Biochemical and genetic markers of mineral bone disease in South African patients with chronic kidney disease

A thesis submitted to the Faculty of Health Sciences, University of the Witwatersrand in fulfilment of the requirements for the degree of Doctor of Philosophy. Johannesburg, 2017.Background Abnormalities of mineral bone disease have been consistently associated with adverse clinical outcomes in patients with chronic kidney disease (CKD). The consequences of these changes have also been shown to differ across races. However, in Africa the impact of derangements of CKD -mineral and bone disorder (CKD-MBD) on patients with CKD is largely unknown. In addition, studies from the USA have reported racial variations in markers of CKD and it remains unclear whether genetic factors may explain this discrepancy in the levels of biochemical markers of CKD-MBD across ethnic groups. Therefore, this study has been conducted to determine the existence of racial differences in the levels of fibroblast growth factor 23(FGF23) and traditional markers of mineral bone metabolism in a heterogeneous African CKD population, and to provide important insights into the pattern and genetic variability of CKD-MBD in sub-Saharan Africa. Methods This was a cross sectional multicenter study carried out from April 2015 to May 2016, involving two hundred and ninety three CKD patients from three renal units in Johannesburg, South Africa. The retrospective arm of this study involved two hundred and thirteen patients undergoing maintenance haemodialysis (MHD) from two dialysis centers in Johannesburg between January 2009 and March 2016. The first part of this study described the pattern of CKD-MBD in MHD patients using traditional markers of CKD-MBD. The second part of the study looked into the spectrum of CKD-MBD and racial variations in markers of CKD-MBD in pre dialysis and dialysis patients. This was followed by the genetic aspect of the study that examined the influence of vitamin D receptor polymorphisms on biochemical markers of mineral bone disorders. Lastly, the study also evaluated the association between markers of CKD-MBD and mortality in MHD patients. Results The prevalence of hyperparathyroidism (iPTH>150 pg/mL), hyperphosphataemia, hypocalcaemia and 25-hydroxyvitamin D deficiency (150 pg/mL and total alkaline phosphatase > 112 U/L) suggestive of high turnover bone disease, was present in 47.3 % of the study population. The odds ratios for developing secondary hyperparathyroidism with hypocalcaemia and hyperphosphataemia were 5.32 (95% CI 1.10 - 25.9, P =0.03) and 3.06 (95 % CI 1.15 - 8.10, P =0.02) respectively. The 293 CKD patients (208 blacks, 85 whites) had an overall mean age of 51.1±13.6 years, and black patients were significantly younger than the white patients (48.4 ±.13.6 versus 57.1±15.5 years; p<0.001). In comparison to whites, blacks had higher median iPTH (498 [37-1084] versus 274[131-595] pg/ml; P=0.03), alkaline phosphatase (122[89-192] versus 103[74-144] U/L; P=0.03) and mean 25- hydroxyvitamin D (26.8±12.7 versus 22.7 ±12.2 ng/ml, P=0.01) levels, while their median FGF23 (100 [34-639] versus 233[80-1370] pg/ml; P=0.002) and mean serum phosphate (1.3±0.5 versus 1.5±0.5, P =0.001) levels were significantly lower. With the exception of vitamin D receptor (VDR) Taq I polymorphism, the distribution of the VDR polymorphisms differs significantly between blacks and whites. In hemodialysis patients, the BsmI Bb genotype was significantly associated with moderate secondary hyperparathyroidism (OR, 3.88; 95 CI 1.13-13.25, P=0.03) and severe hyperparathyroidism (OR, 2.54; 95 CI 1.08-5.96, P=0.03). Patients with high total alkaline phosphatase (TAP) had significantly higher risk of death compared to patients with TAP 2.75 mmol/L was associated with increased risk of death compared to patients within levels of 2.10–2.37 mmol/L (HR 6.34, 95% CI 1.40–28.76; P = 0.02). The HR for death in white patients compared to black patients was 6.88; 95% CI 1.82–25.88; P = 0.004. Conclusions Secondary hyperparathyroidism and 25–hydroxyvitamin D deficiency were common in our haemodialysis patients. The study also highlighted the existence of racial differences in the circulating markers of mineral bone disorders in our African CKD population. In addition, the study showed that both moderate and severe secondary hyperparathyroidism are predicted by the BsmI Bb genotype, and the over expression of this genotype in black patients may partly explain the ethnic variations in the severity of secondary hyperparathyroidism in the CKD population. High levels of serum alkaline phosphatase, hypercalcaemia, and white race are associated with increased risk of death in MHD patients.LG201

Biochemical and genetic markers of mineral bone disease in South African patients with chronic kidney disease

A thesis submitted to the Faculty of Health Sciences, University of the Witwatersrand in fulfilment of the requirements for the degree of Doctor of Philosophy. Johannesburg, 2017.Background Abnormalities of mineral bone disease have been consistently associated with adverse clinical outcomes in patients with chronic kidney disease (CKD). The consequences of these changes have also been shown to differ across races. However, in Africa the impact of derangements of CKD -mineral and bone disorder (CKD-MBD) on patients with CKD is largely unknown. In addition, studies from the USA have reported racial variations in markers of CKD and it remains unclear whether genetic factors may explain this discrepancy in the levels of biochemical markers of CKD-MBD across ethnic groups. Therefore, this study has been conducted to determine the existence of racial differences in the levels of fibroblast growth factor 23(FGF23) and traditional markers of mineral bone metabolism in a heterogeneous African CKD population, and to provide important insights into the pattern and genetic variability of CKD-MBD in sub-Saharan Africa. Methods This was a cross sectional multicenter study carried out from April 2015 to May 2016, involving two hundred and ninety three CKD patients from three renal units in Johannesburg, South Africa. The retrospective arm of this study involved two hundred and thirteen patients undergoing maintenance haemodialysis (MHD) from two dialysis centers in Johannesburg between January 2009 and March 2016. The first part of this study described the pattern of CKD-MBD in MHD patients using traditional markers of CKD-MBD. The second part of the study looked into the spectrum of CKD-MBD and racial variations in markers of CKD-MBD in pre dialysis and dialysis patients. This was followed by the genetic aspect of the study that examined the influence of vitamin D receptor polymorphisms on biochemical markers of mineral bone disorders. Lastly, the study also evaluated the association between markers of CKD-MBD and mortality in MHD patients. Results The prevalence of hyperparathyroidism (iPTH>150 pg/mL), hyperphosphataemia, hypocalcaemia and 25-hydroxyvitamin D deficiency (150 pg/mL and total alkaline phosphatase > 112 U/L) suggestive of high turnover bone disease, was present in 47.3 % of the study population. The odds ratios for developing secondary hyperparathyroidism with hypocalcaemia and hyperphosphataemia were 5.32 (95% CI 1.10 - 25.9, P =0.03) and 3.06 (95 % CI 1.15 - 8.10, P =0.02) respectively. The 293 CKD patients (208 blacks, 85 whites) had an overall mean age of 51.1±13.6 years, and black patients were significantly younger than the white patients (48.4 ±.13.6 versus 57.1±15.5 years; p<0.001). In comparison to whites, blacks had higher median iPTH (498 [37-1084] versus 274[131-595] pg/ml; P=0.03), alkaline phosphatase (122[89-192] versus 103[74-144] U/L; P=0.03) and mean 25- hydroxyvitamin D (26.8±12.7 versus 22.7 ±12.2 ng/ml, P=0.01) levels, while their median FGF23 (100 [34-639] versus 233[80-1370] pg/ml; P=0.002) and mean serum phosphate (1.3±0.5 versus 1.5±0.5, P =0.001) levels were significantly lower. With the exception of vitamin D receptor (VDR) Taq I polymorphism, the distribution of the VDR polymorphisms differs significantly between blacks and whites. In hemodialysis patients, the BsmI Bb genotype was significantly associated with moderate secondary hyperparathyroidism (OR, 3.88; 95 CI 1.13-13.25, P=0.03) and severe hyperparathyroidism (OR, 2.54; 95 CI 1.08-5.96, P=0.03). Patients with high total alkaline phosphatase (TAP) had significantly higher risk of death compared to patients with TAP 2.75 mmol/L was associated with increased risk of death compared to patients within levels of 2.10–2.37 mmol/L (HR 6.34, 95% CI 1.40–28.76; P = 0.02). The HR for death in white patients compared to black patients was 6.88; 95% CI 1.82–25.88; P = 0.004. Conclusions Secondary hyperparathyroidism and 25–hydroxyvitamin D deficiency were common in our haemodialysis patients. The study also highlighted the existence of racial differences in the circulating markers of mineral bone disorders in our African CKD population. In addition, the study showed that both moderate and severe secondary hyperparathyroidism are predicted by the BsmI Bb genotype, and the over expression of this genotype in black patients may partly explain the ethnic variations in the severity of secondary hyperparathyroidism in the CKD population. High levels of serum alkaline phosphatase, hypercalcaemia, and white race are associated with increased risk of death in MHD patients.LG201

Actualizing Nigeria’s Vision 20:2020: Imperatives of the Construction Sector

Nigeria’s vision 20:2020 is aimed at placing the country in the league of the first 20 global economies by the year 2020 with a minimum GDP of US$900 billion and per capita income of no less than US$4000 per annum. The Nigerian construction sector provides the much needed physical infrastructure for economic development which is critical toward realizing this laudable vision. The sector’s contribution to overall GDP dropped from 3.76% achieved in 2008 to 3.16% in 2009 and 2.86% in 2010. The Building and Construction sector also recorded a growth rate which slowed down from 12.8% in 2008 to 11.97% in 2009 and 11.85% in 2010. In 2011, the sector recorded a growth rate of 12.26% which is below the target of 19.0% set in the Transformation agenda. The study investigates through empirical means the impacts of the factors influencing the performance of the sector in providing the infrastructural base that contributes to national development. Bret Frischmann’s theory of infrastructure and commons management was adopted to put the work in context. Relative Importance Indices (RII) of 17 relevant factors surveyed revealed that low investment in the construction sector, low involvement of private sector in the provision of infrastructural facilities, lack of policy to promote indigenous contactors, reverse order of industrial development and monumental corruption in the sector with RII of 0.88, 0.84, 0.84, 0.80, and 0.79 respectively are the most significant factors. It is recommended that in order to achieve the vision in the year 2020 there is need for investment in infrastructure development, resuscitation of the decayed infrastructure, private financing of public projects and the need for capacity building. Keywords: Vision 20:2020, construction sector, economic development, infrastructure, Nigeria

Biochemical markers of mineral bone disorder in South African patients on maintenance haemodialysis

Background and objective: Despite the high mortality and morbidity associated with abnormalities in mineral and bone metabolism in haemodialysis patients, there is limited data on the pattern of mineral bone disorder in African CKD population. Therefore, the purpose of this study was to describe the pattern of mineral bone disease by evaluating biochemical parameters in patients on maintenance haemodialysis (MHD).Methods: We evaluated the serum/plasma intact parathyroid hormone (iPTH), corrected calcium, phosphate, total alkaline phosphatase (TALP) and 25 –OH vitamin D levels of two hundred and seven patients undergoing MHD at two dialysis centers in Johannesburg.Results: The MHD patients (133 men, 74 women) had a mean age of 54.5±15.6 years with a median dialysis vintage of 24 months (IQR, 12-48) and a mean kt/V of 1.45±0.28. The prevalence of hyperparathyroidism (iPTH &gt;150 pg/ml), hyperphosphataemia, hypocalcaemia and 25-OH vitamin D deficiency (&lt;30 ng/ml) was 73.4%, 57.0%, 20.3% and 80.7 % respectively. The combination of markers of bone turnover (iPTH &gt;150pg/ml and TALP&gt; 112 U/L) suggestive of high turnover bone disease, was present in 47.3 % of the study population. In multiple-logistic regression analysis, the odds ratio for developing hyperparathyroidism with hypocalcaemia and hyperphosphataemia were 5.32 (95% CI 1.10 - 25.9, P = 0.03) and 3.06(95 % CI 1.15 - 8.10, P=0.02) respectively. Ninety eight (47.3%) of the MHD patients had iPTH within the recommended kidney disease improving global outcome (KDIGO) guidelines.Conclusion: Secondary hyperparathyroidism and 25–OH vitamin D deficiency were common in our haemodialysis patients. Hypocalcaemia and hyperphosphataemia were strong predictors for developing secondary hyperparathyroidism.Keywords: Biochemical markers, guidelines, mineral bone disorder, haemodialysi

Preliminary Survey of Ectoparasites Infesting Chickens (Gallus domesticus) in Four Areas of Sokoto Metropolis

A faunistical study was undertaken to determine the prevalence of ectoparasites of chickens in four areas of Sokoto metropolis, Nigeria, on 160 chickens raised under free-range system. Both the skin and plucked feathers were thoroughly searched for the presence of ectoparasites between July and December 2009. The results indicate that all the chickens (100%) harboured ectoparasites. Five lice, two mites, two tick and one flea species were identified with the following prevalences: the shaft louse, Menopon gallinae (8.1%), the chicken body louse, Menacanthus stramineus (6.9%), then the wing louse, Lipeurus caponis (5.0%), the body and feather louse, Gonoides gigas (4.4%) and finally the fluff louse Gonoicotes gallinae (3.1%). The two tick species were Argas persicus (8.8%) and Ixodid larvae (5.6%). The two mite species were Cnemidocoptes mutans (9.4%) and Cnemidocoptes gallinae (8.1%). The sticktight flea Echidnophaga gallinacea was the only flea species found (10.6%). No association was found between ectoparasitism and sex, breed and fur colour (P &gt; 0.05), however a strong positive association was observed with fur texture (P &lt; 0.05). This study has shown that ectoparasites are highly prevalent on traditionally managed chickens in the study areas. Further detailed study with particular reference to ectoparasitism and assessment of their impact is recommended.Keywords: Ectoparasites, Free range, Chickens, Prevalence, Infestation, SokotoNigerian Journal of Basic and Applied Science (2011), 19 (2): 173-18

A Comparative Analysis of Nutrients and Mineral Elements Content of Andropogon gayanus Kunth and Pennisetum pedicellatum Trin

Comparative studies on the nutrients and mineral elements content of the two grass species was conducted at Gangam Rangeland, Shagari L.G.A., Sokoto state. Sokoto lies on latitude 12.000 and 13.600N and longitude 4.800 and 6.500E and altitude 350m above sea level. The result show that P. pedicellatum had high crude protein (Cp) ad crude fibre (Cf) content than A. gayanus. The high Cp content was attributed to its leafy nature (having abundant leaves) as Cp is more concentrated in leaves, whereas the high Cf content was possibly due to its stemmy nature particularly at the end of the growing period. However, in terms of Ether extract (Ee) andAsh content, A. gayanus had more. The high Ash content was probably as a result of high mineral elements content of the grass species. On the other hand, A. gayanus had high Phosphorus (P), Potassium (K), Magnesium (Mg), Iron (Fe), Copper (Cu) and Zinc (Zn) content, while P. pedicellatum has high Calcium (Ca) and Sodium (Na) content. The high mineral elements content of A. gayanus made the grass more useful for grazing and feeding of livestock. The high Ca content of P. pedicellatum may account for its high Cf content as Ca forms structural components of cell walls and membranes.Keywords: Nutrients content, Andropogon gayanus, Pennisetum pedicellatum, Shagari LGA

The Influence of Construction Project Team Effectiveness in Higher Institutions’ Building Projects: A Case from Nigeria

Projects are required to meet the stakeholders’ requirements on the stipulated time, quality and budget. The achievement of such requirements is related to team effectiveness. However, there is poor project time and cost performance in Nigeria such that the constructions initiated mostly escalate beyond the cost and time budgeted. The construction project teams in Nigeria are shrouded with dysfunctions leading to undesirable project outcomes. This study aims to examine the influence of project team effectiveness on project performance of higher educational institutions’ construction in Nigeria. A quantitative survey design was employed where 150 questionnaires were administered to construction projects team members in four higher educational institutions in Bauchi state, Nigeria. The result indicated that the team effectiveness factors of communication, role and responsibility as well as team relationships have a substantial influence on project performance. However, goal and objectives, leadership, as well as trust and values factors, do not have significant influence. Overall, the result shows that the variation in the project performance can be explained substantially by changes in the construction project team effectiveness (Adj. R2 =.585). The implication of this finding is that project performance in Nigerian higher educational institutions can be significantly improved by strengthening communications, roles and responsibilities as well as relationships among team members. Thus, this research contributed to the existing body of knowledge on the linkage between team effectiveness and project performance in the Nigeria higher educational institutions' construction projects. The study, therefore, recommended the improvement of team effectiveness factors of the industry by all projects’ stakeholders and participants

The Influence of Construction Project Team Effectiveness in Higher Institutions’ Building Projects: A Case from Nigeria

Projects are required to meet the stakeholders’ requirements on the stipulated time, quality and budget. The achievement of such requirements is related to team effectiveness. However, there is poor project time and cost performance in Nigeria such that the constructions initiated mostly escalate beyond the cost and time budgeted. The construction project teams in Nigeria are shrouded with dysfunctions leading to undesirable project outcomes. This study aims to examine the influence of project team effectiveness on project performance of higher educational institutions’ construction in Nigeria. A quantitative survey design was employed where 150 questionnaires were administered to construction projects team members in four higher educational institutions in Bauchi state, Nigeria. The result indicated that the team effectiveness factors of communication, role and responsibility as well as team relationships have a substantial influence on project performance. However, goal and objectives, leadership, as well as trust and values factors, do not have significant influence. Overall, the result shows that the variation in the project performance can be explained substantially by changes in the construction project team effectiveness (Adj. R2 =.585). The implication of this finding is that project performance in Nigerian higher educational institutions can be significantly improved by strengthening communications, roles and responsibilities as well as relationships among team members. Thus, this research contributed to the existing body of knowledge on the linkage between team effectiveness and project performance in the Nigeria higher educational institutions' construction projects. The study, therefore, recommended the improvement of team effectiveness factors of the industry by all projects’ stakeholders and participants

High Serum Alkaline Phosphatase, Hypercalcaemia, Race, and Mortality in South African Maintenance Haemodialysis Patients

Objective. To determine the association between serum total alkaline phosphatase (TAP) and mortality in African maintenance haemodialysis patients (MHD). Patients and Methods. The study enrolled a total of 213 patients on MHD from two dialysis centers in Johannesburg between January 2009 and March 2016. Patients were categorized into a low TAP group (≤112 U/L) versus a high TAP group (&gt;112 U/L) based on a median TAP of 112 U/L. Results. During the follow-up period of 7 years, there were 55 (25.8%) deaths. After adjusting for cofounders such as age, other markers of bone disorder, and comorbidity (diabetes mellitus), patients in the high TAP group had significantly higher risk of death compared to patients in the low TAP group (hazard ratio, 2.50; 95% CI 1.24-5.01, P = 0.01). Similarly, serum calcium &gt;2.75 mmol/L was associated with increased risk of death compared to patients within levels of 2.10-2.37 mmol/L (HR 6.34, 95% CI 1.40-28.76; P = 0.02). The HR for death in white patients compared to black patients was 6.88; 95% CI 1.82-25.88; P = 0.004. Conclusion. High levels of serum alkaline phosphatase, hypercalcaemia, and white race are associated with increased risk of death in MHD patients

Biochemical markers of mineral bone disorder in South African patients on maintenance haemodialysis.

Background and objective: Despite the high mortality and morbidity associated with abnormalities in mineral and bone metabolism in haemodialysis patients, there is limited data on the pattern of mineral bone disorder in African CKD population. Therefore, the purpose of this study was to describe the pattern of mineral bone disease by evaluating biochemical parameters in patients on maintenance haemodialysis (MHD). Methods: We evaluated the serum/plasma intact parathyroid hormone (iPTH), corrected calcium, phosphate, total alkaline phosphatase (TALP) and 25 \u2013OH vitamin D levels of two hundred and seven patients undergoing MHD at two dialysis centers in Johannesburg. Results: The MHD patients (133 men, 74 women) had a mean age of 54.5\ub115.6 years with a median dialysis vintage of 24 months (IQR, 12-48) and a mean kt/V of 1.45\ub10.28. The prevalence of hyperparathyroidism (iPTH &gt;150 pg/ml), hyperphosphataemia, hypocalcaemia and 25-OH vitamin D deficiency (&lt;30 ng/ml) was 73.4%, 57.0%, 20.3% and 80.7 % respectively. The combination of markers of bone turnover (iPTH &gt;150pg/ml and TALP&gt; 112 U/L) suggestive of high turnover bone disease, was present in 47.3 % of the study population. In multiple-logistic regression analysis, the odds ratio for developing hyperparathyroidism with hypocalcaemia and hyperphosphataemia were 5.32 (95% CI 1.10 - 25.9, P = 0.03) and 3.06(95 % CI 1.15 - 8.10, P=0.02) respectively. Ninety eight (47.3%) of the MHD patients had iPTH within the recommended kidney disease improving global outcome (KDIGO) guidelines. Conclusion: Secondary hyperparathyroidism and 25\u2013OH vitamin D deficiency were common in our haemodialysis patients. Hypocalcaemia and hyperphosphataemia were strong predictors for developing secondary hyperparathyroidism