Prescribing patterns and medications costs in patients on maintenance hemodialysis and peritoneal dialysis.

BACKGROUND AND HYPOTHESIS: Polypharmacy is a significant clinical issue for patients on dialysis but has been incompletely studied. We investigated the prevalence and costs of polypharmacy in a population-based cohort of participants treated with hemodialysis (HD) or peritoneal dialysis (PD). METHODS: We studied adults aged ≥ 20 years in Alberta, Canada receiving maintenance HD or PD as of March 31, 2019. We characterized participants as users of 0-29 drug categories of interest and those aged ≥ 65 as users/non-users of potentially inappropriate medications (PIM). We calculated the number of drug categories, daily pill burden, total annual cost, and annual cost per participant, and compared this to an age- and sex-matched cohort from the general Alberta population. RESULTS: Among 2 248 participants (mean age 63 years; 39% female) on HD (n = 1 781) or PD (n = 467), the median number of prescribed drug categories was 6 [interquartile range (IQR) 4, 8]; median daily pill burden was 8.0 (IQR 4.6, 12.6) pills/day, with 5% prescribed ≥ 21.7 pills/day, and 16.5% prescribed ≥ 15 pills/day. Twelve % were prescribed at least one drug that is contraindicated in kidney failure. The median annual per participant cost was ${\$}$3,831, totaling approximately ${\$}$11.6 million annually for all participants. When restricting to the 1 063 participants aged ≥ 65, the median number of PIM categories was 2 (IQR 1, 2), with a median PIM pill burden of 1.2 pills/day (IQR 0.5, 2.4). Compared to PD participants, HD participants had similar daily pill burden, higher use of PIM, and higher annual per participant cost. Pill burden and associated costs for participants on dialysis were more than 3-fold and 10-fold higher, respectively, compared to the matched participants from the general population. CONCLUSION: Participants on dialysis have markedly higher use of prescription medications and associated costs than the general population. Effective methods to de-prescribe in the dialysis population are needed.

Changes in kidney function follow living donor nephrectomy.

Better understanding of kidney function after living donor nephrectomy and how it differs by donor characteristics can inform patient selection, counselling, and follow-up care. To evaluate this, we conducted a retrospective matched cohort study of living kidney donors in Alberta, Canada between 2002-2016, using linked healthcare administrative databases. We matched 604 donors to 2,414 healthy non-donors from the general population based on age, sex, year of cohort entry, urban residence and the estimated glomerular filtration rate (eGFR) before cohort entry (nephrectomy date for donors and randomly assigned date for non-donors). The primary outcome was the rate of eGFR change over time (median follow-up seven years; maximum 15 years). The median age of the cohort was 43 years, 64% women, and the baseline (pre-donation) eGFR was 100 mL/min/1.73 m2. Overall, from six weeks onwards, the eGFR increased by +0.35 mL/min/1.73 m2 per year (95% confidence interval +0.21 to +0.48) in donors and significantly decreased by -0.85 mL/min/1.73 m2 per year (-0.94 to -0.75) in the matched healthy non-donors. The change in eGFR between six weeks to two years, two to five years, and over five years among donors was +1.06, +0.64, and -0.06 mL/min/1.73 m2 per year, respectively. In contrast to the steady age-related decline in kidney function in non-donors, post-donation kidney function on average initially increased by 1 mL/min/1.73 m2 per year attributable to glomerular hyperfiltration, which began to plateau by five years post-donation. Thus, the average change in eGFR over time is significantly different between donors and non-donors.

Statin use and the risk of acute kidney injury in older adults.

BACKGROUND: As more patients at lower cardiovascular (CV) risk are treated with statins, the balance between cardiovascular benefits and the risk of adverse events becomes increasingly important. METHODS: We did a population-based cohort study (May 1, 2002 to March 30, 2013) using province-wide laboratory and administrative data in Alberta. We studied new statin users aged 66 years of age and older who were not receiving renal replacement therapy at baseline. We assessed statin use at 30-day intervals to allow time-varying assessment of statin exposure in Cox proportional hazards models that examined the relation between statin use and hospitalization with acute kidney injury (AKI). RESULTS: Of the 128,140 new statin users, 47 and 46% were prescribed high- and medium-intensity regimens at the index date. During median follow-up of 4.6 years (interquartile range 2.2, 7.4), 9118 individuals were hospitalized for AKI. Compared to non-use, the use of high- and medium-intensity statin regimens was associated with significant increases in the adjusted risks of hospitalization with AKI: hazard ratios 1.16 [95% confidence interval (CI) 1.10, 1.23] and 1.07 (95% CI 1.01, 1.13), respectively. Risks of AKI were higher among women than men, and among users of angiotensin converting enzyme inhibitors/angiotensin receptor blockers than non-users, and among diuretic users (p for interaction 0.002, 0.01, and 0.04 respectively). CONCLUSIONS: We found a graded, independent association between the intensity of statin use and the risk of hospitalization with AKI, although the absolute magnitude of the excess risk was small.

In-Center Nocturnal Hemodialysis Versus Conventional Hemodialysis: A Systematic Review of the Evidence.

BACKGROUND: Owing to its longer treatment duration-up to 8 hours per dialysis treatment-in-center thrice-weekly nocturnal hemodialysis (HD) is receiving greater attention. To better understand the evidence for in-center nocturnal HD, we sought to systematically review the literature to determine the effects of in-center nocturnal HD versus conventional HD on clinically relevant outcomes. STUDY DESIGN: We searched MEDLINE, Embase, Evidence-Based Medicine Reviews (EBMR), Web of Science, and Scopus from the earliest date in the database to November 2016. SETTING & POPULATION: Adults receiving in-center nocturnal HD compared with those receiving conventional HD. SELECTION CRITERIA FOR STUDIES: All quasi-experimental and observational studies were considered; randomized trials were sought but not found. PREDICTOR: Nocturnal vs conventional in-center HD. OUTCOMES: Indexes of blood pressure and left ventricular hypertrophy, markers of anemia, measures of bone mineral metabolism, nutrition, quality of life, sleep quality, episodes of intradialytic hypotension, hospitalization, and mortality. RESULTS: Of 2,086 identified citations, 21 met the inclusion criteria, comprising a total of 1,165 in-center nocturnal HD patients and 15,865 conventional HD patients. Although there was substantial heterogeneity in reporting of outcomes, we pooled data for measures of blood pressure, anemia, and mineral metabolism. Though heterogeneity was generally high, in-center nocturnal HD was associated with improved systolic blood pressure (-3.18 [95% CI, -5.58 to -0.78) mm Hg, increased hemoglobin levels (0.53 [95% CI, 0.11-0.94] g/dL), and lower serum phosphate levels (-0.97 [95% CI, -1.48 to -0.46] mg/dL). LIMITATIONS: No randomized trials have been conducted to address the clinical effects of in-center nocturnal HD. The quality of the observational literature contributing to the results of this review was generally poor to moderate. Confounded outcomes are a significant concern. Publication bias and outcome reporting bias remain possibilities. CONCLUSIONS: Relative to conventional HD, in-center nocturnal HD was associated with improvements in several clinically relevant outcomes. Other benefits may not have been detected due to small sample sizes of included studies; no prespecified outcome was worse with in-center nocturnal HD.

Impact of using two dialyzers in parallel on phosphate clearance in hemodialysis patients: a randomized trial.

BACKGROUND: Dietary restriction and phosphate binders are the main interventions used to manage hyperphosphatemia in people on hemodialysis, but have limited efficacy. Modifying conventional dialysis regimens to enhance phosphate clearance as an alternative approach remains relatively unstudied. METHODS: This was a 10-week, 2-arm, randomized crossover study. Participants were prevalent dialysis patients ( n = 32) with consecutive serum phosphate levels >1.6 mmol/L and on stable doses of a phosphate binder. Following a 2-week run-in period, participants were randomized to initiate dialysis using two high flux dialyzers in parallel (blood flow ≥350 mL/min, dialysate flow 800 mL/min) or standard dialysis using one high flux dialyzer (blood flow ≥350 mL/min, dialysate flow of 800 mL/min). Each regimen was 3 weeks in duration. After a 2-week washout period, participants received the alternate regimen. The primary outcome was the mean difference in phosphate clearance by dialyzer strategy. Secondary outcomes were phosphate removal and pre-dialysis serum phosphate. RESULTS: Phosphate clearance for the double dialyzer strategy did not differ significantly from the single dialyzer strategy [mean difference 7.5 mL/min (95% confidence interval, 95% CI, -6.1, 21.0), P = 0.28]. There was no difference in total phosphate removal and pre-dialysis phosphate between the double and single dialyzer strategies [total phosphate removal mean difference -0.2 mmol (95% CI -4.1, 3.7), P = 0.93; pre-dialysis mean difference 0.01 mmol/L (95% CI -0.18, 0.21), P = 0.88]. There was no difference in the proportion of participants who experienced at least one episode of intradialytic hypotension (32 versus 47%, P = 0.13). A limitation of the study was frequent protocol deviations in the dialysis prescription. CONCLUSIONS: In this study, the use of two dialyzers in parallel did not increase phosphate clearance, phosphate removal or pre-dialysis serum phosphorus when compared with a standard dialysis treatment strategy. Future studies should continue to evaluate novel methods of phosphate removal using conventional hemodialysis.

Comparison of Clinical Outcomes and Adverse Events Associated With Glucose-Lowering Drugs in Patients With Type 2 Diabetes: A Meta-analysis.

IMPORTANCE: Numerous glucose-lowering drugs are used to treat type 2 diabetes. OBJECTIVE: To estimate the relative efficacy and safety associated with glucose-lowering drugs including insulin. DATA SOURCES: Cochrane Library Central Register of Controlled Trials, MEDLINE, and EMBASE databases through March 21, 2016. STUDY SELECTION: Randomized clinical trials of 24 weeks' or longer duration. DATA EXTRACTION AND SYNTHESIS: Random-effects network meta-analysis. MAIN OUTCOMES AND MEASURES: The primary outcome was cardiovascular mortality. Secondary outcomes included all-cause mortality, serious adverse events, myocardial infarction, stroke, hemoglobin A1c (HbA1C) level, treatment failure (rescue treatment or lack of efficacy), hypoglycemia, and body weight. RESULTS: A total of 301 clinical trials (1,417,367 patient-months) were included; 177 trials (56,598 patients) of drugs given as monotherapy; 109 trials (53,030 patients) of drugs added to metformin (dual therapy); and 29 trials (10,598 patients) of drugs added to metformin and sulfonylurea (triple therapy). There were no significant differences in associations between any drug class as monotherapy, dual therapy, or triple therapy with odds of cardiovascular or all-cause mortality. Compared with metformin, sulfonylurea (standardized mean difference [SMD], 0.18 [95% CI, 0.01 to 0.34]), thiazolidinedione (SMD, 0.16 [95% CI, 0.00 to 0.31]), DPP-4 inhibitor (SMD, 0.33 [95% CI, 0.13 to 0.52]), and α-glucosidase inhibitor (SMD, 0.35 [95% CI, 0.12 to 0.58]) monotherapy were associated with higher HbA1C levels. Sulfonylurea (odds ratio [OR], 3.13 [95% CI, 2.39 to 4.12]; risk difference [RD], 10% [95% CI, 7% to 13%]) and basal insulin (OR, 17.9 [95% CI, 1.97 to 162]; RD, 10% [95% CI, 0.08% to 20%]) were associated with greatest odds of hypoglycemia. When added to metformin, drugs were associated with similar HbA1C levels, while SGLT-2 inhibitors offered the lowest odds of hypoglycemia (OR, 0.12 [95% CI, 0.08 to 0.18]; RD, -22% [-27% to -18%]). When added to metformin and sulfonylurea, GLP-1 receptor agonists were associated with the lowest odds of hypoglycemia (OR, 0.60 [95% CI, 0.39 to 0.94]; RD, -10% [95% CI, -18% to -2%]). CONCLUSIONS AND RELEVANCE: Among adults with type 2 diabetes, there were no significant differences in the associations between any of 9 available classes of glucose-lowering drugs (alone or in combination) and the risk of cardiovascular or all-cause mortality. Metformin was associated with lower or no significant difference in HbA1C levels compared with any other drug classes. All drugs were estimated to be effective when added to metformin. These findings are consistent with American Diabetes Association recommendations for using metformin monotherapy as initial treatment for patients with type 2 diabetes and selection of additional therapies based on patient-specific considerations.

Impact of age on the association between CKD and the risk of future coronary events.

BACKGROUND: Elucidation of the relationship between age, kidney function, and absolute coronary risk would facilitate efforts to promote chronic kidney disease (CKD) as a high-risk state for future vascular events and justify current recommendations for statin treatment in CKD. STUDY DESIGN: Population-based study. SETTING & PARTICIPANTS: 1,268,538 people with data for estimated glomerular filtration rate and albuminuria who were treated in a single Canadian province. PREDICTORS: CKD risk groups (G1, G2, G3a, G3b, and G4 had estimated glomerular filtration rate ≥90, 60-89.9, 45-59.9, 30-44.9, and 15-29.9 mL/min/1.73 m2, respectively; A1, A2, and A3 had albuminuria with albumin-creatinine ratio [ACR]<30 mg/g or dipstick urinalysis negative, ACR of 30-300 mg/g or dipstick trace or 1+, and ACR >300 mg/g or dipstick ≥ 2+, respectively) and age (<40, 40-49, ≥50 years). OUTCOMES: Rates of coronary death or nonfatal myocardial infarction (expressed per 1,000 person-years), stratified by age, sex, and CKD stage. MEASUREMENTS: The first available serum creatinine value and the corresponding date were set as the index serum creatinine value and index date, respectively. ACR or dipstick urinalysis data were obtained from the periods defined by 6 months before and after the index creatinine value. RESULTS: Absolute rates of coronary death or nonfatal myocardial infarction were consistently greater than 10 per 1,000 person-years for people with CKD and 50 years or older, regardless of CKD stage. However, absolute rates of the composite outcome were consistently less than 10 per 1,000 person-years for those younger than 50 years. LIMITATIONS: Single Canadian province, median follow-up only 4.0 years. CONCLUSIONS: People with CKD who are 50 years or older should be considered at the highest risk of coronary events. In contrast, consideration of other risk factors will be required when assessing future risk among people with CKD who are younger than 50 years.

Association between LDL-C and risk of myocardial infarction in CKD.

LDL cholesterol (LDL-C) is an important marker of coronary risk in the general population, but its utility in people with CKD is unclear. We studied 836,060 adults from the Alberta Kidney Disease Network with at least one measurement of fasting LDL-C, estimated GFR (eGFR), and proteinuria between 2002 and 2009. All participants were free of stage 5 CKD at cohort entry. We followed participants from first eGFR measurement to March 31, 2009; we used validated algorithms applied to administrative data to ascertain primary outcome (hospitalization for myocardial infarction) and Cox regression to calculate adjusted hazard ratios (HRs) for myocardial infarction by LDL-C categories within eGFR strata. During median follow-up of 48 months, 7762 patients were hospitalized for myocardial infarction, with incidence highest among participants with the lowest eGFR. Compared with 2.6-3.39 mmol/L (referent), the risk associated with having LDL-C above 4.9 mmol/L seemed greatest for GFR≥90 ml/min per 1.73 m(2) and least for eGFR=15-59.9 ml/min per 1.73 m(2). Specifically, the adjusted HRs (95% confidence intervals) of myocardial infarction associated with LDL-C of ≥4.9 compared with 2.6-3.39 mmol/L in participants with eGFR=15-59.9, 60-89.9, and ≥90 ml/min per 1.73 m(2) were 2.06 (1.59, 2.67), 2.30 (2.00, 2.65), and 3.01 (2.46, 3.69). In conclusion, the association between higher LDL-C and risk of myocardial infarction is weaker for people with lower baseline eGFR, despite higher absolute risk of myocardial infarction. Increased LDL-C may be less useful as a marker of coronary risk among people with CKD than the general population.

Risk of coronary events in people with chronic kidney disease compared with those with diabetes: a population-level cohort study.

BACKGROUND: Diabetes is regarded as a coronary heart disease risk equivalent-ie, people with the disorder have a risk of coronary events similar to those with previous myocardial infarction. We assessed whether chronic kidney disease should be regarded as a coronary heart disease risk equivalent. METHODS: We studied a population-based cohort with measures of estimated glomerular filtration rate (eGFR) and proteinuria from Alberta, Canada. We used validated algorithms based on hospital admission and medical-claim data to classify participants with baseline history of myocardial infarction or diabetes and to ascertain which patients were admitted to hospital for myocardial infarction during follow-up (the primary outcome). For our primary analysis, we defined baseline chronic kidney disease as eGFR 15-59·9 mL/min per 1·73 m(2) (stage 3 or 4 disease). We used Poisson regression to calculate unadjusted rates and relative rates of myocardial infarction during follow-up for five risk groups: people with previous myocardial infarction (with or without diabetes or chronic kidney disease), and (of those without previous myocardial infarction), four mutually exclusive groups defined by the presence or absence of diabetes and chronic kidney disease. FINDINGS: During a median follow-up of 48 months (IQR 25-65), 11,340 of 1,268,029 participants (1%) were admitted to hospital with myocardial infarction. The unadjusted rate of myocardial infarction was highest in people with previous myocardial infarction (18·5 per 1000 person-years, 95% CI 17·4-19·8). In people without previous myocardial infarction, the rate of myocardial infarction was lower in those with diabetes (without chronic kidney disease) than in those with chronic kidney disease (without diabetes; 5·4 per 1000 person-years, 5·2-5·7, vs 6·9 per 1000 person-years, 6·6-7·2; p<0·0001). The rate of incident myocardial infarction in people with diabetes was substantially lower than for those with chronic kidney disease when defined by eGFR of less than 45 mL/min per 1·73 m(2) and severely increased proteinuria (6·6 per 1000 person-years, 6·4-6·9 vs 12·4 per 1000 person-years, 9·7-15·9). INTERPRETATION: Our findings suggest that chronic kidney disease could be added to the list of criteria defining people at highest risk of future coronary events. FUNDING: Alberta Heritage Foundation for Medical Research.

Using linked administrative data to study periprocedural mortality in obesity and chronic kidney disease (CKD).

Both obesity and chronic kidney disease (CKD) are associated with adverse periprocedural outcomes, but it is unknown how these two common conditions interact to influence risk. We examined the feasibility of combining a new procedure-related, obesity-specific flag with administrative and laboratory data and assessed the joint association between obesity and CKD with mortality. Since 2007, Alberta physicians may claim a fee supplement for performing eligible surgical and non-surgical procedures on patients with documented BMI ≥ 35 kg/m(2). We linked this information to the Alberta Kidney Disease Network registry. Participants were classified into four mutually exclusive groups based on the presence/absence of both obesity (BMI ≥ 35 kg/m(2)) and CKD (eGFR < 60 mL/min/1.73 m(2)). Mortality was assessed at 30 days following the index procedure. Of 393 659 participants, 9% were obese. Overall, 8% had obesity only, 78% neither obesity nor CKD, 13% CKD only and 1% both obesity and CKD. Unadjusted risks of mortality at 30 days were 0.3, 0.4, 2.0 and 2.1%, respectively--but decreased to 0.1, 0.2, 0.3 and 0.3%, respectively, after adjustment for age, sex, socioeconomic status, procedure type and other comorbidities. Administrative data can be feasibly combined with disease registries to study obesity-related outcomes. Results from the linked dataset demonstrated face validity--subjects with both obesity and CKD were at increased risk of periprocedural mortality, and this was driven in part by differences in age and comorbidity.

Associations between body mass index and all-cause mortality: A systematic review and meta-analysis.

Fasting insulin and c-reactive protein confound the association between mortality and body mass index. An increase in fat mass may mediate the associations between hyperinsulinemia, hyperinflammation, and mortality. The objective of this study was to describe the "average" associations between body mass index and the risk of mortality and to explore how adjusting for fasting insulin and markers of inflammation might modify the association of BMI with mortality. MEDLINE and EMBASE were searched for studies published in 2020. Studies with adult participants where BMI and vital status was assessed were included. BMI was required to be categorized into groups or parametrized as non-first order polynomials or splines. All-cause mortality was regressed against mean BMI squared within seven broad clinical populations. Study was modeled as a random intercept. ß coefficients and 95% confidence intervals are reported along with estimates of mortality risk by BMIs of 20, 30, and 40 kg/m2 . Bubble plots with regression lines are drawn, showing the associations between mortality and BMI. Splines results were summarized. There were 154 included studies with 6,685,979 participants. Only five (3.2%) studies adjusted for a marker of inflammation, and no studies adjusted for fasting insulin. There were significant associations between higher BMIs and lower mortality risk in cardiovascular (unadjusted ß -0.829 [95% CI -1.313, -0.345] and adjusted ß -0.746 [95% CI -1.471, -0.021]), Covid-19 (unadjusted ß -0.333 [95% CI -0.650, -0.015]), critically ill (adjusted ß -0.550 [95% CI -1.091, -0.010]), and surgical (unadjusted ß -0.415 [95% CI -0.824, -0.006]) populations. The associations for general, cancer, and non-communicable disease populations were not significant. Heterogeneity was very large (I2 ≥ 97%). The role of obesity as a driver of excess mortality should be critically re-examined, in parallel with increased efforts to determine the harms of hyperinsulinemia and chronic inflammation.

Frailty and Clinical Outcomes in Patients Treated With Hemodialysis: A Prospective Cohort Study.

Rationale and Objective: Frailty is common among people with kidney failure treated with hemodialysis (HD). The objective was to describe how frailty evolves over time in people treated by HD, how improvements in frailty and frailty markers are associate with clinical outcomes, and the characteristics that are associated with improvement in frailty. Study Design: Prospective cohort study. Setting and Participants: Adults initiating thrice weekly in-center HD in Canada. Exposure: We classified frailty using a 5-point score (3 or more indicates frailty) based on physical inactivity, slowness or weakness, poor endurance or exhaustion, and malnutrition. We categorized the frailty trajectory as never present, improving, deteriorating, and always present. Outcomes: All-cause death, hospitalizations, and placement into long-term care. Analytical Approach: We examined the association between time-varying frailty measures and these outcomes using Cox and negative binomial models, after adjustment for potential confounders. Results: 985 participants were included and followed up for a median of 33 months; 507 (51%) died, 761 (77%) experienced ≥1 hospitalization and 115 (12%) entered long-term care. Overall, 760 (77%) reported frailty during follow-up. Three-quarters (78%) of those with frailty at baseline remained frail throughout the follow-up, 46% without baseline frailty became frail, and 23% with baseline frailty became nonfrail. Higher frailty scores were associated with an increased risk of mortality (fully adjusted HR, 1.58 per unit; 95% CI, 1.39-1.80) and an increased rate of hospitalization (RR, 1.16 per unit; 95% CI, 1.09-1.23). Compared with those who were frail throughout the follow-up, participants with frailty at baseline but improving during follow-up showed a lower mortality (HR, 0.59; 95% CI, 0.42-0.81), and a lower rate of hospitalization (RR, 0.70; 95% CI, 0.56-0.87). Limitations: There was missing data on frailty at baseline and during follow-up. Conclusions: Frailty was associated with a higher risk of poor outcomes compared with those without frailty, and participants whose status improved from frail to nonfrail showed better clinical outcomes than those who remained frail. These findings emphasize the importance of identifying and implementing effective treatments for frailty in patients receiving maintenance HD.

Long-Term Outcomes for Living Kidney Donors With Early Guideline-Concordant Follow-up Care: A Retrospective Cohort Study.

Background: Current guidelines recommend that living kidney donors receive lifelong annual follow-up care to monitor kidney health. In the United States, the reporting of complete clinical and laboratory data for kidney donors has been mandated for the first 2 years post-donation; however, the long-term impact of early guideline-concordant care remains unclear. Objective: The primary objective of this study was to compare long-term post-donation follow-up care and clinical outcomes of living kidney donors with and without early guideline-concordant follow-up care. Design: Retrospective, population-based cohort study. Setting: Linked health care databases were used to identify kidney donors in Alberta, Canada. Patients: Four hundred sixty living kidney donors who underwent nephrectomy between 2002 and 2013. Measurements: The primary outcome was continued annual follow-up at 5 and 10 years (adjusted odds ratio with 95% confidence interval, LCLaORUCL). Secondary outcomes included mean change in estimated glomerular filtration rate (eGFR) over time and rates of all-cause hospitalization. Methods: We compared long-term follow-up and clinical outcomes for donors with and without early guideline-concordant care, defined as annual physician visit and serum creatinine and albuminuria measurement for the first 2 years post-donation. Results: Of the 460 donors included in this study, 187 (41%) had clinical and laboratory evidence of guideline-concordant follow-up care throughout the first 2 years post-donation. The odds of receiving annual follow-up for donors without early guideline-concordant care were 76% lower at 5 years (aOR 0.180.240.32) and 68% lower at 10 years (aOR 0.230.320.46) compared with donors with early care. The odds of continuing follow-up remained stable over time for both groups. Early guideline-concordant follow-up care did not appear to substantially influence eGFR or hospitalization rates over the longer term. Limitations: We were unable to confirm whether the lack of physician visits or laboratory data in certain donors was due to physician or patient decisions. Conclusions: Although policies directed toward improving early donor follow-up may encourage continued follow-up, additional strategies may be necessary to mitigate long-term donor risks.

Contexte: Les lignes directrices actuelles recommandent que les donneurs de rein vivants soient suivis annuellement, et ce, à vie, afin de surveiller leur santé rénale. Aux États-Unis, la déclaration des données cliniques et des données de laboratoire complètes pour les donneurs de rein est exigée pour les deux premières années suivant le don. On ignore cependant les répercussions à long terme pour ceux qui reçoivent des soins précoces conformes aux lignes directrices. Objectif: Le principal objectif de cette étude était de comparer les soins de suivi post-don à long terme et les résultats cliniques des donneurs de rein vivants, selon qu'ils avaient reçu ou non des soins de suivi précoces conformes aux recommandations. Type d'étude: Étude de cohorte rétrospective basée sur une population. Cadre: Les banques de données couplées du système de santé ont été utilisées pour identifier les donneurs de rein de l'Alberta (Canada). Sujets: L'étude porte sur 460 donneurs de rein vivants ayant subi leur néphrectomie entre 2002 et 2013. Mesures: Le principal critère d'évaluation était un suivi annuel continu à 5 et à 10 ans post-don (rapport de cotes corrigé avec intervalle de confiance de 95 % [LICRRcLSC]). Les résultats secondaires comprenaient la variation moyenne du débit de filtration glomérulaire estimé (DFGe) au fil du temps et les taux d'hospitalisation toutes causes confondues. Méthodologie: Nous avons comparé le suivi à long terme et les résultats cliniques de donneurs qui avaient reçu ou non des soins précoces conformes aux directives, définis par une visite annuelle chez le médecin et des mesures de la créatinine sérique et de l'albuminurie pour les deux premières années post-don. Résultats: Des 460 donneurs inclus à l'étude, 187 (41 %) disposaient de preuves de suivi conformes aux directives, soit de données cliniques et de laboratoire, pour les deux premières années post-don. Les chances d'avoir un suivi annuel pour les donneurs qui n'avaient pas reçu de soins précoces conformes aux directives étaient de 76 % inférieures à 5 ans (RRc: 0,180,240,32) et de 68 % inférieures à 10 ans (RRc: 0,230,320,46) par rapport aux donneurs qui en avaient reçu. Les chances de poursuivre le suivi sont demeurées stables au fil du temps pour les deux groupes. Le fait d'avoir reçu des soins de suivi précoces conformes aux recommandations ne semble pas avoir eu d'incidence importante sur les mesures de DFGe ou les taux d'hospitalisation à long terme. Limites: Nous n'avons pas été en mesure de confirmer si l'absence de visites chez le médecin ou le manque de données de laboratoire chez certains donneurs était dû à des décisions du médecin ou du patient. Conclusion: Bien que les politiques visant à améliorer le suivi précoce des donneurs d'organes puissent encourager la poursuite du suivi, des stratégies supplémentaires pourraient être nécessaires pour atténuer les risques à long terme pour ces personnes.

Multiple versus single and other estimates of baseline proteinuria status as predictors of adverse outcomes in the general population.

BACKGROUND: The association of proteinuria and adverse clinical outcomes is well established. The optimal method of classifying proteinuria status for study participants in whom it is measured multiple times is unknown, especially when the frequency of measurement varies between participants. STUDY DESIGN: Population-based longitudinal study. SETTING & PARTICIPANTS: All adults with at least one outpatient serum creatinine measurement in the province of Alberta, Canada. FACTOR: Proteinuria (dipstick, albumin-creatinine ratio [ACR]). OUTCOMES: All-cause mortality, end-stage renal disease, or doubling of serum creatinine level. MEASURES: All outpatient urine dipstick and ACR measurements in the 6-month period before and after the first (index) estimated glomerular filtration rate were used to establish baseline proteinuria. Dipstick measures were analyzed as ceiling (median value up to the next integer), floor (median value down to the next integer), high (single highest dipstick value), low (single lowest dipstick value), and first (first available dipstick value only). Measurements of ACR were evaluated similarly and a median (median of all ACR measurements) value was added. RESULTS: Of 920,985 participants, 17% (n = 160,548) had multiple dipstick urinalysis measurements and 22% (n = 22,814) had multiple ACR measurements. With single measurements, absolute rates of mortality and renal outcomes were lower in every proteinuria category compared with multiple measurements. In contrast, the relative increase in rate ratio was greater with increasing proteinuria in patients with single measurements compared with those with multiple measurements. In all classification systems evaluated, more severe proteinuria was associated with significantly higher rates of both outcomes (all P for trend <0.001). LIMITATIONS: Lack of a gold standard for choosing between methods. CONCLUSIONS: Rates of adverse outcomes related to multiple baseline proteinuria/albuminuria measurements were similar, independent of the measure of baseline proteinuria that was used to combine results. In contrast, discarding follow-up measurements and relying on only the first measurement led to lower estimates of absolute and relative risk for each proteinuria category.

Clinical risk implications of the CKD Epidemiology Collaboration (CKD-EPI) equation compared with the Modification of Diet in Renal Disease (MDRD) Study equation for estimated GFR.

BACKGROUND: The CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) creatinine-based equation for estimated glomerular filtration rate (eGFR) is more accurate than the MDRD (Modification of Diet in Renal Disease) Study equation. However, it has not been determined whether the improvement in risk categorization applies to all segments of the population. STUDY DESIGN: Population-based cohort study. SETTING & PARTICIPANTS: Adults (aged ≥18 years) who did not have kidney failure at baseline and had at least one serum creatinine measurement and dipstick proteinuria evaluation in a province-wide laboratory registry from Alberta, Canada, in 2002-2007 (N = 1,010,988). PREDICTOR: eGFR categories of ≥90, 60-89, 45-59, 30-44, and 15-29 mL/min/1.73 m(2). OUTCOMES: All-cause mortality, acute myocardial infarction, end-stage renal disease, and doubling of serum creatinine level. MEASUREMENTS: GFR was estimated by the CKD-EPI and MDRD Study equations. RESULTS: The CKD-EPI equation reclassified 22.6% and 1.2% of participants to a higher and lower eGFR category, respectively, and decreased the prevalence of CKD stages 3 and 4 from 9.2% to 7.3%. Of 70,071 participants with eGFR(MDRD) of 45-59 mL/min/1.73 m(2), 30.8% were reclassified to eGFR(CKD-EPI) of 60-89 mL/min/1.73 m(2), and after adjusting for potential confounders, participants reclassified had a lower risk of all-cause mortality (incidence rate ratio [IRR], 0.77; 95% CI, 0.69-0.86), acute myocardial infarction (IRR, 0.73; 95% CI, 0.60-0.88), end-stage renal disease (IRR, 0.55; 95% CI, 0.32-0.94), and doubling of creatinine level (IRR, 0.78; 95% CI, 0.59-1.04) compared with those not reclassified. Similar findings were observed for those reclassified to a higher eGFR category from other eGFR(MDRD) categories. Net reclassification improvements based on eGFR categories were positive for all outcomes (range, 0.146-0.256; all P < 0.001). LIMITATIONS: Relatively short follow-up (median, 2.8 years), lack of data for some potential confounders (eg, smoking), and mainly white participants. CONCLUSIONS: These results suggest that the CKD-EPI equation more accurately categorizes individuals regarding clinical risk than the MDRD Study equation.

Using proteinuria and estimated glomerular filtration rate to classify risk in patients with chronic kidney disease: a cohort study.

BACKGROUND: The staging system for chronic kidney disease relies almost exclusively on estimated glomerular filtration rate (eGFR), although proteinuria is also associated with adverse outcomes. OBJECTIVE: To validate a 5-category system for risk stratification based on the combination of eGFR and proteinuria. DESIGN: Retrospective cohort study. SETTING: A provincial laboratory registry in Alberta, Canada, and a representative sample of noninstitutionalized U.S. adults. PATIENTS: A derivation data set of 474 521 adult outpatients, 2 independent internal validation cohorts with 51 356 and 460 623 patients, and an external validation cohort of 14 358 patients. MEASUREMENTS: Glomerular filtration rate, estimated by using the Modification of Diet in Renal Disease Study equation, and proteinuria, measured by using urine albumin-to-creatinine ratio or dipstick urinalysis. Outcomes included all-cause mortality and a composite renal outcome of kidney failure or doubling of serum creatinine level. RESULTS: Over a median follow-up of 38 months in the internal validation cohorts, higher risk categories (indicating lower eGFR or more proteinuria) were associated with a graded increase in the risk for the composite renal outcome. The projected number of U.S. adults assigned to risk categories 3 and 4 in the alternate system was 3.9 million, compared with 16.3 million assigned to stage 3 and 4 in the current staging system. The alternate system was more likely to correctly reclassify persons who did not develop the renal outcome than those who did, although some persons developed the renal outcome despite reclassification to a lower category. However, all analyses of patients reclassified to a lower category showed that substantially fewer such patients developed the renal outcome than did not. Correct reclassification by the alternate system was more likely when proteinuria was measured by using albumin-to-creatinine ratio than with dipstick testing, and also more likely for the composite renal outcome than for mortality. LIMITATION: The study had a short follow-up time. CONCLUSION: Using proteinuria in combination with eGFR may reduce unnecessary referrals for care at the cost of not referring or delaying referral for some patients who go on to develop kidney failure. PRIMARY FUNDING SOURCE: Alberta Heritage Foundation for Medical Research interdisciplinary research team grant.

Mortality and Resource Use Among Individuals With Chronic Kidney Disease or Cancer in Alberta, Canada, 2004-2015.

Importance: Although the public is aware that cancer is associated with excess mortality and adverse outcomes, the clinical consequences of chronic kidney disease (CKD) are not well understood. Objective: To compare the clinical consequences of incident severe CKD and the first diagnosis with a malignant tumor, focusing on the 10 leading causes of cancer in men and women residing in Canada. Design, Setting, and Participants: This population-based cohort study enrolled individuals aged 19 years and older with severe CKD or certain types of cancer between 2004 and 2015 in Alberta, Canada. Data were analyzed in November 2021. Exposures: Individuals were categorized as having severe CKD (based on estimated glomerular filtration rate <30 mL/min/1.73 m2 or nephrotic albuminuria without dialysis or kidney transplantation) or nonmetastatic or metastatic cancer (defined by a diagnosis of lung, breast, colorectal, prostate, bladder, thyroid, kidney or renal pelvis, uterus, pancreas, or oral cancer). Main Outcomes and Measures: All-cause mortality, number of hospitalizations, total number of hospital days, and placement into long-term care were calculated after diagnosis. Results: Of 200 494 individuals in the cohort (104 559 women [52.2%]; median [IQR] age, 66.8 [55.9-77.7] years), 51 159 (25.5%) had incident severe CKD, 115 504 (57.6%) had nonmetastatic cancer, and 33 831 (16.9%) had metastatic cancer. Kaplan-Meier 1-year survival was 83.3% (95% CI, 83.0%-83.6%) for patients with CKD, 91.2% (95% CI, 91.0%-91.4%) for patients with nonmetastatic cancer, and 52.8% (95% CI, 52.2%-53.3%) for patients with metastatic cancer. Kaplan-Meier 5-year survival was 54.6% (95% CI, 54.2%-55.1%) for patients with CKD, 76.6% (95% CI, 76.3%-76.8%) for patients with nonmetastatic cancer, and 33.9% (95% CI, 33.3%-34.4%) for patients with metastatic cancer. Compared with nonmetastatic cancer, the age-, sex-, and comorbidity-adjusted relative rate of death was similar for CKD (adjusted relative rate, 1.00; 95% CI, 0.97-1.03; P = .92) during the first year of follow-up and was higher for CKD at years 1 to 5 (adjusted relative rate 1.23; 95% CI, 1.19-1.26). During the first year of follow-up, for patients with CKD, adjusted rates of placement in long-term care (adjusted relative rate, 0.88; 95% CI, 0.82-0.94) and hospitalization (adjusted relative rate, 0.65; 95% CI, 0.64-0.66) were lower than rates for patients with nonmetastatic cancer; however, those rates were higher for the CKD group than for the nonmetastatic cancer group during years 1 to 5 (long-term care placement, adjusted relative rate, 1.36; 95% CI, 1.29-1.43; hospitalization, adjusted relative rate, 1.55; 95% CI, 1.52-1.58). As expected, adjusted rates of long-term care placement and hospitalization were higher for patients with metastatic cancer than for the other 2 groups. Conclusions and Relevance: In this study, mortality, hospitalization, and likelihood of placement into long-term care were similar for CKD and nonmetastatic cancer. These data highlight the importance of CKD as a public health problem.

Higher estimated glomerular filtration rates may be associated with increased risk of adverse outcomes, especially with concomitant proteinuria.

The estimated glomerular filtration rate (eGFR) is a powerful predictor of adverse outcomes, but most attention has focused on studies in the setting of reduced eGFR. Here we tested whether patients with an eGFR higher than 60-89.9 ml/min per 1.73 m(2) could also be at elevated risk of adverse outcomes. Further, we tested whether concomitant proteinuria further increases the risk of outcomes among individuals with an eGFR equal to or above 90 ml/min per 1.73 m(2), as it does for those with reduced eGFR. Using data from a population-based outpatient laboratory data set of 1,526,437 patients, we measured adjusted associations between eGFR calculated by the modification of diet in renal disease equation, urine dipstick proteinuria, and adverse clinical outcomes. The adjusted risk of all-cause mortality was lowest at an eGFR of 60-74.9 ml/min per 1.73 m(2) (referent) and increased at both lower and higher levels of eGFR. Specifically, the hazard ratio of death was 3.7 and 1.8 among patients with an eGFR equal to or above 105 and 90-104.9 ml/min per 1.73 m(2), respectively, compared to the referent group. Similar results were seen when the CKD-EPI equation (sensitivity analyses) was used to assess eGFR. Higher levels of eGFR were not associated with the risk of kidney failure or myocardial infarction. Thus, the presence and severity of proteinuria was significantly associated with graded increases in the risk of clinical outcomes for both lower and higher eGFR. We do not know, however, whether the finding at higher eGFR could be due to inadequacies of the eGFR formula at low serum creatinine levels.

Efficacy of statins for primary prevention in people at low cardiovascular risk: a meta-analysis.

BACKGROUND: Statins were initially used to improve cardiovascular outcomes in people with established coronary artery disease, but recently their use has become more common in people at low cardiovascular risk. We did a systematic review of randomized trials to assess the efficacy and harms of statins in these individuals. METHODS: We searched MEDLINE and EMBASE (to Jan. 28, 2011), registries of health technology assessments and clinical trials, and reference lists of relevant reviews. We included trials that randomly assigned participants at low cardiovascular risk to receive a statin versus a placebo or no statin. We defined low risk as an observed 10-year risk of less than 20% for cardiovascular-related death or nonfatal myocardial infarction, but we explored other definitions in sensitivity analyses. RESULTS: We identified 29 eligible trials involving a total of 80,711 participants. All-cause mortality was significantly lower among patients receiving a statin than among controls (relative risk [RR] 0.90, 95% confidence interval [CI] 0.84-0.97) for trials with a 10-year risk of cardiovascular disease < 20% [primary analysis] and 0.83, 95% CI 0.73-0.94, for trials with 10-year risk < 10% [sensitivity analysis]). Patients in the statin group were also significantly less likely than controls to have nonfatal myocardial infarction (RR 0.64, 95% CI 0.49-0.84) and nonfatal stroke (RR 0.81, 95% CI 0.68-0.96). Neither metaregression nor stratified analyses suggested statistically significant differences in efficacy between high-and low-potency statins, or larger reductions in cholesterol. INTERPRETATION: Statins were found to be efficacious in preventing death and cardiovascular morbidity in people at low cardiovascular risk. Reductions in relative risk were similar to those seen in patients with a history of coronary artery disease.

Cost-effectiveness of the use of low- and high-potency statins in people at low cardiovascular risk.

BACKGROUND: Although statins have been shown to reduce the risk of cardiovascular events in patients at low cardiovascular risk, their absolute benefit is small in the short term, which may adversely affect cost-effectiveness. We sought to determine the long-term cost-effectiveness (beyond the duration of clinical trials) of low- and high-potency statins in patients at low cardiovascular risk and to estimate the impact on Canada's publicly funded health care system. METHODS: Using Markov modelling, we performed a cost-utility analysis in which we compared low-potency statins (fluvastatin, lovastatin, pravastatin and simvastatin) and high-potency statins (atorvastatin and rosuvastatin) with no statins in a simulated cohort of low-risk patients over a lifetime horizon. Model outcomes included costs (in 2010 Canadian dollars), quality-adjusted life-years (QALYs) gained and the cost per QALY gained. RESULTS: Over a lifetime horizon, the cost of managing a patient at low cardiovascular risk was estimated to be about $10,100 without statins, $15,200 with low-potency statins and $16,400 with high-potency statins. The cost per QALY gained with high-potency statins (v. no statins) was $21 300; the use of low-potency statins was not considered economically attractive. These results were robust to sensitivity analyses, although their use became economically unattractive when the duration of benefit from statin use was assumed to be less than 10 years. INTERPRETATION: Use of high-potency statins in patients at low cardiovascular risk was associated with a cost per QALY gained that was economically attractive by current standards, assuming that the benefit from statin use would continue for at least 10 years. However, the overall expenditure on statins would be substantial, and the ramifications of this practice should be carefully considered by policy-makers.