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Calcineurin inhibitors (CNIs) are the mainstay of immunosuppression in kidney transplantation. Interpatient variability in the disposition of calcineurin inhibitors is a well-researched phenomenon and has a well-established genetic contribution. There is great diversity in the makeup of African genomes, but very little is known about the pharmacogenetics of CNIs and transplant outcomes. This review focuses on genetic variants of calcineurin inhibitors' metabolizing enzymes (CYP3A4, CYP3A5), related molecules (POR, PPARA) and membrane transporters involved in the metabolism of calcineurin inhibitors. Given the genetic diversity across the African continent, it is imperative to generate pharmacogenetic data, especially in the era of personalized medicine and emphasizes the need for studies specific to African populations. The study of allelic variants in populations where they have greater frequencies will help answer questions regarding their impact. We aim to fill the knowledge gaps by reviewing existing research and highlighting areas where African research can contribute.
Research on the pharmacogenetics of calcineurin inhibitors in kidney transplant recipients is truly wanting in data from the African continent. Given Africa's vast genetic diversity, it is necessary to intensify efforts to generate data from Africa in this field.
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[This corrects the article DOI: 10.1016/j.ekir.2024.02.699.].
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Black African populations are more genetically diverse than others, but genetic variants have been studied primarily in European populations. The present study examined the association of four single nucleotide polymorphisms (SNPs) of the fibroblast growth factor receptor 2, associated with breast cancer in nonAfrican populations, with breast cancer in Black, southern African women. Genomic DNA was extracted from whole blood samples of 1,001 patients with breast cancer and 1,006 controls (without breast cancer), and the rs2981582, rs35054928, rs2981578, and rs11200014 polymorphisms were analyzed using allelespecific Kompetitive allelespecific PCR™, and the χ2 or Fisher's exact tests were used to compare the genotype frequencies. There was no association between those SNPs and breast cancer in the studied cohort, although an association was identified between the C/C homozygote genotype for rs2981578 and invasive lobular carcinoma. These results show that genetic biomarkers of breast cancer risk in European populations are not necessarily associated with risk in subSaharan African populations. African populations are more heterogenous than other populations, and the information from this population can help focus genetic risks of cancer in this understudied population.
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Neoplasias de la Mama , Receptor Tipo 2 de Factor de Crecimiento de Fibroblastos , Femenino , Humanos , Neoplasias de la Mama/patología , Estudios de Casos y Controles , Predisposición Genética a la Enfermedad , Genotipo , Polimorfismo de Nucleótido Simple , Receptor Tipo 2 de Factor de Crecimiento de Fibroblastos/genética , Receptor Tipo 2 de Factor de Crecimiento de Fibroblastos/metabolismo , Población Negra/genética , SudáfricaRESUMEN
Background Sarcoidosis is a granulomatous multisystem disease of uncertain aetiology. The disease has major inflammatory and immune components; however, the immunopathogenesis is not well understood. Micro ribonucleic acids (microRNAs) are classes of miniature, single-stranded, non-coding RNAs. Their key recognised role includes mediating the silencing of target genes post-transcriptionally. Recently, the role of miRNAs has gained interest in numerous disorders, suggested as being involved in pathogenesis of those diseases and acting as disease markers. Very little is known about the role of miRNAs in sarcoidosis, with nothing known regarding miRNAs in South African patients. The main objective, therefore, was to investigate the serum expression of approximately 800 miRNAs in patients with sarcoidosis compared with race-, age- and gender-matched healthy controls. Methods A total of six patients and six matched controls participated in this study. Whole blood samples were collected in EDTA tubes, processed and the plasma retained. RNA was extracted from the stored plasma samples using the QIAGEN miRNeasy Mini Kit® and concentrated using a salt-ethanol precipitation. The extracted miRNA was profiled using an nCounter® miRNA human v3 expression assay and data analysed using the nSolver™ Analysis Software. Results After excluding one sample/control pair because of cellular RNA contamination, the remaining five patient and five matched control samples were analysed, and 145 miRNAs were found to be potentially differentially expressed. On applying a Bonferroni correction, the only miRNA that was significantly different was miRNA let-7a-5p, which was significantly overexpressed (141-fold change; p<0.0003) in patients compared with controls. Conclusion This is the first miRNA report of differentially expressed miRNAs in the serum of patients with sarcoidosis and matched healthy controls in South Africa. The results obtained suggest that miRNAs may play a role in sarcoidosis pathogenesis. Whether these molecules have diagnostic or prognostic implications, needs future studies recruiting larger patient cohorts.
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PURPOSE: Treatment decision making for patients with breast cancer increasingly depends on analysis of markers or systems for estimating risk of breast cancer recurrence. Breast cancer intrinsic subtypes and risk of recurrence (ROR) scores have been found to be valuable in predicting survival and determining optimal treatment for individual patients. We studied the association of breast cancer survival with the PAM50 gene expression assay in HIV-positive and HIV-negative patients. METHOD: RNA was extracted from formalin-fixed paraffin-embedded specimens of histologically confirmed invasive carcinoma and was purified using the AllPrep® DNA/RNA FFPE kit, Qiagen (Hilden, Germany). The NanoString RUO PAM50 algorithm was used to determine the molecular subtype and the risk of recurrence score of each sample. The overall and disease-free survival were determined with comparison made among HIV-positive and -negative patients. We then generated Kaplan-Meier survival curves, calculated p-values and estimated hazard ratios and their 95% confidence intervals using Cox regression models. RESULTS: Of the 384 RNA samples analysed, 98.4% met the required RNA quality standard and the specified QC threshold for the test. Luminal B was the most common PAM50 intrinsic subtype and 82.1% of patients were at high risk for disease recurrence based on ROR score. HIV infection, PAM50-based HER2-enriched and basal-like intrinsic subtypes, and high ROR were associated with poor overall and disease-free survival. HIV-positive patients with luminal A & B subtypes had significantly worse survival outcomes than HIV-negative luminal patents. CONCLUSION: Aggressive tumour biology was common in our cohort. HIV infection, PAM50 HER2-enriched,basal-like intrinsic subtypes and high ROR score were associated with poor overall and disease-free survival. HIV infection impacted survival in patients with luminal subtypes only.
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Neoplasias de la Mama , Infecciones por VIH , Humanos , Femenino , Neoplasias de la Mama/patología , Pronóstico , Estudios de Cohortes , Infecciones por VIH/complicaciones , Sudáfrica/epidemiología , Recurrencia Local de Neoplasia/genética , ARN , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismo , Biomarcadores de TumorRESUMEN
PURPOSE: Breast cancer is a heterogeneous disease with different gene expression profiles, treatment options and outcomes. In South Africa, tumors are classified using immunohistochemistry. In high-income countries multiparameter genomic assays are being utilized with implications for tumor classification and treatment. METHODS: In a cohort of 378 breast cancer patients from the SABCHO study, we investigated the concordance between tumor samples classified by IHC and the PAM50 gene assay. RESULTS: IHC classified patients as ER-positive (77.5%), PR-positive (70.6%), and HER2-positive (32.3%). These results, together with Ki67, were used as surrogates for intrinsic subtyping, and showed 6.9% IHC-A-clinical, 72.7% IHC-B-clinical, 5.3% IHC-HER2-clinical and 15.1% triple negative cancer (TNC). Typing using the PAM50 gave 19.3% luminal-A, 32.5% luminal-B, 23.5% HER2-enriched and 24.6% basal-like. The basal-like and TNC had the highest concordance, while the luminal-A and IHC-A group had the lowest concordance. By altering the cutoff for Ki67, and realigning the HER2/ER/PR-positive patients to IHC-HER2, we improved concordance with the intrinsic subtypes. CONCLUSION: We suggest that the Ki67 be changed to a cutoff of 20-25% in our population to better reflect the luminal subtype classifications. This change would inform treatment options for breast cancer patients in settings where genomic assays are unaffordable.
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Neoplasias de la Mama , Humanos , Femenino , Neoplasias de la Mama/patología , Sudáfrica/epidemiología , Antígeno Ki-67/genética , Inmunohistoquímica , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismo , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Receptores de Progesterona/genética , Receptores de Progesterona/metabolismoRESUMEN
INTRODUCTION: Racial disparities are known in the occurrence of kidney disease with excess risks found among people of African descent. Apolipoprotein L1 (APOL1) gene variants G1 and G2 are associated with kidney disease among HIV infected individuals of African descent in the USA as well as among black population in South Africa. We set out to investigate the prevalence of these high-risk variants and their effects on kidney disease among HIV infected patients in Northern Nigeria with hitherto limited information despite earlier reports of high population frequencies of these alleles from the Southern part of the country. METHODS: DNA samples obtained from the whole blood of 142 participants were genotyped for APOL1 G1 and G2 variants after initial baseline investigations including assessment of kidney function. Participants comprised 50 HIV positive patients with no evidence of kidney disease, 52 HIV negative individuals with no kidney disease and 40 HIV positive patients with chronic kidney disease (CKD) evidenced by persistent proteinuria and/or reduced eGFR, who also had a kidney biopsy. All the HIV positive patients were newly diagnosed and treatment naïve. RESULTS: The distribution of the APOL1 genotypes among the study participants revealed that 24.6% had a G1 risk allele and 19.0% a G2. The frequency of the High Risk Genotype (HRG) was 12.5% among those with CKD compared to 5.8% in the HIV negative group and zero in the HIV positive no CKD group. Having the HRG was associated with a higher odds for developing HIV Associated Nephropathy (HIVAN) (2 vs 0 risk alleles: OR 10.83, 95% CI 1.38-84.52; P = 0.023; 2 vs 0 or 1 risk alleles: OR 5.5, 95% CI 0.83-36.29; P = 0.07). The HRG was also associated with higher odds for Focal Segmental Glomerulosclerosis (FSGS) (2 vs 0 risk alleles: OR 13.0, 95% CI 2.06-81.91; P = 0.006 and 2 vs 0 or 1 risk alleles: OR 9.0, 95%CI 1.62-50.12; P = 0.01) when compared to the control group. CONCLUSION: This study showed a high population frequency of the individual risk alleles of the APOL1 gene with higher frequencies noted among HIV positive patients with kidney disease. There is high association with the presence of kidney disease and especially FSGS and HIVAN among treatment naive HIV patients carrying two copies of the HRG.
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Nefropatía Asociada a SIDA , Glomeruloesclerosis Focal y Segmentaria , Infecciones por VIH , Insuficiencia Renal Crónica , Nefropatía Asociada a SIDA/diagnóstico , Nefropatía Asociada a SIDA/epidemiología , Nefropatía Asociada a SIDA/genética , Apolipoproteína L1/genética , Apolipoproteínas/genética , Predisposición Genética a la Enfermedad , Genotipo , Glomeruloesclerosis Focal y Segmentaria/genética , Infecciones por VIH/complicaciones , Infecciones por VIH/epidemiología , Infecciones por VIH/genética , Humanos , Lipoproteínas HDL/genética , Nigeria/epidemiología , Insuficiencia Renal Crónica/genética , Factores de RiesgoRESUMEN
BACKGROUND: The prevalence of chronic kidney disease (CKD) is increasing worldwide; black patients have an increased risk of developing CKD and end stage kidney disease (ESKD) at significantly higher rates than other races. METHODS: A cross sectional study was carried out on black patients with CKD attending the kidney outpatient clinic at Charlotte Maxeke Johannesburg Academic Hospital (CMJAH) in South Africa, between September 2019 to March 2020. Demographic and clinical data were extracted from the ongoing kidney outpatient clinic records and interviews, and were filled in a questionnaire. Patients provided blood and urine for laboratory investigations as standard of care, and data were descriptively and inferentially entered into REDcap and analysed using STATA version 17. Multivariable logistic regression analysis was used to identify demographic and clinical variables associated with advanced CKD. RESULTS: A total of 312 black patients with CKD were enrolled in the study with a median age of 58 (IQR 46-67) years; 58% patients had advanced CKD, 31.5% of whom had grossly increased proteinuria, 96.7% had hypertension, 38.7% had diabetes mellitus and 38.1% had both hypertension and diabetes mellitus. In patients with advanced CKD, the median age was 61 (IQR 51-69) years, eGFR 33 (30-39) mL/min/1.73 m2, serum bicarbonate 22 (IQR 20-24), haemoglobin 12.9 (IQR 11.5-14.0) g/dl and serum uric acid 0.43 (IQR 0.37-0.53). The prevalence of metabolic acidosis was 62.4%, anemia 46.4% and gout 30.9% among those with advanced CKD, while the prevalence of metabolic acidosis and anaemia was 46.6% and 25.9% respectively in those with early CKD. Variables with higher odds for advanced CKD after multivariable logistic regression analysis were hypertension (OR 3.3, 95% CI 1.2-9.2, P = 0.020), diabetes mellitus (OR 1.8, 95% CI 1.1-3.3, P = 0.024), severe proteinuria (OR 3.5, 95% CI 1.9-6.5, P = 0.001), angina (OR 2.5, 95% CI 1.2-5.1, P = 0.008), anaemia (OR 2.9, 95% CI 1.7-4.9, P = 0.001), hyperuricemia (OR 2.4, 95% CI 1.4-4.1, P = 0.001), and metabolic acidosis (OR 2.0, 95% CI 1.2-3.1, P = 0.005). Other associations with advanced CKD were loss of spouse (widow/widower) (OR 3.2, 95% CI 1.4-7.4, P = 0.006), low transferrin (OR 2.4, 95% CI 1.1-5.1, P = 0.028), hyperkalemia (OR 5.4, 95% CI 1.2-24.1, P = 0.029), use of allopurinol (OR 2.4, 95% CI 1.4-4.3, P = 0.005) and doxazosin (OR 1.9, 95% CI 1.2-3.1, P = 0.006). CONCLUSION: Hypertension and diabetes mellitus were strongly associated with advanced CKD, suggesting a need for primary and secondary population-based prevention measures. Metabolic acidosis, anemia with low transferrin levels, hyperuricemia and hyperkalemia were highly prevalent in our patients, including those with early CKD, and they were strongly associated with advanced CKD, requiring clinicians and dietitians to be proactive in supporting the needs of CKD patients in meeting their daily dietary requirements towards preventing and slowing the progression of CKD.
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Acidosis , Anemia , Diabetes Mellitus , Hiperpotasemia , Hipertensión , Hiperuricemia , Insuficiencia Renal Crónica , Acidosis/complicaciones , Anciano , Alopurinol , Anemia/complicaciones , Anemia/epidemiología , Bicarbonatos , Estudios Transversales , Diabetes Mellitus/epidemiología , Doxazosina , Hemoglobinas , Humanos , Hiperpotasemia/complicaciones , Hipertensión/complicaciones , Hipertensión/epidemiología , Hiperuricemia/complicaciones , Persona de Mediana Edad , Prevalencia , Proteinuria/complicaciones , Proteinuria/epidemiología , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/epidemiología , Sudáfrica/epidemiología , Centros de Atención Terciaria , Transferrinas , Ácido ÚricoRESUMEN
BACKGROUND: Early age at menarche and tall stature are associated with increased breast cancer risk. We examined whether these associations were also positively associated with mammographic density, a strong marker of breast cancer risk. METHODS: Participants were 10,681 breast-cancer-free women from 22 countries in the International Consortium of Mammographic Density, each with centrally assessed mammographic density and a common set of epidemiologic data. Study periods for the 27 studies ranged from 1987 to 2014. Multi-level linear regression models estimated changes in square-root per cent density (âPD) and dense area (âDA) associated with age at menarche and adult height in pooled analyses and population-specific meta-analyses. Models were adjusted for age at mammogram, body mass index, menopausal status, hormone therapy use, mammography view and type, mammographic density assessor, parity and height/age at menarche. RESULTS: In pooled analyses, later age at menarche was associated with higher per cent density (ßâPD = 0.023 SE = 0.008, P = 0.003) and larger dense area (ßâDA = 0.032 SE = 0.010, P = 0.002). Taller women had larger dense area (ßâDA = 0.069 SE = 0.028, P = 0.012) and higher per cent density (ßâPD = 0.044, SE = 0.023, P = 0.054), although the observed effect on per cent density depended upon the adjustment used for body size. Similar overall effect estimates were observed in meta-analyses across population groups. CONCLUSIONS: In one of the largest international studies to date, later age at menarche was positively associated with mammographic density. This is in contrast to its association with breast cancer risk, providing little evidence of mediation. Increased height was also positively associated with mammographic density, particularly dense area. These results suggest a complex relationship between growth and development, mammographic density and breast cancer risk. Future studies should evaluate the potential mediation of the breast cancer effects of taller stature through absolute breast density.
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Densidad de la Mama , Neoplasias de la Mama , Adulto , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/etiología , Estudios Transversales , Femenino , Humanos , Mamografía/métodos , Menarquia , Grupos de Población , Embarazo , Factores de RiesgoRESUMEN
BACKGROUND: There is a wide spectrum of kidney pathology in human immunodeficiency virus (HIV) infection, affecting all structures of the kidney. The histology of HIV chronic kidney disease (CKD) is diverse, ranging from HIV-associated nephropathy (HIVAN) to focal glomerulosclerosis (FSGS), HIV-immune complex disease (HIV-ICD), other glomerulopathies and tubulo-interstitial nephritis. Definitive diagnosis is by kidney biopsy, an invasive procedure. However, serum and urinary biomarkers may be useful in predicting the histological diagnosis of HIVAN. PURPOSE: We wished to determine the utility of serum and urinary biomarkers in predicting the histological diagnosis of HIVAN. PATIENTS AND METHODS: We measured neutrophil gelatinase-associated lipocalin (NGAL), cystatin C, transforming growth factor (TGF)-ß isoforms and bone morphogenetic protein (BMP)-7 in the serum and urine in patients with different histological forms of HIV glomerular disease. RESULTS: In HIVAN, we demonstrated increased levels of serum cystatin C and increased levels of serum and urinary NGAL. Urinary TGF-ß1 and TGF-ß2 levels were elevated in HIV-positive patients with CKD but were not significantly different in the different HIV histologies, while urinary BMP-7 levels were elevated in minimal change disease. CONCLUSION: This study confirmed the presence of increased serum and urinary biomarkers of tubular injury in patients with HIVAN, and increased urinary biomarkers of fibrosis in HIV CKD, and may indicate their value as a non-invasive diagnostic tool for the diagnosis of HIVAN.
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PURPOSE: Breast cancer outcomes in sub-Saharan Africa is reported to be poor, with an estimated five-year survival of 50% when compared to almost 90% in high-income countries. Although several studies have looked at the effect of HIV in breast cancer survival, the effect of ARTs has not been well elucidated. METHODS: All females newly diagnosed with invasive breast cancer from May 2015-September 2017 at Charlotte Maxeke Johannesburg Academic and Chris Hani Baragwanath Academic Hospital were enrolled. We analysed overall survival and disease-free survival, comparing HIV positive and negative patients. Kaplan-Meier survival curves were generated with p-values calculated using a log-rank test of equality while hazard ratios and their 95% confidence intervals (CIs) were estimated using Cox regression models. RESULTS: Of 1019 patients enrolled, 22% were HIV positive. The overall survival (95% CI) was 53.5% (50.1-56.7%) with a disease-free survival of 55.8% (52.1-59.3) after 4 years of follow up. HIV infection was associated with worse overall survival (HR (95% CI): 1.50 (1.22-1.85), p < 0.001) and disease-free survival (OR (95% CI):2.63 (1.71-4.03), p < 0.001), especially among those not on ART at the time of breast cancer diagnosis. Advanced stage of the disease and hormone-receptor negative breast cancer subtypes were also associated with poor survival. CONCLUSION: HIV infection was associated with worse overall and disease-free survival. HIV patients on ARTs had favourable overall and disease-free survival and with ARTs now being made accessible to all the outcome of women with HIV and breast cancer is expected to improve.
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Neoplasias de la Mama , Infecciones por VIH , Neoplasias de la Mama/tratamiento farmacológico , Supervivencia sin Enfermedad , Femenino , Infecciones por VIH/tratamiento farmacológico , Humanos , Modelos de Riesgos Proporcionales , Sudáfrica/epidemiologíaRESUMEN
BACKGROUND: Molecular analysis has shown that breast carcinomas can be classified into several intrinsic subtypes, with implications for management and prognosis. In the majority of pathology laboratories molecular analysis of each case is not possible and immunohistochemistry is used for subtyping. This includes analysis of hormone receptors as well as HER2-neu and Ki67. The methodology for the interpretation of the proliferation index using Ki67 remains an area of uncertainty. We investigated the degree of agreement between different methods of Ki67 interpretation. MATERIALS AND METHODS: We analyzed 204 breast core biopsies diagnostic of breast carcinoma using visual estimation/eyeballing (EB), ImmunoRatio, and counting by 2 pathologists (CP1 and CP2). The correlation between the different methods and the interobserver agreement between the 2 pathologists was assessed. Specific analysis was also done with respect to classification of cases into low Ki67 groups (using Ki67 values<14% and <20%) since this is critical in classifying tumors into luminal A and luminal B subtypes. RESULTS: Correlation between the different methods was best achieved comparing ImmunoRatio and CP1, and worst comparing CP1 and EB. Correlation was better when considering interobserver variability (CP1 vs. CP2). Comparing the number of cases classified as low Ki67 (<14% and <20%) the Cohen κ statistic varied from κ=0.267 to 0.814 with different methods. When limiting the analysis to cases with a Ki67 of 10% to 25% according to any method, there was greater disagreement. CONCLUSIONS: At the higher and lower Ki67 levels, the correlation between the methods of assessment was acceptable, however, at levels close to the cut-off values for lumial A versus luminal B, several patients would be differently classified by the different methods and therefore potentially receive suboptimal management.
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Neoplasias de la Mama , Inmunohistoquímica , Antígeno Ki-67/metabolismo , Índice Mitótico , Receptor ErbB-2/metabolismo , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Femenino , HumanosRESUMEN
BACKGROUND: Individuals of African descent are at higher risk of developing kidney disease than their European counterparts, and HIV infection is associated with increased risk of nephropathy. Despite a safe renal profile in the clinical trials, long-term use of tenofovir disoproxil fumarate (TDF) has been associated with proximal renal tubulopathy although the underlying mechanisms remain undetermined. We aim to establish the prevalence of and risk factors for TDF-induced kidney tubular dysfunction (KTD) among HIV-I and II individuals treated with TDF in south-west Nigeria. Association between TDF-induced KTD and genetic polymorphisms in renal drug transporter genes and the APOL1 (Apolipoprotein L1) gene will be examined. METHODS: This study has two phases. An initial cross-sectional study will screen 3000 individuals attending the HIV clinics in south-west Nigeria for KTD to determine the prevalence and risk factors. This will be followed by a case-control study of 400 KTD cases and 400 matched controls to evaluate single nucleotide polymorphism (SNP) associations. Data on socio-demographics, risk factors for kidney dysfunction and HIV history will be collected by questionnaire. Blood and urine samples for measurements of severity of HIV disease (CD4 count, viral load) and renal function (creatinine, eGFR, phosphate, uric acid, glucose) will also be collected. Utility of urinary retinol binding protein (RBP) and N-acetyl-beta-D-glucosaminidase (NAG) levels as surrogate markers of KTD will be evaluated. Genomic DNA will be extracted from whole blood and SNP analyses performed using the rhAMP SNP genotyping assays. Statistical analysis including univariate and multivariate logistic regression analyses will be performed to identify factors associated with KTD. DISCUSSION: In spite of TDF being the most commonly used antiretroviral agent and a key component of many HIV treatment regimens, it has potential detrimental effects on the kidneys. This study will establish the burden and risk factors for TDF-induced KTD in Nigerians, and explore associations between KTD and polymorphisms in renal transporter genes as well as APOL1 risk variants. This study may potentially engender an approach for prevention as well as stemming the burden of CKD in sub-Saharan Africa where GDP per capita is low and budgetary allocation for health is inadequate.
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Fármacos Anti-VIH/efectos adversos , Seropositividad para VIH/complicaciones , Enfermedades Renales/inducido químicamente , Túbulos Renales/efectos de los fármacos , Polimorfismo de Nucleótido Simple , Tenofovir/efectos adversos , Adulto , Fármacos Anti-VIH/uso terapéutico , Población Negra/genética , Estudios de Casos y Controles , Estudios Transversales , Femenino , Seropositividad para VIH/tratamiento farmacológico , VIH-1 , VIH-2 , Humanos , Enfermedades Renales/epidemiología , Enfermedades Renales/genética , Túbulos Renales/patología , Túbulos Renales/fisiología , Masculino , Nigeria/epidemiología , Pruebas de Farmacogenómica , Prevalencia , Proyectos de Investigación , Factores de Riesgo , Factores Socioeconómicos , Tenofovir/uso terapéutico , Carga ViralRESUMEN
BACKGROUND: Anaemia is a common presenting feature among patients with chronic kidney disease (CKD) and it is associated with poor clinical outcomes and quality of life. It is not clear if growth differentiation factor-15 (GDF-15) or hepcidin are useful as early markers of iron deficiency anaemia (IDA) among non-dialysis CKD patients. We therefore evaluated the diagnostic validity of GDF-15 and hepcidin as biomarkers of IDA among non-dialysis CKD patients in Johannesburg, South Africa. METHOD: An analytic cross-sectional study was conducted among non-dialysis CKD patients (n = 312) and apparently healthy controls (n = 184) from June to December 2016 at an Academic Hospital, in Johannesburg, South Africa. An interviewer administered proforma was used to obtain the socio-biological and clinical characteristics of the participants. Serum levels of GDF-15 and hepcidin were determined. Predictive logistic regression models were built and post estimation receiver operator characteristics were determined to evaluate diagnostic validity of hepcidin and GDF-15 for absolute and functional iron deficiency anaemia. RESULTS: About half (50.6%) of the participants were female while the participants' mean age was 49.7 ± 15.8 years. The predictive value of diagnosing absolute IDA among CKD patients using GDF-15 was 74.02% (95% CI: 67.62-80.42%) while the predictive value of diagnosing functional IDA among CKD patients using hepcidin was 70.1% (95% CI: 62.79-77.49%).There was a weak negative correlation between hepcidin levels and GFR (r = - 0.19, p = 0.04) in anaemic CKD patients, and between serum GDF-15 and haemoglobin (r = - 0.34, p = 0.001). Serum ferritin (ß = 0.00389, P-value< 0.001), was a predictor of log hepcidin. MCHC (ß = - 0.0220, P-value 0.005) and CKD stage (ß = 0.4761, P-value < 0.001), race (ß = 0.3429, P-value = 0.018) were predictors of log GDF-15. Both GDF-15 (adj OR: 1.0003, 95%CI: 1.0001-1.0005, P = 0.017) and hepcidin (adj OR: 1.003, 95%CI: 1.0004-1.0055, P = 0.023) were associated with iron deficiency anaemia after multiple linear regression modelling. CONCLUSION: Serum GDF-15 is a potential biomarker of absolute IDA, while hepcidin levels can predict functional IDA among CKD patients.
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Anemia Ferropénica/diagnóstico , Factor 15 de Diferenciación de Crecimiento/sangre , Hepcidinas/sangre , Insuficiencia Renal Crónica/sangre , Adulto , Anemia Ferropénica/sangre , Anemia Ferropénica/etiología , Biomarcadores/sangre , Estudios Transversales , Femenino , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Curva ROC , Insuficiencia Renal Crónica/complicaciones , SudáfricaRESUMEN
BACKGROUND: Overeating and obesity are elevated in children of parents who have undergone weight loss surgery. Parents who have undergone weight loss surgery often report their personal history of obesity interferes with their knowledge, skills, and self-efficacy in developing their children's healthy habits, thus reducing the likelihood of addressing obesogenic environmental factors. OBJECTIVES: This study examines whether a 6-session parent-based prevention after bariatric surgery online intervention is feasible and acceptable for parents. The study also explores the program's signal of efficacy in improving short-term outcomes related to decreased long-term risks for obesity by examining short-term impact on targeted parental cognitions, feeding practices, and child eating behaviors and physical activity habits. SETTING: University Hospital, United States. METHODS: Parents were recruited using flyers, clinician referrals, and social media. Measures assessed parental feeding practices, children's eating behaviors, daily hours of screen time, and outdoor play. RESULTS: Ten families enrolled and 7 completed the study. Parents found the intervention relevant and suitable for addressing their parenting concerns. Parental feeding behaviors, such as restriction and pressure to eat, reduced while tracking of sweets and high-fat snacks increased. Children reduced both emotional overeating and undereating. Children's daily hours of screen time reduced as well as their outdoor play time. CONCLUSIONS: Parent-based prevention after bariatric surgery aimed at helping parents who have undergone weight loss surgery engineer healthier family lifestyles is feasible, acceptable, and associated with reduced obesogenic risk factors.
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Cirugía Bariátrica , Conducta Alimentaria , Niño , Humanos , Obesidad , Responsabilidad Parental , Padres , Encuestas y CuestionariosRESUMEN
INTRODUCTION: Inflammation plays a major role in the development of atherosclerosis and cardiovascular morbidity and mortality in chronic kidney disease (CKD) patients. Toll-like receptor-4 (TLR4) is a major receptor for lipopolysaccharides (endotoxin) and other ligands involved in the pathogenesis of inflammation. We determined whether endotoxin levels and the presence of TLR4 polymorphisms are associated with markers of inflammation and atherosclerosis among South African CKD patients. MATERIALS AND METHODS: Endotoxin, lipopolysaccharide binding protein (LBP), serum CD14 (sCD14), interleukin-8 (IL-8), monocyte chemoattractant protein-1 (MCP-1) and carotid intima media thickness (CIMT) were measured in 160 participants (120 CKD patients and 40 controls). Associations between endotoxins and CIMT in the presence of sCD14, IL-8 and MCP-1, were assessed using odds ratios. Participants were screened for the presence of Asp299Gly and Thr399Ile TLR4 polymorphisms, and CIMT and inflammatory markers were compared between subjects with and without TLR4 polymorphisms. RESULTS: Endotoxin levels correlated with sCD14 (r = 0.441, p<0.001) and MCP-1 (r = 0.388, p<0.001) levels while increased CIMT was associated with MCP-1 (r = 0.448, p<0.001), sCD14 levels (r = 0.476, p<0.001), LBP (r = 0.340, p<0.001), and IL-8 (r = 0.395, p<0.001). Atherosclerosis was associated with endotoxin levels (odds ratio: 4.95; 95% confidence interval: 2.52-9.73; p<0.001), and was predicted by higher serum levels of inflammatory markers. Analysis of patients with TLR4 polymorphisms showed reduced serum levels of inflammatory markers and CIMT values compared with the patients carrying the wild type TLR4 alleles. CONCLUSION: The study demonstrated associations between circulating endotoxaemia, systemic inflammation and accelerated atherosclerosis among South African CKD patients, and showed that the atherogenic predictive power of endotoxaemia was significantly increased by the presence of elevated levels of inflammatory markers. Additional findings, which must be confirmed, suggest that TLR4 polymorphisms are associated with low levels of inflammatory markers and CIMT values.
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Aterosclerosis/complicaciones , Población Negra/estadística & datos numéricos , Grupos de Población/estadística & datos numéricos , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/epidemiología , Adulto , Grosor Intima-Media Carotídeo , Estudios de Cohortes , Susceptibilidad a Enfermedades , Femenino , Genotipo , Humanos , Inflamación/complicaciones , Masculino , Polimorfismo Genético , Insuficiencia Renal Crónica/genética , Insuficiencia Renal Crónica/metabolismo , Riesgo , Receptor Toll-Like 4/genéticaRESUMEN
INTRODUCTION: Apolipoprotein L1 (APOL1) plays an important role in cholesterol metabolism and attenuation of low-density lipoprotein (LDL) oxidation. While protecting against Trypanosoma brucei rhodesiense infection, APOL1 risk alleles confer greater risk for CKD and cardiovascular disease among patients of African descent. OBJECTIVES: We investigated whether APOL1 risk variants are associated with atherosclerosis and oxidized LDL (OxLDL) levels among black South African CKD patients. METHODS: A cross-sectional study of 120 adult CKD patients and 40 controls was undertaken. DNA samples of participants were genotyped for APOL1 G1 and G2 variants. High-sensitivity C-reactive protein, serum lipids, and OxLDL levels were measured, and carotid doppler ultrasonography was performed on all participants. RESULTS: APOL1 alleles rs73885319, rs60910145, and rs71785313 had minor allele frequencies of 9.2, 8.8, and 17.5%, respectively, in the patients, and 8.8, 8.8, and 13.8%, respectively, in the controls. Of the 9 patients with 2 APOL1 risk alleles, 77.8% were compound G1/G2 heterozygotes and 22.2% were G2 homozygotes. Carriers of at least 1 APOL1 risk allele had a 3-fold increased risk of subclinical atherosclerosis (odds ratio 3.19; 95% confidence interval: 1.64-6.19; p = 0.01) compared to individuals with no risk alleles. Patients with 1 or 2 APOL1 risk alleles showed a significant increase in OxLDL levels when compared with those without the APOL1 risk allele. CONCLUSION: These findings suggest an increased risk for atherosclerosis in carriers of a single APOL1 risk variant, and the presence of APOL1 risk variants was associated with increased serum OxLDL levels in black South African CKD patients.
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Apolipoproteína L1/genética , Aterosclerosis/sangre , Aterosclerosis/genética , Lipoproteínas LDL/sangre , Insuficiencia Renal Crónica/sangre , Insuficiencia Renal Crónica/genética , Adulto , Aterosclerosis/epidemiología , Población Negra , Proteína C-Reactiva , Grosor Intima-Media Carotídeo , Estudios Transversales , ADN/genética , Femenino , Frecuencia de los Genes , Genotipo , Humanos , Pruebas de Función Renal , Masculino , Persona de Mediana Edad , Insuficiencia Renal Crónica/epidemiología , Sudáfrica/epidemiologíaRESUMEN
BACKGROUND: Serum creatinine is suboptimal as a biomarker in the early diagnosis of contrast-induced nephropathy (CIN). In this study, we investigated a panel of novel biomarkers in the early diagnosis of CIN and in assessing patient outcomes. METHODS: This single-centre, nested, prospective case-controlled study included 30 patients with CIN and 60 matched controls. Serum and urine samples were collected before contrast administration and at 24 hours, 48 hours, and ≥5 days after contrast administration. Concentrations of NGAL, cystatin C, ß 2M, IL18, IL10, KIM1, and TNFα were determined using Luminex and ELISA assays. Outcomes were biomarker diagnostic discrimination performance for CIN and mortality after generation of area under receiver operating characteristic curves (AUROCs). RESULTS: Median serum levels for 24 h cystatin C (p < 0.01) and 48 h ß 2M levels (p < 0.001) and baseline urine NGAL (p=0.02) were higher in CIN patients compared to controls with AUROCs of 0.75, 0.78, and 0.74, respectively, for the early diagnosis of CIN. Serum ß 2M levels were higher in CIN patients at all time points. Elevated baseline serum concentrations of IL18 (p < 0.001), ß 2M (p=0.04), TNFα (p < 0.001), and baseline urine KIM (p=0.01) and 24 h urine NGAL (p=0.02) were significantly associated with mortality. Baseline serum concentrations of IL18, ß 2M, and TNFα showed the best discrimination performance for mortality with AUROCs, all >0.80. Baseline NGAL was superior for excluding patients at risk for CIN, with positive and negative predictive ranges of 0.50-0.55 and 0.81-0.88, respectively. Cystatin C (p=0.003) and ß 2M (p=0.03) at 24 h independently predicted CIN risk. ß 2M predicted increased mortality of 40% at baseline and 50% at 24 hours. CONCLUSION: Serum cystatin C at 24 h was the best biomarker for CIN diagnosis, while baseline levels of serum IL18, ß 2M, and TNFα were best for predicting prognosis.
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The offspring of parents with obesity are at an increased risk of developing this condition themselves because of genetic and environmental factors. One subgroup that may be at particularly high risk of developing obesity is the offspring of parents who have undergone weight loss surgery (PWLS). To date, little research has focused on these offspring or their parents. This systematic review addresses this gap by integrating available literature and assessing the quality of the evidence. To be included, studies were required to have researched characteristics of the offspring of PWLS or parental feeding practices within this population. After review, 12 studies met inclusion criteria. Findings include evidence for heightened risk of obesity among children of PWLS. However, research suggests these children may experience positive, although time-limited, health outcomes after their parents' surgeries. Quality of the evidence was rated as low, primarily because of the lack of randomized controlled studies and information regarding available interventions specifically targeting this vulnerable population. This review underscores the need for research to improve understanding of PWLS families to better support them and capitalize on postbariatric surgery benefits.
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Cirugía Bariátrica , Padres , Niño , Conducta Alimentaria , Humanos , ObesidadRESUMEN
INTRODUCTION: South Africa urgently needs more doctors. We examined perceptions of patients and students to provide evidence for optimum student-patient ratios and substantiate solutions for this dilemma. METHODS: We interviewed 118 patients and invited 120 students to complete a self-administered questionnaire from four specialities in an academic hospital in Johannesburg. RESULTS: The total sample size was 238 participants. A total of 91/118 (77%) patients and 78/120 (65%) students were female. Almost all the patients had some level of education, with most patients having received at least a secondary education (71/120). More than half of the students (69/120) were final year students. A third (41/118) of the patients were unaware they were admitted to a teaching hospital. Half of the patients (60/118) thought they had the right to refuse interaction with students. Patients and students preferred smaller groups of between 1-3 and 4-8 students at a bedside tutorial (p < 0.001), although patients preferred smaller groups (1-3) compared with the students (4-8). Majority of patients said they never refused consent to students, while a third of students reported at least up to three patients refusing consent to be examined. The most frequent reason cited by students for refusal of consent by patients was the exposure to excessive numbers of students and healthcare professionals. CONCLUSION: Medical schools should consider patient safeguards while responding to the country's need for more doctors. The Medical Council and medical schools need to draw up professional guidelines on patient-student interactions, including the role of patients in this setting.