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Patients with severely decreased glomerular filtration rate (GFR) (i.e., chronic kidney disease [CKD] G4+) are at increased risk for kidney failure, cardiovascular disease (CVD) events (including heart failure), and death. However, little is known about the variability of outcomes and optimal therapeutic strategies, including initiation of kidney replacement therapy (KRT). Kidney Disease: Improving Global Outcomes (KDIGO) organized a Controversies Conference with an international expert group in December 2016 to address this gap in knowledge. In collaboration with the CKD Prognosis Consortium (CKD-PC) a global meta-analysis of cohort studies (n = 264,515 individuals with CKD G4+) was conducted to better understand the timing of clinical outcomes in patients with CKD G4+ and risk factors for different outcomes. The results confirmed the prognostic value of traditional CVD risk factors in individuals with severely decreased GFR, although the risk estimates vary for kidney and CVD outcomes. A 2- and 4-year model of the probability and timing of kidney failure requiring KRT was also developed. The implications of these findings for patient management were discussed in the context of published evidence under 4 key themes: management of CKD G4+, diagnostic and therapeutic challenges of heart failure, shared decision-making, and optimization of clinical trials in CKD G4+ patients. Participants concluded that variable prognosis of patients with advanced CKD mandates individualized, risk-based management, factoring in competing risks and patient preferences.

Perioperative medicine is changing rapidly, and with this change comes the opportunity to improve upon current models of care delivery and integration within the health care system. Perioperative models of care are structured or conceptual arrangements for surgical patients before, during and after their surgery. Models of care such as the Perioperative Surgical Home and Enhanced Recovery After Surgery pathways are increasingly used to guide the structure of perioperative care delivery with an aim to improve patient outcomes and experience in Canadian settings. In this narrative review, we summarize the origins of these perioperative models of care. They are fundamentally different in scope and level of evidence. Both models have potential benefits and limitations to their broad implementation in our health care system. As currently developed, both models are limited in their application to patients with chronic disease. We discuss how these models of care can be used to develop integrated horizontal and vertical perioperative pathways in a Canadian setting. Such integration is a potential solution that will improve their applicability to patients with medically complex conditions and in times when health care systems are under pressure. We describe this approach using the example of patients with kidney failure receiving dialysis. La medecine perioperatoire evolue rapidement, ce qui est propice a l'amelioration des modeles de soins actuels et a leur integration au systeme de sante. Les modeles de soins perioperatoires sont des approches structurees ou conceptuelles a l'intention des patients de chirurgie avant, durant et apres leur intervention. Les modeles de soins perioperatoires, tels que les approches PSH (Perioperative Surgical Home) et ERAS (Enhanced Recovery After Surgery) sont de plus en plus utilises pour orienter la structure et la prestation des soins perioperatoires dans le but d'ameliorer les resultats et l'experience des patients dans les milieux de soins au Canada. Dans la presente syn-these narrative, nous retracons l'origine de ces modeles de soins perioperatoires. Ils sont fondamentalement differents aux plans de leur portee et de leur niveau de preuves. Mais leur deploiement a grande echelle dans nos systemes de sante comporte des avantages et des inconvenients potentiels. Dans l'etat actuel de leur developpe-ment, les 2 modeles ont une applicabilite limitee pour les patients atteints de maladies chroniques. Nous discutons de la facon dont ils peuvent etre utilises pour developper des approches horizontales et verticales integrees au contexte canadien. Cette integration est une solution envisageable qui ameliorera leur application aux patients atteints de maladies complexes, a une epoque ou les systemes de sante sont sous pression. Nous decrivons cette approche en prenant l'exemple des insuffisants renaux dialyses., Although the field of perioperative medicine is growing and evolving, a widely accepted current definition is the 'integrated, multi-disciplinary medical care of patients from the moment of contemplation of surgery [...]

BackgroundDiabetes mellitus and hypertension are risk factors for acute kidney injury (AKI). Whether estimated glomerular filtration rate (eGFR) and urine albumin-creatinine ratio (ACR) remain risk factors for AKI in the presence and absence of these conditions is uncertain.Study designMeta-analysis of cohort studies.Setting & population8 general-population (1,285,045 participants) and 5 chronic kidney disease (CKD; 79,519 participants) cohorts.Selection criteria for studiesCohorts participating in the CKD Prognosis Consortium.PredictorsDiabetes and hypertension status, eGFR by the 2009 CKD Epidemiology Collaboration creatinine equation, urine ACR, and interactions.OutcomeHospitalization with AKI, using Cox proportional hazards models to estimate HRs of AKI and random-effects meta-analysis to pool results.ResultsDuring a mean follow-up of 4 years, there were 16,480 episodes of AKI in the general-population and 2,087 episodes in the CKD cohorts. Low eGFRs and high ACRs were associated with higher risks of AKI in individuals with or without diabetes and with or without hypertension. When compared to a common reference of eGFR of 80mL/min/1.73m(2) in nondiabetic patients, HRs for AKI were generally higher in diabetic patients at any level of eGFR. The same was true for diabetic patients at all levels of ACR compared with nondiabetic patients. The risk gradient for AKI with lower eGFRs was greater in those without diabetes than with diabetes, but similar with higher ACRs in those without versus with diabetes. Those with hypertension had a higher risk of AKI at eGFRs>60mL/min/1.73m(2) than those without hypertension. However, risk gradients for AKI with both lower eGFRs and higher ACRs were greater for those without than with hypertension.LimitationsAKI identified by diagnostic code.ConclusionsLower eGFRs and higher ACRs are associated with higher risks of AKI among individuals with or without either diabetes or hypertension.

BackgroundAcute kidney injury (AKI) is a serious global public health problem. We aimed to quantify the risk of AKI associated with estimated glomerular filtration rate (eGFR), albuminuria (albumin-creatinine ratio [ACR]), age, sex, and race (African American and white).Study designCollaborative meta-analysis.Setting & population8 general-population cohorts (1,285,049 participants) and 5 chronic kidney disease (CKD) cohorts (79,519 participants).Selection criteria for studiesAvailable eGFR, ACR, and 50 or more AKI events.PredictorsAge, sex, race, eGFR, urine ACR, and interactions.OutcomeHospitalized with or for AKI, using Cox proportional hazards models to estimate HRs of AKI and random-effects meta-analysis to pool results.Results16,480 (1.3%) general-population cohort participants had AKI over a mean follow-up of 4 years; 2,087 (2.6%) CKD participants had AKI over a mean follow-up of 1 year. Lower eGFR and higher ACR were strongly associated with AKI. Compared with eGFR of 80mL/min/1.73m(2), the adjusted HR of AKI at eGFR of 45mL/min/1.73m(2) was 3.35 (95% CI, 2.75-4.07). Compared with ACR of 5mg/g, the risk of AKI at ACR of 300mg/g was 2.73 (95% CI, 2.18-3.43). Older age was associated with higher risk of AKI, but this effect was attenuated with lower eGFR or higher ACR. Male sex was associated with higher risk of AKI, with a slight attenuation in lower eGFR but not in higher ACR. African Americans had higher AKI risk at higher levels of eGFR and most levels of ACR.LimitationsOnly 2 general-population cohorts could contribute to analyses by race; AKI identified by diagnostic code.ConclusionsReduced eGFR and increased ACR are consistent strong risk factors for AKI, whereas associations of AKI with age, sex, and race may be weaker in more advanced stages of CKD.

Background: Acute kidney injury (AKI) is associated with increased morbidity and mortality after liver resection. Patients with hepatocellular carcinoma (HCC) have a higher risk of AKI owing to the underlying association between hepatic and renal dysfunction. Use of the Acute Kidney Injury Network (AKIN) diagnostic criteria is recommended for patients with cirrhosis, but remains poorly studied following liver resection. We compared the prognostic value of the AKIN creatinine and urine output criteria in terms of postoperative outcomes following liver resection for HCC. Methods: All patients who underwent a liver resection for HCC from January 2010 to June 2016 were included. We used AKIN urine output and creatinine criteria to assess for AKI within 48 hours of surgery. Results: Eighty liver resections were performed during the study period. Cirrhosis was confirmed in 80%. Median hospital stay was 9 (interquartile range 7-12) days, and 30-day mortality was 2.5%. The incidence of AKI was higher based on the urine output than on the creatinine criterion (53.8% v. 20%), and was associated with prolonged hospitalization and 30-day postoperative mortality when defined by serum creatinine (hospital stay: 11.2 v. 20.1 d, p = 0.01; mortality: 12.5% v. 0%, p < 0.01), but not urine output (hospital stay: 15.6 v. 10 d, p = 0.05; mortality: 2.3% v. 2.7%, p > 0.99). Conclusion: The urine output criterion resulted in an overestimation of AKI and compromised the prognostic value of AKIN criteria. Revision may be required to account for the exacerbated physiologic postoperative reduction in urine output in patients with HCC. Contexte : L'insuffisance renale aigue (IRA) est associee a une morbidite et a une mortalite accrues apres une resection hepatique. Les patients atteints d'un carcinome hepatocellulaire (CHC) sont exposes a un risque plus grand d'IRA en raison du lien sous-jacent entre l'insuffisance hepatique et l'insuffisance renale. Les criteres diagnostiques de l'Acute Kidney Injury Network (AKIN) sont recommandes chez les patients cirrhotiques, mais ils n'ont pas ete bien etudies dans les cas de resection hepatique. Nous avons compare la valeur pronostique des criteres de l'AKIN tels que la creatinine et le debit urinaire pour ce qui est des resultats postoperatoires suite a une resection hepatique pour CHC. Methodes : Tous les patients soumis a une resection hepatique pour CHC entre janvier 2010 et juin 2016 ont ete inclus. Nous avons utilise les criteres de l'AKIN concernant le debit urinaire et la creatinine pour evaluer l'IRA dans les 48 heures suivant la chirurgie. Resultats : Quatre-vingt resections hepatiques ont ete effectuees pendant la periode de l'etude. La cirrhose a ete confirmee dans 80 % des cas. Le sejour hospitalier median a dure 9 jours (intervalle interquartile 7-12 jours) et la mortalite a 30 jours a ete de 2,5 %. L'incidence de l'IRA a ete plus elevee selon le critere debit urinaire que selon le critere creatinine (53,8 % c. 20 %), et a ete associee a un sejour plus long et a une mortalite a 30 jours plus elevee suite a l'intervention selon le critere creatinine serique (sejour hospitalier : 11,2 c. 20,1 j, p = 0,01; mortalite : 12,5 % c. 0 %, p < 0,01), mais non selon le critere debit urinaire (sejour hospitalier : 15,6 c. 10 j, p = 0,05; mortalite : 2,3 % c. 2,7 %, p > 0,99). Conclusion : Le critere debit urinaire a donne lieu a une surestimation de l'IRA et a reduit la valeur pronostique des criteres de l'AKIN. Une revision serait peut-etre necessaire pour tenir compte de la reduction physiologique plus marquee du debit urinaire en periode postoperatoire chez les patients atteints d'un CHC., Postoperative acute kidney injury (AKI) is reported in approximately 15% of patients undergoing liver resections, and is associated with increased morbidity and mortality. (1-3) Multiple predisposing factors have been described, [...]

Radiographic contrast agents cause acute kidney injury (AKI), yet the underlying pathogenesis is poorly understood. Nod-like receptor pyrin containing 3-deficient (Nlrp3-deficient) mice displayed reduced epithelial cell injury and inflammation in the kidney in a model of contrast-induced AKI (CI-AKI). Unexpectedly, contrast agents directly induced tubular epithelial cell death in vitro that was not dependent on Nlrp3. Rather, contrast agents activated the canonical Nlrp3 inflammasome in macrophages. Intravital microscopy revealed diatrizoate (DTA) uptake within minutes in perivascular [CX.sub.3][CR1.sup.+] resident phagocytes in the kidney. Following rapid filtration into the tubular luminal space, DTA was reabsorbed and concentrated in tubular epithelial cells via the brush border enzyme dipeptidase-1 in volume-depleted but not euvolemic mice. [LysM-GFP.sup.+] macrophages recruited to the kidney interstitial space ingested contrast material transported from the urine via direct interactions with tubules. CI-AKI was dependent on resident renal phagocytes, IL-1, leukocyte recruitment, and dipeptidase-1. Levels of the inflammasome-related urinary biomarkers IL-18 and caspase-1 were increased immediately following contrast administration in patients undergoing coronary angiography, consistent with the acute renal effects observed in mice. Taken together, these data show that CI-AKI is a multistep process that involves immune surveillance by resident and infiltrating renal phagocytes, Nlrp3-dependent inflammation, and the tubular reabsorption of contrast via dipeptidase-1., Introduction Contrast-induced acute kidney injury (CI-AKI) is caused by iodinated contrast media for diagnostic imaging (1). Most patients with normal kidney function who receive contrast will not experience any renal [...]