Neglected and Emerging Infections of The Kidney.

Individuals, societies, and the environment are affected by neglected and emerging diseases. These diseases result in a variety of severe outcomes, including permanent disabilities, chronic diseases such as chronic kidney disease, and even mortality. Consequences include high health care expenditures, loss of means of support, social stigma, and social exclusion. The burden of these diseases is exacerbated in low- and middle-income countries owing to poverty, inadequate fundamental infrastructure, and the absence of health and social protection systems. The World Health Organization is committed to promoting the following public health strategies to prevent and control neglected tropical diseases: preventive chemotherapy; intensive case management; vector control; provision of safe drinkable water, sanitation, and hygiene; and veterinary public health. In addition, it promotes a One Health strategy, which is a collaborative, multisectoral, and interdisciplinary approach to achieving the greatest health outcomes by recognizing the interdependence of human beings, animals, plants, and their shared environment. This article provides knowledge and strategies for the prevention and treatment of neglected and emerging diseases, with a particular concentration on kidney diseases, as part of a comprehensive approach to One Health.

Chronic Kidney Disease Burden in Low-Resource Settings: Regional Perspectives.

The burden of chronic kidney disease (CKD) has increased exponentially worldwide but more so in low- and middle-income countries. Specific risk factors in these regions expose their populations to an increased risk of CKD, such as genetic risk with APOL1 among populations of West African heritage or farmers with CKD of unknown etiology that spans various countries across several continents to immigrant/indigenous populations in both low- and high-income countries. Low- and middle-income economies also have the double burden of communicable and noncommunicable diseases, both contributing to the high prevalence of CKD. The economies are characterized by low health expenditure, sparse or nonexistent health insurance and welfare programs, and predominant out-of-pocket spending for medical care. This review highlights the challenges in populations with CKD from low-resource settings globally and explores how health systems can help ameliorate the CKD burden.

Maximum accuracy obesity indices for screening metabolic syndrome in Nigeria: A consolidated analysis of four cross-sectional studies.

BACKGROUND: In sub-Saharan Africa, there is no precise use of metabolic syndrome (MetS) definitions and risk factors screening indices in many clinical and public health services. Methods proposed and used in Western populations are adopted without validation within the local settings. The aim of the study is to assess obesity indices and cut-off values that maximise screening of MetS and risk factors in the Nigerian population. METHOD: A consolidated analysis of 2809 samples from four population-based cross-sectional study of apparently healthy persons≥18 years was carried out. Optimal waist circumference (WC) and waist-to-height ratio (WHtR) cut points for diagnosing MetS and risk factors were determined using Optimal Data Analysis (ODA) model. The stability of the predictions of the models was also assessed. RESULTS: Overall mean values of BMI, WC and WHtR were 24.8±6.0kgm(-2), 84.0±11.3cm and 0.52±0.1 respectively. Optimal WC cut-off for discriminating MetS and diabetes was 83cm in females and 85cm in males, and 82cm in females and 89cm in males, respectively. WC was stable in discriminating diabetes than did WHtR and BMI, while WHtR showed better stability in predicting MetS than WC and BMI. CONCLUSION: The study shows that the optimal WC that maximises classification accuracy of MetS differs from that currently used for sub-Saharan ethnicity. The proposed global WHtR of 0.50 may misclassify MetS, diabetes and hypertension. Finally, the WC is a better predictor of diabetes, while WHtR is a better predictor of MetS in this sample population.

Prevalence of CKD-MBD in pre-dialysis patients using biochemical markers in Enugu, South-East Nigeria.

BACKGROUND: As kidney function declines, there is a progressive deterioration in mineral homeostasis with disruption of normal serum and tissue concentration of phosphorus and calcium, and changes in circulating levels of hormones-parathyroid hormone (PTH), calcitriol (1,25(OH)2 D), and Fibroblast growth factor-23 (FGF-23). OBJECTIVE: This study was aimed at determining the prevalence of markers of CKD-MBD in pre-dialysis patients. METHODS: We evaluated consecutively 168 subjects made up of 85 CKD patients and 83 healthy controls, who were attending the renal clinics and medical outpatient of University of Nigeria Teaching Hospital, Enugu. GFR was estimated and serum calcium, phosphorus, alkaline phosphatase, PTH, and 25(OH) D levels assayed. RESULTS: The prevalence of various mineral bone disease abnormalities were 70% hyper-phosphatemia, 85% hyper-parathyroidism, and 100% low levels of 25 (OH) D among the patients. Estimated GFR correlated negatively with both serum phosphorus, and PTH. Age of the patients ranged from18-76 years with a male to female ratio of 1.7:1. Chronic Glomerulonephritis (CGN), hypertension and diabetes mellitus caused CKD in 75% of the patients. There was no significant decrease in serum calcium levels of patients compared to controls. The patients did not have pathologically raised alkaline phosphatase, although their mean level was significantly higher than that of the control group. CONCLUSION: Low 25 (OH) D levels (insufficiency/deficiency), hyperparathyroidism, and hyper-phosphatemia were the obvious markers of CKD-MBD in our pre-dialysis patients. These should be evaluated at presentation in these patients.

Heart rate variability on antihypertensive drugs in black patients living in sub-Saharan Africa.

BACKGROUND: Compared with Caucasians, African Americans have lower heart rate variability (HRV) in the high-frequency domain, but there are no studies in blacks born and living in Africa. METHODS: In the Newer versus Older Antihypertensive agents in African Hypertensive patients trial (NCT01030458), patients (30-69 years) with uncomplicated hypertension (140-179/90-109 mmHg) were randomized to single-pill combinations of bisoprolol/hydrochlorothiazide (R) or amlodipine/valsartan (E). 72 R and 84 E patients underwent 5-min ECG recordings at randomization and 8, 16 and 24 weeks. HRV was determined by fast Fourier transform and autoregressive modelling. RESULTS: Heart rate decreased by 9.5 beats/min in R patients with no change in E patients (- 2.2 beats/min). R patients had reduced total (- 0.13 ms²; p = 0.0038) and low-frequency power (- 3.6 nu; p = 0.057), higher high-frequency (+ 3.3 nu; p = 0.050) and a reduced low- to high-frequency ratio (- 0.08; p = 0.040). With adjustment for heart rate, these differences disappeared, except for the reduced low-frequency power in the R group (- 4.67 nu; p = 0.02). Analyses confined to 39 R and 47 E patients with HRV measurements at all visits or based on autoregressive modelling were confirmatory. CONCLUSION: In native black African patients, antihypertensive drugs modulate HRV, an index of autonomous nervous tone. However, these effects were mediated by changes in heart rate except for low-frequency variability, which was reduced on beta blockade independent of heart rate.

High population frequencies of APOL1 risk variants are associated with increased prevalence of non-diabetic chronic kidney disease in the Igbo people from south-eastern Nigeria.

BACKGROUND: Continental Africa is facing an epidemic of chronic kidney disease (CKD). APOL1 risk variants have been shown to be strongly associated with an increased risk for non-diabetic kidney disease including HIV nephropathy, primary non-monogenic focal and segmental glomerulosclerosis, and hypertension-attributed nephropathy among African ancestry populations in the USA. The world's highest frequencies of APOL1 risk alleles have been reported in West African nations, overlapping regions with a high incidence of CKD and hypertension. One such region is south-eastern Nigeria, and therefore we sought to quantify the association of APOL1 risk alleles with CKD in this region. METHODS: APOL1 risk variants were genotyped in a case-control sample set consisting of non-diabetic, CKD patients (n = 44) and control individuals (n = 43) from Enugu and Abakaliki, Nigeria. RESULTS: We found a high frequency of two APOL1 risk alleles in the general population of Igbo people of south-eastern Nigeria (23.3%). The two APOL1 risk allele frequency in the CKD patient group was 66%. Logistic regression analysis under a recessive inheritance model showed a strong and significant association of APOL1 two-risk alleles with CKD, yielding an odds ratio of 6.4 (unadjusted p = 1.2E-4); following correction for age, gender, HIV and BMI, the odds ratio was 4.8 (adjusted p = 5.1E-03). CONCLUSION: APOL1 risk variants are common in the Igbo population of south-eastern Nigeria, and are also highly associated with non-diabetic CKD in this area. APOL1 may explain the increased prevalence of CKD in this region.

Progress report on the first sub-Saharan Africa trial of newer versus older antihypertensive drugs in native black patients.

BACKGROUND: The epidemic surge in hypertension in sub-Saharan Africa is not matched by clinical trials of antihypertensive agents in Black patients recruited in this area of the world. We mounted the Newer versus Older Antihypertensive agents in African Hypertensive patients (NOAAH) trial to compare, in native African patients, a single-pill combination of newer drugs, not involving a diuretic, with a combination of older drugs including a diuretic. METHODS: Patients aged 30 to 69 years with uncomplicated hypertension (140 to 179/90 to 109 mmHg) and ≤2 associated risk factors are eligible. After a four week run-in period off treatment, 180 patients have to be randomized to once daily bisoprolol/hydrochlorothiazide 5/6.25 mg (R) or amlodipine/valsartan 5/160 mg (E). To attain blood pressure <140/<90 mmHg during six months, the doses of bisoprolol and amlodipine should be increased to 10 mg/day with the possible addition of up to 2 g/day α-methyldopa. RESULTS: At the time of writing of this progress report, of 206 patients enrolled in the run-in period, 140 had been randomized. At randomization, the R and E groups were similar (P ≥ 0.11) with respect to mean age (50.7 years), body mass index (28.2 kg/m(2)), blood pressure (153.9/91.5 mmHg) and the proportions of women (53.6%) and treatment naïve patients (72.7%). After randomization, in the R and E groups combined, blood pressure dropped by 18.2/10.1 mmHg, 19.4/11.2 mmHg, 22.4/12.2 mmHg and 25.8/15.2 mmHg at weeks two (n = 122), four (n = 109), eight (n = 57), and 12 (n = 49), respectively. The control rate was >65% already at two weeks. At 12 weeks, 12 patients (24.5%) had progressed to the higher dose of R or E and/or had α-methyldopa added. Cohort analyses of 49 patients up to 12 weeks were confirmatory. Only two patients dropped out of the study. CONCLUSIONS: NOAAH (NCT01030458) demonstrated that blood pressure control can be achieved fast in Black patients born and living in Africa with a simple regimen consisting of a single-pill combination of two antihypertensive agents. NOAAH proves that randomized clinical trials of cardiovascular drugs in the indigenous populations of sub-Saharan Africa are feasible.

Rationale and design of the Newer Versus Older Antihypertensive Agents in African Hypertensive Patients (NOAAH) trial.

BACKGROUND: Sub-Saharan Africa experiences an epidemic surge in hypertension. Studies in African Americans led to the recommendation to initiate antihypertensive treatment in Blacks with a diuretic or a low-dose fixed combination including a diuretic. We mounted the Newer versus Older Antihypertensive Agents in African Hypertensive Patients (NOAAH) trial to compare in native African patients a fixed combination of newer drugs, not involving a diuretic, with a combination of older drugs including a diuretic. METHODS: Patients aged 30-69 years with uncomplicated hypertension (140-179/90-109 mmHg) and two or fewer associated risk factors are eligible. After a 4-week run-in period off treatment, 180 patients will be randomized to once daily bisoprolol/hydrochlorothiazide 5/6.25 mg or amlodipine/valsartan 5/160 mg. To attain and maintain blood pressure below 140/90 mmHg during 6 months of follow-up, the doses of bisoprolol and amlodipine in the combination tablets will be increased to 10 mg/day with the possible addition of α-methyldopa or hydralazine. NOAAH is powered to demonstrate a 5-mmHg between-group difference in sitting systolic pressure with a two-sided p-value of 0.01 and 90% power. NOAAH is investigator-led and complies with the Helsinki declaration. RESULTS: Six centers in four sub-Saharan countries started patient recruitment on September 1, 2010. On December 1, 195 patients were screened, 171 were enrolled, and 51 were randomized and followed up. The trial will be completed in the third quarter of 2011. CONCLUSIONS: NOAAH (NCT01030458) is the first randomized multicenter trial of antihypertensive medications in hypertensive patients born and living in sub-Saharan Africa.

High prevalence and low awareness of hypertension in a market population in enugu, Nigeria.

Background. A community-based study put the prevalence of hypertension in Nigeria at 32.8%. Market workers in Nigeria lead sedentary life style and often depend on salt-laden fast food while at work. Method. An unselected population of market workers were screened for hypertension and its risk factors by a pretested, structured questionnaire, clinical examination, and laboratory investigation. Hypertension was defined as BP ≥ 140 and/or ≥ 90 mmHg or being on drug therapy. Results. Forty-two percent of the screened population were hypertensive. Of this number, 70.6% did not know they were hypertensive before the screening. More males than females (P = .022) were hypertensive. Prevalence of hypertension increased with age from 5.4% in the age group <20 years to 80% in the age group ≥70 years. Conclusion. The prevalence of hypertension in market workers in this study was 42%, and the majority of them were unaware of their disease.

The enormity of chronic kidney disease in Nigeria: the situation in a teaching hospital in South-East Nigeria.

Background. The magnitude of the problem of chronic kidney disease (CKD) is enormous, and the prevalence keeps rising. To highlight the burden of CKD in developing countries, the authors looked at end-stage renal disease (ESRD) patients seen at the University of Nigeria Teaching Hospital (UNTH), Enugu, South-East Nigeria. Method. ESRD patients seen from 01/05/1990 to 31/12/2003 were recruited. Records from A&E Department, medical-out-patients, wards and dialysis unit were used. Results. A total of 1001 male versus 537 female patients were reviewed. About 593 male versus 315 female patients had haemodialysis. The mean age was 42.55 +/- 15.43 years and 86.5% were <60 years. Primary renal disease could not be determined in 51.6% while hypertension and glomerulonephritis accounted for -17.2% and 14.6%, respectively. Death from renal causes constituted 22.03% of medical deaths. Conclusion. The prognosis for CKD patients in Nigeria is abysmal. Only few patients had renal-replacement-therapy (RRT). The prohibitive cost precludes many patients. This underscores the need for preventive measures to reduce the impact of CKD in the society.

A community-based study of hypertension and cardio-metabolic syndrome in semi-urban and rural communities in Nigeria.

BACKGROUND: The prevalence of cardio-metabolic syndrome (CMS) is increasing worldwide. In people of African descent, there is higher prevalence of hypertension and complications than other races. Bearing in mind these facts, we looked at the CMS in the general population and the population with hypertension. Using the new International Diabetes Federation (IDF) definitions of CMS, we studied its prevalence in semi-urban and rural communities in South-east Nigeria in relation to hypertension. METHOD: This is a cross sectional population based study involving 1458 adults aged from 25 to 64 years. Diagnosis of CMS was based on the new IDF criteria using the anthropometric measurements for Europids as there is none yet for blacks. Hypertension was defined according to the WHO/ISH criteria. RESULTS: The overall prevalence of CMS was 18.0% in the semi-urban community as against 10.0% in the rural community increasing to 34.7% and 24.7% respectively in the population with hypertension. The prevalence of co-morbidities - hyperglycaemia, abdominal obesity, and hypertriglceridaemia were 13.9%, 41.1% and 23.9% while in the hypertensive populations they were 21.2%, 55.0% and 31.3% in the general population in both communities combined. Except for low HDL cholesterol, every other co-morbidity was higher in hypertensive population than the general population. CONCLUSION: The high prevalence of CMS in the semi-urban population especially for the population with hypertension underscores the double burden of disease in developing countries. The lesson is while infections and infestations are being tackled in these countries the non-communicable diseases should not be neglected.

Left ventricular hypertrophy in African Black patients with chronic renal failure at first evaluation.

OBJECTIVE: Chronic kidney disease (CKD) is a major cause of cardiovascular morbidity and mortality all over the world. The combined effect of volume and pressure overload seen in patients with CKD is the primary cause of left ventricular hypertrophy (LVH). Though it accounts for a significant proportion of patients dying in hospitals in Nigeria, information on CKD in African Blacks is lacking. This study evaluates the prevalence of LVH and factors affecting it in pre-dialysis patients by using echocardiography. DESIGN, SETTING AND PATIENTS: One hundred consecutive patients with CKD who were attending the medical outpatient and renal clinics of University of Nigeria Teaching Hospital, Enugu, who satisfied the inclusion criteria were screened for the study. Eighty-eight patients completed the study. Forty-five age- and sex-matched subjects were selected as controls. Clinical and laboratory parameters and echocardiographic indices were measured. RESULTS: Left ventricular hypertrophy (LVH), defined in absolute terms as left ventricular mass index >134 g/m2 in men and >110 g/m2 in women was present in 95.5% of patients and 6.7% of controls. The most prevalent type of LVH was eccentric hypertrophy, which was found in 54.6%, while concentric was seen in 40.9%. Hypertension was present in 85.2% of the patients. The predominant causes of CKD were chronic glomerulonephritis (43.2%), hypertension (25%), and diabetes mellitus (14.8%). All the patients studied had advanced CKD, either stage 4 or 5 of the Kidney Disease Outcome Quality Initiative classification of CKD. Stepwise method of multiple linear regressions identified mean arterial pressure (32%), hemoglobin concentration (22%), male sex (17%), and creatinine clearance (24%) as predictors of LVH in CKD. CONCLUSION: This study showed a strong association between CKD and LVH in patients in developing countries at the time of first evaluation by a nephrologist. It demonstrated a high prevalence of LVH in patients at first evaluation. The patients were often anemic and had severe hypertension even at first presentation. Early detection and treatment of causes of CKD should be pursued aggressively at the primary prevention level, as has been advocated by the International Society of Nephrology to reduce the effects of CKD and its attendant complications in the society.