Bharati V. Mittal

Hypertension in the Developing World: Challenges and Opportunities

Hypertension is a major public health problem and a leading cause of death and disability in developing countries. One-quarter of the worlds adult population has hypertension, and this is likely to increase to 29% by 2025. Modeled projections indicate an increase to 1.15 billion hypertensive patients by 2025 in developing countries. There is variability in the global prevalence of hypertension: hypertension is present in approximately 35% of the Latin American population, 20%-30% of the Chinese and Indian population, and approximately 14% in Sub-Saharan African countries. This heterogeneity has been attributed to several factors, including urbanization with its associated changes in lifestyle, racial ethnic differences, nutritional status, and birth weight. Compounding this high burden of hypertension is a lack of awareness and insufficient treatment in those with hypertension. The public health response to this challenge should drive greater promotion of awareness efforts, studies of risk factors for hypertension, and understanding of the impact of lifestyle changes. Also important are efforts to develop multipronged strategies for hypertension management in developing nations.

Prevalence and risk factors of chronic kidney disease in the Thai adult population: Thai SEEK study

BACKGROUND Previous reports of chronic kidney disease (CKD) prevalence in Thailand varied from 4.3% to 13.8%. However, there were methodological concerns with these reports in terms of generalization and the accuracy of estimation. This study was, therefore, conducted to determine CKD prevalence and its risk factors in Thai adult populations. METHODS The population-based Thai Screening and Early Evaluation of Kidney Disease (SEEK) study was conducted with cross-sectional stratified-cluster sampling. Serum creatinine was analysed using the modified Jaffe method and then standardized with isotope dilution mass spectrometry. RESULTS The study included 3,459 subjects were included in the study. The mean age was 45.2 years (SE = 0.8), and 54.5% were female. Six hundred and twenty-six subjects were identified as having CKD, which evidenced an overall CKD prevalence of 17.5% [95% confidence interval (95% CI) = 14.6-20.4%]. The CKD prevalence of Stages I, II, III and IV were 3.3% (95% CI = 2.5%, 4.1%), 5.6% (95% CI = 4.2%, 7.0%), 7.5% (95% CI = 6.2%, 8.8%) and 1.1% (95% CI = 0.7%, 1.5%), respectively. The prevalence of CKD was higher in Bangkok, the Northern and Northeastern regions than in the Central and Southern regions. Seven factors (i.e. age, gender, diabetes, hypertension, hyperuricaemia, history of kidney stones and the use of traditional medicines) were associated with CKD. Only 1.9% of the subjects were aware that they had CKD. CONCLUSIONS CKD prevalence in the Thai population is much higher than previously known and published. Early stages of CKD seem to be as common as later stages. However, albuminuria measurement was not confirmed and adjusting for persistent positive rates resulted in the prevalence of 14.4%. Furthermore, the awareness of CKD was quite low in the Thai population.

Epidemiology and risk factors of chronic kidney disease in India - results from the SEEK (Screening and Early Evaluation of Kidney Disease) study.

BackgroundThere is a rising incidence of chronic kidney disease that is likely to pose major problems for both healthcare and the economy in future years. In India, it has been recently estimated that the age-adjusted incidence rate of ESRD to be 229 per million population (pmp), and >100,000 new patients enter renal replacement programs annually.MethodsWe cross-sectionally screened 6120 Indian subjects from 13 academic and private medical centers all over India. We obtained personal and medical history data through a specifically designed questionnaire. Blood and urine samples were collected.ResultsThe total cohort included in this analysis is 5588 subjects. The mean ± SD age of all participants was 45.22 ± 15.2 years (range 18–98 years) and 55.1% of them were males and 44.9% were females. The overall prevalence of CKD in the SEEK-India cohort was 17.2% with a mean eGFR of 84.27 ± 76.46 versus 116.94 ± 44.65 mL/min/1.73 m2 in non-CKD group while 79.5% in the CKD group had proteinuria. Prevalence of CKD stages 1, 2, 3, 4 and 5 was 7%, 4.3%, 4.3%, 0.8% and 0.8%, respectively.ConclusionThe prevalence of CKD was observed to be 17.2% with ~6% have CKD stage 3 or worse. CKD risk factors were similar to those reported in earlier studies.It should be stressed to all primary care physicians taking care of hypertensive and diabetic patients to screen for early kidney damage. Early intervention may retard the progression of kidney disease. Planning for the preventive health policies and allocation of more resources for the treatment of CKD/ESRD patients are imperative in India.

A prospective evaluation of renal replacement therapy modality eligibility

BACKGROUND Patient eligibility for renal replacement therapy (RRT) modalities is frequently debated, but little prospective data are available from large patient cohorts. METHODS We prospectively evaluated medical and psychosocial eligibility for the three RRT modalities in patients with chronic kidney disease (CKD) stages III-V who were enrolled in an ongoing prospective cohort study conducted at seven North American nephrology practices. RESULTS Ninety-eight percent of patients were considered medically eligible for haemodialysis (HD), 87% of patients were assessed as medically eligible for peritoneal dialysis (PD) and 54% of patients were judged medically eligible for transplant. Age was the leading cause of non-eligibility for both PD and transplant. Anatomical concerns (adhesions, hernias) were the second most frequent concern for PD eligibility followed by weight. Weight was also a concern for transplant eligibility. The proportion of patients medically eligible for RRT did not vary by CKD stage. There was, however, significant inter-centre variation in the proportion of patients medically eligible for PD and transplant. Ninety-five percent of patients were considered psychosocially eligible for HD, 83% of patients were assessed as psychosocially eligible for PD and 71% of patients were judged psychosocially eligible for transplant. The percentage of patients who were assessed as having neither medical nor psychosocial contraindications for RRT was 95% for HD, 78% for PD and 53% for transplant. CONCLUSIONS Most CKD patients are considered by their medical care providers to be suitable for PD. Enhanced patient education, promotion of home dialysis for suitable patients and empowerment of patient choice are expected to augment growth of home dialysis modalities.

Association of anemia and erythropoiesis stimulating agents with inflammatory biomarkers in chronic kidney disease

Inflammatory cytokines are important predictors of cardiovascular mortality especially in patients with chronic kidney disease. Here we explored the relationship of anemia and epoetin treatment to inflammatory cytokine levels in patients with chronic kidney disease. One hundred non-dialysis patients with chronic kidney disease over 18 years of age were evenly split into anemic and non-anemic cohorts. Of the 50 anemic patients, 23 were receiving erythropoiesis stimulating agents treatments. Levels of tumor necrosis factor (TNF)-alpha were found to be significantly higher and serum albumin was significantly lower with trends towards higher interleukin (IL)-6 and IL-8 in anemic compared to non-anemic patients. Further analysis by multiple logistic regression found that anemic patients treated with erythropoiesis stimulating agents had significantly higher odds for the upper two quartiles for IL-6, IL-8 and TNF-alpha compared to non-anemic patients. Our study found that the anemia of chronic kidney disease was associated with up regulation of TNF-alpha, and possibly IL-6 and IL-8 along with increased levels of these proinflammatory cytokines in patients treated with epoetin.

Endothelial activation markers in anemic non-dialysis chronic kidney disease patients.

Background/Aims: Anemia in chronic kidney disease is an independent predictor of cardiovascular disease (CVD). We explored the relationship between anemia and markers of inflammation and endothelial activation in non-dialysis chronic kidney disease (ND-CKD) patients to understand this mechanism. Methods: Cross-sectional analysis was performed on 30 adult ND-CKD patients for markers of inflammation and endothelial activation using a multiplexed immunoassay. Data were analyzed according to the anemic status defined by the modified World Health Organization criteria. Results: Seventeen patients were classified as anemic. Baseline characteristics by anemic status were similar except that anemic patients were older (p = 0.006), had lower estimated glomerular filtration rate (eGFR; p = 0.01) and higher prevalence of CVD (p = 0.02). Compared to non-anemic patients, log-transformed values of fibrinogen (p = 0.012); von Willebrand factor (vWF, p = 0.008), vascular cell adhesion molecule-1 (VCAM-1, p = 0.025) and C-reactive protein (p = 0.043) were elevated in anemic patients. Serum ferritin (p = 0.93) and serum albumin (p = 0.06) were not different. Age and eGFR-adjusted logistic regression analysis showed that anemic patients had increased odds for a composite of higher median values of fibrinogen, vWF and VCAM-1 (p = 0.01, odds ratio 8.1, 95% CI 1.08–111.0). Conclusion: We report the association of anemia with elevated markers of endothelial activation in ND-CKD patients. Longitudinal studies are needed to confirm our findings.

De novo multifocal renal cell carcinoma in the renal allograft

A 30-year-old Caucasian male on chronic hemodialysis presents with a 4-day history of right flank pain accompanied by fever, nausea, and anorexia. On physical examination, he had a heart rate of 100 beats per minute and a blood pressure of 147/95 mm Hg. The abdomen was soft. There was no tenderness or guarding over the allograft, and lymph nodes were not enlarged. His remaining examination was unremarkable. Blood and urine cultures were negative. The patient had undergone ultrasonographic examination of the allograft every year since 1998 with evidence of simple cysts in the parenchyma (Figure la) and a persistent fluid collection adjacent to the lower pole representing a lymphocele. A CT scan of the abdomen showed two sub-centimeter low-density lesions within the enlarged right transplanted kidney, suspicious for an infectious or neoplastic process. A persistent and stable right lower quadrant lymphocele was also present. Aspiration of the lymphocele yielded sterile fluid without evidence of infection. A transplant nephrectomy was performed.

Modulation of Platelet Activation in Chronic Kidney Disease Patients on Erythropoiesis-Stimulating Agents:

Background: Clinical trials demonstrate either no benefit or increased risk of cardiovascular events and mortality in patients with chronic kidney disease (CKD) targeted for higher hemoglobin levels, who are treated with erythropoiesis-stimulating agents (ESAs). The mechanism underlying this observation remains unexplained. Methods and Results: We assessed platelet activation by measuring soluble P-selectin (sPsel), CD40 ligand (CD40L), and circulating microparticles (CMP) in patients with CKD. Higher hemoglobin levels were associated with increased Psel levels in patients on ESAs but not in ESA-naïve anemic and nonanemic patients. Psel positively correlated with CMP and CD40L in both anemic and nonanemic patients. Multivariate linear regression analysis revealed an association between increased Psel levels and hemoglobin concentration in patients receiving ESAs. Conclusions: Anemic CKD patients on ESAs demonstrate increased levels of markers of platelet activation. These observations suggest a potentially complex interplay between platelet activation, impaired kidney function, and treatment of CKD anemia with ESAs.

Contents Vol. 110, 2008

p21 Takis Anagnostopoulos Symposium: Renal and Epithelial Physiology and Pathophysiology June 26–27, 2008, Hôpital Necker, Paris, France Guest Editors: Planelles, G.; Edelman, A. (Paris)