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Identifying people at risk for progressive chronic kidney disease and connecting them with recommended care is crucial for providing timely and optimal treatment. The ASSIST-CKD (A programme to Spread eGFR [estimated glomerular filtration rate] graph Surveillance for the early identification, Support and Treatment of people with progressive CKD [chronic kidney disease]) trial evaluated the effect of graphical eGFR reporting to primary care physicians on late presentation to a nephrologist in the United Kingdom. Trial data were obtained from the UK Renal Registry. Although the results were neutral, the data generated from the ASSIST-CKD trial are informative and provide useful estimates of the intervention effect. The trial also provides valuable insights into the challenges of implementing complex interventions in busy health care environments, which can be used to guide the designs of future interventions., (Copyright © 2024 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

INTRODUCTIONAcute kidney injury and chronic kidney disease (CKD) are common in hospitalized patients. To inform clinical decision making, more accurate information regarding risk of long-term progression to kidney failure is required.METHODSWe enrolled 1538 hospitalized patients in a multicenter, prospective cohort study. Monocyte chemoattractant protein 1 (MCP-1/CCL2), uromodulin (UMOD), and YKL-40 (CHI3L1) were measured in urine samples collected during outpatient follow-up at 3 months. We followed patients for a median of 4.3 years and assessed the relationship between biomarker levels and changes in estimated glomerular filtration rate (eGFR) over time and the development of a composite kidney outcome (CKD incidence, CKD progression, or end-stage renal disease). We paired these clinical studies with investigations in mouse models of renal atrophy and renal repair to further understand the molecular basis of these markers in kidney disease progression.RESULTSHigher MCP-1 and YKL-40 levels were associated with greater eGFR decline and increased incidence of the composite renal outcome, whereas higher UMOD levels were associated with smaller eGFR declines and decreased incidence of the composite kidney outcome. A multimarker score increased prognostic accuracy and reclassification compared with traditional clinical variables alone. The mouse model of renal atrophy showed greater Ccl2 and Chi3l1 mRNA expression in infiltrating macrophages and neutrophils, respectively, and evidence of progressive renal fibrosis compared with the repair model. The repair model showed greater Umod expression in the loop of Henle and correspondingly less fibrosis.CONCLUSIONSBiomarker levels at 3 months after hospitalization identify patients at risk for kidney disease progression.FUNDINGNIH.

Background: Whether the survival benefit of β-blockers in congestive heart failure (CHF) from randomized trials extends to patients with advanced chronic kidney disease (CKD) [estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2 but not receiving dialysis] is uncertain., Methods: This was a retrospective cohort study using administrative datasets. Older adults from Ontario, Canada, with incident CHF (median age 79 years) from April 2002 to March 2014 were included. We matched new users of β-blockers to nonusers on age, sex, eGFR categories (>60, 30-60, <30), CHF diagnosis date and a high-dimensional propensity score. Using Cox proportional hazards models, we examined the association of β-blocker use versus nonuse with all-cause mortality., Results: We matched 5862 incident β-blocker users (eGFR >60, n = 3136; eGFR 30-60, n = 2368; eGFR <30, n = 358). There were 2361 mortality events during follow-up. β-Blocker use was associated with reduced all-cause mortality [adjusted hazard ratio (HR) 0.58, 95% confidence interval (CI) 0.54-0.64]. This result was consistent across all eGFR categories (>60: adjusted HR 0.55, 95% CI 0.49-0.62; 30-60: adjusted HR 0.63, 95% CI 0.55-0.71; <30: adjusted HR 0.55, 95% CI 0.41-0.73; interaction term, P = 0.30). The results were consistent in an intention-to-treat analysis and with β-blocker use treated as a time-varying exposure., Conclusions: β-Blocker use is associated with reduced all-cause mortality in elderly patients with CHF and CKD, including those with an eGFR <30. Randomized trials that examine β-blockers in patients with CHF and advanced CKD are needed., (© The Author(s) 2019. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Importance: The severity of acute kidney injury (AKI) is usually determined based on the maximum serum creatinine concentration. However, the trajectory of kidney function recovery could be an additional important dimension of AKI severity., Objective: To assess whether the trajectory of kidney function recovery within 72 hours after AKI is associated with long-term risk of clinical outcomes., Design, Setting, and Participants: This prospective, multicenter cohort study enrolled 1538 adults with or without AKI 3 months after hospital discharge between December 1, 2009, and February 28, 2015. Statistical analyses were completed November 1, 2018. Participants with or without AKI were matched based on demographic characteristics, site, comorbidities, and prehospitalization estimated glomerular filtration rate. Participants with AKI were classified as having resolving or nonresolving AKI based on previously published definitions. Resolving AKI was defined as a decrease in serum creatinine concentration of 0.3 mg/dL or more or 25% or more from maximum in the first 72 hours after AKI diagnosis. Nonresolving AKI was defined as AKI not meeting the definition for resolving AKI., Main Outcomes and Measures: The primary outcome was a composite of major adverse kidney events (MAKE), defined as incident or progressive chronic kidney disease, long-term dialysis, or all-cause death during study follow-up., Results: Among 1538 participants (964 men; mean [SD] age, 64.6 [12.7] years), 769 (50%) had no AKI, 475 (31%) had a resolving AKI pattern, and 294 (19%) had a nonresolving AKI pattern. After a median follow-up of 4.7 years, the outcome of MAKE occurred in 550 (36%) of all participants. The adjusted hazard ratio for MAKE was higher for patients with resolving AKI (adjusted hazard ratio, 1.52; 95% CI, 1.01-2.29; P = .04) and those with nonresolving AKI (adjusted hazard ratio 2.30; 95% CI, 1.52-3.48; P < .001) compared with participants without AKI. Within the population of patients with AKI, nonresolving AKI was associated with a 51% greater risk of MAKE (95% CI, 22%-88%; P < .001) compared with resolving AKI. The higher risk of MAKE among patients with nonresolving AKI was explained by a higher risk of incident and progressive chronic kidney disease., Conclusions and Relevance: This study suggests that the 72-hour period immediately after AKI distinguishes the risk of clinically important kidney-specific long-term outcomes. The identification of different AKI recovery patterns may improve patient risk stratification, facilitate prognostic enrichment in clinical trials, and enable recognition of patients who may benefit from nephrology consultation.

Objectives: Little is known about the health and health-care patterns of patients with diabetes according to their estimated glomerular filtration rates, especially within a publicly funded health-care system., Methods: Using linked health-care databases in Ontario, Canada, we performed a population-based study of adults 50 years of age and older (mean age, 68 years) with prevalent diabetes on January 1, 2014. We categorized patients according to their levels of kidney function (estimated glomerular filtration rate ≥90, 60 to 89, 30 to 59, 15 to 29 or <15 mL/min/1.73 m 2 , or the receipt of ongoing maintenance dialysis). We then followed patients for 2 years to determine: 1) their level of contact with health-care providers (i.e. visits to family doctors, specialists); 2) their use and repeated use of acute medical services (i.e. hospitalizations and emergency department encounters; 3) diabetes-related monitoring and screening (i.e. glycated hemoglobin and cholesterol tests, vision screening); 4) glycemic and lipid control; and 5) diabetes-related outcomes., Results: There were 569,384 patients in our study. Most had estimated glomerular filtration rates between 60 and 89 mL/min/1.73 m 2 . At baseline, patients with lower kidney function had longer durations of diabetes and more comorbidities. Over 2 years of follow up, they had higher burdens of medical care, excessive diabetes monitoring and were underscreened for diabetes-related complications. Although metabolic control was reasonable across groups, patients with low kidney function had more hospital encounters and more diabetes-related complications., Conclusions: Patients with diabetes and low kidney function are a vulnerable population that faces health system challenges and care gaps. Suggestions for policy and practice are discussed., (Copyright © 2018 Diabetes Canada. Published by Elsevier Inc. All rights reserved.)

Background: The risk for venous thromboembolism (VTE) is elevated with albuminuria or a low estimated glomerular filtration rate (eGFR). However, the VTE risk due to the combined effects of eGFR and albuminuria are unknown., Study Design: Population-based cohort study., Settings & Participants: 694,956 adults in Ontario, Canada, from 2002 to 2012., Factors: eGFR and albumin-creatinine ratio (ACR)., Outcome: VTE., Results: 15,180 (2.2%) VTE events occurred during the study period. Both albuminuria and eGFR were independently associated with VTE. The association of albuminuria and VTE differed by level of eGFR (P for ACR × eGFR interaction < 0.001). After considering the competing risk for death, there was a 61% higher rate of VTE in patients with normal eGFRs (eGFRs>90mL/min/1.73m 2 ) and heavy albuminuria (ACR>300mg/g) compared with those with normal eGFRs and no albuminuria (subdistribution HR, 1.61; 95% CI, 1.38-1.89). Among those with reduced kidney function (eGFR, 15-29mL/min/1.73m 2 ), the risk for VTE was only minimally increased, irrespective of albuminuria (subdistribution HRs of 1.23 [95% CI, 1-1.5] and 1.09 [95% CI, 0.82-1.45] for ACR<30 and >300mg/g, respectively)., Limitations: Only single determinations of ACR and eGFR were used. Diagnostic/International Classification of Diseases codes were used to define VTE., Conclusions: Albuminuria increases the risk for VTE markedly in patients with normal eGFRs compared with those with lower eGFRs., (Copyright © 2017 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Early evidence suggests proteinuria is independently associated with incident atrial fibrillation (AF). We sought to investigate whether the association of proteinuria with incident AF is altered by kidney function., Methods and Results: Retrospective cohort study using administrative healthcare databases in Ontario, Canada (2002-2015). A total of 736 666 patients aged ≥40 years not receiving dialysis and with no previous history of AF were included. Proteinuria was defined using the urine albumin-to-creatinine ratio (ACR) and kidney function by the estimated glomerular filtration rate (eGFR). The primary outcome was time to AF. Cox proportional models were used to determine the hazard ratio for AF censored for death, dialysis, kidney transplant, or end of follow-up. Fine and Grey models were used to determine the subdistribution hazard ratio for AF, with death as a competing event. Median follow-up was 6 years and 44 809 patients developed AF. In adjusted models, ACR and eGFR were associated with AF ( P <0.0001). The association of proteinuria with AF differed based on kidney function (ACR × eGFR interaction, P <0.0001). Overt proteinuria (ACR, 120 mg/mmol) was associated with greater AF risk in patients with intact (eGFR, 120) versus reduced (eGFR, 30) kidney function (adjusted hazard ratios, 4.5 [95% CI, 4.0-5.1] and 2.6 [95% CI, 2.4-2.8], respectively; referent ACR 0 and eGFR 120). Results were similar in competing risk analyses., Conclusions: Proteinuria increases the risk of incident AF markedly in patients with intact kidney function compared with those with decreased kidney function. Screening and preventative strategies should consider proteinuria as an independent risk factor for AF., (© 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

Background: Bedside estimates of the risk for hypoglycemia by estimated glomerular filtration rate (eGFR), urine albumin-creatinine ratio (ACR), and use of antihyperglycemic medications would be helpful., Study Design: Population-based cohort study., Setting & Participants: Older adults (mean age, 75 years) in Ontario, Canada, from April 2002 through March 2013., Factors: eGFR stage, ACR stage, and use of antihyperglycemic medications., Outcome: 3-year incidence rate of a hospital encounter with hypoglycemia (emergency department or inpatient encounter)., Results: In users and nonusers of antihyperglycemic medications, there was a graded increase in risk for hypoglycemia by eGFR stage. Incidence rates in antihyperglycemic medication users were 82 (95% CI, 71-94), 122 (95% CI, 115-130), 235 (95% CI, 218-254), 379 (95% CI, 349-413), 596 (95% CI, 524-678), and 785 (95% CI, 689-894) encounters per 10,000 person-years when eGFR was ≥90, 60 to <90, 45 to <60, 30 to <45, 15 to <30, and <15mL/min/1.73m 2 or the patient was receiving dialysis, respectively (P<0.001). Corresponding values in nonusers were 2 (95% CI, 2-4), 3 (95% CI, 3-4), 3 (95% CI, 2-4), 7 (95% CI, 5-9), 14 (95% CI, 9-22), and 55 (95% CI, 43-71) encounters/10,000 person-years, respectively (P<0.001). A similar relationship was evident by eGFR and ACR risk category., Limitations: Only hypoglycemia episodes that were associated with a hospital encounter were assessed. Results cannot be generalized to younger patients., Conclusions: In older adults, the risk for hypoglycemia is higher in those with lower kidney function. Our results may aid the patient-provider dialogue and inform future studies to prevent hypoglycemia in an at-risk population., (Copyright © 2017 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Background and Objectives: The risk of gout across CKD stages is not well described., Design, Setting, Participants, & Measurements: We performed a retrospective cohort study using linked health care databases from Ontario, Canada from 2002 to 2010. The primary outcome was the 3-year cumulative incidence of gout, on the basis of diagnostic codes. We presented our results by level of kidney function (eGFR≥90 ml/min per 1.73 m 2 , 60-89, 45-59, 30-44, 15-29, and chronic dialysis) and by sex. Additional analyses examined the risk of gout adjusting for clinical characteristics, incidence of gout defined by the receipt of allopurinol or colchicine, and gout risk in a subpopulation stratified by the level of eGFR and albuminuria., Results: Of the 282,925 adults aged ≥66 years, the mean age was 75 years and 57.9% were women. The 3-year cumulative incidence of gout was higher in older adults with a lower level of eGFR. In women, the 3-year cumulative incidence of gout was 0.6%, 0.7%, 1.3%, 2.2%, and 3.4%, and in men the values were 0.8%, 1.2%, 2.5%, 3.7%, and 4.6%, respectively. However, patients on chronic dialysis had a lower 3-year cumulative incidence of gout (women 2.0%, men 2.9%) than those with more moderate reductions in kidney function ( i.e. , eGFR 15-44 ml/min per 1.73 m 2 ). The association between a greater loss of kidney function and a higher risk of diagnosed gout was also evident after adjustment for clinical characteristics and in all additional analyses., Conclusions: Patients with a lower level of eGFR had a higher 3-year cumulative incidence of gout, with the exception of patients receiving dialysis. Results can be used for risk stratification., (Copyright © 2017 by the American Society of Nephrology.)

Background: The interaction between baseline kidney function and the performance of biomarkers of acute kidney injury (AKI) on the development of AKI is unclear., Study Design: Post hoc analysis of prospective cohort study., Setting & Participants: The 1,219 TRIBE-AKI Consortium adult cardiac surgery cohort participants., Predictor: Unadjusted postoperative urinary biomarkers of AKI measured within 6 hours of surgery., Outcome: AKI was defined as AKI Network stage 1 (any AKI) or higher, as well as a doubling of serum creatinine level from the preoperative value or the need for post-operative dialysis (severe AKI)., Measurements: Stratified analyses by preoperative estimated glomerular filtration rate (eGFR) ≤ 60 versus > 60mL/min/1.73m(2)., Results: 180 (42%) patients with preoperative eGFRs≤60mL/min/1.73m(2) developed clinical AKI compared with 246 (31%) of those with eGFRs>60mL/min/1.73m(2) (P<0.001). For log2-transformed biomarker concentrations, there was a significant interaction between any AKI and baseline eGFR for interleukin 18 (P=0.007) and borderline significance for liver-type fatty acid binding protein (P=0.06). For all biomarkers, the adjusted relative risk (RR) point estimates for the risk for any AKI were higher in those with elevated baseline eGFRs compared with those with eGFRs≤60mL/min/1.73m(2). However, the difference in magnitude of these risks was low (adjusted RRs were 1.04 [95% CI, 0.99-1.09] and 1.11 [95% CI, 1.07-1.15] for those with preoperative eGFRs≤60mL/min/1.73m(2) and those with higher eGFRs, respectively). Although no biomarker displayed an interaction for baseline eGFR and severe AKI, log2-transformed interleukin 18 and kidney injury molecule 1 had significant adjusted RRs for severe AKI in those with and without baseline eGFRs≤60mL/min/1.73m(2)., Limitations: Limited numbers of patients with severe AKI and post-operative dialysis., Conclusions: The association between early postoperative AKI urinary biomarkers and AKI is modified by preoperative eGFR. The degree of this modification and its impact on the biomarker-AKI association is small across biomarkers. Our findings suggest that distinct biomarker cutoffs for those with and without a preoperative eGFR≤60mL/min/1.73m(2) is not necessary., (Published by Elsevier Inc.)

Background: Early detection and treatment of chronic kidney disease (CKD) is important for slowing progression to renal failure and preventing cardiovascular events, but CKD is often not recognized and patients are referred to nephrologists too late for timely management. Automated laboratory reporting of estimated glomerular filtration rate (eGFR) has been introduced in many health systems to improve CKD recognition, but its impact on large, US-based health systems remains unclear., Research Design: Retrospective time-series study examined change in renal care services and CKD recognition across VA health care system facilities in 2000-2009. Hierarchical generalized linear models were used to estimate immediate and long-term impacts of eGFR reporting across facilities on monthly rates of outpatient CKD diagnoses, utilization of CKD diagnostic tests (urine microalbumin and kidney ultrasound), and outpatient nephrology visits., Results: Rates of CKD recognition through diagnoses in patient medical records changed an average of 11.4 additional diagnosed patients per 10,000 in the general outpatient population per month, with sustained long-term increases in CKD diagnoses (P<0.001). Diagnostic microalbumin and kidney ultrasound testing increased significantly, with long-term increases in microalbumin testing (P<0.001) and short-term increases in kidney ultrasound (P=0.01-0.04) rates across the VHA. There was no significant change in nephrology consultation rates., Conclusions: Automated eGFR reporting was associated with moderate system-level improvements in documentation of CKD diagnoses and use of diagnostic tests, but had no impact on nephrology consultation. To effectively reduce the large burden of disease and its associated complications, further strategies are needed to identify and provide timely treatment to those with CKD.

Knowing a person's fracture risk according to their kidney function, gender, and age may influence clinical management and decision-making. Using healthcare databases from Ontario, Canada, we conducted a cohort study of 679,114 adults of 40 years and over (mean age 62 years) stratified at cohort entry by estimated glomerular filtration rate ((eGFR) 60 and over, 45-59, 30-44, 15-29, and under 15 ml/min per 1.73 m(2)), gender, and age (40-65 and over 65 years). The primary outcome was the 3-year cumulative incidence of fracture (proportion of adults who fractured (hip, forearm, pelvis, or proximal humerus) at least once within 3-years of follow-up). Additional analyses examined the fracture incidence per 1000 person-years, hip fracture alone, stratification by prior fracture, stratification by eGFR and proteinuria, and 3-year cumulative incidence of falls with hospitalization. The 3-year cumulative incidence of fracture significantly increased in a graded manner in adults with a lower eGFR for both genders and both age groups. The 3-year cumulative incidence of fracture in women over 65 years of age across the 5 eGFR groups were 4.3%, 5.8%, 6.5%, 7.8%, and 9.6%, respectively. Corresponding estimates for men over 65 years were 1.6%, 2.0%, 2.7%, 3.8%, and 5.0%, respectively. Similar graded relationships were found for falls with hospitalization and additional analyses. Thus, many adults with chronic kidney disease will fall and fracture. Results can be used for prognostication and guidance of sample size requirements for fracture prevention trials.

Background and Objectives: Early detection of CKD is important for slowing progression to renal failure and preventing cardiovascular events. Automated laboratory reporting of estimated GFR (eGFR) has been introduced in many health systems to improve CKD recognition, but its effect in large, United States-based health systems remains unclear., Design, Setting, Participants, & Measurements: Using Veterans Affairs (VA) laboratory and administrative data, two nonoverlapping national cohorts of patients receiving care in VA medical centers before (n=66,323) and after (n=16,670) implementation of automated eGFR reporting between 2004 and 2010 were identified. Recognition was assessed by the presence of new CKD diagnostic codes, use of additional diagnostic testing, outpatient nephrology visits, or overall CKD recognition (receipt of at least one of these outcomes) for each patient during the 12-month period after their first eligible creatinine or eGFR laboratory result. Generalized estimating equations were used to assess change before and after automated eGFR reporting., Results: Overall CKD recognition increased from 22.1% of veterans before eGFR reporting to 27.5% in the post-eGFR reporting period (odds ratio [OR], 1.19; 95% CI, 1.12 to 1.27; P<0.001). Higher overall CKD recognition was driven largely by increased documentation of CKD diagnosis codes in medical records (OR, 1.31; 95% CI, 1.21 to 1.41; P<0.001) and diagnostic testing for CKD (OR, 1.13; 95% CI, 1.03 to 1.24; P<0.01) rather than outpatient nephrology consultation. Automated eGFR reporting was not associated with greater CKD recognition among black or older patients (P=0.07)., Conclusions: Automated eGFR laboratory reporting improved documentation of CKD diagnoses but had no effect on nephrology consultation. These findings suggest that to advance CKD care, further strategies are needed to ensure appropriate follow-up evaluation to confirm and effectively evaluate CKD.

Background: Kidney transplants from living donors with an estimated glomerular filtration rate (eGFR) < 80 mL/min per 1.73 m(2) may be at risk for increased graft loss compared with a recipient who receives a kidney from a living donor with a higher eGFR., Methods: This retrospective cohort study considered 2057 living kidney donors and their recipients from July 1993 to March 2010 at five centres in Ontario, Canada, and linked them to population-based, universal healthcare databases. Recipients were divided into five groups based on their donor's baseline eGFR. The median (inter-quartile range) for the lowest eGFR group was 73 (68-77) mL/min per 1.73 m(2). Subjects were followed for a median of 6 years (IQR: 3-10 years)., Results: There was no significant difference in the adjusted hazard ratio (HR) for graft loss when comparing recipients in each eGFR category to the referent group (≥110 mL/min per 1.73 m(2)). The adjusted HRs (95% CI) from the lowest (<80 mL/min per 1.73 m(2)) to highest (100-109.9 mL/min per 1.73 m(2)) eGFR categories were 1.27 (0.84-1.92), 1.43 (0.96-2.14), 1.23 (0.86-1.77) and 1.23 (0.85-1.77), respectively. Similar results were observed when dichotomizing the baseline donor eGFR using a cut-point of 80 mL/min per 1.73 m(2)-adjusted HR 1.01 [95% confidence interval (95% CI) (0.76-1.44)]., Conclusions: Further research in this setting should clarify whether additional tests (i.e. measured GFR) should be performed in potential donors whose eGFR is considered borderline, whether eGFR values should be standardized to body surface area, and the outcomes for donors after nephrectomy.

Many guidelines suggest that angiotensin-converting enzyme inhibitors and angiotensin-II receptor antagonists (collectively referred to as renin, angiotensin, aldosterone system blockers (RAAS blockers)) are the preferred treatment for hypertension in most patients with chronic kidney disease (CKD). Improving the recognition of CKD with the introduction of eGFR reporting was intended to have more patients recognized with and treated for this disease. To quantify this, we examined trends in RAAS-blocker use over an 88-month period before and after routine eGFR reporting in southwestern Ontario, Canada. An intervention analysis with seasonal time-series modeling on linked health administrative data for 45,361 ambulatory residents with CKD (eGFR stages 3-5) older than 65 years was performed with a primary outcome of RAAS-blocker usage. The reporting of eGFR was associated with a significant increase in the use of RAAS blockers, as the prescription rate was 571 per 1000 patients with CKD prior to reporting but improved to 607 per 1000 after reporting. There was a significant increase in RAAS-blocker use attributable to eGFR reporting of 19 per 1000 CKD patients. Since about 8% of the adult population has CKD, this equates to about 15,200 new patients receiving RAAS-blocker treatment by 1 year after the introduction of eGFR reporting in community laboratories. Thus, eGFR reporting contributes to improved, guideline-appropriate care of older patients with CKD.

The Kidney Disease Outcomes Quality Initiative (K/DOQI) guidelines suggest that clinicians use the estimated glomerular filtration rate (eGFR) measurements and minimize the use of timed urine creatinine clearance collection. The intent of this change was to improve recognition of chronic kidney disease. Here we used time-series modeling and intervention analyses to determine the effect of publication of the K/DOQI guidelines and the introduction of widespread eGFR reporting with prompts on physician ordering of 24-h urine collection for creatinine clearance. In this setting, clinical practice guidelines did not influence creatinine clearance testing; however, the direct introduction of eGFR reporting with prompts into physician workflow resulted in a sudden and significant 23.5% decrease in creatinine clearance collection over the 43 months analyzed. Thus, eGFR reporting with prompts may have produced a clinical practice change because it is integrated directly into physician workflow. Changing physician practice patterns may require more than publishing guidelines; rather it is more likely to occur through educational and structural changes to practice.

Background and Objectives: The effect of increased fluid intake on kidney function is unclear. This study evaluates the relationship between urine volume and renal decline over 6 years in a large community-based cohort., Design, Setting, Participants, & Measurements: This prospective cohort study was undertaken in Canada from 2002 to 2008. We obtained 24-hour urine samples from adult participants with an estimated GFR (eGFR) ≥60 ml/min per 1.73 m(2) at study entry. Percentage annual change in eGFR from baseline was categorized as average decline <1% per year, between 1% and 4.9% (mild-to-moderate decline) or ≥5% (rapid decline)., Results: 2148 participants provided valid 24-hour urine samples, grouped as <1 L/d (14.5%); 1 to 1.9 L/d (51.5%); 2 to 2.9 L/d (26.3%); and ≥3 L/d (7.7%). Baseline eGFR for each category of urine volume was 90, 88, 84, and 87 ml/min per 1.73 m(2), respectively. Overall, eGFR declined by 1% per year, with 10% demonstrating rapid decline and 40% demonstrating mild-to-moderate decline. An inverse, graded relationship was evident between urine volume and eGFR decline: For each increasing category of 24-hour urine volume, percentage annual eGFR decline was progressively slower, from 1.3%, 1.0%, 0.8%, to 0.5%, respectively; P = 0.02. Compared with those with urine volume 1 to 1.9 L/d, those with urine volume ≥3 L/d were significantly less likely to demonstrate mild-to-moderate decline (adjusted odds ratio 0.66; 95% confidence interval 0.46 to 0.94) or rapid decline (adjusted odds ratio 0.46; 95% confidence interval 0.23 to 0.92); adjusted for age, gender, baseline eGFR, medication use for hypertension (including diuretics), proteinuria, diabetes, and cardiovascular disease., Conclusions: In this community-based cohort, decline in kidney function was significantly slower in those with higher versus lower urine volume.

Background and Objectives: The diagnostic accuracy of cystatin C estimated GFR (eGFR) by various cystatin C equations have varied in different studies. We hypothesized that the GFR level of enrolled patients affects the diagnostic accuracy of a cystatin C equation., Design, Setting, Participants, & Measurements: We analyzed 240 consecutively enrolled children at a single Canadian center in a prospective and cross-sectional study. Cystatin C was analyzed with nephelometry, and cystatin C eGFR was estimated by the equations validated in children. GFR was measured by technetium-99m-diethylene-triamine penta-acetic acid (⁹⁹m)Tc DTPA)., Results: We compared various cystatin C equations across GFR strata < 60, < 90, ≥ 135, and ≥ 150 ml/min per 1.73 m² for an accurate prediction and appropriate classification of the measured GFR. The CKiD, Zappitelli-CysEq, and Zappitelli-CysCrEq equations had a higher accuracy, estimated by eGFR values within 10% and 30% of the respective (99m)Tc DTPA, in the GFR categories < 60 and < 90 ml/min per 1.73 m², whereas the Bökenkamp, Bouvet, and Filler equations had a greater accuracy in the GFR categories ≥ 135 and ≥ 150 ml/min per 1.73 m². The Bouvet, CKiD, Filler, Zappitelli-CysEq, and Zappitelli-CysCrEq equations had a greater sensitivity to classify GFR < 60 and < 90 ml/min per 1.73 m², whereas the Bökenkamp equation had a higher sensitivity for GFR ≥ 135 and ≥ 150 ml/min per 1.73 m²., Conclusions: The diagnostic accuracy of various cystatin C equations varies with GFR. This issue needs consideration while applying these equations in clinical practice and for further research on eGFR equations.

Background: Many laboratories now report estimated glomerular filtration rate (eGFR) when a serum creatinine measurement is ordered. A summary of the impact of eGFR reporting in health care systems around the world for which it has been adopted is lacking., Study Design: Systematic review of MEDLINE, EMBASE, other major databases, and conference proceedings of major nephrology meetings., Setting & Population: Any health care system in which eGFR reporting was introduced., Selection Criteria for Studies: Published studies or abstracts reporting patient, clinician, or health system outcomes of eGFR reporting., Intervention: eGFR reporting., Outcomes: Volume of referrals or consults seen by nephrologists, changes in characteristics of patients who were seen, and prescription rates of kidney-related medications., Results: 22 studies (10 full text and 12 conference abstracts) were identified in 2004-2010 from 5 countries. Nephrologist referrals and consultations increased after eGFR reporting, ranging from 13%-270%. The greatest increases in referrals were seen for the elderly, females, and those with stage 3 or higher chronic kidney disease (eGFR <60 mL/min/1.73 m(2)). Change in renin-angiotensin-aldosterone system-blocking drug use ranged from increases of 0%-6%., Limitations: Studies were highly variable in definition of outcomes. Reports were not available for many health care systems in which eGFR reporting was implemented., Conclusions: eGFR reporting has been associated with greater identification of patients with decreased kidney function in most health care systems that have reported its impact., (Copyright © 2011 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Serum creatinine alone can be difficult to interpret as a measure of kidney function such that chronic kidney disease might be under-recognized in the general population. In the province of Ontario, Canada, all outpatient laboratories now report estimated glomerular filtration rate (eGFR) in addition to serum creatinine. To determine the impact of this reporting on clinical practice, we linked health administrative data for more than 8 million adults of age 25 years or older over an almost 10-year period and conducted a population-based intervention analysis with seasonal time-series modeling to determine overall trends in the number and type of patients seen by nephrologists. Compared to the period when only serum creatinines were reported, the number of patients seen in consultation by nephrologists increased after eGFR reporting by an average of 24% (an absolute increase of 2.9 consults per 100,000 adults), an increase of about 23 consults per nephrologist per year. The greatest increases were seen in women (39% increase) and those 80 years of age and older (58% increase). Our study found that eGFR reporting was associated with a sudden increase in the number of nephrology consults. However, it remains to be seen whether the routine reporting of eGFR results in improved treatment and outcomes for those with chronic kidney disease.

Background: Knowledge of the long-term prognosis of patients with diarrhea-associated hemolytic uremic syndrome (HUS) is important for patient counseling and follow-up. Estimates in the literature are highly variable, and previous studies did not use a healthy control group to establish outcomes attributable to HUS., Study Design: Prospective cohort study., Setting & Participants: 19 children who recovered from HUS after contamination of their municipal water supply by Escherichia coli O157:H7., Predictor: Outcomes of children who recovered from HUS were compared with a control group of 64 children who were healthy at the time of the outbreak. Both groups were similar in their demographics and follow-up testing., Outcomes & Measurements: Proteinuria, blood pressure, glomerular filtration rate (GFR) estimated by using serum creatinine or cystatin C level, and biochemical measures 5 years after the outbreak., Results: More children who recovered from HUS showed microalbuminuria than controls (20% versus 3%; relative risk, 6.0; 95% confidence interval, 1.1 to 32.8). There were no differences between groups in blood pressure or GFR when estimated by using serum creatinine level. GFR estimated by using cystatin C level was lower after HUS compared with controls (100 versus 110 mL/min/1.73 m(2); P = 0.02), but no child had a GFR less than 80 mL/min/1.73 m(2). Other results, including fasting glucose, albumin, and C-reactive protein levels, did not differ between groups., Limitations: Although the homogenous nature of this outbreak is a strength, long-term results may generalize less well to patients with other strains of toxigenic E coli or in other settings., Conclusions: The prognosis of patients with HUS in this cohort was better than in other studies. Ongoing follow-up will clarify the clinical relevance of microalbuminuria and mild decreases in GFR 5 years after HUS recovery.

Background and Aims: National Kidney Foundation Kidney Disease Outcomes Quality Initiative (KDOQI) guidelines recommend that all people with a glomerular filtration rate (GFR) <60 ml/min/1.73 m(2) undergo evaluation for anaemia and metabolic bone disease. We aim to report the prevalence of metabolic complications in adults with low GFR., Methods: Analysis of 15,802 non-institutionalised adult participants in the Third National Health and Nutrition Survey (NHANES III), a cross-sectional population-based survey conducted in the United States between 1986 and 1994. Renal function was estimated according the modification of diet in renal disease equation 7 (MDRD GFR), the Cockcroft-Gault formula and by the serum creatinine cut-off points described by Couchoud and colleagues. Haemoglobin <110 g/l occurred in 42.2% [95% confidence interval (CI) 28.3-56.0] of patients with MDRD GFR <30 ml/min/1.73 m(2) [stage 3 chronic kidney disease (CKD)] and 3.5% (95% CI 2.4-4.7) of patients with MDRD GFR between 30 and 60 ml/min/1.73 m(2) (stage 4-5 CKD). Corresponding prevalences for calcium <2.15 mmol/l were 8.2 (95% CI 1.6-14.8) and 3.4 (95% CI 1.7-5.2); for phosphate >1.6 mmol/l, 15.1 (95% CI 5.0-25.3) and 0.3 (95% CI 0-0.6); and for bicarbonate <23 mmol/l, 32.7 (95% CI 19.6-45.9) and 5.7 (95% CI 3.3-8.2), respectively. Similar results were obtained when patients were categorised by the Cockcroft-Gault formula or Couchoud's cut-off points., Conclusions: The prevalence of complications in stage 3 CKD is low. These data do not support the recommendation for routine screening for metabolic complications of renal insufficiency in adults seen in primary care settings whose GFR exceeds 30 ml/min/1.73 m(2)., (Copyright 2007 S. Karger AG, Basel.)

The Kidney Disease Outcomes Quality Initiative has recommended the use of GFR estimating equations to detect silent chronic kidney disease (CKD) in the community. The benefit of general reporting of CKD must be balanced with the harm of mislabeling people who do not have CKD. The popular Cockcroft-Gault (CG) and Modification of Diet in Renal Disease (MDRD) GFR estimating equations were compared with the recently devised Rule equation in a representative community population sample (2166) divided into subsamples with (385) and without (1781) previous renal impairment. The prevalence of CKD was CG > MDRD >> Rule estimates. The magnitude of difference in prevalence of CKD as detected by the MDRD and CG versus the Rule equation increases markedly when the subsamples with (30.8 and 29.7 versus 17.5%) and without (12 and 11.3 versus 3.0%) previous kidney impairment are compared. General demographic and potential or known risk factors were used in a logistic regression model to assess the association with CKD. The MDRD estimates note female gender (odds ratio 2.19; 95% confidence interval 1.63 to 2.95) and both MDRD and the Rule equations identify hypertension and diabetes as significant CKD risk factors. All estimating equations identify age to be associated with CKD. The annualized serial decline in GFR was CG > MDRD > Rule estimates. Only the Rule GFR estimates detected a greater decline in renal impaired versus unimpaired populations. The calibrated Rule equation seems to perform better than CG and MDRD (CKD 3 versus 11.3 to 12%) but lacks validation against gold standards for community-based screening.

Background: Accurate glomerular filtration rate (GFR) assessment in patients with liver cirrhosis is important for prognostication, chronic kidney disease staging, drug dosing and identifying combined liver-kidney transplantation candidates. The objective of this study was to review the accuracy of measured creatinine clearance (MCrCl) from timed urine collections for estimating true GFR., Methods: A systematic review and individual patient meta-analysis was performed. MEDLINE, old MEDLINE, Index Medicus and Cochrane library bibliographic databases and conference proceedings were searched up to June 2004. Reference lists of relevant studies were searched and experts were contacted. Comparative diagnostic studies describing stable adult patients with cirrhosis categorized according to the Child-Pugh classification were included if a gold standard GFR measurement was performed within 3 days of MCrCl. Individual patient data were abstracted from graphs of primary articles to allow a pooled analysis of agreement between renal measures., Results: Seven studies of 193 patients from 1974 to 2002 were summarized. MCrCl overestimated inulin clearance (CIn) by a mean of +13 ml/min/1.73 m2 and the limits of agreement (mean of the differences+/-2 SD) were +60 ml/min/1.73 m2 and -34 ml/min/1.73 m2. This overestimation was highest in patients with lower GFR. The mean clearance ratios [95% confidence interval (CI)] between MCrCl and CIn in the high (> or =60 ml/min/1.73 m2) and low (<60 ml/min/1.73 m2) GFR subgroups were 1.18 (1.12-1.23) and 1.49 (1.33-1.66), respectively (P<0.0001). Fourteen percent of patients with a MCrCl > or =60 ml/min/1.73 m2 had a CIn of <30 ml/min/1.73 m2., Conclusions: For patients with liver cirrhosis, MCrCl from timed urine collections consistently overestimates the true GFR. For patients requiring complete clinical evaluation, GFR assessment by CIn is justified.

The use of outpatient laboratory databases to identify people with a low GFR may be part of an effective strategy to increase their use of treatments to prevent kidney failure. All renal function data from 17 independent outpatient laboratories in Eastern Ontario were combined to determine the proportion of adults with at least one serum creatinine measurement during a 1-yr period. The detection rates of low GFR were measured using different algorithms, and what proportion of identified low GFR was transient was considered. Canadian census data were used to calculate rates and proportions. Renal function testing was common. Of the 1,090,000 adult residents, 32% of the entire population and 63% of seniors had at least one serum creatinine measured during the study year. Sixteen percent of the population (49% of those with tests performed) had at least one GFR <80 ml/min per 1.73 m2, 5% (16%) had at least one GFR <60 ml/min per 1.73 m2, and 0.6% (1.7%) had at least one GFR <30 ml/min per 1.73 m2. Low GFR were usually not transient: 68% of individuals with subsequent testing at least 30 d later had a similar or worse GFR. Ambulatory laboratory database case finding, particularly in older patients, seems to be a promising method for easily identifying large segments of the population with persistent reductions in GFR. Whether such identification leads to improved health outcomes warrants further study.

End-stage renal disease is an important and costly health problem. Strategies for its prevention are urgently needed. Knowledge of the population-based prevalence of renal insufficiency in nondiabetic adults would inform such strategies. Black and white nondiabetic adult participants in the Third National Health and Nutrition Examination Survey were analyzed. The analysis was stratified by age, gender, and race, and four clinically applicable methods were used to assess renal function. There were 13,251 complete records for analysis. By the Modification of Diet in Renal Diseases (MDRD) GFR (GFR) prediction Equation 7, 58% (95% confidence interval [CI], 56 to 60%) of the total adult nondiabetic black and white US population had MDRD GFR below 80 ml/min per 1.73m(2), 13% (95% CI, 11 to 14%) below 60 ml/min per 1.73m(2), and 0.26% (95% CI, 0.19 to 0.33%) below 30 ml/min per 1.73m(2). By the Cockcroft-Gault formula, the equivalent figures were 39% (95% CI, 37 to 41%), 14% (95% CI, 12% - 16%), and 0.81% (95% CI, 0.46 to 1.2%), respectively. The findings of an unexpectedly high prevalence of low clearance and the increased prevalence of low clearance with age were consistent across the four clearance estimation methods used and for each race-sex stratum. The absolute magnitude of the prevalence of low clearance was, however, dependent on the clearance method used. Assessed by estimation from serum creatinine, low clearance may be very common, particularly with advancing age. The prognosis (in terms of risk for progression and end-stage renal disease) of low clearance in unreferred populations may differ from that in referred populations and requires further study.

Acute kidney injury (AKI) has been reported to be associated with excess risks of death, kidney disease progression and cardiovascular events although previous studies have important limitations. To further examine this, we prospectively studied adults from four clinical centers surviving three months and more after hospitalization with or without AKI who were matched on center, pre-admission CKD status, and an integrated priority score based on age, prior cardiovascular disease or diabetes mellitus, preadmission estimated glomerular filtration rate (eGFR) and treatment in the intensive care unit during the index hospitalization between December 2009-February 2015, with follow-up through November 2018. All participants had assessments of kidney function before (eGFR) and at three months and annually (eGFR and proteinuria) after the index hospitalization. Associations of AKI with outcomes were examined after accounting for pre-admission and three-month post-discharge factors. Among 769 AKI (73% Stage 1, 14% Stage 2, 13% Stage 3) and 769 matched non-AKI adults, AKI was associated with higher adjusted rates of incident CKD (adjusted hazard ratio 3.98, 95% confidence interval 2.51-6.31), CKD progression (2.37,1.28-4.39), heart failure events (1.68, 1.22-2.31) and all-cause death (1.78, 1.24-2.56). AKI was not associated with major atherosclerotic cardiovascular events in multivariable analysis (0.95, 0.70-1.28). After accounting for degree of kidney function recovery and proteinuria at three months after discharge, the associations of AKI with heart failure (1.13, 0.80-1.61) and death (1.29, 0.84-1.98) were attenuated and no longer significant. Thus, assessing kidney function recovery and proteinuria status three months after AKI provides important prognostic information for long-term clinical outcomes.

Background Mental health problems, particularly anxiety and depression, are common in patients with chronic kidney disease (CKD) and negatively impact quality of life, treatment adherence and mortality. However, the degree to which mental health and addiction services are utilized by those with CKD is unknown. We examined the history of mental health and addiction service use of individuals across levels of kidney function. Methods We performed a population-based cross-sectional study using linked healthcare databases from Ontario, Canada from 2009 to 2017. We abstracted the prevalence of individuals with mental health and addiction service use within the previous 3 years across levels of kidney function [estimated glomerular filtration rate (eGFR) ≥60, 45 to <60, 30 to <45, 15 to <30, <15 ml/min/1.73 m2 and maintenance dialysis]. We calculated prevalence ratios (PRs) to compare prevalence across kidney function strata, while adjusting for age, sex, year of cohort entry, urban versus rural location, area-level marginalization and Charlson comorbidity index. Results Of 5 956 589 adults, 9% (n  = 534 605) had an eGFR <60 ml/min/1.73 m2 or were receiving maintenance dialysis. Fewer individuals with an eGFR <60 ml/min/1.73 m2 had a history of any mental health and addiction service utilization (crude prevalence range 28–31%) compared with individuals with an eGFR ≥60 ml/min/1.73 m2 (35%). Compared with an eGFR ≥60 ml/min/1.73 m2, the lowest prevalence of individuals with any mental health and addiction service utilization was among those with an eGFR of 15 to <30 ml/min/1.73 m2 {adjusted PR 0.86 [95% confidence interval (CI) 0.85 to 0.88]}, an eGFR <15 ml/min/1.73 m2 [adjusted PR 0.81 (95% CI 0.76–0.86)] and those receiving maintenance dialysis [adjusted PR 0.83 (95% CI 0.81–0.84)]. Less use of outpatient services accounted for differences in service utilization. Conclusions Mental health and addiction service utilization is common but less so in individuals with advanced CKD in Ontario, Canada. [ABSTRACT FROM AUTHOR]

BackgroundAcute kidney injury (AKI) is common after cardiac surgery and is associated with adverse patient outcomes. Urinary cystatin C (CysC) level is a biomarker of proximal tubule function and may increase earlier in AKI than serum creatinine level.Study designProspective cohort study.Settings & participantsThe TRIBE AKI (Translational Research Investigating Biomarker Endpoints in AKI) Consortium prospectively enrolled 1,203 adults and 299 children and adolescents at 8 institutions in 2007-2009.Index testUrinary CysC (in milligrams per liter) within the first 12 hours after surgery.OutcomeSerum creatinine-based AKI was defined as AKI Network stage 1 (mild AKI) and doubling of serum creatinine from the preoperative value or need for dialysis during hospitalization (severe AKI).Other measurementsAnalyses were adjusted for characteristics used clinically for AKI risk stratification, including age, sex, race, estimated glomerular filtration rate, diabetes, hypertension, heart failure, nonelective surgery, cardiac catheterization within 72 hours, type of surgery, myocardial infarction, and cardiopulmonary bypass time longer than 120 minutes.ResultsUrinary CysC level measured in the early postoperative period (0-6 and 6-12 hours postoperatively) correlated with both mild and severe AKI in adults and children. However, after analyses were adjusted for other factors, the effect was attenuated for both forms of AKI in both cohorts.LimitationsLimited numbers of patients with severe AKI and in-hospital dialysis treatment.ConclusionsUrinary CysC values are not associated significantly with the development of AKI after cardiac surgery in adults and children.

Background Curcumin is a commonly used herbal supplement with anti-inflammatory and anti-fibrotic properties. Animal studies and small human trials suggest that curcumin reduces albuminuria in patients with chronic kidney disease (CKD). Micro-particle curcumin is a new, more bioavailable formulation of curcumin. Methods To determine whether micro-particle curcumin versus placebo slows the progression of albuminuric CKD we conducted a randomized, double-blind, placebo-controlled trial with 6-month follow-up. We included adults with albuminuria [a random urine albumin-to-creatinine ratio >30 mg/mmol (265 mg/g) or a 24-h urine collection with more than 300 mg of protein] and an estimated glomerular filtration rate (eGFR) between 15 and 60 mL/min/1.73 m2 within the 3 months before randomization. We randomly allocated participants 1:1 to receive micro-particle curcumin capsules (90 mg/day) or matching placebo for 6 months. After randomization, the co-primary outcomes were the changes in albuminuria and the eGFR. Results We enrolled 533 participants, but 4/265 participants in the curcumin group and 15/268 in the placebo group withdrew consent or became ineligible. The 6-month change in albuminuria did not differ significantly between the curcumin and placebo groups [geometric mean ratio 0.94, 97.5% confidence interval (CI) 0.82 to 1.08, P  = .32]. Similarly, the 6-month change in eGFR did not differ between groups (mean between-group difference –0.22 mL/min/1.73 m2, 97.5% CI –1.38 to 0.95, P  = .68). Conclusions Ninety milligrams of micro-particle curcumin daily did not slow the progression of albuminuric CKD over 6 months. Trial registration ClinicalTrials.gov Identifier: NCT02369549. [ABSTRACT FROM AUTHOR]

Background Trimethoprim-sulfamethoxazole (TMP-SMX) can cause hyperkalemia by reducing renal potassium excretion. We assessed the risk of hyperkalemia after initiating TMP-SMX versus amoxicillin and determined if this risk is modified by a patient's baseline kidney function [estimated glomerular filtration rate (eGFR)]. Methods We conducted a population-based cohort study in Ontario, Canada involving adults ≥66 years of age newly treated with TMP-SMX (n  = 58 999) matched 1:1 with those newly treated with amoxicillin (2008–2020). The primary outcome was a hospital encounter with hyperkalemia defined by a laboratory serum potassium value ≥5.5 mmol/L within 14 days of antibiotic treatment. Secondary outcomes included a hospital encounter with acute kidney injury (AKI) and all-cause hospitalization. Risk ratios (RRs) were obtained using a modified Poisson regression. Results A hospital encounter with hyperkalemia occurred in 269/58 999 (0.46%) patients treated with TMP-SMX versus 80/58 999 (0.14%) in those treated with amoxicillin {RR 3.36 [95% confidence interval (CI) 2.62–4.31]}. The absolute risk of hyperkalemia in patients treated with TMP-SMX versus amoxicillin increased progressively with decreasing eGFR (risk difference of 0.12% for an eGFR ≥60 ml/min/1.73 m2, 0.42% for eGFR 45–59, 0.85% for eGFR 30–44 and 1.45% for eGFR <30; additive interaction P  < .001). TMP-SMX versus amoxicillin was associated with a higher risk of a hospital encounter with AKI [RR 3.15 (95% CI 2.82–3.51)] and all-cause hospitalization [RR 1.43 (95% CI 1.34–1.53)]. Conclusions The 14-day risk of a hospital encounter with hyperkalemia was higher in patients newly treated with TMP-SMX versus amoxicillin and the risk was highest in patients with a low eGFR. [ABSTRACT FROM AUTHOR]

Background Chronic pain is common, and its management is complex in patients with chronic kidney disease (CKD), but limited data are available on opioid prescribing. We examined opioid prescribing for non-cancer and non-end-of-life care in patients with CKD. Methods This was a population-based retrospective cohort study using administrative databases in Ontario, Canada which included adults with CKD defined by an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 from 1 November 2012 to 31 December 2018 and estimated the proportion of opioid prescriptions (type, duration, dose, potentially inappropriate prescribing, etc.) within 1 year of cohort entry. Prescriptions had to precede dialysis, kidney transplant or death. Results We included 680 445 adults with CKD, and 198 063 (29.1%) were prescribed opioids. Codeine (14.9%) and hydromorphone (7.2%) were the most common opioids. Among opioid users, 24.3% had repeated or long-term use, 26.1% were prescribed high doses and 56.8% were new users. Opioid users were more likely to be female, had cardiac disease or a mental health diagnosis, and had more healthcare visits. The proportions for potentially inappropriate prescribing indicators varied (e.g. 50.1% with eGFR <30 were prescribed codeine, and 20.6% of opioid users were concurrently prescribed benzodiazepines, while 7.2% with eGFR <30 mL/min/1.73 m2 were prescribed morphine, and 7.0% were received more than one opioid concurrently). Opioid prescriptions declined with time (2013 cohort: 31.1% versus 2018 cohort: 24.5%; p <0.0001), as did indicators of potentially inappropriate prescribing. Conclusions Opioid use was common in patients with CKD. While opioid prescriptions and potentially inappropriate prescribing have declined in recent years, interventions to improve pain management without the use of opioids and education on safer prescribing practices are needed. [ABSTRACT FROM AUTHOR]

We examined a novel database linking national donor registry identifiers to records from a US pharmaceutical claims warehouse (2007‐2015) to describe opioid and NSAID prescription patterns among LKDs during the first year postdonation, divided into three periods: 0‐14 days, 15‐182 days, and 183‐365 days. Associations of opioid and NSAID prescription fills with baseline factors were examined by logistic regression (adjusted odds ratio, LCLaORUCL). Among 23,565 donors, opioid prescriptions were highest during days 0‐14 (36.6%), but 12.6% of donors filled opioids during days 183‐365. NSAID prescriptions rose from 0.5% during days 0‐14 to 3.3% during days 183‐365. Women filled opioids more commonly than men, and black donors filled both opioids and NSAIDs more commonly than white donors. After covariate adjustment, significant correlates of opioid prescription fills during days 183‐365 included obesity (aOR,1.241.381.53), less than college education (aOR,1.191.311.43), smoking (aOR,1.331.451.58), and nephrectomy complications (aOR,1.111.291.49). NSAID prescription fills in year 1 were not associated with differences in estimated glomerular filtration rate, incidence of proteinuria or new‐onset hypertension at the first and second year postdonation. Prescription fills for opioids and NSAIDs for LKDs varied with demographic and clinic traits. Future work should examine longer‐term outcome implications to help inform safe analgesic regimen choices after donation. [ABSTRACT FROM AUTHOR]

Background: Effects of oral anticoagulation in chronic kidney disease (CKD) are uncertain. Purpose: To evaluate the benefits and harms of vitamin K antagonists (VKAs) and non–vitamin K oral anticoagulants (NOACs) in adults with CKD stages 3 to 5, including those with dialysis-dependent end-stage kidney disease (ESKD). Data Sources: English-language searches of MEDLINE, EMBASE, and Cochrane databases (inception to February 2019); review bibliographies; and ClinicalTrials.gov (25 February 2019). Study Selection: Randomized controlled trials evaluating VKAs or NOACs for any indication in patients with CKD that reported efficacy or bleeding outcomes. Data Extraction: Two authors independently extracted data, assessed risk of bias, and rated certainty of evidence. Data Synthesis: Forty-five trials involving 34 082 participants who received anticoagulation for atrial fibrillation (AF) (11 trials), venous thromboembolism (VTE) (11 trials), thromboprophylaxis (6 trials), prevention of dialysis access thrombosis (8 trials), and cardiovascular disease other than AF (9 trials) were included. All but the 8 trials involving patients with ESKD excluded participants with creatinine clearance less than 20 mL/min or estimated glomerular filtration rate less than 15 mL/min/1.73 m 2. In AF, compared with VKAs, NOACs reduced risks for stroke or systemic embolism (risk ratio [RR], 0.79 [95% CI, 0.66 to 0.93]; high-certainty evidence) and hemorrhagic stroke (RR, 0.48 [CI, 0.30 to 0.76]; moderate-certainty evidence). Compared with VKAs, the effects of NOACs on recurrent VTE or VTE-related death were uncertain (RR, 0.72 [CI, 0.44 to 1.17]; low-certainty evidence). In all trials combined, NOACs seemingly reduced major bleeding risk compared with VKAs (RR, 0.75 [CI, 0.56 to 1.01]; low-certainty evidence). Limitation: Scant evidence for advanced CKD or ESKD; data mostly from subgroups of large trials. Conclusion: In early-stage CKD, NOACs had a benefit–risk profile superior to that of VKAs. For advanced CKD or ESKD, there was insufficient evidence to establish benefits or harms of VKAs or NOACs. Primary Funding Source: None. (PROSPERO: CRD42017079709) This meta-analysis of 45 trials compares the benefits and harms of vitamin K antagonists and non–vitamin K oral anticoagulants in patients with chronic kidney disease stages 3 to 5. [ABSTRACT FROM AUTHOR]

Background In primary care, patients with chronic kidney disease (CKD) are frequently prescribed excessive doses of antibiotics relative to their kidney function. We examined whether nephrology comanagement is associated with improved prescribing in primary care. Methods In a retrospective propensity score–matched cross-sectional study, we studied the appropriateness of antibiotic prescriptions by primary care physicians to Ontarians ≥66 years of age with CKD Stages 4 and 5 (estimated glomerular filtration rate <30 mL/min/1.73 m2 not receiving dialysis) from 1 April 2003 to 31 March 2014. Comanagement was defined as having at least one outpatient visit with a nephrologist within the year prior to antibiotic prescription date. We compared the rate of appropriately dosed antibiotics in primary care between 3937 patients who were comanaged by a nephrologist and 3937 patients who were not. Results Only 1184 (30%) of 3937 noncomanaged patients had appropriately dosed antibiotic prescriptions prescribed by a primary care physician. Nephrology comanagement was associated with an increased likelihood that an appropriately dosed prescription was prescribed by a primary care physician; however, the magnitude of the effect was modest [1342/3937 (34%); odds ratio 1.20 (95% confidence interval 1.09–1.32); P < 0.001]. Conclusion The majority of antibiotics prescribed by primary care physicians are inappropriately dosed in CKD patients, whether or not a nephrologist is comanaging the patient. Nephrologists have an opportunity to increase awareness of appropriate dosing of medications in primary care through the patients they comanage. [ABSTRACT FROM AUTHOR]

Importance: In observational studies, increased water intake is associated with better kidney function.Objective: To determine the effect of coaching to increase water intake on kidney function in adults with chronic kidney disease.Design, Setting, and Participants: The CKD WIT (Chronic Kidney Disease Water Intake Trial) randomized clinical trial was conducted in 9 centers in Ontario, Canada, from 2013 until 2017 (last day of follow-up, May 25, 2017). Patients had stage 3 chronic kidney disease (estimated glomerular filtration rate [eGFR] 30-60 mL/min/1.73 m2 and microalbuminuria or macroalbuminuria) and a 24-hour urine volume of less than 3.0 L.Interventions: Patients in the hydration group (n = 316) were coached to drink more water, and those in the control group (n = 315) were coached to maintain usual intake.Main Outcomes and Measures: The primary outcome was change in kidney function (eGFR from baseline to 12 months). Secondary outcomes included 1-year change in plasma copeptin concentration, creatinine clearance, 24-hour urine albumin, and patient-reported overall quality of health (0 [worst possible] to 10 [best possible]).Results: Of 631 randomized patients (mean age, 65.0 years; men, 63.4%; mean eGFR, 43 mL/min/1.73 m2; median urine albumin, 123 mg/d), 12 died (hydration group [n = 5]; control group [n = 7]). Among 590 survivors with 1-year follow-up measurements (95% of 619), the mean change in 24-hour urine volume was 0.6 L per day higher in the hydration group (95% CI, 0.5 to 0.7; P < .001). The mean change in eGFR was -2.2 mL/min/1.73 m2 in the hydration group and -1.9 mL/min/1.73 m2 in the control group (adjusted between-group difference, -0.3 mL/min/1.73 m2 [95% CI, -1.8 to 1.2; P = .74]). The mean between-group differences (hydration vs control) in secondary outcomes were as follows: plasma copeptin, -2.2 pmol/L (95% CI, -3.9 to -0.5; P = .01); creatinine clearance, 3.6 mL/min/1.73 m2 (95% CI, 0.8 to 6.4; P = .01); urine albumin, 7 mg per day (95% CI, -4 to 51; P = .11); and quality of health, 0.2 points (95% CI, -0.3 to 0.3; P = .22).Conclusions and Relevance: Among adults with chronic kidney disease, coaching to increase water intake compared with coaching to maintain the same water intake did not significantly slow the decline in kidney function after 1 year. However, the study may have been underpowered to detect a clinically important difference.Trial Registration: clinicaltrials.gov Identifier: NCT01766687. [ABSTRACT FROM AUTHOR]

Importance: Some patients will develop chronic kidney disease after a hospitalization with acute kidney injury; however, no risk-prediction tools have been developed to identify high-risk patients requiring follow-up.Objective: To derive and validate predictive models for progression of acute kidney injury to advanced chronic kidney disease.Design, Setting, and Participants: Data from 2 population-based cohorts of patients with a prehospitalization estimated glomerular filtration rate (eGFR) of more than 45 mL/min/1.73 m2 and who had survived hospitalization with acute kidney injury (defined by a serum creatinine increase during hospitalization > 0.3 mg/dL or > 50% of their prehospitalization baseline), were used to derive and validate multivariable prediction models. The risk models were derived from 9973 patients hospitalized in Alberta, Canada (April 2004-March 2014, with follow-up to March 2015). The risk models were externally validated with data from a cohort of 2761 patients hospitalized in Ontario, Canada (June 2004-March 2012, with follow-up to March 2013).Exposures: Demographic, laboratory, and comorbidity variables measured prior to discharge.Main Outcomes and Measures: Advanced chronic kidney disease was defined by a sustained reduction in eGFR less than 30 mL/min/1.73 m2 for at least 3 months during the year after discharge. All participants were followed up for up to 1 year.Results: The participants (mean [SD] age, 66 [15] years in the derivation and internal validation cohorts and 69 [11] years in the external validation cohort; 40%-43% women per cohort) had a mean (SD) baseline serum creatinine level of 1.0 (0.2) mg/dL and more than 20% had stage 2 or 3 acute kidney injury. Advanced chronic kidney disease developed in 408 (2.7%) of 9973 patients in the derivation cohort and 62 (2.2%) of 2761 patients in the external validation cohort. In the derivation cohort, 6 variables were independently associated with the outcome: older age, female sex, higher baseline serum creatinine value, albuminuria, greater severity of acute kidney injury, and higher serum creatinine value at discharge. In the external validation cohort, a multivariable model including these 6 variables had a C statistic of 0.81 (95% CI, 0.75-0.86) and improved discrimination and reclassification compared with reduced models that included age, sex, and discharge serum creatinine value alone (integrated discrimination improvement, 2.6%; 95% CI, 1.1%-4.0%; categorical net reclassification index, 13.5%; 95% CI, 1.9%-25.1%) or included age, sex, and acute kidney injury stage alone (integrated discrimination improvement, 8.0%; 95% CI, 5.1%-11.0%; categorical net reclassification index, 79.9%; 95% CI, 60.9%-98.9%).Conclusions and Relevance: A multivariable model using routine laboratory data was able to predict advanced chronic kidney disease following hospitalization with acute kidney injury. The utility of this model in clinical care requires further research. [ABSTRACT FROM AUTHOR]

This study uses Canadian administrative health databases to estimate gestational age–specific serum creatinine levels before, during, and after pregnancy among women without antecedent kidney disease. [ABSTRACT FROM AUTHOR]

The article discusses a study which examined the effectiveness of nitrofurantoin in the treatment of urinary tract infection (UTI) among older female patients. Topics discussed include a comparison of the effectiveness of nitrofurantoin with other antibiotics, the use of nitrofurantoin in older women with reduced kidney function, and reductions in estimated glomerular filtration rate.

Background: Evidence from animal and human studies suggests a protective effect of higher water intake on kidney function and cardiovascular disease (CVD). Here the associations between water intake, chronic kidney disease (CKD) and CVD were examined in the general population. Methods: We conducted a cross-sectional analysis of the 2005-2006 National Health and Nutrition Examination Survey. Non-pregnant adults with an estimated glomerular filtration rate (eGFR) ≥30 ml/min/1.73 m2 who were not taking diuretics were included. Total water intake from foods and beverages was categorized as low (<2.0 l/day), moderate (2.0-4.3 l/day) and high (>4.3 l/day). We examined associations between low total water intake and CKD (eGFR 30-60 ml/min/1.73 m2) and self-reported CVD. Results: Of 3,427 adults (mean age 46 (range 20-84); mean eGFR 95 ml/min/1.73 m2 (range 30-161)), 13% had CKD and 18% had CVD. CKD was higher among those with the lowest (<2.0 l/day) vs. highest total water intake (>4.3 l/day) (adjusted odds ratio (OR) 2.52; 95% confidence interval (CI) 0.91-6.96). When stratified by intake of (1) plain water and (2) other beverages, CKD was associated with low intake of plain water: adjusted OR 2.36 (95% CI 1.10-5.06), but not other beverages: adjusted OR 0.87 (95% CI 0.30-2.50). There was no association between low water intake and CVD (adjusted OR 0.76; 95% CI 0.37-1.59). Conclusions: Our results provide additional evidence suggesting a potentially protective effect of higher total water intake, particularly plain water, on the kidney. Copyright © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Large, population-based administrative healthcare databases can be used to identify patients with chronic kidney disease (CKD) when serum creatinine laboratory results are unavailable. We examined the validity of algorithms that used combined hospital encounter and physician claims database codes for the detection of CKD in Ontario, Canada. Methods: We accrued 123,499 patients over the age of 65 from 2007 to 2010. All patients had a baseline serum creatinine value to estimate glomerular filtration rate (eGFR). We developed an algorithm of physician claims and hospital encounter codes to search administrative databases for the presence of CKD. We determined the sensitivity, specificity, positive and negative predictive values of this algorithm to detect our primary threshold of CKD, an eGFR <45 mL/min per 1.73 m2 (15.4% of patients). We also assessed serum creatinine and eGFR values in patients with and without CKD codes (algorithm positive and negative, respectively). Results: Our algorithm required evidence of at least one of eleven CKD codes and 7.7% of patients were algorithm positive. The sensitivity was 32.7% [95% confidence interval: (95% CI): 32.0 to 33.3%]. Sensitivity was lower in women compared to men (25.7 vs. 43.7%; p <0.001) and in the oldest age category (over 80 vs. 66 to 80; 28.4 vs. 37.6 %; p < 0.001). All specificities were over 94%. The positive and negative predictive values were 65.4% (95% CI: 64.4 to 66.3%) and 88.8% (95% CI: 88.6 to 89.0%), respectively. In algorithm positive patients, the median [interquartile range (IQR)] baseline serum creatinine value was 135 μmol/L (106 to 179 μmol/L) compared to 82 μmol/L (69 to 98 μmol/L) for algorithm negative patients. Corresponding eGFR values were 38 mL/min per 1.73 m2 (26 to 51 mL/min per 1.73 m2) vs. 69 mL/min per 1.73 m2 (56 to 82 mL/min per 1.73 m2), respectively. Conclusions: Patients with CKD as identified by our database algorithm had distinctly higher baseline serum creatinine values and lower eGFR values than those without such codes. However, because of limited sensitivity, the prevalence of CKD was underestimated. [ABSTRACT FROM AUTHOR]

Objective: The study objective was to examine the utility of using proteinuria in preoperative risk stratification for acute kidney injury. Acute kidney injury is a common and important complication for patients undergoing cardiac surgery. Proteinuria, which reflects structural damage to the glomeruli or renal tubules, may aid the prediction of acute kidney injury. Methods: The urine albumin to creatinine ratio and dipstick proteinuria concentration were prospectively measured in 1159 patients undergoing cardiac surgery. The cohort was organized into 4 clinical risk categories based on the preoperative urine albumin to creatinine ratio: 10 mg/g or less (≤1.1 mg/mmol), 11 to 29 mg/g (1.2–3.3 mg/mmol), 30 to 299 mg/g (3.4–33.8 mg/mmol), and 300 mg/g or greater (≥33.9 mg/mmol). The primary outcome was postoperative acute kidney injury, defined by the Acute Kidney Injury Network stage I criterion (serum creatinine increase ≥ 50% or ≥ 0.3 mg/dL; 26.5 μmol/L). Results: An increase in the incidence of acute kidney injury was noted across the urine albumin to creatinine ratio categories. Adding the urine albumin to creatinine ratio to the clinical model to predict acute kidney injury improved the area under the curve from 0.67 to 0.70 (P < .001), and the continuous net reclassification improvement was 29% (P < .001). The urine albumin to creatinine ratio was also independently associated with the risk of in-hospital dialysis and intensive care unit and hospital lengths of stay. Surgery status and preoperative glomerular filtration rate were effect modifiers; the association was stronger among those undergoing elective surgery and those with an estimated glomerular filtration rate of 45 mL/min/1.73 m2 or greater. Conclusions: Preoperative proteinuria provides graded stratification risk for acute kidney injury and is an independent predictor of other outcomes in patients undergoing cardiac surgery. [ABSTRACT FROM AUTHOR]

Background. Little evidence justifies the avoidance of glyburide in patients with impaired renal function. We aimed to determine if renal function modifies the risk of hypoglycaemia among patients using glyburide.Methods. We conducted a nested case–control study using administrative records and laboratory data from Ontario, Canada. We included outpatients 66 years of age and older with diabetes mellitus and prescriptions for glyburide, insulin or metformin. We ascertained hypoglycaemic events using administrative records and estimated glomerular filtration rates (eGFR) using serum creatinine concentrations.Results. From a cohort of 19,620 patients, we identified 204 cases whose eGFR was ≥ 60 mL/min/1.73 m2 (normal renal function) and 354 cases whose eGFR was < 60 mL/min/1.73 m2 (impaired renal function). Compared to metformin, glyburide is associated with a greater risk of hypoglycaemia in patients with both normal [adjusted odds ratio (OR) 9.0, 95% confidence interval (95% CI) 4.9–16.4] and impaired renal function (adjusted OR 6.0, 95% CI 3.8–9.5). We observed a similar relationship when comparing insulin to metformin; the risk was greater in patients with normal renal function (adjusted OR 18.7, 95% CI 10.5–33.5) compared to those with impaired renal function (adjusted OR 7.9, 95% CI 5.0–12.4). Tests of interaction showed that among glyburide users, renal function did not significantly modify the risk of hypoglycaemia, but among insulin users, impaired renal function is associated with a lower risk.Conclusions. In this population-based study, impaired renal function did not augment the risk of hypoglycaemia associated with glyburide use. [ABSTRACT FROM AUTHOR]

Background: Two small, randomized trials provide conflicting evidence about the benefits of plasma exchange for patients with acute renal failure at the onset of multiple myeloma.Objective: To assess the effect of 5 to 7 plasma exchanges on a composite outcome in patients with acute renal failure at the onset of multiple myeloma.Design: Randomized, open, controlled trial, stratified by chemotherapy and dialysis dependence, conducted from 1998 to 2004.Setting: Hospital plasma exchange units in 14 Canadian medical centers.Participants: 104 patients between 18 and 81 years of age with acute renal failure at the onset of myeloma.Intervention: Study participants were randomly assigned to conventional therapy plus 5 to 7 plasma exchanges of 50 mL per kg of body weight of 5% human serum albumin for 10 days or conventional therapy alone. Ninety-seven participants completed the 6-month follow-up.Measurements: The primary outcome was a composite measure of death, dialysis dependence, or glomerular filtration rate less than 0.29 mL x s(-2) x m(-2) (<30 mL/min per 1.73 m2).Results: At enrollment, the plasma exchange and control groups were similar for dialysis dependence, chemotherapy, sex, age, hypercalcemia, serum albumin level, 24-hour urine protein level, serum creatinine level, and Durie-Salmon staging. The primary composite end point occurred in 33 of 57 (57.9%) patients in the plasma exchange group and in 27 of 39 (69.2%) patients in the control group (difference between groups, 11.3% [95% CI, -8.3% to 29.1%]; P = 0.36). One third of patients in each group died.Limitations: The study was small, used a composite outcome, and did not use renal biopsy as an inclusion criterion. Recruiting physicians were blinded to treatment allocation but not to treatment thereafter.Conclusions: In patients with acute renal failure at the onset of multiple myeloma, there is no conclusive evidence that 5 to 7 plasma exchanges substantially reduce a composite outcome of death, dialysis dependence, or glomerular filtration rate less than 0.29 mL.s(-2).m(-2) (<30 mL/min per 1.73 m2) at 6 months. [ABSTRACT FROM AUTHOR]