Association of Genetic Polymorphisms of TGF-ß1, HMOX1, and APOL1 With CKD in Nigerian Patients With and Without HIV.

RATIONALE & OBJECTIVE: Recent studies in the human immunodeficiency virus (HIV)-infected population have suggested that there are genetic predispositions to the development of chronic kidney disease (CKD) in this context. We investigated the association of genetic polymorphisms of the genes encoding apolipoprotein L1 (APOL1), transforming growth factor ß1 (TGF-ß1; a profibrotic cytokine), and heme oxygenase 1 (HMOX1) with prevalent CKD among adults with and without HIV infection. STUDY DESIGN: Case-control study. SETTING & PARTICIPANTS: West African adults including 217 HIV-infected patients with CKD (HIV+/CKD+ group), 595 HIV-infected patients without CKD (HIV+/CKD- group), 269 with CKD and no HIV infection (HIV-/CKD+ group), and 114 with neither CKD nor HIV (HIV-/CKD- group). EXPOSURE: The genetic polymorphisms with reference single-nucleotide polymorphism (rs) identification numbers rs1800469 (TGF-ß1), rs1800470 (TGF-ß1), rs121918282 (TGF-ß1); rs60910145 (APOL1 G1 risk allele), rs73885319 (APOL1 G1 risk allele), rs71785313 (APOL1 G2 risk allele), and rs743811 (HMOX1); HIV. OUTCOME: CKD. ANALYTICAL APPROACH: Single-nucleotide polymorphism (SNP) genotyping of rs1800469 (TGF-ß1), rs1800470 (TGF-ß1), rs121918282 (TGF-ß1); rs60910145 (APOL1), rs73885319 (APOL1), rs71785313 (APOL1), and rs743811 (HMOX1) was performed. Hardy-Weinberg equilibrium was evaluated for all SNPs, and minor allele frequencies were reported. A case-control analysis was performed, and multivariable logistic regression was used to control for potential confounders. RESULTS: Minor allele frequencies for TGF-ß1 (rs1800469, rs1800470, and rs1800471), APOL1 (rs60910145, rs73885319, and rs71785313), and HMOX1 (rs743811) were 0.25, 0.46, 0.46, 0.44, 0.45, 0.17, and 0.14, respectively. Among HIV-positive individuals, only TGF-ß1 rs1800470 (GG vs AA), APOL1 (in the recessive model), and hypertension were associated with prevalent CKD (adjusted ORs of 0.44 [95% CI, 0.20-0.97], 2.54 [95% CI, 1.44-4.51], and 2.17 [95% CI, 1.35-3.48], respectively). No SNP polymorphisms were associated with prevalent CKD among HIV-negative individuals. LIMITATIONS: The lack of histopathology data for proper categorization of the type of HIV-related nephropathy. CONCLUSIONS: APOL1 polymorphisms were highly prevalent in this population and among adult patients infected with HIV and were associated with increased CKD risk. The TGF-ß1 (rs1800470) polymorphism was associated with reduced risk, and HMOX1 polymorphisms were unassociated with CKD.

Pattern of prescription of anti-hypertensive medications in a tertiary health care facility in Abuja, Nigeria.

INTRODUCTION: Marked changes have been made in the pharmacotherapy of hypertension over the years. In sub-Saharan Africa, hypertension pharmacotherapy is often thought to include only thiazide diuretics, beta blockers and centrally acting medications and, it is unclear if and how often calcium channel blockers, angiotensin converting enzyme inhibitors and angiotensin receptor blockers are used. OBJECTIVE: To examine the anti-hypertensive prescription pattern in a tertiary health centre in Nigeria to determine how it conforms to current guidelines. METHOD: 590 newly diagnosed hypertensive patients presenting at the Cardiology Unit of University of Abuja Teaching Hospital over a three-year period were studied. RESULT: Calcium channel blockers were the most frequently prescribed anti-hypertensive medications (66.9% of all cases) and centrally acting medications were prescribed in only 5.01% of cases. Single-pill combination either alone or in combination with other antihypertensive medications were prescribed in 17.3% cases. Of these, calcium channel blocker-based combinations constituted the most frequently used multiple drug combinations. 94.6% of the patients required more than one medication for blood pressure control. CONCLUSION: Anti-hypertensive pharmacotherapy in Abuja, Nigeria, compares favorably with the current recommendations in the prescription pattern of anti-hypertensive medications.

Prevalence of metabolic syndrome among hypertensive patients in Abuja, Nigeria.

BACKGROUND: It is well known that factors like high blood pressure, hyperglycemia, dyslipidemia, obesity and hyperuricemia tend to cluster together giving rise to what is called metabolic syndrome. In spite of the high prevalence of hypertension in Nigeria, there is a dearth of data describing the prevalence of metabolic syndrome in Nigerian hypertensive patients. We therefore set out to look at the prevalence of metabolic syndrome in hypertensive patients presenting to the cardiology clinic of a tertiary institution in Abuja, Nigeria. METHODS: Metabolic syndrome was defined in patients according to the World Health Organisation's definition. RESULTS: Of the 362 patients studied, 56.9% were male and 43.1% were female. The mean age was 51.80 +/- 11.63 years, mean duration of hypertension was 8.90 +/- 3.95 years, mean body mass index was 29.36 +/- 6.12 kg/m2 and mean arterial blood pressure was 110.28 +/- 18.17 mm Hg. Overall, 13.0% of the study population had metabolic syndrome; 16.7% of females and 10.2% of males. CONCLUSION: The prevalence of metabolic syndrome among hypertensive patients in Abuja, Nigeria is comparable to rates observed in some general populations in Europe. This might imply the epidemiological transition in disease pattern already being experienced in many parts of sub-Saharan Africa.

Blood Pressure Control and its Determinants among Patients with Chronic Kidney Disease in a Nigerian Tertiary Hospital: A Cross-Sectional Study.

Background: Hypertension is a common cardiovascular risk factor associated with adverse renal and cardiovascular outcomes in chronic kidney disease patients. Significant reduction in these adverse outcomes could be achieved through adequate blood pressure control in those with hypertension. This study aimed to determine the prevalence of poor blood pressure control and associated factors among chronic kidney disease patients with hypertension in a Nigerian tertiary hospital. Methodology: This was a cross-sectional study that determined the prevalence of poor blood pressure control and its associated factors among chronic kidney disease patients with hypertension. Poor blood pressure control was defined as blood pressure ≥ 140/90mmHg. Factors associated with blood pressure control were determined on multivariate analysis. P-value less than 0.05 was considered significant. Results: A total of 494 chronic kidney disease patients with hypertension were studied. The mean age of patients was 48.77+13.06 with a range of 17-95 years. There were 303 (61.3%) males and 191 (38.7%) females. A total of 44.5% of the patients had end-stage renal disease while all patients were on antihypertensive medications. The common causes of chronic kidney disease were hypertension (35%), diabetes mellitus (26.5%), and chronic glomerulonephritis (12.1%).Poor blood pressure control was found in 74.4% of chronic kidney disease patients. The predictors of poor blood pressure control were age (AOR: 0.65; CI: 0.45-0.94; p=0.02), use of multiple anti-hypertensives (AOR: 1.99; CI: 1.36-2.90; p=<0.001) and the presence of significant proteinuria (AOR: 1.47; CI: 1.02-2.14; p=0.04). Conclusion: The majority of patients with chronic kidney disease had poor blood pressure control. Those who were young had significant proteinuria, and those who used≥ 3 antihypertensive medications were more likely to have poor blood control. There is a need to optimize BP management in chronic kidney disease patients in order to reduce adverse outcomes.

Fibroblast Growth Factor 23 (FGF 23) and intact parathyroid hormone (iPTH) as markers of mineral bone disease among Nigerians with non-diabetic kidney disease.

Background: Excess cardiovascular burden in patients with chronic kidney disease (CKD) has been attributed to the occurrence of CKD-Mineral Bone Disease (CKD - MBD). This study aimed to determine the spectrum of CKD-MBD among Nigerians with CKD using Fibroblast Growth Factor 23 (FGF 23) and intact Parathyroid Hormone (iPTH). Methods: Cross sectional survey of 105 patients with non-diabetic CKD and 104 controls. Information obtained were demographics, aetiology of CKD, features of CKD-MBD. Serum iPTH and FGF 23 were assayed. Results: The mean ages were 48.7±15.3 vs 48.6±17.4 years while 54.7% and 45.2% were males for cases and controls, respectively. The mean plasma FGF 23 (392.8±35.3 vs 133.8±22.7 RU/mL and plasma iPTH (289±25.6 vs 118±10.8 ng/L, respectively. The frequency of elevated FGF 23 (45.7% vs 24.0%, p<0.01) and abnormal iPTH (53.3% vs 14.1%, p- 0.01) were higher in cases. The prevalence of MBD were (59.0% vs 14.4%, p<0.01) in cases and controls while dialysis status OR 2.94, 95% CI (1.2803-5.3645), and elevated FGF 23 OR, 1.87, 95% CI (1.1782-5.4291) were associated with CKD-MBD. Conclusion: The study demonstrated high prevalence of CKD-MBD among patients with non-diabetic CKD while FGF23 and iPTH were useful assays in the diagnosis of CKD-MBD among Nigerians with CKD.

Association of clinical signs of chorioamnionitis with histological chorioamnionitis and neonatal outcomes.

BACKGROUND: Chorioamnionitis is a risk factor for fetal and neonatal outcomes. Therefore, predicting histological chorioamnionitis (HCA) and neonatal outcomes using clinical parameters could be helpful in management and preventing morbidities. OBJECTIVE: To determine if parameters of clinical chorioamnionitis (CCA) would be associated with HCA and neonatal outcomes. STUDY DESIGN: In this cohort study using a retrospective design, we analyzed the performance of signs of CCA in predicting HCA, and neonatal outcomes. Data were extracted from the electronic health record for all neonates with documented CCA delivered at our institution from 2011 to 2016. We compared our findings based on the old ACOG definition of CCA and the new definition released in 2017 - maternal fever plus any of fetal tachycardia, maternal leukocytosis, and purulent vaginal discharge. Maternal tachycardia and uterine tenderness were removed from the new criteria. Neonatal laboratory samples on admission, 12 h and 24 h were used to define the three time points of neonatal suspected sepsis. RESULTS: There were 530 mothers-infant dyads with chorioamnionitis. Seventy-three were preterm, and 457 were term. Eighty-eight percent of the preterm mothers had CCA, and HCA was present in 62.5% of 72 preterm placentas. Preterm infants with placental HCA significantly had lower birth weight, gestational age, placental weight, and more infants with lower 5-minute Apgar scores, compared to those with no HCA. In preterm infants, maternal urinary tract infection was significantly associated with decreased odds for HCA (OR 0.22, CI 0.10 - 0.71). More preterm babies with suspected sepsis criteria at the 3 time points had HCA (all p ≤ .01). In the term cohort, 95.4% and 65.6% had CCA and HCA, respectively. In term infants (n = 457), maternal leukocytosis (p = .002) and prolonged rupture of membranes (PROM; p = 002) were associated with HCA. Suspected sepsis was associated with PROM (p = .04), HCA (p = .0001), and maternal leukocytosis (p ≤ .05) in at least 1 of the 3 time points. CONCLUSION: Though maternal leukocytosis was significantly associated with the presence of HCA in the term cohort, there were no CCA criteria that accurately predicted presence of HCA in either the preterm or the term infants.

Ionothermal synthesis of activated carbon from waste PET bottles as anode materials for lithium-ion batteries.

Waste polyethylene terephthalate (PET) bottles have become a significant post-consumer plastic waste with attendant environmental problems. Hence, ionothermal synthesis has been used to prepare activated carbon (AC) anode materials from waste PET for both high performance and sustainable lithium-ion batteries (LIB). Particularly, using choline chloride deep eutectic salts (CU-DES) does not require post-synthesis washing and thereby reduces the complexity of the process and produces materials with unique low-surface area, higher levels of graphitization/ordering, and high nitrogen doping in the obtained ACs. The results show that the AC produced using CU-DES (PET-CU-A-ITP2) gave good electrochemical performance. Even though the material possesses a low surface area (∼23 m2 g-1), it displays a gravimetric capacity (GC) of ∼460 mA h g-1 and a coulombic efficiency (CE) of ∼53% in the 1st cycle and very good cycling performance with a capacity retention of 98% from the 2nd to the 100th cycle. The superior electrochemical performance of the PET-CU-A-ITP2 anode was found to be due to its better graphitization/ordering and dense structure which results in higher capacity, formation of less solid electrolyte interphase, and higher CE. These results show that dense carbons can be exploited as high-performance anodes in LIBs. Also, this research presents both a pathway for waste PET management and a waste-energy approach that could offer cheaper and greener LIBs to meet the sustainable development goals.

Prevalence of Chronic Kidney Disease as a Marker of Hypertension Target Organ Damage in Africa: A Systematic Review and Meta-Analysis.

INTRODUCTION: Hypertension is a major global cause of cardiovascular disease and death with rising worldwide prevalence, particularly in low-income countries. With low awareness, poor treatment, and low control of hypertension in Africans, there is an increased number of patients with target organ damage (TOD), especially chronic kidney disease (CKD), as a consequence of hypertension. The aim of our study is to assess the prevalence of CKD from studies in Africa reporting TOD related to hypertension. METHODS: We performed a search of PubMed/MEDLINE, Web of Science, EBSCOhost, and African Journals Online (AJOL) for studies reporting on CKD as TOD in patients with hypertension. The pooled estimate of CKD was then presented by subregions, age group, eGFR equations, and urban or rural location. RESULTS: We identified 1,334 articles from which 12 studies were included for quantitative analysis. The studies included 5297 participants from 6 countries (Ghana, Nigeria, Uganda, Tanzania, Democratic Republic of Congo, and South Africa). The pooled prevalence of CKD was 17.8% (95% CI 13.0-23.3%), and CKD was significantly more prevalent in West Africa (21.3% (95% CI: 16.1-27.0); p < 0.0001) and in studies conducted in urban settings (p < 0.001). CKD prevalence was not significantly different by type of GFR equation or age. CONCLUSION: This study reports a high prevalence of CKD related to hypertension with a higher prevalence in urban than rural areas. This emphasizes the role of hypertension in causing kidney damage, and the need for strategies to improve awareness, treatment, and control of hypertension in Africans. This study is registered with PROSPERO registration number CRD42018089263.

Urinary Transforming Growth Factor-Beta 1 (uTGF-ß1) and Prevalent CKD Risk in HIV-Positive Patients in West Africa.

INTRODUCTION: This study investigated the association of urinary transforming growth factor-ß1 (uTGF-ß1) with prevalent chronic kidney disease (CKD) in the HIV-infected population. METHODS: HIV-positive patients without CKD (HIV+CKD-, n = 194) and 114 with CKD (HIV+CKD+) who did not have hypertension, diabetes mellitus, or hepatitis B or C, had their urinary protein-creatinine ratio (uPCR), serum transforming growth factor (TGF)-ß1, and uTGF-ß1 measured. uTGF-ß1-creatinine ratios (uTGF-ß1Cr) were calculated. Spearman correlation was used to determine the association between uTGF-ß1Cr and various attributes, and the Cuzick trend test was used to assess the presence of a linear trend in median uTGF-ß1Cr levels across the stages of CKD. Multivariable robust linear regression models were used to assess independent association with variability in uTGF-ß1Cr and estimated glomerular filtration rate (eGFR) levels. RESULTS: The age of the participants was 38.3 ± 10.3 years with 73.4% women. The median uTGF-ß1Cr was higher among HIV+CKD+ (4.85 ng/mmol [25th-75th percentile 1.96-12.35] vs. 2.95 [1.02-5.84]; P = 0.001]). There was significant correlation between uTGF-ß1Cr and age (P = 0.02), eGFR (P = 0.001), and uPCR (P < 0.001) in the HIV+CKD+ group. Among the HIV+CKD+ patients, there was gradual reduction in the median level of uTGF-ß1Cr with CKD severity (P = 0.04). HIV+CKD+ patients had significantly higher levels of uTGF-ß1Cr after controlling for potential confounders. Using eGFR as dependent variable, proteinuria explained the changes associated with uTGF-ß1Cr levels. CONCLUSION: HIV+CKD+ patients express higher levels of uTGF-ß1 especially in the early stages of CKD apparently related to proteinuria levels.

Acute kidney injury among paediatric emergency room admissions in a tertiary hospital in South West Nigeria: a cohort study.

BACKGROUND: Epidemiological data on paediatric acute kidney injury (AKI) in sub-Saharan Africa are limited and largely retrospective. We performed a prospective study of AKI among patients admitted through the emergency room. METHODS: Children admitted to the post-neonatal emergency room of the University College Hospital, Ibadan, Nigeria between February 2016 and January 2017 were studied. AKI was defined by Kidney Disease: Improving Global Outcomes serum creatinine criteria. AKI ascertainment relied on serum creatinine measurements carried out in routine care by post-admission Day 1. We compared in-hospital mortality by post-admission Day 7 for patients with and without AKI (no-AKI). RESULTS: Of the 1344 children admitted to the emergency room, 331 were included in the study. AKI occurred in 112 patients (33.8%) with a median age of 3.1 years [interquartile range (IQR) 0.9-9.4] and was Stage 3 in 50.5% of the cases. The no-AKI group had a median age of 1.8 (IQR 0.7-5.8) years. The underlying diagnoses in patients with AKI were sepsis (33.0%), malaria (12.5%) and primary renal disorders (13.4%). Twenty-four of the patients with AKI underwent dialysis: haemodialysis in 20 and peritoneal dialysis in 4. By Day 7 of admission, 7 of 98 (7.1%) patients in the AKI group had died compared with 5 of 175 (2.9%) patients in the no-AKI group [odds ratio 2.6 (95% confidence interval 0.8-8.5)]. Outcome data were not available for 58 (17.5%) patients. CONCLUSIONS: AKI is common among paediatric emergency room admissions in a tertiary care hospital in sub-Saharan Africa. It is associated with high mortality risk that may be worse in settings without dialysis.

Static skinfold thickness in African newborns as an index of fetal nutritional assessment.

BACKGROUND: Fetal malnutrition (FM) has grave implications for the neonate and is reliably assessed by the CANSCORE which is time-consuming. Static skinfold thickness, a measure of adiposity, is a validated method of assessing malnutrition in older children. AIM: To establish if static skinfold measurements in neonates can serve as a reliable measure of FM. OBJECTIVE: To compare static skinfold thickness measurements in neonates using the CANSCORE for the identification of FM. METHOD: 252 consecutive term neonates delivered at University College Hospital, Ibadan, Nigeria had their CANSCOREs and static skinfold thickness measured within 24 hours of delivery. Using correlation and linear regression analysis, static skinfold thickness cut-off points for FM were determined using a reference CANSCORE of <25. RESULTS: Prevalence of FM was 20.2% and 26.2% using the CANSCORE and the sum of five skinfold thickness measurements, respectively. The mean (SD) skinfold thicknesses were triceps 3.91 mm (0.74), biceps 2.84 mm (0.55), subscapular 3.79 mm (0.91), supra-iliac 2.64 mm (0.62), quadriceps 4.43 mm (1) and the sum of all measurements 17.61 mm (3.16). All the skinfold thickness measurements correlated significantly with the CANSCORE, but the sum of the five had the best correlation. The quadriceps had the highest specificity of 85.6% and lowest sensitivity of 54.9%, while the sum of all had a sensitivity of 66.7% and specificity of 84.0%. CONCLUSION: The sum of all five skinfold measurements might be a useful screening tool for FM in view of its objectivity, convenience and simplicity, but it is not sufficiently sensitive or specific to replace the CANSCORE in the identification of FM in neonates.

Prevalence of dyslipidemia in normoglycemic subjects with newly diagnosed high blood pressure in Abuja, Nigeria.

BACKGROUND: High blood pressure and dyslipidemia additively increases the risk of cardiovascular disease. There is a high prevalence of high blood pressure in Nigeria, but there are little data regarding the prevalence of dyslipidemia in subjects with high blood pressure. OBJECTIVE: In this observational prospective study, we examined the prevalence of dyslipidemia in newly diagnosed normoglycemic subjects with high blood pressure. METHODS: A total of 171 subjects presenting with high blood pressure for the first time in the cardiology and nephrology clinics at the University of Abuja Teaching Hospital were studied. Height, weight, and blood pressure were measured. Total cholesterol, low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) were determined in fasting plasma. The total cholesterol/HDL-C and non-HDL-C values were calculated. These measures were then classified according to the 2001 report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults. RESULTS: Of the 171 subjects studied, 84 (49%) were male and 87 (51%) were female. Low HDL-C was present in 71 (45.8%), elevated LDL-C in 29 (17%), elevated total cholesterol in 19 (11.1%), and elevated triglyceride in 13 (7.6%), whereas eight (4.7%) of the study population had combined elevated total cholesterol and triglyceride. Female subjects had higher total cholesterol and lower HDL-C than male subjects, but these differences were not statistically significant. Obese subjects, compared to the nonobese, had significantly higher LDL-C and total cholesterol/HDL-C ratios in males and significantly higher triglyceride levels in females. CONCLUSIONS: Given the prevalence of dyslipidemia seen in this study, we suggest that fasting lipid measurements should be performed in all Nigerians with high blood pressure. These data suggest the need for health education and lifestyle modifications in hypertensive Nigerians to reduce both types of risk factors.