PURPOSE OF REVIEW:The consequences of climate change, including heat and extreme weather events impact kidney function in adults and children. The impacts of climate change on kidney development during gestation and thereby on kidney function later in life have been poorly described. Clinical evidence is summarized to highlight possible associations between climate change and nephron mass. RECENT FINDINGS:Pregnant women are vulnerable to the effects of climate change, being less able to thermoregulate, more sensitive to the effects of dehydration, and more susceptible to infections. Exposure to heat, wildfire smoke, drought, floods and climate-related infections are associated with low birth weight, preterm birth and preeclampsia. These factors are associated with reduced nephron numbers, kidney dysfunction and higher blood pressures in offspring in later life. Exposure to air pollution is associated with higher blood pressures in children and has variable effects on estimated glomerular filtration rate. SUMMARY:Climate change has important impacts on pregnant women and their unborn children. Being born too small or too soon is associated with life-time risk of kidney disease. Climate change may therefore have a dual effect of impacting fetal kidney development and contributing to cumulative postnatal kidney injury. The impact on population kidney health of future generations may be significant.

Neoadjuvant chemoradiation followed by surgical resection (trimodality therapy, TMT) is the standard of care for resectable esophageal cancer, based on the phase III CROSS trial. However, little data exists to characterize the population of patients that receive TMT, compared to those treated with definitive chemoradiation (bimodality therapy, BMT). We conducted a single institution retrospective review of consecutive patients with resectable esophageal cancer treated with BMT or TMT from 2009-2019. Relevant clinical variables were analyzed for association with TMT using univariate logistic regression and multivariable logistic regression. Overall survival (OS) was analyzed using the log-rank test and cox proportional hazards regression. We identified 95 patients, of which 51 (54%) underwent resection. Of BMT patients, 14 (32%) declined resection or were deemed medically inoperable at presentation. Lower Charlson comorbidity index (p = 0.01), adenocarcinoma histology (p = 0.02), lower nodal-stage (p = 0.01), dysphagia at presentation (p = 0.004), increased distance from radiotherapy center (p = 0.08), no chemotherapy cycles held during radiation (p = 0.003), and meeting CROSS-eligibility (p = 0.007) were independently associated with TMT on multivariable analysis (MVA), after controlling for significant covariates. Improved OS was observed with TMT (p<0.001), with median OS of 40.5 months (95% CI = 33.1-83.1) compared to 18.7 months (95% CI = 14.6-22.2) for BMT. On MVA, only TMT was associated with improved OS (HR = 0.38, 95% CI = 0.22-0.64, p<0.001). Furthermore, improved OS was associated with TMT in the subset of patients that did not meet criteria for CROSS-eligibility (p = 0.001). Our data affirms an OS benefit with TMT. We identified variables significantly associated with TMT, which may inform clinical decision-making. Targeted intervention strategies are warranted to mitigate effects of relevant variables and increase resection rates.

Sub-Saharan Africa has extremely high stroke prevalence and case fatality. Most Sub-Saharan African regions are uncharted in terms of stroke characteristics, epidemiology, and burden. We report here the results from the first stroke registry in Guinea.

Quality of life (QOL) derangements and psychosocial distress are common in head and neck cancer (HNC) patients undergoing treatment and in the first year of survivorship, however there is no data suggesting the most effective interventions in this population. We hypothesize that patients would benefit from a more rigorous approach to identifying and addressing their needs related to these domains. The objectives of this study were to 1) determine the incidence rates of depression and anxiety and evaluate QOL both before and at various time points following completion of treatment in HNC patients, and 2) measure patient interest in several proposed interventions.

Introduction: Sub-Saharan Africa (SSA) has the highest stroke prevalence along with a case fatality that amounts to 40%. We aimed to assess the effect of a minimal setting stroke unit in SSA Public hospital on stroke mortality and main medical complications. Materials and Methods: The study was set in Conakry, Guinea, Ignace Deen public referral hospital. Clinical characteristics, hospital mortality and main medical stroke complications rates (pneumonia, urinary tract infections, sores and venous thromboembolism) of admitted stroke patients after the installation of a minimal stroke unit equipped with heart rate, blood pressure and blood oxygen saturation monitoring and portable oxygen concentrator (POST) were compared to a similar number of stroke patients admitted before the stroke unit creation (PRE). Results: PRE (n = 318) and POST (n = 361) stroke, patients were comparable in term of age (61 ± 14 vs. 60 ± 14.8 years, p = 0.24), sex (56 vs. 50% males, p = 0.09), High blood pressure rate (76.7 vs. 79%, p = 0.44), stroke subtype (ischemic in 72 vs. 78% of cases, p = 0.05) and NIHSS (11 ± 4 vs. 11 ± 4, p = 0.85). Diabetes was more frequent in the PRE group (19 vs. 9%, p < 0.001). Mortality was significantly lower in the POST group (7.2 vs. 22.3%, p < 0.0001) as well as medical complications (4.1 vs. 27.7%, p < 0.001) and lower pneumonia rate (3.3 vs. 14.5%, p < 0.001). Conclusions: Minimally equipped stroke units significantly reduce stroke mortality and main medical complications in SSA.

Background Change in albuminuria has strong biological plausibility as a surrogate endpoint for progression of chronic kidney disease, but empirical evidence to support its validity is lacking. We aimed to determine the association between treatment effects on early changes in albuminuria and treatment effects on clinical endpoints and surrograte endpoints, to inform the use of albuminuria as a surrogate endpoint in future randomised controlled trials. Methods In this meta-analysis, we searched PubMed for publications in English from Jan 1, 1946, to Dec 15, 2016, using search terms including "chronic kidney disease", "chronic renal insufficiency", "albuminuria", "proteinuria", and "randomized controlled trial"; key inclusion criteria were quantifiable measurements of albuminuria or proteinuria at baseline and within 12 months of follow-up and information on the incidence of end-stage kidney disease. We requested use of individual patient data from the authors of eligible studies. For all studies that the authors agreed to participate and that had sufficient data, we estimated treatment effects on 6-month change in albuminuria and the composite clinical endpoint of treated end-stage kidney disease, estimated glomerular filtration rate of less than 15 mL/min per 1.73 m(2), or doubling of serum creatinine. We used a Bayesian mixed-effects meta-regression analysis to relate the treatment effects on albuminuria to those on the clinical endpoint across studies and developed a prediction model for the treatment effect on the clinical endpoint on the basis of the treatment effect on albuminuria. Findings We identified 41 eligible treatment comparisons from randomised trials (referred to as studies) that provided sufficient patient-level data on 29 979 participants (21 206 [71%] with diabetes). Over a median follow-up of 3.4 years (IQR 2.3-4.2), 3935 (13%) participants reached the composite clinical endpoint. Across all studies, with a meta-regression slope of 0.89 (95% Bayesian credible interval [BCI] 0.13-1.70), each 30% decrease in geometric mean albuminuria by the treatment relative to the control was associated with an average 27% lower hazard for the clinical endpoint (95% BCI 5-45%; median R-2 0.47, 95% BCI 0.02-0.96). The association strengthened after restricting analyses to patients with baseline albuminuria of more than 30 mg/g (ie, 3.4 mg/mmol; R-2 0.72, 0.05-0.99]). For future trials, the model predicts that treatments that decrease the geometric mean albuminuria to 0.7 (ie, 30% decrease in albuminuria) relative to the control will provide an average hazard ratio (HR) for the clinical endpoint of 0.68, and 95% of sufficiently large studies would have HRs between 0.47 and 0.95. Interpretation Our results support a role for change in albuminuria as a surrogate endpoint for the progression of chronic kidney disease, particularly in patients with high baseline albuminuria; for patients with low baseline levels of albuminuria this association is less certain. Copyright (c) 2019 Elsevier Ltd. All rights reserved.

Rationale & Objective: Chronic kidney disease (CKD) is complicated by abnormalities that reflect disruption in filtration, tubular, and endocrine functions of the kidney. Our aim was to explore the relationship of specific laboratory result abnormalities and hypertension with the estimated glomerular filtration rate (eGFR) and albuminuria CKD staging framework. Study Design: Cross-sectional individual participant-level analyses in a global consortium. Setting & Study Populations: 17 CKD and 38 general population and high-risk cohorts. Selection Criteria for Studies: Cohorts in the CKD Prognosis Consortium with data for eGFR and albuminuria, as well as a measurement of hemoglobin, bicarbonate, phosphorus, parathyroid hormone, potassium, or calcium, or hypertension. Data Extraction: Data were obtained and analyzed between July 2015 and January 2018. Analytical Approach: We modeled the association of eGFR and albuminuria with hemoglobin, bicarbonate, phosphorus, parathyroid hormone, potassium, and calcium values using linear regression and with hypertension and categorical definitions of each abnormality using logistic regression. Results were pooled using random-effects meta-analyses. Results: The CKD cohorts (n = 254,666 participants) were 27% women and 10% black, with a mean age of 69 (SD, 12) years. The general population/high-risk cohorts (n = 1,758,334) were 50% women and 2% black, with a mean age of 50 (16) years. There was a strong graded association between lower eGFR and all laboratory result abnormalities (ORs ranging from 3.27 [95% CI, 2.68-3.97] to 8.91 [ 95% CI, 7.22-10.99] comparing eGFRs of 15 to 29 with eGFRs of 45 to 59 mL/min/1.73 m(2)), whereas albuminuria had equivocal or weak associations with abnormalities (ORs ranging from 0.77 [95% CI, 0.60-0.99] to 1.92 [95% CI, 1.65-2.24] comparing urinary albumin-creatinine ratio > 300 vs < 30 mg/g). Limitations: Variations in study era, health care delivery system, typical diet, and laboratory assays. Conclusions: Lower eGFR was strongly associated with higher odds of multiple laboratory result abnormalities. Knowledge of risk associations might help guide management in the heterogeneous group of patients with CKD.

Abstract Objective To evaluate the associations between adiposity measures (body mass index, waist circumference, and waist-to-height ratio) with decline in glomerular filtration rate (GFR) and with all cause mortality. Design Individual participant data meta-analysis. Setting Cohorts from 40 countries with data collected between 1970 and 2017. Participants Adults in 39 general population cohorts (n=5 459 014), of which 21 (n=594 496) had data on waist circumference; six cohorts with high cardiovascular risk (n=84 417); and 18 cohorts with chronic kidney disease (n=91 607). Main outcome measures GFR decline (estimated GFR decline ≥40%, initiation of kidney replacement therapy or estimated GFR <10 mL/min/1.73 m2) and all cause mortality. Results Over a mean follow-up of eight years, 246 607 (5.6%) individuals in the general population cohorts had GFR decline (18 118 (0.4%) end stage kidney disease events) and 782 329 (14.7%) died. Adjusting for age, sex, race, and current smoking, the hazard ratios for GFR decline comparing body mass indices 30, 35, and 40 with body mass index 25 were 1.18 (95% confidence interval 1.09 to 1.27), 1.69 (1.51 to 1.89), and 2.02 (1.80 to 2.27), respectively. Results were similar in all subgroups of estimated GFR. Associations weakened after adjustment for additional comorbidities, with respective hazard ratios of 1.03 (0.95 to 1.11), 1.28 (1.14 to 1.44), and 1.46 (1.28 to 1.67). The association between body mass index and death was J shaped, with the lowest risk at body mass index of 25. In the cohorts with high cardiovascular risk and chronic kidney disease (mean follow-up of six and four years, respectively), risk associations between higher body mass index and GFR decline were weaker than in the general population, and the association between body mass index and death was also J shaped, with the lowest risk between body mass index 25 and 30. In all cohort types, associations between higher waist circumference and higher waist-to-height ratio with GFR decline were similar to that of body mass index; however, increased risk of death was not associated with lower waist circumference or waist-to-height ratio, as was seen with body mass index. Conclusions Elevated body mass index, waist circumference, and waist-to-height ratio are independent risk factors for GFR decline and death in individuals who have normal or reduced levels of estimated GFR.

Background: Canagliflozin reduces the risk of kidney failure in patients with type 2 diabetes mellitus and chronic kidney disease, but effects on specific cardiovascular outcomes are uncertain, as are effects in people without previous cardiovascular disease (primary prevention). Methods: In CREDENCE (Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation), 4401 participants with type 2 diabetes mellitus and chronic kidney disease were randomly assigned to canagliflozin or placebo on a background of optimized standard of care. Results: Primary prevention participants (n=2181, 49.6%) were younger (61 versus 65 years), were more often female (37% versus 31%), and had shorter duration of diabetes mellitus (15 years versus 16 years) compared with secondary prevention participants (n=2220, 50.4%). Canagliflozin reduced the risk of major cardiovascular events overall (hazard ratio [HR], 0.80 [95% CI, 0.67-0.95]; P=0.01), with consistent reductions in both the primary (HR, 0.68 [95% CI, 0.49-0.94]) and secondary (HR, 0.85 [95% CI, 0.69-1.06]) prevention groups (P for interaction=0.25). Effects were also similar for the components of the composite including cardiovascular death (HR, 0.78 [95% CI, 0.61-1.00]), nonfatal myocardial infarction (HR, 0.81 [95% CI, 0.59-1.10]), and nonfatal stroke (HR, 0.80 [95% CI, 0.56-1.15]). The risk of the primary composite renal outcome and the composite of cardiovascular death or hospitalization for heart failure were also consistently reduced in both the primary and secondary prevention groups (P for interaction >0.5 for each outcome). Conclusions: Canagliflozin significantly reduced major cardiovascular events and kidney failure in patients with type 2 diabetes mellitus and chronic kidney disease, including in participants who did not have previous cardiovascular disease.

Nephron number in humans varies up to 13-fold, likely reflecting the impact of multiple factors on kidney development, including inherited body size and ethnicity, as well as maternal health and nutrition, fetal exposure to gestational diabetes or preeclampsia and other environmental factors, which may potentially be modifiable. Such conditions predispose to low or high offspring birth weight, growth restriction or preterm birth, which have all been associated with increased risks of higher blood pressures and/or kidney dysfunction in later life. Low birth weight, preterm birth, and intrauterine growth restriction are associated with reduced nephron numbers. Humans with hypertension and chronic kidney disease tend to have fewer nephrons than their counterparts with normal blood pressures or kidney function. A developmentally programmed reduction in nephron number therefore enhances an individual's susceptibility to hypertension and kidney disease in later life. A low nephron number at birth may not lead to kidney dysfunction alone except when severe, but in the face of superimposed acute or chronic kidney injury, a kidney endowed with fewer nephrons may be less able to adapt, and overt kidney disease may develop. Given that millions of babies are born either too small, too big or too soon each year, the population impact of altered renal programming is likely to be significant. Many gestational exposures are modifiable, therefore urgent attention is required to implement public health measures to optimize maternal, fetal, and child health, to prevent or mitigate the consequences of developmental programming, to improve the health future generations.

Background: SGLT2 inhibitors have to date been recommended as add-on therapy for patients whose HbA1c is not at goal, typically >7%, based on the initial clinical trials. We sought to determine if ...

Background Change in albuminuria as a surrogate endpoint for progression of chronic kidney disease is strongly supported by biological plausibility, but empirical evidence to support its validity in epidemiological studies is lacking. We aimed to assess the consistency of the association between change in albuminuria and risk of end-stage kidney disease in a large individual participant-level meta-analysis of observational studies. Methods In this meta-analysis, we collected individual-level data from eligible cohorts in the Chronic Kidney Disease Prognosis Consortium (CKD-PC) with data on serum creatinine and change in albuminuria and more than 50 events on outcomes of interest. Cohort data were eligible if participants were aged 18 years or older, they had a repeated measure of albuminuria during an elapsed period of 8 months to 4 years, subsequent end-stage kidney disease or mortality follow-up data, and the cohort was active during this consortium phase. We extracted participant-level data and quantified percentage change in albuminuria, measured as change in urine albumin-to-creatinine ratio (ACR) or urine protein-to-creatinine ratio (PCR), during baseline periods of 1, 2, and 3 years. Our primary outcome of interest was development of end-stage kidney disease after a baseline period of 2 years. We defined an end-stage kidney disease event as initiation of kidney replacement therapy. We quantified associations of percentage change in albuminuria with subsequent end-stage kidney disease using Cox regression in each cohort, followed by random-effects meta-analysis. We further adjusted for regression dilution to account for imprecision in the estimation of albuminuria at the participant level. We did multiple subgroup analyses, and also repeated our analyses using participant-level data from 14 clinical trials, including nine clinical trials not in CKD-PC. Findings Between July, 2015, and June, 2018, we transferred and analysed data from 28 cohorts in the CKD-PC, which included 693 816 individuals (557 583 [80%] with diabetes). Data for 675 904 individuals and 7461 end-stage kidney disease events were available for our primary outcome analysis. Change in ACR was consistently associated with subsequent risk of end-stage kidney disease. The adjusted hazard ratio (HR) for end-stage kidney disease after a 30% decrease in ACR during a baseline period of 2 years was 0.83 (95% CI 0.74-0.94), decreasing to 0.78 (0.66-0.92) after further adjustment for regression dilution. Adjusted HRs were fairly consistent across cohorts and subgroups (ie, estimated glomerular filtration rate, diabetes, and sex), but the association was somewhat stronger among participants with higher baseline ACR than among those with lower baseline ACR (p interaction < 0.0001). In individuals with baseline ACR of 300 mg/g or higher, a 30% decrease in ACR over 2 years was estimated to confer a more than 1% absolute reduction in 10-year risk of end-stage kidney disease, even at early stages of chronic kidney disease. Results were generally similar when we used change in PCR and when study populations from clinical trials were assessed. Interpretation Change in albuminuria was consistently associated with subsequent risk of end-stage kidney disease across a range of cohorts, lending support to the use of change in albuminuria as a surrogate endpoint for end-stage kidney disease in clinical trials of progression of chronic kidney disease in the setting of increased albuminuria. Copyright (c) 2019 Elsevier Ltd. All rights reserved.

The Chronic Kidney Disease (CKD) Prognosis Consortium is a collaborative author of the above-mentioned article. The CKD Prognosis Consortium investigators/collaborators are as follows:•African American Study of Kidney Disease and Hypertension (AASK): Brad Astor, Lawrence J. Appel; Canadian Study of Prediction of Death, Dialysis and Interim Cardiovascular Events (CanPREDDICT): Adeera Levin, Mila Tang, Ognjenka Djurdjev; Cleveland Clinic CKD Registry Study (CCF): Sankar D. Navaneethan, Stacey E. Jolly, Jesse D. Schold, Joseph V. Nally Jr.; Chronic Renal Impairment in Birmingham (CRIB): David C. Wheeler, Jonathan Emberson, John Townend, Martin Landray; Chronic Renal Insufficiency Cohort Study (CRIC): Harold I. Feldman, Chi-yuan Hsu, James P. Lash, Lawrence J. Appel; Chronic Renal Insufficiency Standards Implementation Study (CRISIS): Philip A. Kalra, James P. Ritchie, Raman Maharajan, Rachel J. Middleton, Donal J. O’Donoghue; German Chronic Kidney Disease Study (GCKD): Kai-Uwe Eckardt, Markus P. Schneider, Anna Köttgen, Florian Kronenberg, Barbara Bärthlein; Geisinger Health System: Alex R. Chang, Jamie A. Green, H. Lester Kirchner, Kevin Ho; Grampian Laboratory Outcomes, Morbidity and Mortality Studies – 2 (GLOMMS2): Angharad Marks, Corri Black, Gordon J. Prescott, Nick Fluck; Gonryo Study: Masaaki Nakayama, Mariko Miyazaki, Tae Yamamoto, Gen Yamada; Hong Kong CKD Studies: Angela Yee-Moon Wang, Sharon Cheung, Sharon Wong, Jessie Chu, Henry Wu; Ontario Institute for Clinical Evaluative Sciences, Provincial Kidney, Dialysis and Transplantation program (ICES KDT): Amit X. Garg, Eric McArthur, Danielle M. Nash; Maccabi Health System: Varda Shalev, Gabriel Chodick; Multifactorial Approach and Superior Treatment Efficacy in Renal Patients with the Aid of a Nurse Practitioner (MASTERPLAN): Peter J. Blankestijn, Jack F.M. Wetzels, Arjan D. van Zuilen, Jan A. van den Brand; Modification of Diet in Renal Disease Study (MDRD): Andrew S. Levey, Lesley A. Inker, Mark J. Sarnak, Hocine Tighiouart; Nanjing CKD Network Cohort Study (Nanjing CKD): Haitao Zhang; NephroTest Study (NephroTest): Benedicte Stengel, Marie Metzger, Martin Flamant, Pascal Houillier, Jean-Philippe Haymann; National Renal Healthcare Program – Uruguay (NRHP-URU): Pablo G. Rios, Nelson Mazzuchi, Liliana Gadola, Verónica Lamadrid, Laura Sola; New Zealand Diabetes Cohort Study (NZDCS): John F. Collins, C. Raina Elley, Timothy Kenealy; Parcours de Soins des Personnes Agées (PSPA): Olivier Moranne, Cecile Couchoud, Cecile Vigneau; Primary-Secondary Care Partnership to Prevent Adverse Outcomes in Chronic Kidney Disease (PSP CKD): Nigel J. Brunskill, Rupert W. Major, David Shepherd, James F. Medcalf; Racial and Cardiovascular Risk Anomalies in CKD Cohort (RCAV): Csaba P. Kovesdy, Kamyar Kalantar-Zadeh, Miklos Z. Molnar, Keiichi Sumida, Praveen K. Potukuchi; Reduction of Endpoints in Non-insulin Dependent Diabetes Mellitus with the Angiotensin II Antagonist Losartan (RENAAL): Hiddo J.L. Heerspink, Dick de Zeeuw, Barry Brenner; Stockholm CREAtinine Measurements Cohort (SCREAM): Juan Jesus Carrero, Alessandro Gasparini, Abdul Rashid Qureshi, Carl-Gustaf Elinder; Second Manifestations of ARTerial Disease Study (SMART): Frank L.J. Visseren, Yolanda van der Graaf; Swedish Renal Registry CKD Cohort (SRR CKD): Marie Evans, Maria Stendahl, Staffan Schön, Mårten Segelmark, Karl-Göran Prütz; Sunnybrook Cohort: David M. Naimark, Navdeep Tangri; West of Scotland CKD Study: Patrick B. Mark, Jamie P. Traynor, Colin C. Geddes, Peter C. Thomson.•CKD Prognosis Consortium Steering Committee: Alex R. Chang, Josef Coresh (Chair), Ron T. Gansevoort, Morgan E. Grams, Anna Köttgen, Andrew S. Levey, Kunihiro Matsushita, Mark Woodward, Luxia Zhang.•CKD Prognosis Consortium Data Coordinating Center: Shoshana H. Ballew (Assistant Project Director), Jingsha Chen (Programmer), Josef Coresh (Principal Investigator), Morgan E. Grams (Director of Nephrology Initiatives), Lucia Kwak (Programmer), Kunihiro Matsushita (Director), Yingying Sang (Lead Programmer), Aditya Surapaneni (Programmer), Mark Woodward (Senior Statistician).•Kidney Disease Improving Global Outcomes (KDIGO) Controversies Conference on Prognosis and Optimal Management of Patients with Advanced CKD: Kai-Uwe Eckardt (Conference Co-Chair), Brenda R. Hemmelgarn (Conference Co-Chair), David C. Wheeler (KDIGO Co-Chair), Wolfgang C. Winkelmayer (KDIGO Co-Chair), John Davis (CEO), Danielle Green (Managing Director), Michael Cheung (Chief Scientific Officer), Tanya Green (Communications Director), Melissa McMahan (Programs Director). Predicting timing of clinical outcomes in patients with chronic kidney disease and severely decreased glomerular filtration rateKidney InternationalVol. 93Issue 6PreviewPatients with chronic kidney disease and severely decreased glomerular filtration rate (GFR) are at high risk for kidney failure, cardiovascular disease (CVD) and death. Accurate estimates of risk and timing of these clinical outcomes could guide patient counseling and therapy. Therefore, we developed models using data of 264,296 individuals in 30 countries participating in the international Chronic Kidney Disease Prognosis Consortium with estimated GFR (eGFR)s under 30 ml/min/1.73m2. Median participant eGFR and urine albumin-to-creatinine ratio were 24 ml/min/1.73m2 and 168 mg/g, respectively. Full-Text PDF Open Archive

Sodium retention and volume overload are the main determinants of poor response to renin‐angiotensin‐aldosterone system (RAAS) inhibition in patients with diabetes. As volume excess can exist without symptoms, biomarkers are needed to identify a priori which patients are volume overloaded and may experience less benefit from RAAS inhibition. N‐terminal pro‐brain natriuretic peptide (NT‐proBNP) is released in the setting of increased cardiac wall stress and volume overload. We conducted a post hoc analysis among 5081 patients with type 2 diabetes mellitus participating in the ALTITUDE trial to investigate whether NTproBNP can predict the effects of additional therapy with aliskiren on cardio‐renal endpoints. Aliskiren compared to placebo reduced the risk of the primary cardio‐renal endpoint events by 20% (95% confidence interval [CI] 16 to 61) and 2% (95% CI –42 to 30) in the two lowest NT‐proBNP tertiles, and it increased the risk by 25% (95% CI –4 to 96) in the highest NT‐proBNP tertile (P value for trend = 0.009). Similar trends were observed for the cardiovascular and end‐stage renal disease endpoints. Effects of aliskiren compared to placebo on safety outcomes (hyperkalaemia and hospitalization for acute kidney injury) were independent of NT‐proBNP. In conclusion, baseline NT‐proBNP may be used as a marker to predict the response to aliskiren with regard to cardio‐renal outcomes when added to standard therapy with RAAS inhibition.

The CROSS (Chemoradiotherapy for Oesophageal Cancer Followed by Surgery Study) trial published in 2012 demonstrated impressive overall survival (OS) for esophageal carcinoma patients treated with trimodality therapy involving preoperative chemoradiation followed by esophagectomy. This study notably used a lower dose of radiation (41.4 Gy) compared to previous trials (50.4 Gy). A randomized study comparing these two doses is likely not feasible; therefore, we studied trends and outcomes of 41.4 Gy and 50.4 Gy using the National Cancer Data Base (NCDB). Patients diagnosed with localized esophageal adenocarcinoma or squamous cell carcinoma from 2004 to 2015 who received definitive chemoradiation (bimodality therapy) or trimodality therapy were identified in the NCDB. Only patients who received radiation doses of 41.4 or 50.4 Gy were included. Kaplan-Meier and Cox regression analyses were performed to compare OS between patients receiving 41.4 Gy and 50.4 Gy as part of bimodality or trimodality therapy. Of the 9,671 patients who met criteria for inclusion, only 6.8% received 41.4 Gy during 2004-2011, increasing to 11.6% between 2012 and 2015 (p<0.001). Just under half of the patients receiving each dose proceeded to surgery (48% for 41.4 Gy vs. 47% for 50.4 Gy). Median follow up was 21 months. For trimodality patients, median and 2-year OS for the 41.4 (n=361) and 50.4 Gy (n=4257) groups were 39.0 vs. 37.2 months and 67% vs. 64%, respectively (p=0.03). Pathologic complete response rates were similar at 7% for 41.4 Gy vs. 8% for 50.4 Gy (p=0.20). For those receiving bimodality therapy, median and 2-year OS for the 41.4 (n=423) and 50.4 Gy (n=4630) groups were 15.4 vs. 17.2 months and 34% vs. 39%, respectively (p=0.01). After controlling for significant covariates on multivariable analysis including T-stage, N-stage, Charlson-Deyo comorbidity index, age, and insurance status, 41.4 Gy was associated with improved OS in the trimodality setting (HR 0.84, 95% CI 0.71-0.98, p=0.03) but worse OS in the bimodality setting (HR 1.14, 95% CI 1.01-1.28, p=0.03). Ninety-day post-operative mortality in trimodality patients trended towards being significantly higher for 50.4 Gy (7.1%) vs. 41.4 Gy (3.9%) (p=0.056). The use of 41.4 Gy has increased over time but still remains low. This lower dose was associated with significantly improved OS in the trimodality setting, whereas 50.4 Gy was superior in the bimodality setting. These results suggest that higher radiation doses may be harmful in the trimodality setting, and dose comparisons may warrant further investigation.

Citation for published version (APA): Idzerda, N. M. A., Persson, F., Pena, M. J., Brenner, B. M., Brunel, P., Chaturvedi, N., ... Heerspink, H. J. L. (2018). N-terminal pro-brain natriuretic peptide (NT-proBNP) predicts the cardio-renal response to aliskiren in patients with type 2 diabetes at high renal and cardiovascular risk. Diabetes obesity & metabolism, 20(12), 2899-2904. DOI: 10.1111/dom.13465

BACKGROUND:People with diabetes and kidney disease have a high risk of cardiovascular events and progression of kidney disease. Sodium glucose co-transporter 2 inhibitors lower plasma glucose by reducing the uptake of filtered glucose in the kidney tubule, leading to increased urinary glucose excretion. They have been repeatedly shown to induce modest natriuresis and reduce HbA1c, blood pressure, weight, and albuminuria in patients with type 2 diabetes. However, the effects of these agents on kidney and cardiovascular events have not been extensively studied in patients with type 2 diabetes and established kidney disease. METHODS:The Canagliflozin and Renal Endpoints in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) trial aims to compare the efficacy and safety of canagliflozin -versus placebo at preventing clinically important kidney and cardiovascular outcomes in patients with diabetes and established kidney disease. CREDENCE is a randomized, double-blind, event-driven, placebo-controlled trial set in in 34 countries with a projected duration of ∼5.5 years and enrolling 4,401 adults with type 2 diabetes, estimated glomerular filtration rate ≥30 to <90 mL/min/1.73 m2, and albuminuria (urinary albumin:creatinine ratio >300 to ≤5,000 mg/g). The study has 90% power to detect a 20% reduction in the risk of the primary outcome (α = 0.05), the composite of end-stage kidney disease, doubling of serum creatinine, and renal or cardiovascular death. CONCLUSION:CREDENCE will provide definitive evidence about the effects of canagliflozin on renal (and cardiovascular) outcomes in patients with type 2 diabetes and established kidney disease. TRIAL REGISTRATION:EudraCT number: 2013-004494-28; ClinicalTrials.gov identifier: NCT02065791.

Introduction: It is essential in the treatment of oncologic patients to set up early diagnosis to chose the adequate surgical and oncological intervention and determine the dietary treatment adjusted to the patient’s nutrititional condition.