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.

Comparison of Neuropsychological Patterns in Nigerians with different Heart Failure Phenotypes.

OBJECTIVE: The aim of this study was to determine the influence of left ventricular dysfunction type on the pattern of neuropsychological dysfunctions among heart failure (HF) subjects. METHOD: A sub-analysis of the data of subjects recruited in a cross-sectional survey of cognitive dysfunction among Nigerians with HF was performed. Cognitive performance on the Community Screening Interview for Dementia (CSI'D), Word List Learning Delayed Recall (WLLDR), Boston Naming Test (BNT), and Modified Token Test (MTT) were compared between heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF). Clinical and echocardiographic correlation analysis with cognitive performance was performed. RESULTS: Subjects with HFpEF were impaired on the WLLDR (71.4% vs. 34.6%, p = .026). The group with HFpEF scored lower on the language domain (definition subscale) of CSI'D (p = .036), and WLLDR (p = .005). The performance on the MTT (p = .185) and BNT (p = .923) were comparable between the two groups. An inverse relationship was found between pulse pressure and delay recall (r = -.565 p = .003) among the cohort with HFpEF whereas body mass index, BMI (r = -.737, p = .023) and tricuspid valve E/A ratio, TVEA (r = -.650, p = .042) showed an inverse relationship with the total CSI'D score in the cohort with HFrEF. CONCLUSIONS: Cognitive dysfunction is largely similar between the two groups. Delay recall is however poorer among subjects with HFpEF. Regular cognitive screening is advocated among HF subjects to prevent non-adherence with therapeutic options.

Spectrum of skin diseases presented at LAUTECH Teaching Hospital, Osogbo, southwest Nigeria.

BACKGROUND: Patterns of skin disease in developing nations are changing as frequencies of non-communicable diseases continue to increase. Appraisal of the current status of the disease profile is of utmost importance for health planning and resource allocation. METHODS: A prospective analysis of 895 cases of outpatient consultation during the years 2005-2010 was conducted. RESULTS: The mean ± standard deviation age of patients was 31.1 ± 19.1 years. Non-infectious skin diseases accounted for 80.9% of all cases. Eczemas/dermatitis (27.0%), urticarias/erythemas (11.0%), fungal infections (9.5%), skin appendage disorders (8.9%), papulosquamous diseases (8.2%), pigmentary diseases (8.2%), viral infections (6.8%), and tumors and malignant skin lesions (5.4%) represented the most common presentations. Atopic dermatitis was the most common type of eczema (29.8%) among children (odds ratio [OR] 1.53, 95% confidence interval [CI] 1.09-2.13; P = 0.013), in whom cornification disorders (OR 3.90, 95% CI 1.73-8.92; P < 0.001) and viral infections (OR 1.80, 95% CI 1.09-3.25; P = 0.021) were also frequent. Adults were more likely to be diagnosed with drug eruptions (OR 3.58, 95% CI 1.09-11.80; P = 0.003), tumors/malignancy (OR 4.97, 95% CI 1.53-16.10; P = 0.030), or autoimmune connective tissue disorders (OR 8.13, 95% CI 1.09-60.20; P = 0.015). Female subjects were significantly affected by urticarias (OR 1.53, 95% CI 1.00-2.33; P = 0.030) and papulosquamous diseases (OR 1.80, 95% CI 1.09-3.03; P = 0.019). CONCLUSIONS: The present pattern shows that non-infectious skin diseases are predominant. Occurrences of eczemas and urticarias are increasing at similar rates, whereas infectious skin diseases are decreasing in frequency. Resources and research should be directed towards the prevention of non-infectious skin diseases at this time as the campaign for a cleaner environment continues.

Long-term renal outcome and complications in South Africans with proliferative lupus nephritis.

AIM: To report the long-term outcome and complication profile of South African patients with proliferative lupus nephritis (PLN). METHODS: A retrospective review of 66 patients with biopsy-proven PLN [58 diffuse proliferative LN (Class IV) and 8 focal proliferative LN (Class III)] under our care from January 1995 to December 2009 was done. RESULTS: Thirty-three (50 %) patients reached the composite end point of doubling of serum creatinine, end-stage renal disease (ESRD) or death. The 5-, 10- and 15-year cumulative event-free survival rates were 54, 34 and 27 %, respectively. Variables associated with the composite end point were simultaneous diagnosis of SLE and LN (p = 0.048); elevated serum creatinine at onset (p = 0.009); elevated systolic blood pressure (SBP) (p < 0.001) and elevated diastolic blood pressure (DBP) (p < 0.001) on follow-up; and non-remission following induction therapy (p < 0.001). The 5-, 10- and 15-year renal survival rates in our patients were 63, 52 and 52 %, respectively. Hypertension at onset of LN (p = 0.037), nephrotic-range proteinuria (p = 0.033), eGFR < 60 ml/min/1.73 m(2) (p = 0.013) and lack of remission following induction therapy (p < 0.001) were all associated with development of end-stage renal disease (ESRD). Elevated SBP on follow-up (95 % CI 1.03-1.34, p = 0.017) was the only factor associated with composite end point while failure to achieve remission following induction therapy was the only factor associated with ESRD on multivariate analysis. Thirty-five (53 %) patients developed complications with persistent leukopenia, gastritis, sepsis, tuberculosis (TB) and herpes zoster being the leading complications. Ovarian failure occurred in 4 (11 %) patients. CONCLUSION: The 5-, 10 and 15-year event-free survival rates were 54, 34 and 27 % and failure to achieve remission following induction therapy predicted poor renal survival on multivariate analysis.

Kidney disease in elderly South Africans.

BACKGROUND: Life expectancy is low in many African countries due to several factors including the ongoing HIV epidemic. However, the global increase in life expectancy has translated to more elderly patients living with chronic kidney disease (CKD). The patterns of kidney disease in the elderly have never been described from sub-Saharan Africa. METHODS: This study was a retrospective study of 111 elderly patients (age ≥ 60 years) who had a renal biopsy performed at the Groote Schuur Hospital in Cape Town between 1st January 2000 and 31st December 2009. RESULTS: The mean age of patients at time of biopsy was 66.3 ± 5.7 years (males: 66.4 ± 5.6; females: 66.3 ± 5.9 years). Primary glomerular diseases were seen in 38.7%, secondary glomerular diseases in 36.0%, tubulointerstitial diseases in 17.1% and diseases classified as miscellaneous in 8.1% of all patients. Nephrotic syndrome was the most common indication for the performance of a renal biopsy (48.6%). Membranous lomerulonephritis (MGN) was the most common type of disease observed (14.4%) and was significantly more frequent in males than in females (p = 0.029). Other common histological diagnoses included diabetes nephropathy (12.6%), chronic glomerulonephritis (5.4%), and lupus nephritis (4.5%). HIV associated nephropathy (HIVAN) was only seen in 1 patient (0.9%). CONCLUSION: The patterns of renal disease currently seen in elderly South Africans closely resembles that reported from other countries but is at complete variance with the pattern reported in the general population of South Africa in which HIV plays a significant role.

QT Interval prolongation and dispersion: Epidemiology and clinical correlates in subjects with newly diagnosed systemic hypertension in Nigeria.

BACKGROUND: The use of easily obtainable clinical and laboratory parameters to identify hypertensive patients with increased cardiovascular risk in resource limited settings cannot be overemphasized. Prolongation of QT intervals and increased dispersion has been associated with increased risk of cardiovascular death. The study aimed at describing the epidemiology of QT interval abnormalities among newly diagnosed hypertensive subjects and associated clinical correlates. MATERIALS AND METHODS: One hundred and forty newly diagnosed hypertensive subjects and 70 controls were used for this study. Clinical and sociodemographic characteristics were obtained. Twelve lead resting electrocardiography, QT dispersion, heart rate corrected minimum and maximum QT intervals were determined manually. Increased QTcmax was defined at QTcmax >440msec. QT parameters were compared between various groups. SPSS 16.0 was used for data analysis. RESULTS: The hypertensive subjects were well matched in age and gender distribution with controls. QTmax and QTcmax were significantly higher among hypertensive subjects than controls (379.7±45.1 vs. 356.7±35.6, 447.5± 49.0 vs. 414.5 ±34.7 ms, respectively, P<0.05). QTd and QTcd were also significantly higher among hypertensive subjects than controls (62.64±25.65 vs. 46.1±17.2, 73.8 ±30.0 vs. 52.5±18.8, respectively, P<0.05). Seventy three (52.14%) of the hypertensive subjects had QTcmax >440ms compared to 21.43% of controls, P=0.01. Increased QTc dispersion was present in 36.4% of hypertensive subjects. Hypertensive subjects with QT abnormalities had significantly higher mean waist hip ratio, mean body mass index and a higher proportion of smoking than controls. CONCLUSION: QT prolongation and increased QTc dispersion are common among newly diagnosed hypertensive Nigerians and seem to be significantly associated with obesity. Effective antihypertensive therapy and control of obesity are important management modality for newly diagnosed hypertensive patients.

Acute kidney injury requiring hemodialysis in the tropics.

The morbidity and mortality from acute kidney injury (AKI) have remained relatively high over the last six decades. The triad of infections, nephrotoxins and obstetric complications are still major causes of acute kidney injury in the tropics. This retrospective study is a five-year audit of acute renal failure (ARF) (or stage 3 AKI) in patients requiring hemodialysis at the renal unit of the Department of Medicine of the Ladoke Akintola University of Technology (LAUTECH) Teaching Hospital, Osogbo, Nigeria. A total of 80 patients with AKI were treated over a five-year period at our center, of which 45 (56.2%) were in ARF, i.e. stage 3 AKI requiring hemodialysis. There were 24 males and 21 females. The most common cause of ARF among the patients was sepsis syndrome 16 (35.5%), while pregnancy-related cases accounted for 15 (33.3%) and nephrotoxins for 6 (13.3%). Five (33%) of the 15 pregnancy-related patients survived, and all were cases of septic abortion. Of the other 10 patients that did not survive, three (30%) had post-partum hemorrhage and seven (70%) post-partum eclampsia. In all, the mortality rate among our AKI presenting for hemodialysis at our center over a given year period was 28.8%. Majority of these were eclampsia related. The causes of ARF still remain the same in the tropics, eclampsia portends poor prognosis. Concerted efforts should be made at limiting this trend by active preventive services and early recognition of high-risk obstetrics cases.

Outcome of patients with membranous lupus nephritis in Cape Town South Africa.

BACKGROUND: The kidney is one of the major target organs affected by systemic lupus erythematosus. Although proliferative forms of lupus nephritis (LN) occur more frequently than membranous LN (MLN), the latter appears to have a more favourable outcome. Only a few studies have reported the outcome of patients with MLN. METHODS: A retrospective analysis of patients with biopsy-confirmed MLN from a single centre in South Africa treated from 1st January 2000 to 31st December 2009. RESULTS: The mean age of the patients (n = 42) at onset of LN was 35.0 ± 12.8 years with 73.8% of the patients being of mixed ancestry (coloureds). Eleven patients (26.2%) reached the composite end point of death or end-stage renal disease or persistent doubling of serum creatinine. The overall median survival and median renal survival times were 82.3 ± 15.5 months (95% confidence interval 52.0-112.6) and 84.5 ± 15.0 months (55.1-113.8), respectively. Also, 5-year event-free survival and renal survival were 64 and 71%, respectively. On multivariate analysis, systolic blood pressure (BP) during follow-up (P = 0.029), diastolic BP during follow-up (P = 0.020) and attainment of complete remission at 6 months (P = 0.033) were factors associated with the composite end points. Although treatment with chloroquine was not significantly associated with the composite end points (P = 0.05), we found that patients who received chloroquine had better renal survival compared with those who did not (P = 0.007). CONCLUSIONS: The outcome of patients with MLN in Cape Town is poorer than for similar patients reported from other centres across the world. Better BP control may significantly influence outcome of disease in these patients.

Coffee consumption could affect the activity of some liver enzymes and other biochemical parameters in healthy drinkers.

OBJECTIVE: To investigate the effect of coffee consumption on some liver function indices in adult male and female Nigerians. SUBJECTS AND METHODS: Thirty apparently healthy subjects, consisting of 18 men and 12 women, were made to consume 2 g of coffee daily for a total of 30 days. Activities of aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP) and plasma concentrations of total and conjugated bilirubin, total protein and albumin were determined using standard methods. RESULTS: Relative to baseline values, coffee consumption raised mean levels of ALT by 4 IU/l (p < 0.001), AST by 2.0 1 U/l (p < 0.001), ALP by 3.0 1 U/l (p < 0.01), total bilirubin by 0.90 mg/dl (p < 0.05) and total protein by 1.1 g/l (p < 0.05). Gender differences were observed. Significantly higher mean ALP concentration was only seen in male subjects, while mean bilirubin concentration was significantly raised in female volunteers alone. On the other hand, the mean total protein and albumin concentrations in individual male and female groups were not significantly altered (p > 0.05 in each case). CONCLUSION: The result obtained from the study suggests that short-term consumption of coffee might have a significant effect on the integrity of the liver function tests studied.

Metabolic syndrome: comparison of occurrence using three definitions in hypertensive patients.

OBJECTIVE: To compare the frequency of occurrence of metabolic syndrome using three international definitions and to study the distribution of cardiovascular risk factors among newly diagnosed hypertensive Nigerian subjects. DESIGN: Cross sectional study. SETTINGS: Cardiology unit of LAUTECH Teaching Hospital, Osogbo, Nigeria. PARTICIPANTS: One hundred forty newly diagnosed hypertensive Nigerian subjects, and 70 normotensive controls (age- and sex-matched) were included in this study. METHODS: Clinical history and relevant laboratory investigations were performed on all study participants. The definition of metabolic syndrome was based on three international definitions: World Health Organization (WHO), International Diabetes Federation (IDF), and National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III). Ethical approval was obtained for the study. Statistical analyses were performed using SPSS 16.0. RESULTS: There was no difference in age and gender distribution between the hypertensive subjects and controls. (55.14 ± 10.83 years, females 53.6% vs. 54.67 ± 10.89 years, females 52.9% respectively, P>0.05). The frequency of occurrence of metabolic syndrome among hypertensives was 34.5% according to WHO, 35.0% according to NCEP ATP III, and 42.5% according to IDF criteria. Visceral obesity and reduced high-density lipoprotein (HDL) were the other common cardiovascular risk factors among newly diagnosed hypertensive subjects. Female hypertensives had a higher prevalence of visceral obesity and low HDL. CONCLUSION: Frequency of occurrence of metabolic syndrome was similar using the NCEP ATP III and WHO definitions. However, the IDF definition resulted in a higher frequency because of the lower cut-off for waist circumference used for identification of visceral obesity. Metabolic syndrome is present in a significant proportion of newly diagnosed hypertensive subjects. Therefore, appropriate screening and treatment are required.

Burden of chronic kidney disease: an international perspective.

CKD is associated with increased cardiovascular mortality and a loss of disability-adjusted life years. Diseases of the genitourinary system were responsible for 928,000 deaths and 14,754,000 disability-adjusted life years in 2004. However, the absence of kidney registries in most of the low- and middle-income countries has made it difficult to ascertain the true burden of CKD in these countries. The global increase in the incidence and prevalence of CKD is being driven by the global increase in the prevalence of diabetes mellitus, hypertension, obesity, and aging. Most patients in low- and middle-income countries die because they cannot access renal replacement therapy because of the exorbitant cost. Community surveys have shown that the number of people with end-stage kidney disease is just the tip of the "CKD iceberg." The preventive strategies to stem the tide of CKD should involve educating the population on how to prevent renal disease; identifying those at risk of developing CKD; raising the awareness of the general public, policy makers, and health care workers; modifying the lifestyle of susceptible individuals; detecting early stage of CKD; arresting or hindering the progression of disease; and creating facilities for global assistance.

Interest in neurology during medical clerkship in three Nigerian medical schools.

BACKGROUND: This study sought to ascertain perception of Nigerian medical students of neurology in comparison with 7 other major medical specialties. To also determine whether neurology was the specialty students consider most difficult and the reasons for this and to appraise their opinion on how neurosciences and neurology were taught in their different universities. METHODS: Self-administered questionnaires were used to obtain information from randomly selected clinical students from 3 medical colleges in Nigeria (University of Ibadan, Ibadan; University of Ilorin, Ilorin; Ladoke Akintola University of Technology, Osogbo). RESULTS: Of 320 questionnaires sent out, 302 were returned given 94% response rate. Students felt they knew neurology least of all the 8 medical specialties, and were not confident of making neurological diagnoses. About 82% of the students indicated they learnt neurology best from bedside teaching, followed by use of medical textbooks. Close to 15% found online resources very useful for learning neurology and 6% indicated that group discussion was quite useful in the acquisition of knowledge on neurology. Histology and biochemistry were the preclinical subjects participants opined were least useful in learning neurology. The most frequent reasons students felt neurology was difficult were problems with understanding neuroanatomy (49%), insufficient exposure to neurological cases (41%), too many complex diagnoses (32%) and inadequate neurology teachers (32%). CONCLUSIONS: Nigerian medical students perceived neurology as the most difficult medical specialty and are not interested in specializing in it. Neurology education could be improved upon by provision of more bedside tutorials and increased availability of online resources to enhance learning. There is need to emphasize increased frequency of small group discussions amongst students so that they will be used to teamwork after graduation.

Natural history and epidemiology of post transplantation diabetes mellitus.

OBJECTIVE: High patient mortality continues to be the major threat to the success of solid organ transplantation despite improvements in the control of immunologic phenomena post-transplantation with improvements in grafts survival. Post-transplantation diabetes mellitus (PTD) occurring commonly in patients receiving immunosuppressives has been identified as a major culprit. AIM: This paper reviews the current concepts of PTD. METHODS: A Medline literature search limited to research /review articles in English language, spanning 1984 January - 2004 June on post transplantation diabetes mellitus or hyperglycemia was done. RESULTS: Post-transplantation diabetes mellitus is a heterogeneous condition of abnormal glucose tolerance with a variable onset, duration and severity. It is defined as a fasting plasma glucose = 7.0 mmol / L (126 mg / dL) and / or a 2 hour plasma glucose during an OGTT = 11.1 mmol / L (200 mg / dL), or a casual plasma glucose = 11.1 mmol / L (200 mg / dL), on 3 or more occasions over a period of at least 3 months. The risk factors predisposing to PTD are age, recipient's ethnicity, immunosuppressive regimen and family history of diabetes. The condition not only increases the risk of graft-related complications such as graft rejection, graft loss and infection, but also is a major determinant of the increased cardiovascular morbidity and mortality. CONCLUSION: The most important risk factor predisposing to the development of PTD is the immunosuppressive drugs. The selection of immunosuppressive regimen should take into account individuals diabetes risk profile and the relative diabetogenicity and risk for diabetes of each immunosuppressant, balancing minimal risk of diabetes with effective immunosuppression.

Diabetic nephropathy--a review of the natural history, burden, risk factors and treatment.

The earliest clinical evidence of diabetic nephropathy is microalbuminuria. Progression from microalbuminuria to overt nephropathy occurs in 20-40% within a 10-year period with approximately 20% of these patients progressing to end-stage renal disease. End-stage renal disease develops in 50% of type-1 diabetes patients with overt nephropathy within 10 years and in more than 75% by 20 years in the absence of treatment. In type-2 diabetes, a greater proportion of patients have microalbuminuria and overt nephropathy at or shortly after diagnosis of diabetes. The incidence of diabetes is increasing worldwide, with subsequent increase in the incidence of diabetic nephropathy. The risk factors identified in the development of DN from longitudinal and cross-sectional studies include race, genetic susceptibility, hypertension, hyperglycemia, hyperfiltration, smoking, advanced age, male sex, and high-protein diet. Treatment interventions in diabetic nephropathy include glycemic control, treatment of hypertension, hyperlipidemia, cessation of smoking, protein restriction, and renal replacement therapy. Multifactorial approach includes combined therapy targeting hyperglycemia, hypertension, microalbuminuria, and dyslipidemia.

Differential control of systolic and diastolic blood pressure in blacks with essential hypertension.

OBJECTIVE: The risk of cardiovascular and renal diseases has been shown to be higher for systolic blood pressure than diastolic blood pressure. The aim of this study was to assess the differential control of systolic and diastolic blood pressure in Nigerians with primary hypertension. DESIGN AND SETTING: This was a prospective observational study carried out at the Medical Outpatient Department of the State Hospital, Abeokuta, Nigeria. Ethical approval for the study was obtained from the ethical committee of the hospital. METHODOLOGY: The study population consisted of 185 consecutive patients (65 males, 120 females), aged 35-85 years with primary hypertension who had been on drugs one- to 25 years prior to the onset of the study. Clinic blood pressure control was assessed during a year period. Six consecutive clinic blood pressure readings were recorded for each patient and the average calculated (systolic blood pressure and diastolic blood pressure separately). Patients were classified into subgroups based on the pattern of blood pressure control. RESULTS: Clinic systolic blood pressure and diastolic blood pressure was controlled in 58 patients (31.4%). Systolic blood pressure control was less frequent than diastolic blood pressure control (35.7% versus 51.4%, p<0.05). Patients with uncontrolled systolic blood pressure were significantly older than patients with only uncontrolled diastolic blood pressure (66.7+/-7.4 versus 52.9+/-8.7 years, p<0.001). CONCLUSION: Systolic blood pressure is less frequently controlled than diastolic blood pressure in Nigerians treated for primary hypertension. This may increase the patient's risk of developing stroke, and cardiovascular and renal complications.