Word count (abstract): words Word count (body -excludes figures, tables and references):3,492 words Short title:Core outcomes in hemodialysis 4 ABSTRACT Background: Survival and quality of life for patients on hemodialysis remain poor despite

Evidence-informed decision-making in clinical care and policy in nephrology is undermined by trials that selectively report a large number of heterogeneous outcomes, many of which are not patient-centered. The Standardized Outcomes in Nephrology−Hemodialysis (SONG-HD) Initiative convened an international consensus workshop on November 7, 2015, to discuss the identification and implementation of a potential core outcome set for all trials in hemodialysis. The purpose of this article is to report qualitative analyses of the workshop discussions, describing the key aspects to consider when establishing core outcomes in trials involving patients on hemodialysis. Key stakeholders including eight patients/caregivers and 47 health professionals (nephrologists, policy makers, industry, researchers) attended the workshop. Attendees suggested that identifying core outcomes required equitable stakeholder engagement to ensure relevance across patient populations; flexibility to consider evolving priorities over time; deconstruction of language and meaning for conceptual consistency and clarity; understanding of potential overlap and associations between outcomes; and an assessment of applicability to the range of interventions in hemodialysis. For implementation, they proposed that core outcomes must have simple, inexpensive and validated outcome measures that could be used in clinical care (quality ndicators) and trials (including pragmatic trials), and endorsement by regulatory agencies. Integrating these recommendations may foster acceptance and optimize the uptake and translation of core outcomes in hemodialysis, leading to more informative research, for better treatment, and improved patient outcomes.

Background: Death with graft function remains an important cause of graft loss among kidney transplant recipients (KTRs). Little is known about the trend of specific causes of death in KTRs in recent years. Methods: We analyzed United States Renal Data System data (1996–2014) to determine 1- and 10-year all-cause and cause-specific mortality in adult KTRs who died with a functioning allograft. We also studied 1- and 10-year trends in the various causes of mortality. Results: Of 210,327 KTRs who received their first kidney transplant from 1996 to 2014, 3.2% died within 1 year after transplant. Cardiovascular deaths constituted the majority (24.7%), followed by infectious (15.2%) and malignant (2.9%) causes; 40.1% of deaths had no reported cause. Using 1996 as the referent year, all-cause as well as cardiovascular mortality declined, whereas mortality due to malignancy did not. For analyses of 10-year mortality, we studied 94,384 patients who received a first kidney transplant from 1996 to 2005. Of those, 22.1% died over 10 years and the causative patterns of their causes of death were similar to those associated with 1-year mortality. Conclusions: Despite the downtrend in mortality over the last 2 decades, a significant percentage of KTRs die in 10-years with a functioning graft, and cardiovascular mortality remains the leading cause of death. These data also highlight the need for diligent collection of mortality data in KTRs.

Mesoamerican nephropathy is a devastating disease of unknown etiology that affects mostly young agricultural workers in Central America. An understanding of the mechanism of injury and the early disease process is urgently needed and will aid in identification of the underlying cause and direct treatment and prevention efforts. We sought to describe the renal pathology in Mesoamerican nephropathy at its earliest clinical appearance in prospectively identified acute case patients in Nicaragua. We considered those with elevated (or increased at least 0.3 mg/dL or 1.5-fold from baseline) serum creatinine, leukocyturia, and either leukocytosis or neutrophilia for inclusion in this biopsy study. Renal tissue was obtained by ultrasound-guided biopsy for examination by light, immunofluorescence, and electron microscopy. All 11 individuals who underwent renal biopsy showed tubulointerstitial nephritis, with varying degrees of inflammation and chronicity. Interstitial cellular infiltrates (predominantly T lymphocytes and monocytes), mostly in the corticomedullary junction; neutrophilic accumulation in the tubular lumens; largely preserved glomeruli; few mild ischemic changes; and no immune deposits were noted. The acute components of tubulointerstitial nephritis were acute tubular cell injury, interstitial edema, and early fibrosis. Chronic tubulointerstitial nephritis included severe tubular atrophy, thickened tubular basement membrane, and interstitial fibrosis. Thus, renal histopathology in Mesoamerican nephropathy reveals primary interstitial disease with intact glomeruli.

Mesoamerican nephropathy (MeN), an epidemic of unexplained kidney disease in Central America, affects mostly young, healthy individuals. Its etiology is a mystery that requires urgent investigation. Largely described as a chronic kidney disease (CKD), no acute clinical scenario has been characterized. An understanding of the early disease process could elucidate an etiology and guide treatment and prevention efforts. We sought to document the earliest clinical signs in patients with suspected MeN in a high-risk population in Nicaragua. Physicians at a local hospital identified suspect cases and documented clinical/laboratory data, demographics, and medical histories. Over a 1-year period, physicians identified 255 mostly young (median 29 years), male (89.5%) patients with elevated creatinine or reduced creatinine clearance. Mean serum creatinine (2.0 ± 0.6 mg/dL) revealed a 2-fold increase from baseline, and half had stage 2 or 3 acute kidney injury. Leukocyturia (98.4%), leukocytosis (81.4%), and neutrophilia (86.2%) predominated. Nausea (59.4%), back pain (57.9%), fever (54.6%), vomiting (50.4%), headache (47.3%), and muscle weakness (45.0%) were common. A typical case of acute MeN presented with elevated (or increased ≥ 0.3 mg/dL or ≥ 1.5-fold from baseline) creatinine, no hypertension or diabetes, leukocyturia, and at least two of fever, nausea or vomiting, back pain, muscle weakness, headache, or leukocytosis and/or neutrophilia. Rapid progression (median 90 days) to CKD was recorded in 8.5% of patients. This evidence can serve as the basis of a sensitive and urgently needed case definition for disease surveillance of early-stage, acute MeN.

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The actual dietary protein intake of adults without and with different stages of chronic kidney disease is not known. To evaluate this we performed cross-sectional analyses of 16,872 adults (20 years of age and older) participating in the National Health and Nutrition Examination Survey 2001-2008 who completed a dietary interview by stage of kidney disease. Dietary protein intake was assessed from 24-h recall systematically collected using the Automated Multiple Pass Method. Complex survey analyses were used to derive population estimates of dietary protein intake at each stage of chronic kidney disease. Using dietary protein intake of adults without chronic kidney disease as the comparator, and after adjusting for age, the mean dietary protein intake was 1.30 g/kg ideal body weight/day (g/kgIBW/d) and was not different from stage 1 or stage 2 (1.28 and 1.25 g/kgIBW/d, respectively), but was significantly different in stage 3 and stage 4 (1.22 and 1.13 g/kgIBW/d, respectively). These mean values appear to be above the Institute of Medicine requirements for healthy adults and the NKF-KDOQI guidelines for stages 3 and 4 chronic kidney disease. Thus, the mean dietary protein intake is higher than current guidelines, even after adjusting for age.

Background Prevalence and factors associated with obstructive and restrictive lung function in people with chronic kidney disease (CKD) is unknown. Study Design Cross-sectional and longitudinal analyses Setting & Participants Participants aged 40–79 years from the NHANES (National Health and Nutrition Examination Survey) 2007–2012 who underwent spirometry testing. Predictor CKD (eGFR >15-<60 ml/min/1.73 m2 or urinary albumin-creatinine ratio ≥30 mg/g) Outcomes Restrictive lung function (defined as FEV1/FVC ≥0.70 and baseline FVC <80% predicted), obstructive lung function (defined as FEV1/FVC <0.70 based on post-bronchodilator spirometric results), and mortality data (available for 2007–2008 and 2009–2010 survey periods). Results 7,610 participants (CKD=1338; Non-CKD=6272) were included. The prevalences of obstructive lung function adjusted to the mean age of 55 years and 50% male in the CKD and non-CKD groups were 15.6% and 13.3%, respectively (p=0.2). Similarly, adjusted prevalences of restrictive lung function in the CKD and non-CKD groups were 9.8% and 6.7%, respectively (p=0.01). Presence of albumin-creatinine ratio > 30 mg/g was associated with obstructive (OR, 1.42; 95% CI, 1.07–1.88) and restrictive lung function (OR, 1.43; 95% CI, 1.01–2.03) in the entire study cohort. eGFR < 60 mL/min/1.73m2 was associated with higher odds of obstructive lung function. In a multivariable Cox model, age (HR, 1.07; 95% CI, 1.04–1.11) and presence of obstructive lung function (HR, 2.68; 95% CI, 1.80–3.97) but not CKD measures were associated with death. Limitations Small proportion of participants with advanced kidney disease Conclusions In a representative sample of US adults, impaired lung function is common in those with and without CKD. Albuminuria was independently associated with both obstructive and restrictive lung function, and eGFR < 60 mL/min/1.73m2 was associated with higher odds of obstructive lung function. Older age and obstructive lung function were associated with higher likelihood of death. Further studies examining the burden of lung disease in advanced CKD are needed.