John W. Stanifer

Although often considered a comorbidity of diabetes or hypertension, kidney disease has numerous complex causes. mportantly, such disease has an indirect impact on global morbidity and mortality by increasing the risks associated with at least five other major killers: cardiovascular diseases, diabetes, hypertension, infection with human immunodeficiency virus (HIV) and malaria. For example, the Global Burden of Disease (GBD) 2015 study estimated that 1.2 million deaths, 19 million disability-adjusted life-years (DALYs) and 18 million years of life lost from cardiovascular diseases were directly attributable to reduced glomerular filtration rates. he GBD 2015 study also estimated that, in 2015, 1.2 million people died from kidney failure, an increase of 32% since 2005. In 2010, an estimated 2.3-7.1 million people with end-stage kidney disease died without access to chronic dialysis. 8 Additionally, each year, around 1.7 million people are thought to die from acute kidney injury. 9 Overall, therefore, an estimated 5-10 million people die annually from kidney disease. Given the limited epidemiological data, the common lack of awareness and the frequently poor access to laboratory services, such numbers probably underestimate the true burden posed by kidney disease. It is therefore possible that, each year, at least as many deaths are attributable to kidney disease as to cancer, diabetes or respiratory diseases, three of the four main categories targeted by the 2013 action plan. n addition, the estimated number of DALYS attributable to kidney disease globally increased from 19 million in 1990 to 33 million in 2013. In 2016, the DALYs associated with chronic kidney disease, along with those associated with cardiovascular disease, cancers, diabetes and neurological disorders, were found to have increased significantly between 1990 and 2015. A report from the GBD 2016 study highlighted the Abstract Kidney disease has been described as the most neglected chronic disease. Reliable estimates of the global burden of kidney disease require more population-based studies, but specific risks occur across the socioeconomic spectrum from poverty to affluence, from malnutrition to obesity, in agrarian to post-industrial settings, and along the life course from newborns to older people. A range of communicable and noncommunicable diseases result in renal complications and many people who have kidney disease lack access to care. The causes, consequences and costs of kidney diseases have implications for public health policy in all countries. The risks of kidney disease are also influenced by ethnicity, gender, location and lifestyle. Increasing economic and health disparities, migration, demographic transition, unsafe working conditions and environmental threats, natural disasters and pollution may thwart attempts to reduce the morbidity and mortality from kidney disease. A multisectoral approach is needed to tackle the global burden of kidney disease. The sustainable development goals (SDGs) emphasize the importance of a multisectoral approach to health. We map the actions towards achieving all of the SDGs that have the potential to improve understanding, measurement, prevention and treatment of kidney disease in all age groups. These actions can also foster treatment innovations and reduce the burden of such disease in future generations.

BACKGROUND: Amid rapid urbanisation, the HIV epidemic, and increasing rates of non-communicable diseases, people in sub-Saharan Africa are especially vulnerable to kidney disease. Little is known about the epidemiology of chronic kidney disease (CKD) in sub-Saharan Africa, so we did a systematic review and meta-analysis examining the epidemiology of the disease. METHODS: We searched Medline, Embase, and WHO Global Health Library databases for all articles published through March 29, 2012, and searched the reference lists of retrieved articles. We independently reviewed each study for quality. We used the inverse-variance random-effects method for meta-analyses of the medium-quality and high-quality data and explored heterogeneity by comparing CKD burdens across countries, settings (urban or rural), comorbid disorders (hypertension, diabetes, HIV), CKD definitions, and time. FINDINGS: Overall, we included 90 studies from 96 sites in the review. Study quality was low, with only 18 (20%) medium-quality studies and three (3%) high-quality studies. We noted moderate heterogeneity between the medium-quality and high-quality studies (n=21; I(2)=47·11%, p<0·0009). Measurement of urine protein was the most common method of determining the presence of kidney disease (62 [69%] studies), but the Cockcroft-Gault formula (22 [24%] studies) and Modification of Diet in Renal Disease formula (17 [19%] studies) were also used. Most of the studies were done in urban settings (83 [93%] studies) and after the year 2000 (57 [63%] studies), and we detected no significant difference in the prevalence of CKD between urban (12·4%, 95% CI 11-14) and rural (16·5%, 13·8-19·6) settings (p=0·474). The overall prevalence of CKD from the 21 medium-quality and high-quality studies was 13·9% (95% CI 12·2-15·7). INTERPRETATION: In sub-Saharan Africa, CKD is a substantial health burden with risk factors that include communicable and non-communicable diseases. However, poor data quality limits inferences and draws attention to the need for more information and validated measures of kidney function especially in the context of the growing burden of non-communicable diseases. FUNDING: Duke University.

Most of the global burden of chronic kidney disease (CKD) is occurring in low- and middle-income countries (LMICs). As a result of rapid urbanization in LMICs, a growing number of populations are exposed to numerous environmental toxins, high infectious disease burdens and increasing rates of noncommunicable diseases. For CKD, this portends a high prevalence related to numerous etiologies, and it presents unique challenges. A better understanding of the epidemiology of CKD in LMICs is urgently needed, but this must be coupled with strong public advocacy and broad, collaborative public health efforts that address environmental, communicable, and non-communicable risk factors.

BACKGROUND: Recent changes to the U.S. Food and Drug Administration boxed warning for metformin will increase its use in persons with historical contraindications or precautions. Prescribers must understand the clinical outcomes of metformin use in these populations. PURPOSE: To synthesize data addressing outcomes of metformin use in populations with type 2 diabetes and moderate to severe chronic kidney disease (CKD), congestive heart failure (CHF), or chronic liver disease (CLD) with hepatic impairment. DATA SOURCES: MEDLINE (via PubMed) from January 1994 to September 2016, and Cochrane Library, EMBASE, and International Pharmaceutical Abstracts from January 1994 to November 2015. STUDY SELECTION: English-language studies that: 1) examined adults with type 2 diabetes and CKD (with estimated glomerular filtration rate less than 60 mL/min/1.73 m2), CHF, or CLD with hepatic impairment; 2) compared diabetes regimens that included metformin with those that did not; and 3) reported all-cause mortality, major adverse cardiovascular events, and other outcomes of interest. DATA EXTRACTION: 2 reviewers abstracted data and independently rated study quality and strength of evidence. DATA SYNTHESIS: On the basis of quantitative and qualitative syntheses involving 17 observational studies, metformin use is associated with reduced all-cause mortality in patients with CKD, CHF, or CLD with hepatic impairment, and with fewer heart failure readmissions in patients with CKD or CHF. LIMITATIONS: Strength of evidence was low, and data on multiple outcomes of interest were sparse. Available studies were observational and varied in follow-up duration. CONCLUSION: Metformin use in patients with moderate CKD, CHF, or CLD with hepatic impairment is associated with improvements in key clinical outcomes. Our findings support the recent changes in metformin labeling. PRIMARY FUNDING SOURCE: U.S. Department of Veterans Affairs. (PROSPERO: CRD42016027708).

Background and objectives Per- and polyfluoroalkyl substances (PFASs) are a large group of manufactured nonbiodegradable compounds. Despite increasing awareness as global pollutants, the impact of PFAS exposure on human health is not well understood, and there are growing concerns for adverse effects on kidney function. Therefore, we conducted a scoping review to summarize and identify gaps in the understanding between PFAS exposure and kidney health. Design, setting, participants, &amp; measurements We systematically searched PubMed, EMBASE, EBSCO Global Health, World Health Organization Global Index, and Web of Science for studies published from 1990 to 2018. We included studies on the epidemiology, pharmacokinetics, or toxicology of PFAS exposure and kidney-related health, including clinical, histologic, molecular, and metabolic outcomes related to kidney disease, or outcomes related to the pharmacokinetic role of the kidneys. Results We identified 74 studies, including 21 epidemiologic, 13 pharmacokinetic, and 40 toxicological studies. Three population-based epidemiologic studies demonstrated associations between PFAS exposure and lower kidney function. Along with toxicology studies ( n =10) showing tubular histologic and cellular changes from PFAS exposure, pharmacokinetic studies ( n =5) demonstrated the kidneys were major routes of elimination, with active proximal tubule transport. In several studies ( n =17), PFAS exposure altered several pathways linked to kidney disease, including oxidative stress pathways, peroxisome proliferators-activated receptor pathways, NF-E2–related factor 2 pathways, partial epithelial mesenchymal transition, and enhanced endothelial permeability through actin filament modeling. Conclusions A growing body of evidence portends PFASs are emerging environmental threats to kidney health; yet several important gaps in our understanding still exist.