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.

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 Food and Drug Administration boxed warning for metformin will increase use in individuals with historical contraindications or precautions. Prescribers must understand 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, congestive heart failure, or chronic liver disease with hepatic impairment. Data Sources MEDLINE (via PubMed) from January 1994 to September 2016; Cochrane Library, EMBASE, and International Pharmaceutical Abstracts from January 1994 to November 2015. Study Selection English-language studies that examined adults with type 2 diabetes and chronic kidney disease with eGFR <60 mL/min/1.73m2, congestive heart failure, or chronic liver disease with hepatic impairment; compared diabetes regimens that included metformin to regimens that did not; and reported all-cause mortality, major adverse cardiovascular events and other outcomes of interest. Data Extraction Two reviewers abstracted data and independently rated study quality and strength of evidence. Data Synthesis Based on quantitative/qualitative syntheses involving 17 observational studies, metformin use is associated with reduced all-cause mortality in patients with chronic kidney disease, congestive heart failure, and chronic liver disease with hepatic impairment, and reduced heart failure readmission in patients with chronic kidney disease and congestive heart failure. Limitations We identified low strength of evidence and sparse data on multiple outcomes of interest. Available studies were observational and had varying follow-up durations. Conclusions Metformin use in patients with moderate chronic kidney disease, congestive heart failure, or chronic liver disease with hepatic impairment is associated with improvements in key clinical outcomes. Our findings support recent changes in metformin labeling. Registration PROSPERO CRD42016027708 Funding Source U.S. Department of Veterans Affairs

Background and objectives Epidemics of CKD of uncertain etiology (CKDu) are emerging around the world. Highlighting common risk factors for CKD of uncertain etiology across various regions and populations may be important for health policy and public health responses.Design, setting, participants, & measurements We searched PubMed, Embase, Scopus and Web of Science databases to identify published studies on CKDu. The search was generated in January of 2015; no language or date limits were used. We used a vote-counting method to evaluate exposures across all studies.Results We identified 1607 articles, of which 26 met inclusion criteria. Eighteen (69%) were conducted in known CKDu-endemic countries: Sri Lanka (38%), Nicaragua (19%), and El Salvador (12%). The other studies were from India, Japan, Australia, Mexico, Sweden, Tunisia, Tanzania, and the United States. Heavy metals, heat stress, and dietary exposures were reported across all geographic regions. In south Asia, family history, agrochemical use, and heavy metal exposures were reported most frequently, whereas altitude and temperature were reported only in studies from Central America. Across all regions, CKDu was most frequently associated with a family history of CKDu, agricultural occupation, men, middle age, snake bite, and heavy metal exposure.Conclusions Studies examining etiologies of CKDu have reported many exposures that are heterogeneous and vary by region. To identify etiologies of CKDu, designing consistent and comparative multisite studies across highrisk populations may help elucidate the importance of region-specific versus global risk factors.

BackgroundIn sub-Saharan Africa, kidney failure has a high morbidity and mortality. Despite this, population-based estimates of prevalence, potential etiologies, and awareness are not available.MethodsBetween January and June 2014, we conducted a household survey of randomly-selected adults in Northern Tanzania. To estimate prevalence we screened for CKD, which was defined as an estimated glomerular filtration rate ≤ 60 ml/min/1.73m2 and/or persistent albuminuria. We also screened for human immunodeficiency virus (HIV), diabetes, hypertension, obesity, and lifestyle practices including alcohol, tobacco, and traditional medicine use. Awareness was defined as a self-reported disease history and subsequently testing positive. We used population-based age- and gender-weights in estimating prevalence, and we used generalized linear models to explore potential risk factors associated with CKD, including living in an urban environment.ResultsWe enrolled 481 adults from 346 households with a median age of 45 years. The community-based prevalence of CKD was 7.0% (95% CI 3.8-12.3), and awareness was low at 10.5% (4.7-22.0). The urban prevalence of CKD was 15.2% (9.6-23.3) while the rural prevalence was 2.0% (0.5-6.9). Half of the cases of CKD (49.1%) were not associated with any of the measured risk factors of hypertension, diabetes, or HIV. Living in an urban environment had the strongest crude (5.40; 95% CI 2.05-14.2) and adjusted prevalence risk ratio (4.80; 1.70-13.6) for CKD, and the majority (79%) of this increased risk was not explained by demographics, traditional medicine use, socioeconomic status, or co-morbid non-communicable diseases (NCDs).ConclusionsWe observed a high burden of CKD in Northern Tanzania that was associated with low awareness. Although demographic, lifestyle practices including traditional medicine use, socioeconomic factors, and NCDs accounted for some of the excess CKD risk observed with urban residence, much of the increased urban prevalence remained unexplained and will further study as demographic shifts reshape sub-Saharan Africa.

Background Well-designed trials are of paramount importance in improving the delivery of care to patients with kidney disease. However, it remains unknown whether contemporary clinical trials within nephrology are of sufficient quality and quantity to meet this need. Study Design Systematic review. Setting & Population Studies registered with ClinicalTrials.gov. Selection Criteria for Studies Interventional (i.e., non-observational) studies (both randomized and nonrandomized) registered between October 2007 and September 2010 were included for analysis. Studies were independently reviewed by physicians and classified by clinical specialty. Predictor Nephrology versus cardiology versus other trials. Outcomes Select clinical trial characteristics. Results Of the 40,970 trials overall, 1054 (2.6%) were classified as nephrology. The majority of nephrology trials were for treatment (75.4%) or prevention (15.7%), with very few diagnostic, screening, or health services research studies. Most nephrology trials were randomized (72.3%), including 24.9% that included a single study group, 64.0% that included parallel groups, and 9.4% that were crossover trials. Nephrology trials, compared with 2264 cardiology trials (5.5% overall), were more likely to be smaller (64.5% versus 48.0% enrolling ≤100 patients), phase I-II (29.0% versus 19.7%), and unblinded (66.2% versus 53.3%; P<0.05 for all). Nephrology trials were also more likely than cardiology trials to include a drug intervention (72.4% versus 41.9%) and were less likely to report having a data monitoring committee (40.3% versus 48.5%; P<0.05 for all). Finally, there were few trials funded by the National Institutes of Health (3.3%, nephrology; 4.2%, cardiology). Limitations Does not include all trials performed worldwide, and frequent categorization of funding source as university may underestimate NIH support. Conclusions Critical differences remain between clinical trials in nephrology and other specialties. Improving care for patients with kidney disease will require a concerted effort to increase the scope, quality, and quantity of clinical trials within nephrology.

A growing body of evidence portends PFASs are emerging environmental threats to kidney health; yet several important gaps in our understanding still exist.