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Background: Prepregnancy kidney dysfunction has been associated with preterm birth, which is the leading cause of neonatal morbidity and mortality; however, the relation is not well understood. We determined the risk of preterm birth in women with prepregnancy kidney dysfunction, defined using pregnancy-specific serum creatinine cut points., Methods: This population-based cohort study in the province of Ontario, Canada, involved women aged 16 to 50 years who had a singleton birth between 2006 and 2016 and measurement of serum creatinine within 10 weeks preceding their estimated conception date. The exposure was abnormally elevated prepregnancy serum creatinine, defined as greater than the 95th percentile (> 77 μmol/L), a value derived from a population-based sample of women without known kidney disease who became pregnant soon after the measurement was obtained. The main outcome was any preterm birth from 23 to 36 weeks' gestation. Secondary outcomes included provider-initiated preterm birth before 37 weeks' gestation and spontaneous preterm birth before 37 weeks., Results: Among 55 946 pregnancies, preterm birth before 37 weeks' gestation occurred in 3956 women (7.1%). The risk of preterm birth before 37 weeks was higher among women with prepregnancy creatinine above the 95th percentile, relative to those with prepregnancy creatinine at or below the 95th percentile (9.1% v. 7.0%; adjusted relative risk [RR] 1.23, 95% confidence interval [CI] 1.09 to 1.38). The effect was significant for provider-initiated preterm birth (adjusted RR 1.30, 95% CI 1.11 to 1.52) but not for spontaneous preterm birth (adjusted RR 1.12, 95% CI 0.91 to 1.37)., Interpretation: Given that prepregnancy kidney dysfunction conferred an increased risk of preterm birth, measurement of serum creatinine (a relatively inexpensive blood test) may form part of the assessment of risk for preterm birth among those planning pregnancy., Competing Interests: Competing interests: Michelle Hladunewich has received grants from Ionis Pharmaceuticals, Calliditas Therapeutics, Pfizer and ChemoCentryx for research projects outside the study reported here. In addition, she has received consulting fees from Alnylam Pharmaceuticals; serves as an editor with UpToDate, for the sections on chronic kidney disease/end-stage renal disease and pregnancy; and is the medical head for glomerulonephritis and pregnancy for the Ontario Renal Network. No other competing interests were declared., (© 2020 Joule Inc. or its licensors.)

Background: Low 25-hydroxyvitamin D is associated with cardiovascular, renal, and infectious risks. Postsurgical patients are susceptible to similar complications, but whether vitamin D deficiency contributes to postoperative complications remains unclear. We tested whether low preoperative vitamin D is associated with cardiovascular events within 30 days after noncardiac surgery., Methods: We evaluated a subset of patients enrolled in the biobank substudy of the Vascular events In noncardiac Surgery patIents cOhort evaluatioN (VISION) study, who were at least 45 yr with at least an overnight hospitalization. Blood was collected preoperatively, and 25-hydroxyvitamin D was measured in stored samples. The primary outcome was the composite of cardiovascular events (death, myocardial injury, nonfatal cardiac arrest, stroke, congestive heart failure) within 30 postoperative days. Secondary outcomes were kidney injury and infectious complications., Results: A total of 3,851 participants were eligible for analysis. Preoperative 25-hydroxyvitamin D concentration was 70 ± 30 nmol/l, and 62% of patients were vitamin D deficient. Overall, 26 (0.7%) patients died, 41 (1.1%) had congestive heart failure or nonfatal cardiac arrest, 540 (14%) had myocardial injury, and 15 (0.4%) had strokes. Preoperative vitamin D concentration was not associated with the primary outcome (average relative effect odds ratio [95% CI]: 0.93 [0.85, 1.01] per 10 nmol/l increase in preoperative vitamin D, P = 0.095). However, it was associated with postoperative infection (average relative effect odds ratio [95% CI]: 0.94 [0.90, 0.98] per 10 nmol/l increase in preoperative vitamin D, P adjusted value = 0.005) and kidney function (estimated mean change in postoperative estimated glomerular filtration rate [95% CI]: 0.29 [0.11, 0.48] ml min 1.73 m per 10 nmol/l increase in preoperative vitamin D, P adjusted value = 0.004)., Conclusions: Preoperative vitamin D was not associated with a composite of postoperative 30-day cardiac outcomes. However, there was a significant association between vitamin D deficiency and a composite of infectious complications and decreased kidney function. While renal effects were not clinically meaningful, the effect of vitamin D supplementation on infectious complications requires further study.

The 2017 Kidney Disease: Improving Global Outcomes (KDIGO) Clinical Practice Guideline on the Evaluation and Care of Living Kidney Donors is intended to assist medical professionals who evaluate living kidney donor candidates and provide care before, during and after donation. The guideline development process followed the Grades of Recommendation Assessment, Development, and Evaluation (GRADE) approach and guideline recommendations are based on systematic reviews of relevant studies that included critical appraisal of the quality of the evidence and the strength of recommendations. However, many recommendations, for which there was no evidence or no systematic search for evidence was undertaken by the Evidence Review Team, were issued as ungraded expert opinion recommendations. The guideline work group concluded that a comprehensive approach to risk assessment should replace decisions based on assessments of single risk factors in isolation. Original data analyses were undertaken to produce a "proof-in-concept" risk-prediction model for kidney failure to support a framework for quantitative risk assessment in the donor candidate evaluation and defensible shared decision making. This framework is grounded in the simultaneous consideration of each candidate's profile of demographic and health characteristics. The processes and framework for the donor candidate evaluation are presented, along with recommendations for optimal care before, during, and after donation. Limitations of the evidence are discussed, especially regarding the lack of definitive prospective studies and clinical outcome trials. Suggestions for future research, including the need for continued refinement of long-term risk prediction and novel approaches to estimating donation-attributable risks, are also provided.In citing this document, the following format should be used: Kidney Disease: Improving Global Outcomes (KDIGO) Living Kidney Donor Work Group. KDIGO Clinical Practice Guideline on the Evaluation and Care of Living Kidney Donors. Transplantation. 2017;101(Suppl 8S):S1-S109.

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 and Objectives: The Fracture Risk Assessment Tool (FRAX) is widely used to predict the 10-year probability of fracture; however, the clinical utility of FRAX in CKD is unknown. This study assessed the predictive ability of FRAX in individuals with reduced kidney function compared with individuals with normal kidney function., Design, Setting, Participants, & Measurements: The discrimination and calibration (defined as the agreement between observed and predicted values) of FRAX were examined using data from the Canadian Multicentre Osteoporosis Study (CaMos). This study included individuals aged ≥40 years with an eGFR value at year 10 of CaMos (defined as baseline). The cohort was stratified by kidney function at baseline (eGFR<60 ml/min per 1.73 m(2) [72.2% stage 3a, 23.8% stage 3b, and 4.0% stage 4/5] versus ≥60 ml/min per 1.73 m(2)) and followed individuals for a mean of 4.8 years for an incident major osteoporotic fracture (clinical spine, hip, forearm/wrist, or humerus)., Results: There were 320 individuals with an eGFR<60 ml/min per 1.73 m(2) and 1787 with an eGFR≥60 ml/min per 1.73 m(2). The mean age was 67±10 years and 71% were women. The 5-year observed major osteoporotic fracture risk was 5.3% (95% confidence interval [95% CI], 3.3% to 8.6%) in individuals with an eGFR<60 ml/min per 1.73 m(2), which was comparable to the FRAX-predicted fracture risk (6.4% with bone mineral density; 8.2% without bone mineral density). A statistically significant difference was not observed in the area under the curve values for FRAX in individuals with an eGFR<60 ml/min per 1.73 m(2) versus ≥60 ml/min per 1.73 m(2) (0.69 [95% CI, 0.54 to 0.83] versus 0.76 [95% CI, 0.70 to 0.82]; P=0.38)., Conclusions: This study showed that FRAX was able to predict major osteoporotic fractures in individuals with reduced kidney function; further study is needed before FRAX should be routinely used in individuals with reduced kidney function., (Copyright © 2015 by the American Society of Nephrology.)

Background: The demographic and clinical correlates of gout after living kidney donation are not well described., Methods: Using a unique database that integrates national registry identifiers of U.S. living kidney donors (1987-2007) with billing claims from a private health insurer (2000-2007), we identified post-donation gout based on medical diagnosis codes or pharmacy fills for gout therapies. The frequencies and demographic correlates of gout after donation were estimated by Cox regression with left- and right-censoring. We also compared the rates of renal diagnoses among donors with and without gout, matched in the ratio 1:3 by age, sex, and race., Results: The study sample of 4,650 donors included 13.1% African Americans. By seven years, African Americans were almost twice as likely to develop gout as Caucasian donors (4.4 vs. 2.4%; adjusted hazard ratio, aHR, 1.8; 95% confidence interval (CI) 1.0-3.2). Post-donation gout risk also increased with older age at donation (aHR per year 1.05) and was higher in men (aHR 2.80). Gout rates were similar in donors and age- and sex-matched general non-donors (rate ratio 0.86; 95% CI 0.66-1.13). Compared to matched donors without gout, donors with gout had more frequent renal diagnoses, reaching significance for acute kidney failure (rate ratio 12.5; 95% CI 1.5-107.0), chronic kidney disease (rate ratio 5.0; 95% CI 2.1-11.7), and other disorders of the kidney (rate ratio 2.2; 95% CI 1.2-4.2)., Conclusion: Donor subgroups at increased risk of gout include African Americans, older donors, and men. Donors with gout have a higher burden of renal complications after demographic adjustment., (© 2015 S. Karger AG, Basel)

Background: Tools to enhance physician searches of Medline and other bibliographic databases have potential to improve the application of new knowledge in patient care. This is particularly true for articles about glomerular disease, which are published across multiple disciplines and are often difficult to track down. Our objective was to develop and test search filters for PubMed, Ovid Medline, and Embase that allow physicians to search within a subset of the database to retrieve articles relevant to glomerular disease., Methods: We used a diagnostic test assessment framework with development and validation phases. We read a total of 22,992 full text articles for relevance and assigned them to the development or validation set to define the reference standard. We then used combinations of search terms to develop 997,298 unique glomerular disease filters. Outcome measures for each filter included sensitivity, specificity, precision, and accuracy. We selected optimal sensitive and specific search filters for each database and applied them to the validation set to test performance., Results: High performance filters achieved at least 93.8% sensitivity and specificity in the development set. Filters optimized for sensitivity reached at least 96.7% sensitivity and filters optimized for specificity reached at least 98.4% specificity. Performance of these filters was consistent in the validation set and similar among all three databases., Conclusions: PubMed, Ovid Medline, and Embase can be filtered for articles relevant to glomerular disease in a reliable manner. These filters can now be used to facilitate physician searching.

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.

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.

Background: Fibric acid derivatives (fibrates) have been shown to increase serum creatinine level in randomized trials., Objective: To assess renal outcomes in elderly adults within 90 days of a new fibrate prescription., Design: Population-based cohort study., Setting: Ontario, Canada., Patients: Patients aged 66 years or older with a new outpatient prescription for a fibrate or ezetimibe (comparator drug) between January 2004 and December 2008., Measurements: Hospitalization for an increase in serum creatinine level (primary outcome) and consultation with a nephrologist, receipt of dialysis for severe acute kidney injury, all-cause mortality, and increases in serum creatinine level (secondary outcomes). All outcomes were assessed within 90 days of a new prescription for ezetimibe or a fibrate., Results: Compared with ezetimibe users (n = 61,831), fibrate users (n = 19,072) were more likely to be hospitalized for an increase in serum creatinine level (adjusted odds ratio, 2.4 [95% CI, 1.7 to 3.3]) and were more likely to consult a nephrologist (absolute risk difference, 0.15% [CI, 0.01% to 0.29%]; adjusted odds ratio, 1.3 [CI, 1.0 to 1.6]). There were no differences between groups in the risk for all-cause mortality or receiving dialysis for severe acute kidney injury. In a subpopulation of 1110 patients (fibrates, n = 220; ezetimibe, n = 890), 9.1% of fibrate users and 0.3% of ezetimibe users had an increase in serum creatinine level of 50% or more (absolute difference, 8.8% [CI, 4.5% to 13.1%]; odds ratio, 29.6 [CI, 8.7 to 100.5]). Risks were greater among fibrate users with chronic kidney disease., Limitations: Because hospitalizations for an increase in serum creatinine level were underestimated, absolute differences may be misleading. Most patients (91%) were prescribed fenofibrate. Serum creatinine levels were measured as part of routine care and were not available for everyone or at predefined times., Conclusion: New fibrate use in elderly adults was associated with an increase in serum creatinine level and a small 90-day absolute increase in hospitalizations and nephrologist consultations. There was no detectable effect on dialysis for severe acute kidney injury or on mortality. The mechanism and clinical significance of the increase in serum creatinine level with fibrates is unclear., Primary Funding Source: Ontario Ministry of Health and Long-Term Care Drug Innovation Fund.

Background and Objectives: Guidelines promote early fistula creation to avoid central venous catheter use. This practice may lead to fistula creations in patients who never receive dialysis. The objective of this study was to estimate the risk of fistula nonuse with long-term follow-up., Design, Setting, Participants, & Measurements: Administrative health data identified 1929 predialysis adults who had their first fistula creation between April of 2002 and March of 2006. Patients were followed for a minimum of 2 years or until they began dialysis, received a kidney transplant, or died., Results: The median follow-up times in patients who started dialysis, died without receiving dialysis, and remained in predialysis were 6.1, 11.5, and 38.7 months, respectively. Eighty-one percent of patients initiated dialysis; 9% of patients died without receiving dialysis, and 10% of patients remained predialysis. Forty percent of patients had their first fistula creation 3-12 months before initiating dialysis (the recommended window). Thirty percent were created within 90 days of starting dialysis; 30% were created more than 1 year before starting dialysis, and 10% were created more than 2 years before starting dialysis. Older patients, females, and patients with less comorbidity were not as likely to initiate dialysis after incident fistula creation., Conclusions: Most patients who underwent fistula creation before starting dialysis eventually received dialysis with extended follow-up, but the risk was significantly modified by age, sex, and comorbidity. Many patients had fistula creations earlier or later than recommended.

Background: Clinical decision support systems (CDSSs) have the potential to improve kidney-related drug prescribing by supporting the appropriate initiation, modification, monitoring, or discontinuation of drug therapy., Study Design: Systematic review. We identified studies by searching multiple bibliographic databases (eg, MEDLINE and EMBASE), conference proceedings, and reference lists of all included studies., Setting & Population: CDSSs used in hospital or outpatient settings for acute kidney injury and chronic kidney disease, including end-stage renal disease (chronic dialysis patients or transplant recipients)., Selection Criteria for Studies: Studies prospectively using CDSSs to aid in kidney-related drug prescribing., Intervention: Computerized or manual CDSSs., Outcomes: Clinician prescribing and patient-important outcomes as reported by primary study investigators. CDSS characteristics, such as whether the system was computerized, and system setting., Results: We identified 32 studies. In 17 studies, CDSSs were computerized, and in 15 studies, they were manual pharmacist-based systems. Systems intervened by prompting for drug dosing adjustments in relation to the level of decreased kidney function (25 studies) or in response to serum drug concentrations or a clinical parameter (7 studies). They were used most in academic hospital settings. For computerized CDSSs, clinician prescribing outcomes (eg, frequency of appropriate dosing) were considered in 11 studies, with all 11 reporting statistically significant improvements. Similarly, manual CDSSs that incorporated clinician prescribing outcomes showed statistically significant improvements in 6 of 8 studies. Patient-important outcomes (eg, adverse drug events) were considered in 7 studies of computerized CDSSs, with statistically significant improvements in 2 studies. For manual CDSSs, 6 studies measured patient-important outcomes and 5 reported statistically significant improvements. Cost-savings also were reported, mostly for manual CDSSs., Limitations: Studies were heterogeneous in design and often limited by the evaluation method used. Benefits of CDSSs may be reported selectively in this literature., Conclusion: CDSSs are available for many dimensions of kidney-related drug prescribing, and results are promising. Additional high-quality evaluations will guide their optimal use., (Copyright © 2011 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

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: Pregnant women with chronic kidney disease (CKD) are at risk of adverse maternal and fetal outcomes. We conducted a systematic review of observational studies that described this risk., Design, Setting, Participants, & Measurements: We searched several databases from their date of inception through June 2010 for eligible articles published in any language. We included any study that reported maternal or fetal outcomes in at least five pregnant women in each group with or without CKD. We excluded pregnant women with a history of transplantation or maintenance dialysis., Results: We identified 13 studies. Adverse maternal events including gestational hypertension, pre-eclampsia, eclampsia, and maternal mortality were reported in 12 studies. There were 312 adverse maternal events among 2682 pregnancies in women with CKD (weighted average of 11.5%) compared with 500 events in 26,149 pregnancies in normal healthy women (weighted average of 2%). One or more adverse fetal outcomes such as premature births, intrauterine growth restriction, small for gestational age, neonatal mortality, stillbirths, and low birth weight were reported in nine of the included studies. Overall, the risk of developing an adverse fetal outcome was at least two times higher among women with CKD compared with those without., Conclusions: This review summarizes current available evidence to guide physicians in their decision-making, advice, and care for pregnant women with CKD. Additional studies are needed to better characterize the risks.

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 and Objectives: It is unclear how to optimally care for chronic kidney disease (CKD). This study compares a new coordinated model to usual care for CKD., Design, Setting, Participants, & Measurements: A randomized trial in nephrology clinics and the community included 474 patients with median estimated GFR (eGFR) 42 ml/min per 1.73 m(2) identified by laboratory-based case finding compared care coordinated by a general practitioner (controls) with care by a nurse-coordinated team including a nephrologist (intervention) for a median (interquartile range [IQR]) of 742 days. 32% were diabetic, 60% had cardiovascular disease, and proteinuria was minimal. Guided by protocols, the intervention team targeted risk factors for adverse kidney and cardiovascular outcomes. Serial eGFR and clinical events were tracked., Results: The average decline in eGFR over 20 months was -1.9 ml/min per 1.73 m(2). eGFR declined by ≥4 ml/min per 1.73 m(2) within 20 months in 28 (17%) intervention patients versus 23 (13.9%) control patients. Control of BP, LDL, and diabetes were comparable across groups. In the intervention group there was a trend to greater use of renin-angiotensin blockers and more use of statins in those with initial LDL >2.5 mmol/L. Treatment was rarely required for anemia, acidosis, or disordered mineral metabolism. Clinical events occurred in 5.2% per year., Conclusions: Patients with stage 3/4 CKD identified through community laboratories largely had nonprogressive kidney disease but had cardiovascular risk. Over a median of 24 months, the nurse-coordinated team did not affect rate of GFR decline or control of most risk factors compared with usual care.

Background and Objectives: Potential cost and effectiveness of a nephrologist/nurse-based multifaceted intervention for stage 3 to 4 chronic kidney disease are not known. This study examines the cost-effectiveness of a chronic disease management model for chronic kidney disease., Design, Setting, Participants, & Measurements: Cost and cost-effectiveness were prospectively gathered alongside a multicenter trial. The Canadian Prevention of Renal and Cardiovascular Endpoints Trial (CanPREVENT) randomized 236 patients to receive usual care (controls) and another 238 patients to multifaceted nurse/nephrologist-supported care that targeted factors associated with development of kidney and cardiovascular disease (intervention). Cost and outcomes over 2 years were examined to determine the incremental cost-effectiveness of the intervention. Base-case analysis included disease-related costs, and sensitivity analysis included all costs., Results: Consideration of all costs produced statistically significant differences. A lower number of days in hospital explained most of the cost difference. For both base-case and sensitivity analyses with all costs included, the intervention group required fewer resources and had higher quality of life. The direction of the results was unchanged to inclusion of various types of costs, consideration of payer or societal perspective, changes to the discount rate, and levels of GFR., Conclusions: The nephrologist/nurse-based multifaceted intervention represents good value for money because it reduces costs without reducing quality of life for patients with chronic kidney disease.

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.)

Background: Information in health administrative databases increasingly guides renal care and policy., Study Design: Systematic review of observational studies., Setting & Population: Studies describing the validity of codes for acute kidney injury (AKI) and chronic kidney disease (CKD) in administrative databases operating in any jurisdiction., Selection Criteria: After searching 13 medical databases, we included observational studies published from database inception though June 2009 that validated renal diagnostic and procedural codes for AKI or CKD against a reference standard., Index Tests: Renal diagnostic or procedural administrative data codes., Reference Tests: Patient chart review, laboratory values, or data from a high-quality patient registry., Results: 25 studies of 13 databases in 4 countries were included. Validation of diagnostic and procedural codes for AKI was present in 9 studies, and validation for CKD was present in 19 studies. Sensitivity varied across studies and generally was poor (AKI median, 29%; range, 15%-81%; CKD median, 41%; range, 3%-88%). Positive predictive values often were reasonable, but results also were variable (AKI median, 67%; range, 15%-96%; CKD median, 78%; range, 29%-100%). Defining AKI and CKD by only the use of dialysis generally resulted in better code validity. The study characteristic associated with sensitivity in multivariable meta-regression was whether the reference standard used laboratory values (P < 0.001); sensitivity was 39% lower when laboratory values were used (95% CI, 23%-56%)., Limitations: Missing data in primary studies limited some of the analyses that could be done., Conclusions: Administrative database analyses have utility, but must be conducted and interpreted judiciously to avoid bias arising from poor code validity., (Copyright © 2010 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Objectives: To evaluate the risk for hypertension, renal impairment, and cardiovascular disease within eight years of gastroenteritis from drinking water contaminated with Escherichia coli O157:H7 and Campylobacter., Design: A prospective cohort study. Setting Walkerton, Ontario, Canada., Participants: 1977 adult participants in the Walkerton Health Study recruited between 2002 and 2005 after an outbreak of gastroenteritis in May 2000, when a municipal water system was contaminated, with no pre-outbreak history of outcome measures., Outcome Measures: Information was collected annually via survey, physical examination, and laboratory assessment. Primary measures were acute gastroenteritis (diarrhoeal illness lasting >3 days, bloody diarrhoea, or >3 loose stools/day), hypertension (blood pressure ≥140/90 mm Hg), and renal impairment (microalbuminuria or estimated glomerular filtration rate <60 ml/min/1.73 m(2)). Self reported physician diagnosis of cardiovascular disease (myocardial infarction, stroke, or congestive heart failure) was a secondary outcome., Results: Acute gastroenteritis at the time of the outbreak was reported by 1067 (54%) of participants. Incident hypertension was detected in 697 (35%) (294 (32%) of group not exposed to acute gastroenteritis v 403 (38%) of exposed group). While 572 (29%) had at least one indicator of renal impairment (266 (29%) of unexposed v 306 (29%) of exposed), only 30 (1.5%) had both (8 (0.9%) of unexposed v 22 (2.1%) of exposed). Cardiovascular disease was reported by 33/1749 (1.9%). The adjusted hazard ratios for hypertension and cardiovascular disease after acute gastroenteritis were 1.33 (95% confidence interval 1.14 to 1.54) and 2.13 (1.03 to 4.43) respectively. The adjusted hazard ratio for the presence of either indicator of renal impairment was 1.15 (0.97 to 1.35) and was 3.41 (1.51 to 7.71) for the presence of both., Conclusion: Gastroenteritis from drinking water contaminated with E coli O157:H7 and Campylobacter was associated with an increased risk for hypertension, renal impairment, and self reported cardiovascular disease. Annual monitoring of blood pressure and periodic monitoring of renal function may be warranted for individuals who experience E coli O157:H7 gastroenteritis.

Endarterectomy is generally recommended for symptomatic high-grade (70 to 99%) stenosis of the internal carotid artery, but whether this procedure is beneficial among patients with chronic kidney disease (CKD) is unknown. In this re-analysis of data from the North American Symptomatic Carotid Endarterectomy Trial, we included patients with symptomatic stenosis and either stage 3 CKD (n = 524) or preserved kidney function (n = 966; estimated GFR > or = 60). For medically treated patients with high-grade stenosis, risk for ipsilateral stroke at 2 yr was significantly higher in patients with CKD than in those with preserved renal function (31.6 versus 19.3%; P = 0.042); carotid endarterectomy significantly reduced this risk by 82 and 51%, respectively. To prevent one ipsilateral stroke, the number needed to treat by endarterectomy was four for patients with CKD and 10 for patients with preserved renal function. Compared with patients with preserved renal function, those with CKD had similar rates of perioperative stroke and death but higher rates of cardiac events. In conclusion, patients with stage 3 CKD and symptomatic high-grade carotid stenosis gain a large benefit in stroke risk reduction after endarterectomy.

Background and Objectives: Patients receiving dialysis have a high burden of cardiovascular disease. Some receive coronary artery revascularization but the optimal method is controversial., Design, Setting, Participants, & Measurements: The authors reviewed any randomized controlled trial or cohort study of 10 or more patients receiving maintenance dialysis which compared coronary artery bypass graft (CABG) to percutaneous intervention (PCI) for revascularization of the coronary arteries. The primary outcomes were short-term (30 d or in-hospital) and long-term (at least 1 year) mortality., Results: Seventeen studies were found. There were no randomized trials: all were retrospective cohort studies from years 1977 to 2002. There were some baseline differences between the groups receiving CABG compared with those receiving PCI, and most studies did not consider results adjusted for such characteristics. Given the variability among studies and their methodological limitations, few definitive conclusions about the optimal method of revascularization could be drawn. In an exploratory meta-analysis, short-term mortality was higher after CABG compared to PCI. A substantial number of patients died over a subsequent 1 to 5 yr, with no difference in mortality after CABG compared to PCI., Conclusions: Although decisions about the optimal method of coronary artery revascularization in dialysis patients are undertaken routinely, it was surprising to see how few data has been published in this regard. Additional research will help inform physician and patient decisions about coronary artery revascularization.

There is a spectrum of acute illness for individuals who ingest toxigenic Escherichia coli, ranging from no symptoms to self-limited gastroenteritis, to full acute hemolytic uremic syndrome. Knowledge of the long-term prognosis of acute toxigenic E. coli ingestion, based on the presentation of acute illness, is important for patient counseling and follow-up. Here, we consider subsequent 5-year renal outcomes for groups of individuals who presented across a spectrum of acute illness during a municipal water outbreak of E. coli O157:H7 in Walkerton, Canada.

Context: Patients with renal disease are at high risk for cardiovascular mortality. Determining which interventions best offset this risk remains a health priority., Objective: To quantify the representation of patients with renal disease in randomized controlled trials for interventions proven efficacious for cardiovascular disease., Data Sources: We searched MEDLINE for trials published from 1985 through 2005 in 11 major medical and subspecialty journals., Study Selection: Randomized controlled trials for chronic congestive heart failure and acute myocardial infarction of treatments that are currently listed as class I or II recommendations in the current American College of Cardiology/American Heart Association guidelines were included., Data Extraction: Two reviewers independently abstracted data on study and patient characteristics, renal measurements, outcomes, and prognostic features., Data Synthesis: A total of 153 trials were reviewed. Patients with renal disease were reported as excluded in 86 (56%) trials. Patients with renal disease were more likely to be excluded from trials that were multicenter; of moderate enrollment size; North American; that tested renin-angiotensin-aldosterone system antagonists and anticoagulants; and that tested chronic congestive heart failure. Only 8 (5%) original articles reported the proportion of enrolled patients with renal disease, and only 15 (10%) reported mean baseline renal function. While 81 (53%) trials performed subgroup analyses of some baseline characteristic in the original article, only 4 (3%) subgroup analyses of treatment stratified by renal disease were performed., Conclusion: Major cardiovascular disease trials frequently exclude patients with renal disease and do not provide adequate information on the renal function of enrollees or the effect of interventions on patients with renal disease.

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: The long-term health consequences of acute bacterial gastroenteritis remain uncertain. We studied the risk of hypertension and reduced kidney function after an outbreak of acute gastroenteritis due to contamination of a regional drinking water supply with Escherichia coli O157:H7 and Campylobacter species., Methods: A total of 1958 adults with no known history of hypertension or kidney disease before the outbreak participated in a long-term follow-up study. Of the participants, 675 had been asymptomatic during the outbreak, 909 had had moderate symptoms of acute self-limited gastroenteritis, and 374 had had severe symptoms that necessitated medical attention. The outcomes of interest were a diagnosis of hypertension or the presence of reduced kidney function and albuminuria during the follow-up period., Results: After a mean follow-up of 3.7 years after the outbreak, hypertension was diagnosed in 27.0% of participants who had been asymptomatic during the outbreak and in 32.3% and 35.9% of those who had had moderate and severe symptoms of acute gastroenteritis respectively (trend p = 0.009). Compared with the asymptomatic participants, those with moderate and severe symptoms of gastroenteritis had an adjusted relative risk of hypertension of 1.15 (95% confidence interval [CI] 0.97-1.35) and 1.28 (95% CI 1.04-1.56) respectively. A similar graded association was seen for reduced kidney function, defined as the presence of an estimated glomerular filtration rate below 60 mL/min per 1.73 m2 (trend p = 0.03). No association was observed between gastroenteritis and the subsequent risk of albuminuria., Interpretation: Acute bacterial gastroenteritis necessitating medical attention was associated with an increased risk of hypertension and reduced kidney function 4 years after infection. Maintaining safe drinking water remains essential to human health, as transient bacterial contaminations may have implications well beyond a period of acute self-limited illness.

Background: Although measuring albuminuria is the preferred method for defining and staging chronic kidney disease (CKD), total urine protein or dipstick protein is often measured instead.Objective: To develop equations for converting urine protein-creatinine ratio (PCR) and dipstick protein to urine albumin-creatinine ratio (ACR) and to test their diagnostic accuracy in CKD screening and staging.Design: Individual participant-based meta-analysis.Setting: 12 research and 21 clinical cohorts.Participants: 919 383 adults with same-day measures of ACR and PCR or dipstick protein.Measurements: Equations to convert urine PCR and dipstick protein to ACR were developed and tested for purposes of CKD screening (ACR ≥30 mg/g) and staging (stage A2: ACR of 30 to 299 mg/g; stage A3: ACR ≥300 mg/g).Results: Median ACR was 14 mg/g (25th to 75th percentile of cohorts, 5 to 25 mg/g). The association between PCR and ACR was inconsistent for PCR values less than 50 mg/g. For higher PCR values, the PCR conversion equations demonstrated moderate sensitivity (91%, 75%, and 87%) and specificity (87%, 89%, and 98%) for screening (ACR >30 mg/g) and classification into stages A2 and A3, respectively. Urine dipstick categories of trace or greater, trace to +, and ++ for screening for ACR values greater than 30 mg/g and classification into stages A2 and A3, respectively, had moderate sensitivity (62%, 36%, and 78%) and high specificity (88%, 88%, and 98%). For individual risk prediction, the estimated 2-year 4-variable kidney failure risk equation using predicted ACR from PCR had discrimination similar to that of using observed ACR.Limitation: Diverse methods of ACR and PCR quantification were used; measurements were not always performed in the same urine sample.Conclusion: Urine ACR is the preferred measure of albuminuria; however, if ACR is not available, predicted ACR from PCR or urine dipstick protein may help in CKD screening, staging, and prognosis.Primary Funding Source: National Institute of Diabetes and Digestive and Kidney Diseases and National Kidney Foundation. [ABSTRACT FROM AUTHOR]

Background: Prepregnancy kidney dysfunction has been associated with preterm birth, which is the leading cause of neonatal morbidity and mortality; however, the relation is not well understood. We determined the risk of preterm birth in women with prepregnancy kidney dysfunction, defined using pregnancy-specific serum creatinine cut points.Methods: This population-based cohort study in the province of Ontario, Canada, involved women aged 16 to 50 years who had a singleton birth between 2006 and 2016 and measurement of serum creatinine within 10 weeks preceding their estimated conception date. The exposure was abnormally elevated prepregnancy serum creatinine, defined as greater than the 95th percentile (> 77 μmol/L), a value derived from a population-based sample of women without known kidney disease who became pregnant soon after the measurement was obtained. The main outcome was any preterm birth from 23 to 36 weeks' gestation. Secondary outcomes included provider-initiated preterm birth before 37 weeks' gestation and spontaneous preterm birth before 37 weeks.Results: Among 55 946 pregnancies, preterm birth before 37 weeks' gestation occurred in 3956 women (7.1%). The risk of preterm birth before 37 weeks was higher among women with prepregnancy creatinine above the 95th percentile, relative to those with prepregnancy creatinine at or below the 95th percentile (9.1% v. 7.0%; adjusted relative risk [RR] 1.23, 95% confidence interval [CI] 1.09 to 1.38). The effect was significant for provider-initiated preterm birth (adjusted RR 1.30, 95% CI 1.11 to 1.52) but not for spontaneous preterm birth (adjusted RR 1.12, 95% CI 0.91 to 1.37).Interpretation: Given that prepregnancy kidney dysfunction conferred an increased risk of preterm birth, measurement of serum creatinine (a relatively inexpensive blood test) may form part of the assessment of risk for preterm birth among those planning pregnancy. [ABSTRACT FROM AUTHOR]

Background: Patients undergoing treatment for cancer are at increased risk of acute kidney injury (AKI). There are few data on AKI incidence and risk factors in the current era of cancer treatment.Methods: We conducted a population-based study of all patients initiating systemic therapy (chemotherapy or targeted agents) for a new cancer diagnosis in Ontario, Canada (2007-2014). The primary outcome was hospitalization with AKI or acute dialysis. We estimated the cumulative incidence of AKI and fitted Fine and Gray models, adjusting for demographics, cancer characteristics, comorbidities, and coprescriptions. We modeled exposure to systemic therapy (the 90-day period following treatments) as a time-varying covariate. We also assessed temporal trends in annual AKI incidence.Results: We identified 163 071 patients initiating systemic therapy of whom 10 880 experienced AKI. The rate of AKI was 27 per 1000 person-years, with overall cumulative incidence of 9.3% (95% CI = 9.1% to 9.6%). Malignancies with the highest 5-year AKI incidence were myeloma (26.0%, 95% CI = 24.4% to 27.7%), bladder (19.0%, 95% CI = 17.6% to 20.5%), and leukemia (15.4%, 95% CI = 14.3% to 16.5%). Advanced cancer stage, chronic kidney disease, and diabetes were associated with increased risk of AKI (adjusted hazard ratios [aHR] = 1.41, 95% CI = 1.28 to 1.54; 1.80, 95% CI = 1.67 to 1.93; and 1.43, 95% CI = 1.37 to 1.50, respectively). In patients aged 66 years or older with universal drug benefits, diuretic, and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker coprescription was associated with higher AKI risk (aHR = 1.20, 95% CI = 1.14 to 1.28; 1.30, 95% CI = 1.23 to 1.38). AKI risk was further accentuated during the 90-day period following systemic therapy (aHR = 2.34, 95% CI = 2.24 to 2.45). The annual incidence of AKI increased from 18 to 52 per 1000 person-years between 2007 and 2014.Conclusion: Cancer-related AKI is common and associated with advanced stage, chronic kidney disease, diabetes, and concomitant receipt of diuretics or angiotensin-converting enzyme inhibitors/angiotensin receptor blockers. Risk is heightened in the 90 days after systemic therapy. Preventive strategies are needed to address the increasing burden of AKI in this population. [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]

Background. It remains unclear which phosphate binders should be preferred for hyperphosphatemia management in chronic kidney disease (CKD). Methods. We performed a systematic review and meta-analysis of randomized trials comparing sevelamer or lanthanum with other phosphate binders in CKD. Results. Fifty-one trials (8829 patients) were reviewed. Compared with calcium-based binders, all-cause mortality was nonsignificantly lower with sevelamer {risk ratio [RR] 0.62 [95% confidence interval (CI) 0.35-1.08]} and lanthanum [RR 0.73 (95% CI 0.18-3.00)], but risk of bias was concerning. Compared with calcium-based binders, sevelamer reduced the risk of hypercalcemia [RR 0.27 (95% CI 0.17-0.42)], as did lanthanum [RR 0.12 (95% CI 0.05-0.32)]. Sevelamer reduced hospitalizations [RR 0.50 (95% CI 0.31-0.81)], but not lanthanum [RR 0.80 (95% CI 0.34-1.93)]. The presence/absence of other clinically relevant outcomes was infrequently reported. Compared with calcium-based binders, sevelamer reduced serum calcium, low-density lipoprotein and coronary artery calcification, but increased intact parathyroid hormone. The clinical relevance of these changes is unknown since corresponding clinical outcomes were not reported. Lanthanum had less favorable impact on biochemical parameters. Sevelamer hydrochloride and sevelamer carbonate were similar in three studies. Sevelamer was similar to lanthanum (three studies) and ironbased binders (three studies). Conclusion. Sevelamer was associated with a nonsignificant reduction in mortality and significantly lower hospitalization rates and hypercalcemia compared with calcium-based binders. However, differences in important outcomes, such as cardiac events, fractures, calciphylaxis, hyperchloremic acidosis and health-related quality of life remain understudied. Lanthanum and iron-based binders did not show superiority for any clinically relevant outcomes. Future studies that fail tomeasure clinically important outcomes (the reason why phosphate binders are prescribed in the first place) will be wasteful. [ABSTRACT FROM AUTHOR]

Background Many older patients have chronic kidney disease (CKD), and a lower dose of anti-depressants paroxetine, mirtazapine and venlafaxine is recommended in patients with CKD to prevent drug accumulation from reduced elimination. Using information available in large population-based healthcare administrative databases, we conducted this study to determine if ignoring the recommendation and prescribing a higher versus lower dose of anti-depressants associates with a higher risk of adverse events. . Methods We conducted a population-based cohort study to describe the 30-day risk of delirium in older adults who initiated a higher vs. lower dose of these three anti-depressants in routine care. We defined delirium using the best proxy available in our data sources - hospitalization with an urgent head computed tomography (CT) scan. We determined if CKD status modified the association between anti-depressant dose and outcome, and examined the secondary outcome of 30 day all-cause mortality. We used multivariable logistic regression analyses to estimate adjusted odds ratios (relative risk (RR)) and 95% confidence intervals. Results We identified adults (mean age 75) in Ontario who started a new study anti-depressant at a higher dose (n = 36,651; 31%) or lower dose (n = 81,160; 69%). Initiating a higher vs. lower dose was not associated with an increased risk of hospitalization with head CT (1.09% vs. 1.27% (adjusted RR 0.90; 95% CI, 0.80 to 1.02), but was associated with a lower risk of allcause mortality (0.76% vs. 0.97% RR 0.82; 95% CI, 0.71 to 0.95). Neither of these relative risks were modified by the presence of CKD (p = 0.16, 0.68, respectively). Conclusions We did not observe an increase in two adverse outcomes when study anti-depressants were initiated at a higher dose in elderly patients with moderate CKD. Contrary to our hypothesis, the 30-day risk of mortality was lower when a higher versus lower dose of anti-depressant was initiated in these patients, a finding which requires corroboration and further study. [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]

Doshi M, Garg AX, Gibney E, Parikh C. Race and renal function early after live kidney donation: an analysis of the United States Organ Procurement and Transplantation Network database. Clin Transplant 2010 DOI: 10.1111/j.1399-0012.2010.01209.x. © 2010 John Wiley & Sons A/S. Among Americans, the risk for kidney disease is higher in individuals of African descent (AA) when compared with Caucasians. We considered whether there are similar racial differences in kidney function soon after donor nephrectomy. Of the 31 928 live kidney donors that donated between the years 2000 and 2005, 16 996 (53%) had post-donation serum creatinine recorded at a mean follow-up of 156 d (range 1-1410 d). A total of 14 525 (85%) were Caucasians and 2471 (15%) were AA. When compared with Caucasians, AA donors were more likely to be younger, heavier, and male, had a higher baseline serum creatinine and a shorter duration of follow-up. After accounting for these differences, the serum creatinine after donation and fractional rise in serum creatinine after donation were similar between the two groups (AA vs. Caucasian donors, 1.3 ± 0.3 vs. 1.2 ± 0.3 mg/dL; 53% vs. 45%) and the post-donation estimated glomerular filtration rate was also similar (57.2 ± 0.6 vs. 56.0 ± 0.2 mL/min per 1.73 m2). We observed no major clinical difference in glomerular filtration rate and ability to compensate for loss of renal mass soon after live kidney donation between Caucasian and AA donors. [ABSTRACT FROM AUTHOR]

Background: Previous meta-analyses suggest that treatment with erythropoiesis-stimulating agents (ESAs) in chronic kidney disease (CKD) increases the risk for death. Additional randomized trials have been recently completed. Purpose: To summarize the effects of ESA treatment on clinical outcomes in patients with anemia and CKD. Data Sources: MEDLINE (January 1966 to November 2009), EMBASE (January 1980 to November 2009), and the Cochrane database (to March 2010) were searched without language restriction. Study Selection: Two authors independently screened reports to identify randomized trials evaluating ESA treatment in people with CKD. Hemoglobin target trials or trials of ESA versus no treatment or placebo were included. Data Extraction: Two authors independently extracted data on patient characteristics, study risks for bias, and the effects of ESA therapy. Data Synthesis: 27 trials (10 452 patients) were identified. A higher hemoglobin target was associated with increased risks for stroke (relative risk [RR], 1.51 [95% CI, 1.03 to 2.21]), hypertension (RR, 1.67 [CI, 1.31 to 2.12]), and vascular access thrombosis (RR, 1.33 [CI, 1.16 to 1.53]) compared with a lower hemoglobin target. No statistically significant differences in the risks for mortality (RR, 1.09 [CI, 0.99 to 1.20]), serious cardiovascular events (RR, 1.15 [CI, 0.98 to 1.33]), or end-stage kidney disease (RR, 1.08 [CI, 0.97 to 1.20]) were observed, although point estimates favored a lower hemoglobin target. Treatment effects were consistent across subgroups, including all stages of CKD. Limitations: The evidence for effects on quality of life was limited by selective reporting. Trials also reported insufficient information to allow analysis of the independent effects of ESA dose on clinical outcomes. Conclusion: Targeting higher hemoglobin levels in CKD increases risks for stroke, hypertension, and vascular access thrombosis and probably increases risks for death, serious cardiovascular events, and end-stage renal disease. The mechanisms for harm remain unclear, and meta-analysis of individual-patient data and trials on fixed ESA doses are recommended to elucidate these mechanisms. Primary Funding Source: None. [ABSTRACT FROM AUTHOR]

Background EMBASE is a popular database used to retrieve biomedical information. Our objective was to develop and test search filters to help clinicians and researchers efficiently retrieve articles with renal information in EMBASE. Study Design We used a diagnostic test assessment framework because filters operate similarly to screening tests. Settings & Participants We divided a sample of 5,302 articles from 39 journals into development and validation sets of articles. Index Test Information retrieval properties were assessed by treating each search filter as a "diagnostic test" or screening procedure for the detection of relevant articles. We tested the performance of 1,936,799 search filters made of unique renal terms and their combinations. Reference Standard & Outcome The reference standard was manual review of each article. We calculated the sensitivity and specificity of each filter to identify articles with renal information. Results The best renal filters consisted of multiple search terms, such as "renal replacement therapy," "renal," "kidney disease," and "proteinuria," and the truncated terms "kidney," "dialy," "neph," "glomerul," and "hemodial." These filters achieved peak sensitivities of 98.7% (95% CI, 97.9-99.6) and specificities of 98.5% (95% CI, 98.0-99.0). The retrieval performance of these filters remained excellent in the validation set of independent articles. Limitations The retrieval performance of any search will vary depending on the quality of all search concepts used, not just renal terms. Conclusions We empirically developed and validated high-performance renal search filters for EMBASE. These filters can be programmed into the search engine or used on their own to improve the efficiency of searching. [ABSTRACT FROM AUTHOR]

Background The long-term health consequences of acute bacterial gastroenteritis remain uncertain. We studied the risk of hypertension and reduced kidney function after an outbreak of acute gastroenteritis due to contamination of a regional drinking water supply with Escherichia coli O157:H7 and Campylobacter species. Methods A total of 1958 adults with no known history of hypertension or kidney disease before the outbreak participated in a long-term follow-up study. Of the participants, 675 had been asymptomatic during the outbreak, 909 had had moderate symptoms of acute self-limited gastroenteritis, and 374 had had severe symptoms that necessitated medical attention. The outcomes of interest were a diagnosis of hypertension or the presence of reduced kidney function and albuminuria during the follow-up period. Results After a mean follow-up of 3.7 years after the outbreak, hypertension was diagnosed in 27.0% of participants who had been asymptomatic during the outbreak and in 32.3% and 35.9% of those who had had moderate and severe symptoms of acute gastroenteritis respectively (trend p = 0.009). Compared with the asymptomatic participants, those with moderate and severe symptoms of gastroenteritis had an adjusted relative risk of hypertension of 1.15 (95% confidence interval [CI] 0.97-1.35) and 1.28 (95% CI 1.04-1.56) respectively. A similar graded association was seen for reduced kidney function, defined as the presence of an estimated glomerular filtration rate below 60 mL/min per 1.73 m2 (trend p = 0.03). No association was observed between gastroenteritis and the subsequent risk of albuminuria. Interpretation Acute bacterial gastroenteritis necessitating medical attention was associated with an increased risk of hypertension and reduced kidney function 4 years after infection. Maintaining safe drinking water remains essential to human health, as transient bacterial contaminations may have implications well beyond a period of acute self-limited illness. [ABSTRACT FROM AUTHOR]

Microalbuminuria three years after recovery fromEscherichia coliO157 hemolytic uremic syndrome due to municipal water contamination.Background.Knowledge of the long-term renal prognosis of diarrhea associated hemolytic uremic syndrome (HUS) is important for patient counseling and follow-up. However, estimates of long-term risk are highly variable, with previous studies not using a healthy control group.Methods.A municipal water system in the small rural town of Walkerton, Ontario, became contaminated withEscherichia coliO157:H7 in 2000. A cohort of 19 children who recovered from HUS was randomly age- and sex-matched to 38 children with no symptoms at the time of the outbreak. Both groups had detailed renal function testing 3 years after the outbreak, including a random urine albumin to creatinine, glomerular filtration rate estimated by Schwartz formula, and automated and manual blood pressure measurements.Results.There were no baseline differences between the groups with respect to age (mean 4.8 years, range 1 to 15), sex, or birth weight (mean 3.4 kg). In follow-up there were no differences between the groups in body surface area (mean 1.0 m2), or in the methods by which renal function was assessed. Compared to the group with no symptoms, patients with HUS demonstrated more microalbuminuria[32% vs. 5%, relative risk 4.8 (95% CI 1.1 to 22.0)], a nonsignificant trend toward lower GFR (124 vs. 134 mL/min per 1.73m2), and no difference in blood pressure.Conclusion.Children may demonstrate microalbuminuria 3 years after recovering from HUS. Longer follow-up is needed to determine if this finding has clinical relevance and utility. [ABSTRACT FROM AUTHOR]

The HEMO study has provided evidence that a higher dialysis dose per session does not improve survival in conventional three times a week hemodialysis (HD). Attention has therefore shifted to HD schedules that vary in frequency and/or duration of dialysis. Although observational data favoring the use of frequent dialysis are steadily accumulating, compelling evidence supporting its superiority is still lacking. Several advances have recently been made with a view to put this form of therapy on much more solid footing. Upcoming research initiatives including clinical trials of frequent HD and the quotidian HD registry will provide a wealth of analytic and descriptive data that will help define the role for frequent HD regimens as a therapy for end-stage renal disease. [ABSTRACT FROM AUTHOR]

Estimating the prevalence of renal insufficiency in seniors requiring long-term care. Background. Renal function declines with age, but little is known about the extent of renal insufficiency among the institutionalized elderly. The objective of this study was to estimate the prevalence of low glomerular filtration rate (GFR) in a large sample of elderly adults living in long-term care facilities, and to compare two commonly used methods for estimating GFR. Methods. A total of 9931 residents aged 65 years and older participated in a retrospective cross-sectional study of 87 long-term care facilities in Ontario. GFR was estimated by the Cockcroft-Gault and Modification of Diet in Renal Disease Study (MDRD) equations. The prevalence of low GFR, using the Cockcroft-Gault equation (<30 mL/min), was compared with the MDRD equation (<30 mL/min/1.73 m2). Results. A total of 17.0% (95% CI 15.6 to 18.5) of men and 14.4% (95% CI 13.6 to 15.3) of women had a serum creatinine concentration above the laboratory reported upper reference limit of normal. The prevalence of both elevated serum creatinine and low GFR were observed to increase with age ( P < 0.0001). The Cockcroft-Gault equation produced a consistently lower estimate of GFR than did the MDRD equation, a discrepancy most pronounced in the oldest residents. Among all men, a low GFR was more prevalent using the Cockcroft-Gault (10.3%, 95% CI 9.2 to 11.5) than MDRD (3.5%, 95% CI 2.8 to 4.2) equation, with a similar difference also seen in women (23.3%, 95% CI 22.4 to 24.3 versus 4.0%, 95% CI 3.6 to 4.5, respectively). Of all residents whose Cockcroft-Gault estimated GFR was under 30 mL/min, 14.7% (95% CI 13.2 to 16.3) were found to have GFR greater than 60 mL/min/1.73 m2 according to the MDRD equation. Conclusion. Age-associated renal impairment is common among elderly long-term care residents, but there exists a clear discrepancy between the Cockcroft-Gault and MDRD equations in predicting GFR. Consideration should be given to medication dose adjustment, based on a practical estimate of GFR. However clarification is needed about which method, if either, is most valid among the frail elderly. Complex patient and societal issues surrounding advanced care directives, treatments associated with renal insufficiency, and, if and when to initiate dialysis, require further attention. [ABSTRACT FROM AUTHOR]

Context: The long-term renal prognosis of patients with diarrhea-associated hemolytic uremic syndrome (HUS) remains controversial. Objectives: To quantify the long-term renal prognosis of patients with diarrhea-associated HUS and to identify reasons for different estimates provided in the literature. Data Sources: We searched MEDLINE and Experta Medica (EMBASE) bibliographic databases and conference proceedings, and we contacted experts until February 2003. We also searched the Institute for Scientific Information index and reference lists of all studies that fulfilled our eligibility criteria. The search strategy included the terms hemolytic-uremic syndrome, purpura, thrombotic thrombocytopenic, Escherichia coli O157, longitudinal studies, kidney diseases, hypertension, and proteinuria Study Selection: Any study that followed up 10 or more patients with primary diarrhea-associated HUS for at least 1 year for renal sequelae. Data Extraction: Two authors independently abstracted data on study and patient characteristics, renal measures, outcomes, and prognostic features. Disagreements were resolved by a third author or by consensus. Data Synthesis: Forty-nine studies of 3476 patients with a mean follow-up of 4.4 years (range, 1-22 years at last follow-up) from 18 countries, 1950 to 2001, were summarized. At the time of recruitment, patients were aged 1 month to 18 years. In the different studies, death or permanent end-stage renal disease (ESRD) ranged from 0% to 30%, with a pooled incidence of 12% (95% confidence interval [CI], 10%-15%). A glomerular filtration rate lower than 80 mL/min per 1.73 m[sup 2], hypertension, or proteinuria was extremely variable and ranged from 0% to 64%, with a pooled incidence of 25% (95% CI, 20%-30%). A higher severity of acute illness was strongly associated with worse long-term prognosis. Studies with a higher proportion of patients with central nervous system symptoms (coma, seizures, or stroke) had a higher proportion of patient... [ABSTRACT FROM AUTHOR]

Context: Use of experimental therapies during but outside of randomized controlled trials (RCTs) has not been studied. Objective: To determine whether initiation of an RCT leads to increased use of the experimental therapy outside the trial. Design and Setting: Data on national apheresis use during 3 Canadian RCTs for multiple sclerosis (1986-1988), thrombotic thrombocytopenic purpura (1982-1988), and myeloma cast nephropathy (1998-2000) were obtained from 19 major medical centers in Canada. The multiple sclerosis and myeloma cast nephropathy trials had data on apheresis use for 3 years prior to and during the trials, which permitted a time-series analysis to determine the impact of the RCTs on the use of apheresis. The ongoing myeloma cast nephropathy trial provided data on the number of patients inside and outside of the RCTs in trial and nontrial centers. Initial and follow-up questionnaires were sent to 24 Canadian physicians in trial and nontrial centers to determine if they had noted an increase in apheresis activity during the trials and, if so, their explanation for it. Main Outcome Measure: Change in number of patients undergoing apheresis for thrombotic thrombocytopenic purpura, multiple sclerosis, and myeloma cast nephropathy prior to and during the respective RCTs compared with all patients undergoing apheresis during the same periods. Results: During all 3 RCTs, there were large increases in use of apheresis. The majority of the increased use of apheresis was outside of the trials: for multiple sclerosis, 30 of 49 patients per year (61% of increase); thrombotic thrombocytopenic purpura, 49 of 56 patients per year (72% of increase); and myeloma cast nephropathy, 60 of 72 patients per year (57% of increase). The myeloma cast nephropathy study noted that this increase occurred in both nontrial and trial centers. Among questionnaire respondents (n = 22; 92% response rate), most physicians noted an increase in apheresis activity during the trials and attr... [ABSTRACT FROM AUTHOR]

The paper by Mjøen et al. raises important concerns about the long-term consequences of living donation, including a long-term increased risk of end-stage renal disease after an individual undergoes donor nephrectomy. These potential risks need to be communicated to future living kidney donors and should be an impetus for ongoing investigation. [ABSTRACT FROM AUTHOR]