Boris Bikbov

Hepatitis C Infection and Chronic Renal Diseases

More than 170 million people worldwide are chronically infected with the hepatitis C virus (HCV), which is responsible for over 1 million deaths resulting from cirrhosis and liver cancers. Extrahepatic manifestations are also relevant and include mixed cryoglobulinemia, lymphoproliferative disorders, and kidney disease. HCV infection is both a cause and a complication of chronic kidney disease, occurring largely in the context of mixed cryoglobulinemia. This infection also represents a major medical and epidemiologic challenge in patients with end-stage renal disease on renal replacement therapy with dialysis or transplantation. In these settings the presence of HCV correlates with higher rates of patient mortality than in HCV-negative subjects on dialysis or undergoing kidney transplant. The major concern is the lack of safe and effective drugs to treat HCV-infected patients with chronic kidney disease. Unfortunately, there are no large-scale clinical trials in this population, especially those receiving renal replacement therapy, so that strong evidence for treatment recommendations is scant. This review article provides the readers with the most recent insights on HCV infection both as cause and complication of chronic kidney disease, discusses pitfalls and limitations of current therapies, and reports on preliminary experience with novel therapeutic agents, as well as directions for future research.

Maintenance Dialysis throughout the World in Years 1990 and 2010

Rapidly rising global rates of chronic diseases portend a consequent rise in ESRD. Despite this, kidney disease is not included in the list of noncommunicable diseases (NCDs) targeted by the United Nations for 25% reduction by year 2025. In an effort to accurately report the trajectory and pattern of global growth of maintenance dialysis, we present the change in prevalence and incidence from 1990 to 2010. Data were extracted from the Global Burden of Disease 2010 epidemiologic database. The results are on the basis of an analysis of data from worldwide national and regional renal disease registries and detailed systematic literature review for years 1980-2010. Incidence and prevalence estimates of provision of maintenance dialysis from this database were updated using a negative binomial Bayesian meta-regression tool for 187 countries. Results indicate substantial growth in utilization of maintenance dialysis in almost all world regions. Changes in population structure, changes in aging, and the worldwide increase in diabetes mellitus and hypertension explain a significant portion, but not all, of the increase because increased dialysis provision also accounts for a portion of the rise. These findings argue for the importance of inclusion of kidney disease among NCD targets for reducing premature death throughout the world.

Chronic kidney disease and cardiovascular risk in six regions of the world (ISN-KDDC): a cross-sectional study

BACKGROUND Chronic kidney disease is an important cause of global mortality and morbidity. Data for epidemiological features of chronic kidney disease and its risk factors are limited for low-income and middle-income countries. The International Society of Nephrologys Kidney Disease Data Center (ISN-KDDC) aimed to assess the prevalence and awareness of chronic kidney disease and its risk factors, and to investigate the risk of cardiovascular disease, in countries of low and middle income. METHODS We did a cross-sectional study in 12 countries from six world regions: Bangladesh, Bolivia, Bosnia and Herzegovina, China, Egypt, Georgia, India, Iran, Moldova, Mongolia, Nepal, and Nigeria. We analysed data from screening programmes in these countries, matching eight general and four high-risk population cohorts collected in the ISN-KDDC database. High-risk cohorts were individuals at risk of or with a diagnosis of either chronic kidney disease, hypertension, diabetes, or cardiovascular disease. Participants completed a self-report questionnaire, had their blood pressure measured, and blood and urine samples taken. We defined chronic kidney disease according to modified KDIGO (Kidney Disease: Improving Global Outcomes) criteria; risk of cardiovascular disease development was estimated with the Framingham risk score. FINDINGS 75,058 individuals were included in the study. The prevalence of chronic kidney disease was 14·3% (95% CI 14·0-14·5) in general populations and 36·1% (34·7-37·6) in high-risk populations. Overall awareness of chronic kidney disease was low, with 409 (6%) of 6631 individuals in general populations and 150 (10%) of 1524 participants from high-risk populations aware they had chronic kidney disease. Moreover, in the general population, 5600 (44%) of 12,751 individuals with hypertension did not know they had the disorder, and 973 (31%) of 3130 people with diabetes were unaware they had that disease. The number of participants at high risk of cardiovascular disease, according to the Framingham risk score, was underestimated compared with KDIGO guidelines. For example, all individuals with chronic kidney disease should be considered at high risk of cardiovascular disease, but the Framingham risk score detects only 23% in the general population, and only 38% in high-risk cohorts. INTERPRETATION Prevalence of chronic kidney disease was high in general and high-risk populations from countries of low and middle income. Moreover, awareness of chronic kidney disease and other non-communicable diseases was low, and a substantial number of individuals who knew they were ill did not receive treatment. Prospective programmes with repeat testing are needed to confirm the diagnosis of chronic kidney disease and its risk factors. Furthermore, in general, health-care workforces in countries of low and middle income need strengthening. FUNDING International Society of Nephrology.

Renal replacement therapy in Europe: a summary of the 2013 ERA-EDTA Registry Annual Report with a focus on diabetes mellitus

Background This article provides a summary of the 2013 European Renal Association–European Dialysis and Transplant Association (ERA-EDTA) Registry Annual Report (available at http://www.era-edta-reg.org), with a focus on patients with diabetes mellitus (DM) as the cause of end-stage renal disease (ESRD). Methods In 2015, the ERA-EDTA Registry received data on renal replacement therapy (RRT) for ESRD from 49 national or regional renal registries in 34 countries in Europe and bordering the Mediterranean Sea. Individual patient data were provided by 31 registries, while 18 registries provided aggregated data. The total population covered by the participating registries comprised 650 million people. Results In total, 72 933 patients started RRT for ESRD within the countries and regions reporting to the ERA-EDTA Registry, resulting in an overall incidence of 112 per million population (pmp). The overall prevalence on 31 December 2013 was 738 pmp (n = 478 990). Patients with DM as the cause of ESRD comprised 24% of the incident RRT patients (26 pmp) and 17% of the prevalent RRT patients (122 pmp). When compared with the USA, the incidence of patients starting RRT pmp secondary to DM in Europe was five times lower and the incidence of RRT due to other causes of ESRD was two times lower. Overall, 19 426 kidney transplants were performed (30 pmp). The 5-year adjusted survival for all RRT patients was 60.9% [95% confidence interval (CI) 60.5–61.3] and 50.6% (95% CI 49.9–51.2) for patients with DM as the cause of ESRD.

Global Cardiovascular and Renal Outcomes of Reduced GFR

The burden of premature death and health loss from ESRD is well described. Less is known regarding the burden of cardiovascular disease attributable to reduced GFR. We estimated the prevalence of reduced GFR categories 3, 4, and 5 (not on RRT) for 188 countries at six time points from 1990 to 2013. Relative risks of cardiovascular outcomes by three categories of reduced GFR were calculated by pooled random effects meta-analysis. Results are presented as deaths for outcomes of cardiovascular disease and ESRD and as disability-adjusted life years for outcomes of cardiovascular disease, GFR categories 3, 4, and 5, and ESRD. In 2013, reduced GFR was associated with 4% of deaths worldwide, or 2.2 million deaths (95% uncertainty interval [95% UI], 2.0 to 2.4 million). More than half of these attributable deaths were cardiovascular deaths (1.2 million; 95% UI, 1.1 to 1.4 million), whereas 0.96 million (95% UI, 0.81 to 1.0 million) were ESRD-related deaths. Compared with metabolic risk factors, reduced GFR ranked below high systolic BP, high body mass index, and high fasting plasma glucose, and similarly with high total cholesterol as a risk factor for disability-adjusted life years in both developed and developing world regions. In conclusion, by 2013, cardiovascular deaths attributed to reduced GFR outnumbered ESRD deaths throughout the world. Studies are needed to evaluate the benefit of early detection of CKD and treatment to decrease these deaths.

Mortality landscape in the Global Burden of Diseases, Injuries and Risk Factors Study

The Global Burden of Diseases, Injuries and Risk Factors Study 2010 (GBD 2010) is an initiative that involved 486 scientists from 302 institutions in 50 countries, under the leadership of a consortium formed by the Institute for Health Metrics and Evaluation of the University of Washington, World Health Organization, the University of Queensland School of Population Health, the Harvard School of Public Health, the Johns Hopkins Bloomberg School of Public Health, the University of Tokyo and Imperial College London. The study has provided a state of the art understanding of the burden of 67 risk factors and their clusters, 291 diseases and injuries on global, regional and national levels in period from 1990 to 2010 for 187 countries. GBD 2010 estimates covered both mortality (expressed in number of deaths, years of life lost (YLL) due to premature mortality) and morbidity (mainly expressed as years lived with disability (YLD)), while the incidence and prevalence were not reported for majority of causes so far, although they were accounted and used for YLD calculations. Finally, each disease and risk factor was presented in terms of the disability-adjusted years of life (DALY) that is merely a sum of YLL and YLD. The major published results of GBD 2010 cover global and regional levels for all diseases and risk factors. Reports focused on specific conditions are also available. At country-level detailed estimates are published for UK, China and USA, and data on other countries are accessible only as aggregate partial representation via web-based tools.

High serum cholesterol: a missed risk factor for chronic kidney disease mortality.

We appreciate the global coverage, comprehensive analytical methods, and meaningful conclusions of Majid Ezzati and colleagues’ report assessing mortality burden due to metabolic risk factors in major non-communicable diseases. However, we would like to underline an important shortcoming in their assumption that cholesterol is not a risk factor for mortality due to chronic kidney disease, thus implying that no deaths are attributable to atherosclerotic renovascular disease. Atherosclerotic renovascular disease is a fairly common disorder in elderly people, with relevant clinical consequences (table). Estimates of disease epidemiology vary greatly according to methods used for diagnosis and studied population. Prominent atherosclerotic renovascular disease was documented in as many as 7% of individuals aged 65 years and older with no history of kidney disease in a USA population-based study using renal duplex sonography. In a similarly aged population and time period, an analysis of an administrative database that accounted only to formal International Classifi cation of Diseases, ninth revison, and Current Procedural Terminology codes, prevalence was 0·54% and incidence was 3·7 per 1000 patient-years. Among patients with other atherosclerotic diseases, diabetes, or hypertension, prevalence of atherosclerotic renovascular disease could reach up to 40%. Of note, the high mortality could be attributable to the independent eff ect of the renal disease, not only to its coexistence with other atherosclerotic lesions. Indeed, evidence is available to show that the presence of atherosclerotic renovascular disease in patients with coronary or peripheral artery disease more than doubles the risk of death, Author’s reply The letters from T Hugh Jones and Schooling and Xu discuss continuing controversies in testosterone replacement therapy in men, further highlighting the need for a large randomised controlled trial to assess the risks for testosterone therapy in men. Although such a trial might not be defi nitive, the current knowledge deficit makes both clinicians and patients reliant on inconsistent expert opinion for treatment decision making, with experts citing selected, poorer quality data. Although the resource investment would be considerable, a large trial would likely reap large economic benefits, as recently shown by the Women’s Health Initiative, from which the return on each US

Hemodialysis practice patterns in the Russia Dialysis Outcomes and Practice Patterns Study (DOPPS), with international comparisons

1 invested is about

The burden of disease in Russia from 1980 to 2016: a systematic analysis for the Global Burden of Disease Study 2016

140. Jones argues that testosterone replacement therapy improves survival and reduces cardiovascular events in men. He makes the important point that the clinical syndrome of male hypogonadism needs both symptoms and low serum testosterone concentrations, and symptoms of hypogonadism were not assessed in either of the recent studies linking testosterone replacement therapy and increased cardiovascular morbidity. This weakness is an inherent problem with reliance on large databases for patient information and is often a weakness of observational studies. A welldesigned clinical trial in symptomatic men with low testosterone is crucial to support the assertion that testosterone replacement therapy benefits cardiovascular morbidity and survival. By contrast, Schooling and Xu argue that available data do not support a benefi t for testosterone replacement therapy, an issue being addressed by a 1 year randomised trial of 800 men with symptomatic low testosterone that is funded by the US National Institutes of Health. Clearly, fi ndings will provide important data. However, meta-analyses of shorter trials have reported confl icting conclusions about cardiovascular events and testosterone replacement. Importantly, the recent meta-analysis by Xu and colleagues was not limited to studies of only men with low testosterone, making the conclusions less clinically relevant for clinicians using published treatment guidelines. Such contradictory analyses show the need for better data for evidence-based medicine in the treatment of male hypogonadism.

Disparities in Chronic Kidney Disease Prevalence among Males and Females in 195 Countries: Analysis of the Global Burden of Disease 2016 Study

Introduction: There is little comparable information about hemodialysis (HD) practices in low‐ and middle income countries, including Russia. Evaluation of HD in Russia and its international comparisons could highlight factors providing opportunities for improvement.