Search

Background & Aims: To evaluate the association between soft drinks (SDs) consumption and estimated glomerular filtration rate (eGFR) in a Mexican adult population., Methods: We used data from the RenMex consortium (n = 2095) that included the Mexican Teachers Cohort Study (34-65 years), the Health Workers Cohort Study (18-90 years), and the Comitán Study (19-91 years). In this cross-sectional study, we assessed SDs consumption (cola and flavored soda) using a food frequency questionnaire (FFQ) and estimated eGFR using the CKD Epidemiology Collaboration equation. Quantile regression was used to assess the association between SDs consumption and eGFR with eGFR as a continuous variable. Multinomial logistic regression models were used for eGFR categories derived from quantile regression (mildly decreased eGFR, ≥72.9-87.9 mL/min/1.73 m 2 and moderately decreased eGFR, <72.9 mL/min/1.73 m 2 )., Results: Mean age of study participants was 47.2 years, 67.5% were women, and 12.2% had diabetes. eGFR was <60 mL/min/1.73 m 2 in 3.7% of study participants. Mildly decreased eGFR was present in 14.8%, and moderately decreased eGFR was present in 10.1% of study participants. Quantile regression results showed that SDs consumption was associated with lower eGFR at the 10th, 25th, 50th and 75th percentile. Based on the final adjusted multinomial model, ≥7 servings/week was positively associated with moderately decreased eGFR relative to <1 serving/week (Relative Risk Ratio = 1.95; 95% CI: 1.07-3.57)., Conclusion: Our results suggest that higher SDs consumption is associated with lower eGFR. Encouraging healthy dietary choices should be part of the management and prevention of CKD., (Copyright © 2024 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Chronic kidney disease (CKD) represents a major challenge for Latin American (LatAm) because of its epidemic proportions. Therefore, the current status and knowledge of CKD in Latin America is not clearly understood. Moreover, there is a paucity of epidemiologic studies that makes the comparison across the countries even more difficult. To address these gaps, a virtual kidney expert opinion meeting of 14 key opinion leaders from Argentina, Chile, Colombia, Costa Rica, Dominican Republic, Ecuador, Guatemala, Mexico, and Panama was held in January 2022 to review and discuss the status of CKD in various LatAm regions. The meeting discussed the following: (i) epidemiology, diagnosis, and treatment of CKD, (ii) detection and prevention programs, (iii) clinical guidelines, (iv) state of public policies about diagnosis and management of chronic kidney disease, and (v) role of innovative therapies in the management of CKD. The expert panel emphasized that efforts should be made to implement timely detection programs and early evaluation of kidney function parameters to prevent the development or progression of CKD. Furthermore, the panel discussed the importance of raising awareness among health care professionals; disseminating knowledge to the authorities, the medical community, and the general population about the kidney and cardiovascular benefits of novel therapies; and the need for timely updating of clinical practice guidelines, regulatory policies, and protocols across the region., (© 2023 Published by Elsevier Inc. on behalf of the International Society of Nephrology.)

Background: The endothelin receptor antagonist atrasentan reduced the risk of kidney failure in patients with type 2 diabetes mellitus and chronic kidney disease (CKD) in the SONAR (Study of Diabetic Nephropathy with Atrasentan) trial, although with a numerically higher incidence of heart failure (HF) hospitalization., Objectives: The purpose of this study was to assess if early changes in B-type natriuretic peptide (BNP) and body weight during atrasentan treatment predict HF risk., Methods: Participants with type 2 diabetes and CKD entered an open-label enrichment phase to assess response to atrasentan 0.75 mg/day. Participants without substantial fluid retention (>3 kg body weight increase or BNP increase to >300 pg/mL), were randomized to atrasentan 0.75 mg/day or placebo. Cox proportional hazards regression was used to assess the effects of atrasentan vs placebo on the prespecified safety outcome of HF hospitalizations., Results: Among 3,668 patients, 73 (4.0%) participants in the atrasentan and 51 (2.8%) in the placebo group developed HF (HR: 1.39; 95% CI: 0.97-1.99; P = 0.072). In a multivariable analysis, HF risk was associated with higher baseline BNP (HR: 2.32; 95% CI: 1.81-2.97) and percent increase in BNP during response enrichment (HR: 1.46; 95% CI: 1.08-1.98). Body weight change was not associated with HF. Exclusion of patients with at least 25% BNP increase during enrichment attenuated the risk of HF with atrasentan (HR: 1.02; 95% CI: 0.66-1.56) while retaining nephroprotective effects (HR: 0.58; 95% CI: 0.44-0.78)., Conclusions: In patients with type 2 diabetes and CKD, baseline BNP and early changes in BNP in response to atrasentan were associated with HF hospitalization, highlighting the importance of natriuretic peptide monitoring upon initiation of atrasentan treatment. (Study Of Diabetic Nephropathy With Atrasentan [SONAR]; NCT01858532)., Competing Interests: Funding Support and Author Disclosures This study was conducted in the framework of the IMI BEAt-DKD program. The BEAt-DKD project has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 115974. This Joint Undertaking receives support from the European Union’s Horizon 2020 research and innovation program and EFPIA. Dr Kohan has served as a consultant for AbbVie, AstraZeneca, Chinook Therapeutics, and Travere Therapeutics. Dr Bakris has received support from T32 National Institutes of Health grant DK07011; has served as a consultant to Merck, Bayer, KBP Biosciences, Ionis, Alnylam, AstraZeneca, Quantum Genomics, Horizon, and Novo Nordisk; and has served on the steering committee of trials for Bayer, Quantum Genomics, Alnylam, and Novo Nordisk. Dr Correa-Rotter has served on advisory boards for Boehringer and AstraZeneca; and has been a speaker for AstraZeneca, Boehringer Ingelheim, AbbVie, Takeda, Amgen, and Janssen. Dr Hou has served as a consultant for and received honoraria from AbbVie and AstraZeneca. Dr Januzzi is supported by the Hutter Family Professorship; is a Trustee of the American College of Cardiology; is a board member of Imbria Pharmaceuticals; has received grant support from Abbott Diagnostics, Applied Therapeutics, Innolife and Novartis; has received consulting income from Abbott Diagnostics, Boehringer Ingelheim, Janssen, Novartis, and Roche Diagnostics; and has participated in clinical endpoint committees/data safety monitoring boards for AbbVie, Siemens, Takeda, and Vifor. Dr Kitzman has received grant funding from Novartis, Bayer, NovoNordisk, and AstraZeneca; honoraria for consulting from AbbVie, Bayer, Merck, Medtronic, Relypsa, Merck, Corvia Medical, Boehringer Ingelheim, NovoNordisk, AstraZeneca, Keyto, Pfizer, and Novartis; stock ownership in Gilead Sciences. Dr Kolansky has participated in clinical endpoint committees for ACI Clinical, George Clinical, and the Baim Institute for Clinical Research. Dr Makino has served on steering committees for AbbVie and Teijin; and has served on advisory boards for Boehringer Ingelheim and Travere Therapeutics. Dr Perkovic has served on steering committees for trials funded by AbbVie, Boehringer Ingelheim, GlaxoSmithKline, Janssen, Novo Nordisk, Retrophin, and Tricida; and has participated in scientific presentations or advisory boards with AbbVie, Astellas, AstraZeneca, Bayer, Baxter, Bristol Myers Squibb, Boehringer Ingelheim, Dimerix, Durect, Eli Lilly, Gilead, GlaxoSmithKline, Janssen, Merck, Mitsubishi Tanabe, Novartis, Novo Nordisk, Pfizer, Pharmalink, Relypsa, Retrophin, Sanofi, Servier, and Tricida. Dr Tobe has participated on a steering committee for Bayer Fidelio/Figaro studies; and has served on the Speakers Bureau of Servier and Pfizer. Dr Parving was the co-chair of the SONAR study steering committee; and has served as a consultant for AbbVie. Dr de Zeeuw has served on advisory boards and/or as a speaker for Bayer, Boehringer Ingelheim, Fresenius, Mitsubishi-Tanabe, and Travere Pharmaceuticals; has served on Steering Committees and/or as a speaker for AbbVie and Janssen; and has served on the Data Safety and Monitoring Committees for Bayer, with honoraria paid to the institution and consultant/speaker. Dr Heerspink is supported by a VIDI (917.15.306) grant from the Netherlands Organisation for Scientific Research; has served as a consultant for AbbVie, Astellas, AstraZeneca, Bayer, Boehringer Ingelheim, Chinook, CSL Pharma, Fresenius, Gilead, Janssen, Merck, Mundipharma, Mitsubishi Tanabe, and Retrophin; and has received grant support from AbbVie, AstraZeneca, Boehringer Ingelheim, and Janssen. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: This study aimed to examine the efficacy and safety of dapagliflozin in the Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease (DAPA-CKD) trial (NCT03036150) by geographic region., Methods: Adults with chronic kidney disease (CKD) with or without type 2 diabetes, with estimated glomerular filtration rate (eGFR) 25 to 75 ml/min per 1.73 m 2 and urinary albumin-to-creatinine ratio (UACR) 200 to 5000 mg/g were randomized to dapagliflozin (10 mg once daily) or placebo. The primary end point was a composite of a sustained decline in eGFR of ≥50%, end-stage kidney disease or death from kidney or cardiovascular causes. We categorized recruiting countries into 4 broad global regions: Asia, Europe, Latin America, and North America. Of 4304 randomized patients, 1346 (31.3%) were from Asia, 1233 (28.6%) from Europe, 912 (21.2%) from Latin America, and 813 (18.9%) from North America., Results: The relative risk of the primary composite end point was lower in patients randomized to dapagliflozin (relative to placebo) in all regions, with hazard ratios (95% CI) of 0.70 (0.48-1.00), 0.60 (0.43-0.85), 0.61 (0.43-0.86), and 0.51 (0.34-0.76) among patients from Asia, Europe, Latin America, and North America, respectively. There was no effect modification by region (interaction P  = 0.77). Occurrence of serious adverse events (SAEs) was lower among patients randomized to dapagliflozin versus placebo (21.9% vs. 26.8%, 34.1% vs. 38.6%, 29.8% vs. 31.5%, and 34.9% vs. 41.0% in Asia, Europe, Latin America, and North America, respectively)., Conclusion: Dapagliflozin reduced kidney and cardiovascular events and prolonged survival in patients with CKD, with and without type 2 diabetes, with no apparent effect modification by geographic region., (© 2022 International Society of Nephrology. Published by Elsevier Inc.)

This pre-specified analysis of DAPA-CKD assessed the impact of sodium-glucose cotransporter 2 inhibition on abrupt declines in kidney function in high-risk patients based on having chronic kidney disease (CKD) and substantial albuminuria. DAPA-CKD was a randomized, double-blind, placebo-controlled trial that had a median follow-up of 2.4 years. Adults with CKD (urinary albumin-to-creatinine ratio 200-5000 mg/g and estimated glomerular filtration rate 25-75 mL/min/1.73m 2 ) were randomized to dapagliflozin 10 mg/day matched to placebo (2152 individuals each). An abrupt decline in kidney function was defined as a pre-specified endpoint of doubling of serum creatinine between two subsequent study visits. We also assessed a post-hoc analysis of investigator-reported acute kidney injury-related serious adverse events. Doubling of serum creatinine between two subsequent visits (median time-interval 100 days) occurred in 63 (2.9%) and 91 (4.2%) participants in the dapagliflozin and placebo groups, respectively (hazard ratio 0.68 [95% confidence interval 0.49, 0.94]). Accounting for the competing risk of mortality did not alter our findings. There was no heterogeneity in the effect of dapagliflozin on abrupt declines in kidney function based on baseline subgroups. Acute kidney injury-related serious adverse events were not significantly different and occurred in 52 (2.5%) and 69 (3.2%) participants in the dapagliflozin and placebo groups, respectively (0.77 [0.54, 1.10]). Thus, in patients with CKD and substantial albuminuria, dapagliflozin reduced the risk of abrupt declines in kidney function., (Copyright © 2021 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Introduction: Mineralocorticoid receptor antagonists (MRAs) and sodium-glucose cotransporter-2 (SGLT2) inhibitors reduce the risk of kidney failure in chronic kidney disease (CKD). We performed an analysis of the Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease (DAPA-CKD) trial by baseline conventional MRA (spironolactone and eplerenone) prescription., Methods: Participants with CKD (estimated glomerular filtration rate [eGFR] 25-75 ml/min per 1.73 m 2 ; urinary albumin-to-creatinine ratio 200-500 mg/g), with or without type 2 diabetes, were randomized 1:1 to dapagliflozin 10 mg or placebo, once daily. The primary outcome was a composite of sustained ≥50% eGFR decline, end-stage kidney disease, or kidney or cardiovascular (CV) death. A prespecified kidney-specific secondary outcome was as the primary outcome but without CV death. Hyperkalemia (serum potassium ≥6.0 mmol/l) was an exploratory end point. Time-to-event analyses (proportional hazards [Cox] regression) assessed dapagliflozin versus placebo in patient subgroups defined by baseline conventional MRA use., Results: A total of 229 of 4304 DAPA-CKD participants (5.3%) were receiving conventional MRAs at baseline (dapagliflozin n = 109, placebo n = 120). The effect of dapagliflozin on the primary outcome was consistent in participants prescribed (hazard ratio [HR] 0.76, 95% CI 0.40-1.47) and not prescribed (HR 0.60, 95% CI 0.50-0.72, P -interaction = 0.59) MRAs. This consistency was maintained for the kidney-specific outcome. The effect of dapagliflozin on hyperkalemia (HR 0.87, 95% CI 0.70-1.09) was consistent among those prescribed (HR 0.94, 95% CI 0.41-2.20) and not prescribed (HR 0.87, 95% CI 0.69-1.10, P -interaction = 0.96) MRAs. Adverse events (AEs) leading to discontinuation and serious AEs were similar between treatment groups, regardless of baseline MRA prescription., Conclusion: Dapagliflozin was similarly safe and efficacious in reducing major adverse kidney outcomes in participants with CKD who were or were not prescribed MRAs at baseline., (© 2021 International Society of Nephrology. Published by Elsevier Inc.)

Objectives: The purpose of this paper was to investigate the effects of dapagliflozin in chronic kidney disease (CKD) patients, with and without heart failure (HF)., Background: Patients with CKD, with and without type 2 diabetes, were enrolled in the DAPA-CKD (Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease) trial. Some patients had HF at baseline., Methods: A total of 4,304 participants were randomized to dapagliflozin 10 mg daily or placebo. The primary composite endpoint was ≥50% decline in estimated glomerular filtration rate, end-stage kidney disease, or kidney/cardiovascular death. Secondary endpoints were a kidney composite (primary endpoint minus cardiovascular death), the composite of cardiovascular death/HF hospitalization, and all-cause death. Analysis of outcomes according to HF history was prespecified., Results: HF patients (n = 468; 11%) were older and had more coronary disease, atrial fibrillation, and type 2 diabetes. Mean estimated glomerular filtration rate was similar in patients with and without HF. Rates of HF hospitalization/cardiovascular death and death from any cause were higher in HF patients, but the secondary kidney failure outcome occurred at the same rate in people with and without HF. Dapagliflozin reduced the risk of the primary outcome equally in patients with HF (HR: 0.58 [95% CI: 0.37-0.91]) and without HF (HR: 0.62 [95% CI: 0.51-0.75]) (P interaction = 0.59). The proportional risk-reductions were similar in patients with and without HF for the cardiovascular death/HF hospitalization composite (HR: 0.68 [95% CI: 0.44-1.05] vs HR: 0.70 [95% CI: 0.51-0.97], respectively; P interaction = 0.90), and all-cause death (HR: 0.56 [95% CI: 0.34-0.93] vs HR: 0.73 [95% CI: 0.54-0.97], respectively; P interaction = 0.39), although absolute risk reductions were larger in HF patients. Adverse event rates were low and did not differ among patients with or without HF., Conclusions: Dapagliflozin reduced the risk of kidney failure and cardiovascular death/HF hospitalization and prolonged survival in CKD patients with or without type 2 diabetes, independently of history of HF. (A Study to Evaluate the Effect of Dapagliflozin on Renal Outcomes and Cardiovascular Mortality in Patients With Chronic Kidney Disease [DAPA-CKD]; NCT03036150)., Competing Interests: Funding Support and Author Disclosures The DAPA-CKD trial was funded by AstraZeneca. Prof McMurray is supported by a British Heart Foundation Centre of Research Excellence Grant RE/18/6/34217; his employer, Glasgow University, has received payment for his work on clinical trials, consulting, and other activities from Alnylam, Amgen, AstraZeneca, Bayer, Bristol Myers Squibb, Cardurion, Cytokinetics, GlaxoSmithKline, Novartis, Pfizer, Theracos; and he has received personal lecture fees from the Corpus, Abbott, Hickma, Sun Pharmaceuticals, and Medsca. Dr Wheeler has received honoraria and/or consultancy fees from Amgen, AstraZeneca, Boehringer Ingelheim, Bayer, GlaxoSmithKline, Janssen, Napp, Mundipharma, Medscape, Merck Sharp and Dohme, Pharmacosmos, Reata, Takeda, and Vifor Fresenius. Drs Stefánsson, Sjöström, and Langkilde are employees and stockholders of AstraZeneca. Dr Correa-Rotter has received honoraria from AbbVie, AstraZeneca, GlaxoSmithKline, Medtronic, and Boehringer Ingelheim; has lectured for Amgen, Janssen, Takeda, AstraZeneca, and Boehringer Ingelheim; and has received research support from GlaxoSmithKline, Novo Nordisk, and AstraZeneca. Dr Chertow has received fees from AstraZeneca for the DAPA-CKD trial steering committee; has received research grants from NIDDK and Amgen; is on the board of directors for Satellite Healthcare; has received fees for advisory boards for Baxter, Cricket, DiaMedica, and Reata; holds stock options for Ardelyx, CloudCath, Durect, DxNow, and Outset; has received fees from Akebia, Sanifit, and Vertex for trial steering committees; and has received fees for DSMB service from Angion, Bayer, and ReCor. Dr Hou has received honoraria from AbbVie and AstraZeneca. Dr Rossing has received honoraria to Steno Diabetes Center Copenhagen for consultancy from AstraZeneca, Astellas, Bayer, Boehringer Ingelheim, Gilead, Novo Nordisk, Merck, Mundipharma, Sanofi, and Vifor; and has received research support from AstraZeneca, and Novo Nordisk. Dr Solomon has received research grants from Actelion, Alnylam, Amgen, AstraZeneca, Bellerophon, Bayer, Bristol Myers Squibb, Celladon, Cytokinetics, Eidos, Gilead, GlaxoSmithKline, Ionis, Lilly, Lone Star Heart, Mesoblast, MyoKardia, National Institutes of Health/National Heart, Lung, and Blood Institute, Neurotronik, Novartis, NovoNordisk, Respicardia, Sanofi Pasteur, and Theracos, and has consulted for Abbott, Action Akros, Alnylam, Amgen, Arena, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Cardior, Cardurion, Corvia, Cytokinetics, Daiichi-Sankyo, Gilead, GlaxoSmithKline, Ironwood, Lilly, Merck, MyoKardia, Novartis, Roche, Takeda, Theracos, Quantum Genetics, Cardurion, AoBiome, Janssen, Cardiac Dimensions, Tenaya, Sanofi-Pasteur, Dinaqor, Tremeau, CellProThera, Moderna, and American Regent. Dr Toto has served as a consultant for AstraZeneca, Amgen, Bayer, Boehringer Ingelheim, Medscape, Otsuka, Reata, and Relypsa. Dr Heerspink has served as a consultant for AbbVie, AstraZeneca, Bayer, Boehringer Ingelheim, Chinook, CSL Pharma, Gilead, Janssen, Merck, Mundi Pharma, Mitsubishi Tanabe, Novo Nordisk, and Retrophin; and has received research support from Abbvie, AstraZeneca, Boehringer Ingelheim, and Janssen. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Immunoglobulin A (IgA) nephropathy is a common form of glomerulonephritis, which despite use of renin-angiotensin-aldosterone-system blockers and immunosuppressants, often progresses to kidney failure. In the Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease trial, dapagliflozin reduced the risk of kidney failure and prolonged survival in participants with chronic kidney disease with and without type 2 diabetes, including those with IgA nephropathy. Participants with estimated glomerular filtration rate (eGFR) 25-75 mL/min/1.73m 2 and urinary albumin-to-creatinine ratio 200-5000 mg/g (22.6-565 mg/mol) were randomized to dapagliflozin 10mg or placebo, as adjunct to standard care. The primary composite endpoint was a sustained decline in eGFR of 50% or more, end-stage kidney disease, or death from a kidney disease-related or cardiovascular cause. Of 270 participants with IgA nephropathy (254 [94%] confirmed by previous biopsy), 137 were randomized to dapagliflozin and 133 to placebo, and followed for median 2.1 years. Overall, mean age was 51.2 years; mean eGFR, 43.8 mL/min/1.73m 2 ; and median urinary albumin-to-creatinine ratio, 900 mg/g. The primary outcome occurred in six (4%) participants on dapagliflozin and 20 (15%) on placebo (hazard ratio, 0.29; 95% confidence interval, 0.12, 0.73). Mean rates of eGFR decline with dapagliflozin and placebo were -3.5 and -4.7 mL/min/1.73m 2 /year, respectively. Dapagliflozin reduced the urinary albumin-to-creatinine ratio by 26% relative to placebo. Adverse events leading to study drug discontinuation were similar with dapagliflozin and placebo. There were fewer serious adverse events with dapagliflozin, and no new safety findings in this population. Thus, in participants with IgA nephropathy, dapagliflozin reduced the risk of chronic kidney disease progression with a favorable safety profile., (Copyright © 2021 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Background: Short-term treatment for people with type 2 diabetes using a low dose of the selective endothelin A receptor antagonist atrasentan reduces albuminuria without causing significant sodium retention. We report the long-term effects of treatment with atrasentan on major renal outcomes., Methods: We did this double-blind, randomised, placebo-controlled trial at 689 sites in 41 countries. We enrolled adults aged 18-85 years with type 2 diabetes, estimated glomerular filtration rate (eGFR) 25-75 mL/min per 1·73 m 2 of body surface area, and a urine albumin-to-creatinine ratio (UACR) of 300-5000 mg/g who had received maximum labelled or tolerated renin-angiotensin system inhibition for at least 4 weeks. Participants were given atrasentan 0·75 mg orally daily during an enrichment period before random group assignment. Those with a UACR decrease of at least 30% with no substantial fluid retention during the enrichment period (responders) were included in the double-blind treatment period. Responders were randomly assigned to receive either atrasentan 0·75 mg orally daily or placebo. All patients and investigators were masked to treatment assignment. The primary endpoint was a composite of doubling of serum creatinine (sustained for ≥30 days) or end-stage kidney disease (eGFR <15 mL/min per 1·73 m 2 sustained for ≥90 days, chronic dialysis for ≥90 days, kidney transplantation, or death from kidney failure) in the intention-to-treat population of all responders. Safety was assessed in all patients who received at least one dose of their assigned study treatment. The study is registered with ClinicalTrials.gov, number NCT01858532., Findings: Between May 17, 2013, and July 13, 2017, 11 087 patients were screened; 5117 entered the enrichment period, and 4711 completed the enrichment period. Of these, 2648 patients were responders and were randomly assigned to the atrasentan group (n=1325) or placebo group (n=1323). Median follow-up was 2·2 years (IQR 1·4-2·9). 79 (6·0%) of 1325 patients in the atrasentan group and 105 (7·9%) of 1323 in the placebo group had a primary composite renal endpoint event (hazard ratio [HR] 0·65 [95% CI 0·49-0·88]; p=0·0047). Fluid retention and anaemia adverse events, which have been previously attributed to endothelin receptor antagonists, were more frequent in the atrasentan group than in the placebo group. Hospital admission for heart failure occurred in 47 (3·5%) of 1325 patients in the atrasentan group and 34 (2·6%) of 1323 patients in the placebo group (HR 1·33 [95% CI 0·85-2·07]; p=0·208). 58 (4·4%) patients in the atrasentan group and 52 (3·9%) in the placebo group died (HR 1·09 [95% CI 0·75-1·59]; p=0·65)., Interpretation: Atrasentan reduced the risk of renal events in patients with diabetes and chronic kidney disease who were selected to optimise efficacy and safety. These data support a potential role for selective endothelin receptor antagonists in protecting renal function in patients with type 2 diabetes at high risk of developing end-stage kidney disease., Funding: AbbVie., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Introduction: High-dose corticosteroids remain the first-line therapy for focal and segmental glomerulosclerosis (FSGS), whereas calcineurin inhibitors (CNIs) are reserved for those patients resistant to corticosteroid therapy., Methods: This is a retrospective cohort analysis in patients with primary FSGS diagnosed between 2007 and 2014. According to the administered treatment, patients were segregated into 3 groups: high-dose prednisone, first-line CNIs plus low-dose prednisone, and rescue CNIs. Cumulative corticosteroid doses were compared as well as response to therapy and long-term renal survival by Cox regression analysis., Results: A total of 66 patients were included (39 treated with high-dose prednisone, 11 treated with first-line CNI, 16 treated with high-dose prednisone followed by rescue CNI). Cumulative doses of prednisone in the high-dose group were 9.3 g (interquartile range [IQR] = 7.5-12.5 g), compared to 2.5 g (IQR = 1.82-3.12 g) in the first-line CNI plus low-dose corticosteroid group and 13.8 g (IQR = 9.2-15.8 g) rescue CNI groups, respectively ( P  < 0.001). Time under corticosteroid management was also higher in the high-dose prednisone group compared to the first-line CNI group. There was a response to treatment in 76.9%, 72.7%, and 87.5% of high-dose prednisone, first-line CNI and rescue CNI groups, with complete remission in 48.7%, 36.4%, and 31.3% respectively. There was no difference in relapse incidence after treatment (48.4%, 44.4%, and 46.7%) or in 5-year renal survival (87.2%, 81.8%, and 87.5%). Baseline proteinuria, biopsy chronicity score, and response to therapy were independent predictors of renal survival., Conclusion: An initial CNI plus low-dose corticosteroid approach in primary FSGS reduces corticosteroid exposure with a response-to-therapy rate similar to that of the currently recommended high-dose corticosteroid regimen. These findings justify a randomized trial to formally test this hypothesis.

Introduction: Despite a systematic increase in the coverage of patients with end-stage renal disease (ESRD) who have received dialytic therapies and transplantation over the past 2 decades, the Mexican health system currently still does not have a program to provide full coverage of ESRD. Our aim was to analyze mortality in patients with ESRD without health insurance., Methods: This was a prospective cohort study of 850 patients with advanced chronic kidney disease (CKD). Risk factors associated with death were calculated using a Cox's proportional hazards model. We used the statistical package SPSS version 22.0 for data analysis., Results: The mean age of patients was 44.8 ± 17.2 years old. At the time of hospital admission, 87.6% of the population did not have a social security program to cover the cost of renal replacement treatment, and 91.3% of families had an income below US$300 per month. During the 3 years of the study, 28.8% of the cohort patients were enrolled in 1 of Mexico's social security programs. The 3-year mortality rate was of 56.7% among patients without access to health insurance, in contrast to 38.2% of patients who had access to a social security program that provided access to renal replacement therapy ( P  < 0.001). Risk factor analysis revealed that not having health insurance increased mortality (risk ratio: 2.64, 95% confidence intervals: 1.84-3.79; P  = 0.001)., Conclusion: Mexico needs a coordinated National Kidney Health and Treatment Program. A program of this nature should provide the basis for an appropriate educational and intervention strategy for early detection, prevention, and treatment of patients with advanced chronic kidney disease.

In order to change the current state of chronic kidney disease knowledge and therapeutics, a fundamental improvement in the understanding of genetic and environmental causes of chronic kidney disease is essential. This article first provides an overview of the existing knowledge gaps in our understanding of the genetic and environmental causes of chronic kidney disease, as well as their interactions. The second part of the article formulates goals that should be achieved in order to close these gaps, along with suggested timelines and stakeholders that are to be involved. A better understanding of genetic and environmental factors and their interactions that influence kidney function in healthy and diseased conditions can provide novel insights into renal physiology and pathophysiology and result in the identification of novel therapeutic or preventive targets to tackle the global public health care problem of chronic kidney disease.

Background: Child and maternal health outcomes have notably improved in Mexico since 1990, whereas rising adult mortality rates defy traditional epidemiological transition models in which decreased death rates occur across all ages. These trends suggest Mexico is experiencing a more complex, dissonant health transition than historically observed. Enduring inequalities between states further emphasise the need for more detailed health assessments over time. The Global Burden of Diseases, Injuries, and Risk Factors Study 2013 (GBD 2013) provides the comprehensive, comparable framework through which such national and subnational analyses can occur. This study offers a state-level quantification of disease burden and risk factor attribution in Mexico for the first time., Methods: We extracted data from GBD 2013 to assess mortality, causes of death, years of life lost (YLLs), years lived with disability (YLDs), disability-adjusted life-years (DALYs), and healthy life expectancy (HALE) in Mexico and its 32 states, along with eight comparator countries in the Americas. States were grouped by Marginalisation Index scores to compare subnational burden along a socioeconomic dimension. We split extracted data by state and applied GBD methods to generate estimates of burden, and attributable burden due to behavioural, metabolic, and environmental or occupational risks. We present results for 306 causes, 2337 sequelae, and 79 risk factors., Findings: From 1990 to 2013, life expectancy from birth in Mexico increased by 3·4 years (95% uncertainty interval 3·1-3·8), from 72·1 years (71·8-72·3) to 75·5 years (75·3-75·7), and these gains were more pronounced in states with high marginalisation. Nationally, age-standardised death rates fell 13·3% (11·9-14·6%) since 1990, but state-level reductions for all-cause mortality varied and gaps between life expectancy and years lived in full health, as measured by HALE, widened in several states. Progress in women's life expectancy exceeded that of men, in whom negligible improvements were observed since 2000. For many states, this trend corresponded with rising YLL rates from interpersonal violence and chronic kidney disease. Nationally, age-standardised YLL rates for diarrhoeal diseases and protein-energy malnutrition markedly decreased, ranking Mexico well above comparator countries. However, amid Mexico's progress against communicable diseases, chronic kidney disease burden rapidly climbed, with age-standardised YLL and DALY rates increasing more than 130% by 2013. For women, DALY rates from breast cancer also increased since 1990, rising 12·1% (4·6-23·1%). In 2013, the leading five causes of DALYs were diabetes, ischaemic heart disease, chronic kidney disease, low back and neck pain, and depressive disorders; the latter three were not among the leading five causes in 1990, further underscoring Mexico's rapid epidemiological transition. Leading risk factors for disease burden in 1990, such as undernutrition, were replaced by high fasting plasma glucose and high body-mass index by 2013. Attributable burden due to dietary risks also increased, accounting for more than 10% of DALYs in 2013., Interpretation: Mexico achieved sizeable reductions in burden due to several causes, such as diarrhoeal diseases, and risks factors, such as undernutrition and poor sanitation, which were mainly associated with maternal and child health interventions. Yet rising adult mortality rates from chronic kidney disease, diabetes, cirrhosis, and, since 2000, interpersonal violence drove deteriorating health outcomes, particularly in men. Although state inequalities from communicable diseases narrowed over time, non-communicable diseases and injury burdens varied markedly at local levels. The dissonance with which Mexico and its 32 states are experiencing epidemiological transitions might strain health-system responsiveness and performance, which stresses the importance of timely, evidence-informed health policies and programmes linked to the health needs of each state., Funding: Bill & Melinda Gates Foundation, Instituto Nacional de Salud Pública., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: Chronic kidney disease is common among sugarcane workers in Central America. The main risk factor seems to be repeated high-intensity work in hot environments. Several cross-sectional studies have been performed but few longitudinal studies., Objectives: The aim of the study was to examine whether kidney function changes over a few months of work during the harvest period., Methods: A group of male sugarcane cutters in Nicaragua (N=29, aged 17-38 years) was examined with renal biomarkers before and after shift on the first day at the start of harvest, on the sixth day during acclimatization, and then in mid-harvest 9 weeks later. A reference group (N=25, mainly office workers) was examined with the same biomarkers at start of harvest, and then at end of harvest 5 months later., Results: The pre-shift renal function decreased significantly during 9 weeks of work in the cane cutters. Mean serum creatinine increased (20%), mean estimated glomerular filtration rate decreased (9%, 10mL/min), serum urea N (BUN) increased (41%), and mean urinary neutrophil gelatinase-associated lipocalin (NGAL) increased (four times). The cane cutters also developed cross-shift increases in these biomarkers, in particular serum creatinine and BUN, and in urinary uric acid. The longitudinal decrease in eGFR tended to be associated with the cross-shift increase in serum creatinine., Conclusions: There was a remarkable decrease of glomerular kidney function, after only 9 weeks of harvest. The cross-shift increase in serum creatinine may be caused by dehydration (pre-renal dysfunction), and when repeated on a daily basis this may cause permanently reduced GFR., (Copyright © 2016 Elsevier Inc. All rights reserved.)

The epidemic of chronic kidney disease in Nicaragua (Mesoamerican nephropathy) has been linked with recurrent dehydration. Here we tested whether recurrent dehydration may cause renal injury by activation of the polyol pathway, resulting in the generation of endogenous fructose in the kidney that might subsequently induce renal injury via metabolism by fructokinase. Wild-type and fructokinase-deficient mice were subjected to recurrent heat-induced dehydration. One group of each genotype was provided water throughout the day and the other group was hydrated at night, after the dehydration. Both groups received the same total hydration in 24 h. Wild-type mice that received delayed hydration developed renal injury, with elevated serum creatinine, increased urinary NGAL, proximal tubular injury, and renal inflammation and fibrosis. This was associated with activation of the polyol pathway, with increased renal cortical sorbitol and fructose levels. Fructokinase-knockout mice with delayed hydration were protected from renal injury. Thus, recurrent dehydration can induce renal injury via a fructokinase-dependent mechanism, likely from the generation of endogenous fructose via the polyol pathway. Access to sufficient water during the dehydration period can protect mice from developing renal injury. These studies provide a potential mechanism for Mesoamerican nephropathy.

Background: &nbsp;The performance of the CKD-EPI and MDRD formulae for estimating glomerular filtration rate (GFR) in patients of Hispanic origin with normal renal function has been poorly explored and requires validation in Mexico.&nbsp;, Material and Method: &nbsp;We included previously healthy Mexican adults. We obtained clinical variables and determined serum creatinine to calculate the CKD-EPI and MDRD-IDMS formulae. These results were compared with the gold standard (GFR measured by Tc99DTPA). We evaluated other clinical variables that could affect the performance of the CKD-EPI formula.&nbsp;, Results: &nbsp;A total of 97 healthy volunteers were included, 55 males and 42 females; the mean age was 35.8 years old (18 to 73). Mean creatinine was 0.76mg/dl (&plusmn;0.18). CKD-EPI performance was significantly better than MDRD-IDMS in all comparisons (bias, correlation and accuracy). The bias difference between the formulae was 6.08ml/min/1.73m2&nbsp;(95% CI 2.58 to 9.58) (p&lt;.001). Individuals with a body mass index (BMI) above 25kg/m2&nbsp;displayed a better performance than the group with a lower BMI (difference of means 7.39ml/min/1.73m2;&nbsp;95% CI 1.17 to 13.6 p&lt;.02). Both formulae overestimated the GFR. BMI was significantly associated with the performance of the CKD-EPI formula (&beta; 0.82; 95% CI 0.085 to 1.56 p=.029).&nbsp;, Conclusions: &nbsp;In healthy Mexican adults, the CKD-EPI formula is a better predictor of the mGFR than the MDRD-IDMS formula. BMI is significantly associated with the performance of the CKD-EPI formula and is better in those with a BMI greater than 25kg/m2. Both formulae overestimate mGFR.

Background: Anemia almost invariably occurs in patients with chronic kidney disease. Limited data are available regarding anemia management in Latin American (LA) hemodialysis (HD) patients., Objective: To evaluate the results of the first anemia survey of the Anemia Committee of the SLANH., Methods: This is a multinational, voluntary survey that collected anemia management data from adult HD patients from independent, non-chain owned HD units, between 09/2009 and 03/2010. T-test, ANOVA, chi-square test and multivariate logistic regression were used for statistical analysis., Results: The survey received responses from 134 HD units of 16 countries providing data from 9,025 patients. Mean values of Hb, ferritin, and transferrin saturation (TSAT) were 10.5 ± 1.8 g/dL, 570 ± 539 µg/l, and 29.8 ± 15%, respectively. Only 32.7% of patients were within the Hb target of 10.5-12.0 g/dL (46.3% were below and 21.1% above). Erythropoietin-stimulating agents (ESAs) were administered to 84.3% patients and 68.3% received intravenous iron (IV). Iron deficiency (TSAT≤20%) was present in 27.5% patients and among those receiving erythropoietin, 47% did not achieve Hb target. The independent variables associated with the lowest Hb level (<10.5 g/dL) were: female gender, TSAT<25% and age<50 years., Conclusions: According to these results, nearly half of LA chronic HD patients did not achieve the recommended Hb target despite wide use of ESAs and IV iron.

Since the first description of the association between chronic kidney disease and heart disease, many epidemiological studies have confirmed and extended this finding. As chronic kidney disease progresses, kidney-specific risk factors for cardiovascular events and disease come into play. As a result, the risk for cardiovascular disease is notably increased in individuals with chronic kidney disease. When adjusted for traditional cardiovascular risk factors, impaired kidney function and raised concentrations of albumin in urine increase the risk of cardiovascular disease by two to four times. Yet, cardiovascular disease is frequently underdiagnosed and undertreated in patients with chronic kidney disease. This group of patients should, therefore, be acknowledged as having high cardiovascular risk that needs particular medical attention at an individual level. This view should be incorporated in the development of guidelines and when defining research priorities. Here, we discuss the epidemiology and pathophysiological mechanisms of cardiovascular risk in patients with chronic kidney disease, and discuss methods of prevention., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Acute kidney injury (AKI) is often associated to acute respiratory distress syndrome (ARDS) due to influenza A/H1N1 virus infection. The profile of angiogenic and inflammatory factors in ARDS patients may be relevant for AKI. We analyzed the serum levels of several angiogenic factors, cytokines, and chemokines in 32 patients with A/H1N1 virus infection (17 with ARDS/AKI and 15 ARDS patients who did not developed AKI) and in 18 healthy controls. Significantly higher levels of VEGF, MCP-1, IL-6, IL-8 and IP-10 in ARDS/AKI patients were detected. Adjusting by confusing variables, levels of MCP-1 ≥150 pg/mL (OR=12.0, p=0.04) and VEGF ≥225 pg/mL (OR=6.4, p=0.03) were associated with the development of AKI in ARDS patients. Higher levels of MCP-1 and IP-10 were significantly associated with a higher risk of death in patients with ARDS (hazard ratio (HR)=10.0, p=0.02; HR=25.5, p=0.03, respectively) even taking into account AKI. Patients with influenza A/H1N1 infection and ARDS/AKI have an over-production of MCP-1, VEGF and IP-10 possibly contributing to kidney injury and are associated to a higher risk of death., (Copyright © 2013 Elsevier Inc. All rights reserved.)

The clinical practice guidelines for the prevention, diagnosis, evaluation and treatment of chronic kidney disease mineral and bone disorders (CKD-BMD) in adults, of the Latin American Society of Nephrology and Hypertension (SLANH) comprise a set of recommendations developed to support the doctor in the management of these abnormalities in adult patients with stages 3-5 kidney disease. This excludes changes associated with renal transplantation. The topics covered in the guidelines are divided into four chapters: 1) Evaluation of biochemical changes, 2) Evaluation of bone changes, 3) Evaluation of vascular calcifications, and 4) Treatment of CKD-MBD. The guidelines are based on the recommendations proposed and published by the Kidney Disease: Improving Global Outcomes (KDIGO) for the prevention, diagnosis, evaluation and treatment of CKD-MBD (KDIGO Clinical practice guidelines for the diagnosis, evaluation, prevention and treatment of Chronic Kidney Disease Mineral and Bone Disorder [CKD-MBD]), adapted to the conditions of patients, institutions and resources available in Latin America, with the support of KDIGO. In some cases, the guidelines correspond to management recommendations directly defined by the working group for their implementation in our region, based on the evidence available in the literature. Each chapter contains guidelines and their rationale, supported by numerous updated references. Unfortunately, there are few controlled studies with statistically sufficient weight in Latin America to support specific recommendations for the region, and as such, most of the references used correspond to studies carried out in other regions. This highlights the need to plan research studies designed to establish the current status of mineral and bone metabolism disorders in Latin America as well as defining the best treatment options for our population.

Objectives: Our aim was to analyze a retrospective cohort of renal transplant recipients to determine the risk factors for infections that require hospitalization., Methods: This was a cohort study that included patients who had received kidney transplants from January 1990 to December 2003. The statistical analysis was performed according to the distribution of variables, and p<0.05 was considered statistically significant., Results: We analyzed 366 transplants in 350 patients, of whom 161 (46%) presented with an episode of infection requiring hospitalization. These 161 patients developed 323 infections (a median of two infections per patient). The incidence rate was 0.46 episodes per 1000 transplant-days. Urinary tract infection, pneumonia, bacteremia, and gastroenteritis were the most common diseases. A high incidence of infections due to Escherichia coli and Enterococcus species, as well as Candida species, was found. By multivariate Cox model, significant risk factors for infections requiring hospitalization were systemic lupus erythematosus (relative risk (RR) 4.8, 95% confidence interval (CI) 1.64-14.1), cancer (RR 3.81, 95% CI 1.05-13.7), previous renal transplant (RR 5.6, 95% CI 1.4-22.4), history of anti-rejection therapy (RR 3.2, 95% CI 1.3-8.0), and a basal serum albumin concentration<3.5mg/dl (RR 1.77, 95% CI 1.17-2.68). Interestingly, dyslipidemia (RR 0.5, 95% CI 0.37-0.69) and end-stage renal disease of unknown etiology (RR 0.5, 95% CI 0.3-0.8) were protective factors against hospitalization., Conclusions: These data suggest that the most common infections requiring hospitalization in our cohort were those caused by microorganisms commonly related with community-acquired infections rather than those classically associated with immunosuppressant therapy. These findings will be useful for refining medical care., (Copyright © 2010 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

It has been shown that reactive oxygen species are involved in chronic puromycin aminonucleoside (PAN) induced nephrotic syndrome (NS) and that a 20% soy protein diet reduces renal damage in this experimental model. The purpose of the present work was to investigate if a 20% soy protein diet is able to modulate kidney nitrotyrosine formation and the activity of renal antioxidant enzymes (catalase, glutathione peroxidase, Cu,Zn- or Mn-superoxide dismutase) which could explain, at least in part, the protective effect of the soy protein diet in rats with chronic NS induced by PAN. Four groups of rats were studied: (1) Control rats fed 20% casein diet, (2) Nephrotic rats fed 20% casein diet, (3) Control rats fed 20% soy protein diet, and (4) Nephrotic rats fed 20% soy protein diet. Chronic NS was induced by repeated injections of PAN and rats were sacrificed at week nine. The soy protein diet ameliorated proteinuria, hypercholesterolemia, and the increase in serum creatinine and blood urea nitrogen observed in nephrotic rats fed 20% casein diet. Kidney nitrotyrosine formation increased in nephrotic rats fed 20% casein diet and this increase was ameliorated in nephrotic rats fed 20% soy protein diet. However, the soy protein diet was unable to modulate the antioxidant enzymes activities in control and nephrotic rats fed 20% soy protein diet. Food intake was similar in the two diet groups. The protective effect of a 20% soy protein diet on renal damage in chronic nephropathy induced by PAN was associated with the amelioration in the renal nitrotyrosine formation but not with the modulation of antioxidant enzymes.

Nephrotic syndrome (NS) is characterized by the presence of proteinuria and hyperlipidemia. However, ingestion of soy protein has a hypolipidemic effect. The present study was designed to determine whether the ingestion of a 20% soy protein diet regulates the expression of hepatic sterol regulatory element binding protein (SREBP)-1, fatty acid synthase (FAS), malic enzyme, beta-hydroxy-beta-methylglutaryl-CoA (HMG-CoA) reductase (r) and synthase (s), and LDL receptor (r), and to assess whether soy protein improves lipid and renal abnormalities in rats with chronic NS. Male Wistar rats were injected with vehicle or with puromycin aminonucleoside to induce NS and were fed either 20% casein or soy protein diets for 64 d. NS rats fed 20% soy protein had improved creatinine clearance and reduced proteinuria, hypercholesterolemia, hypertriglyceridemia, as well as VLDL-triglycerides and LDL cholesterol compared with NS rats fed the 20% casein diet. In addition, the soy protein diet decreased the incidence of glomerular sclerosis, and proinflammatory cytokines in kidney. Ingestion of the soy protein diet by control rats reduced the gene expression of SREBP-1, malic enzyme, FAS and increased HMG-CoAr, HMG-CoAs and LDLr. However, NS rats fed either casein or soy protein diets had low insulin concentrations with reductions in SREBP-1, FAS and malic enzyme expression compared with control rats fed the casein diet. NS rats fed the soy diet also had lower HMG-CoAr and LDLr mRNA levels than NS rats fed casein. In conclusion, the beneficial effects of soy protein on lipid metabolism are modulated in part by SREBP-1. However, in NS rats, the benefit may be through a direct effect of this protein on kidney rather than mediated by changes in expression of hepatic lipid metabolism genes.