviation, accuracy within 30%) of both CKD-EPI and MDRD study equations were assessed with and without the ethnic factors. GFR measurements (mGFR) according iohexol reference method were 100±19mL/min/1.73m2. The MDRD study equation without any ethnic factor underestimates mGFR by -9±16mL/min/1.73m2, whereas the MDRD study equation with the ethnic factor overestimates mGFR by +10±18mL/min/1.73m2. Regarding the CKD-EPI equation, bias and accuracy within 30% are significantly better without than with the ethnic factor. Indeed, bias is 16±2mL/min/1.73m2 and 18±17mL/min/1.73m2 and accuracy is 93% and 76%, without and with the ethnic factor, respectively (P<0.0001). We show for the first time in African population that the performance of CKD-EPI and MDRD study equations is significantly better, in a general population, without the "African-American" ethnic factor. The "African-American" ethnic factor should not be applied in West Africa.

[Fattening diet and metabolic syndrome in Ivory Coast]. / Régime d'engraissement et syndrome métabolique en Côte d'Ivoire.

Metabolic syndrome is a particular state of morbidity characterized by the association of several factors contributing to the increase in the cardiovascular risk. This constellation of factors associates the glucose intolerance and its corollary the hyperglycemia, the overweight, the hypertriglyceridemia, the fall of the HDL-cholesterol and arterial hypertension. In Africa, it is difficult to evaluate in the actual prevalence of the metabolic syndrome. The present study aims was to determine the prediction and prevalence of the metabolic syndrome in a group of nurse--lactating mothers--in Abidjan (Ivory Coast), who were submitted at a particularly rich food lipids. Our populations were composed to 100 lactating women, and we used the definition of « National Cholesterol Education Program-Adult Treatment Panel III ¼. The results obtained showed that the prevalence of the metabolic syndrome is 7%, and 30% of them are presented an abdominal obesity. Our populations were composed to 100 lactating women, which belong to the Ethie where the habit are to eat, after giving birth, high foods lipids for 6 months. We used the definition of "National Cholesterol Education Program-Adult Treatment Panel III" to determine the prevalence of metabolic syndrome in this population and see if the diet has a negative influence. The results obtained showed that the prevalence of the metabolic syndrome is 7%, and 30% of them are presented an abdominal obesity. The risk to develop a metabolic syndrome in this specific population of nurse is particularly big and it's linked to their eating habits.

[Reversible immunosuppression, liver and kidney markers, calcium and phosphorus in the healthy rabbit]. / Immunosuppression reversible, marqueurs du foie, des reins et metabolisme phosphocalcique chez le lapin sain.

AIM: The aim of this study was to determine one or several doses of Methylprednisolone ( MP) who leads a long time of immunosuppression without disrupting phosphor and calcium, liver and kidney markers at the healthy rabbit. MATERIAL AND METHODS: This study was made to fifteen rabbit. Five (5) batches were constituted according to Nacl and Methylpredmisolone administered dose by body weight. Control batch ( Nacl 0,9%); batch I (2,5mg / kg MP); batch II ( 5mg / kg MP); batch III ( 10mg / kg MP) and batch IV ( 15 mg / kg MP). Biochemical parameters were measured by chemical and enzymatic methods. RESULTS: The results of this study showed an immunosuppression during seven days with 10 and 15 mg / kg of MP doses (P < 0.05). The biochemical disturbances were only observed with 15 mg / kg dose where calcium was lowered to day 15 and TGO increased to day 3 according to day 0 (P < 0.05). CONCLUSION: This study showed that the doses which lead a long time of immunosuppression ( 7 days) are 10 and 15 mg / kg of MP, then the dose which does not disrupt the biochemical parameters is 10 mg / kg of MP.