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.

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.

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.

Development and Validation of Nine Deprescribing Algorithms for Patients on Hemodialysis to Decrease Polypharmacy.

BACKGROUND: Polypharmacy is ubiquitous in patients on hemodialysis (HD), and increases risk of adverse events, medication interactions, nonadherence, and mortality. Appropriately applied deprescribing can potentially minimize polypharmacy risks. Existing guidelines are unsuitable for nephrology clinicians as they lack specific instructions on how to deprescribe and which safety parameters to monitor. OBJECTIVE: To develop and validate deprescribing algorithms for nine medication classes to decrease polypharmacy in patients on HD. DESIGN: Questionnaires and materials sent electronically. PARTICIPANTS: Nephrology practitioners across Canada (nephrologists, nurse practitioners, renal pharmacists). METHODS: A literature search was performed to develop the initial algorithms via Lynn's method for development of content-valid clinical tools. Content and face validity of the algorithms was evaluated over three interview rounds using Lynn's method for determining content validity. Canadian nephrology clinicians each evaluated three algorithms (15 clinicians per round, 45 clinicians in total) by rating each algorithm component on a four-point Likert scale for relevance; face validity was rated on a five-point scale. After each round, content validity index of each component was calculated and revisions made based on feedback. If content validity was not achieved after three rounds, additional rounds were completed until content validity was achieved. RESULTS: After three rounds of validation, six algorithms achieved content validity. After an additional round, the remaining three algorithms achieved content validity. The proportion of clinicians rating each face validity statement as "Agree" or "Strongly Agree" ranged from 84% to 95% (average of all five questions, across three rounds). LIMITATIONS: Algorithm development was guided by existing deprescribing protocols intended for the general population and the expert opinions of our study team, due to a lack of background literature on HD-specific deprescribing protocols. There is no universally accepted method for the validation of clinical decision-making tools. CONCLUSIONS: Nine medication-specific deprescribing algorithms for patients on HD were developed and validated by clinician review. Our algorithms are the first medication-specific, patient-centric deprescribing guidelines developed and validated for patients on HD.

CONTEXTE: La polypharmacie est très répandue chez les patients hémodialysés et augmente le risque d'événements indésirables, d'interactions médicamenteuses, d'inobservance au traitement et de mortalité. La déprescription, appliquée de façon appropriée, peut réduire les risques associés à la polypharmacie. Les directives de déprescription existantes ne conviennent cependant pas aux cliniciens en néphrologie puisqu'elles ne renferment aucune indication spécifique sur la manière de procéder ni sur les paramètres de sécurité à surveiller. OBJECTIF: Développer et valider des algorithmes de déprescription pour neuf classes de médicaments en vue de réduire la polypharmacie chez les patients hémodialysés. CONCEPTION: Des questionnaires et des documents envoyés par voie électronique. PARTICIPANTS: Des praticiens en néphrologies de partout au Canada (néphrologues, infirmières-praticiennes, pharmaciens spécialisés en néphrologie). MÉTHODOLOGIE: Une recherche bibliographique a été effectuée pour développer les algorithmes initiaux avec la méthode de Lynn pour le développement d'outils cliniques à contenu validé. Le contenu et la validité apparente des algorithmes ont été évalués au cours de trois cycles d'interviews par la méthode de Lynn pour déterminer la validité d'un contenu. Les praticiens interviewés (15 par cycle, pour un total de 45) ont chacun évalué trois algorithmes en classant la pertinence de leurs composants sur une échelle de Likert en quatre points, et en classant leur validité apparente sur une échelle en cinq points. Après chaque cycle, l'indice de validité du contenu a été calculé pour chaque composant et des correctifs ont été apportés en fonction de la rétroaction. Si la validité du contenu n'était pas atteinte après trois cycles, des cycles supplémentaires étaient effectués jusqu'à ce que celle-ci soit atteinte. RÉSULTATS: Six algorithmes ont atteint la validité après trois cycles de validation. Les trois algorithmes restants l'ont atteint après un cycle supplémentaire. La proportion de cliniciens ayant attribué la mention de validité apparente « d'accord ¼ ou « tout à fait d'accord ¼ se situait entre 84 et 95 % (moyenne des cinq questions, sur trois cycles). LIMITES: Le développement des algorithmes repose sur les protocoles de déprescription existants, destinés à la population générale, et sur l'avis des experts de notre équipe d'étude puisque la documentation portant sur des protocoles de déprescription spécifiques aux patients hémodialysés est insuffisante. Il n'existe aucune méthode universellement acceptée pour valider les outils de décision clinique. CONCLUSION: Neuf algorithmes de déprescription spécifiques aux patients hémodialysés ont été développés et validés par révision des cliniciens. Nos algorithmes sont les premiers guides de déprescription développés et validés spécifiquement pour les médicaments des patients hémodialysés. ENREGISTREMENT DE L'ESSAI: Sans objet ­ il s'agit d'une série de questionnaires.

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.

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.

Associations among estimated glomerular filtration rate, proteinuria, and adverse cardiovascular outcomes.

BACKGROUND AND OBJECTIVES: Most studies of chronic kidney disease (CKD) and outcomes focus on mortality and ESRD, with limited data on other adverse outcomes. This study examined the associations among proteinuria, eGFR, and adverse cardiovascular (CV) events. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This was a population-based longitudinal study with patients identified from province-wide laboratory data from Alberta, Canada, between 2002 and 2007. Selected for this study from a total of 1,526,437 patients were 920,985 (60.3%) patients with at least one urine dipstick measurement and 102,701 patients (6.7%) with at least one albumin-creatinine ratio (ACR) measurement. Time to hospitalization was considered for one of four indications: congestive heart failure (CHF), coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI), peripheral vascular disease (PVD), and stroke/transient ischemic attacks [TIAs] (cerebrovascular accident [CVA]/TIA). RESULTS: After a median follow-up of 35 months, in fully adjusted models and compared with patients with estimated GFR (eGFR) of 45 to 59 ml/min per 1.73 m(2) and no proteinuria, patients with heavy proteinuria by dipstick and eGFR ≥ 60 ml/min per 1.73 m(2) had higher rates of CABG/PCI and CVA/TIA. Similar results were obtained in patients with proteinuria measured by ACR. CONCLUSIONS: Risks of major CV events at a given level of eGFR increased with higher levels of proteinuria. The findings extend current data on risk of mortality and ESRD. Measurement of proteinuria is of incremental prognostic benefit at every level of eGFR. The data support use of proteinuria measurement with eGFR for definition and risk stratification in CKD.

Economic evaluation of erythropoiesis-stimulating agents for anemia related to cancer.

BACKGROUND: Erythropoiesis-stimulating agents (ESA) administered to cancer patients with anemia reduce the need for blood transfusions and improve quality-of-life (QOL). Concerns about toxicity have led to more restrictive recommendations for ESA use; however, the incremental costs and benefits of such a strategy are unknown. METHODS: The authors created a decision model to examine the costs and consequences of ESA use in patients with anemia and cancer from the perspective of the Canadian public healthcare system. Model inputs were informed by a recent systematic review. Extensive sensitivity analyses and scenario analysis rigorously assessed QOL benefits and more conservative ESA administration practices (initial hemoglobin [Hb] <10 g/dL, target Hb < or =12 g/dL, and chemotherapy induced anemia only). RESULTS: Compared with supportive transfusions only, conventional ESA treatment was associated with an incremental cost per quality-adjusted life year (QALY) gained of $267,000 during a 15-week time frame. During a 1.3-year time horizon, ESA was associated with higher costs and worse clinical outcomes. In scenarios where multiple assumptions regarding QOL all favored ESA, the lowest incremental cost per QALY gained was $126,000. Analyses simulating the use of ESA in accordance with recently issued guidelines resulted in incremental cost per QALY gained of > $100,000 or ESA being dominated (greater costs with lower benefit) in the majority of the scenarios, although greater variability in the cost-utility ratio was present. CONCLUSIONS: Use of ESA for anemia related to cancer is associated with incremental cost-effectiveness ratios that are not economically attractive, even when used in a conservative fashion recommended by current guidelines.

Screening for kidney disease on World Kidney Day in Jalisco, Mexico.

BACKGROUND: In 2006, the International Society of Nephrology (ISN) and the International Federation of Kidney Foundations (IFKF) introduced World Kidney Day, to educate the public about the importance of chronic kidney disease (CKD) and its early detection. This prospective study examined the diagnostic yield of screening for CKD in poor neighborhoods in Guadalajara, Mexico, on World Kidney Day. METHODS: On World Kidney Day in 2006 and 2007, 2 screening stations were set up in Guadalajara, with a 2-week promotion period beforehand in the local media. Individuals who were aware that they had CKD and those <18 years of age were excluded. Data were prospectively collected by the staff of the screening programs using a standard form; all participants provided blood and urine specimens for serum creatinine assays and dipstick urinalysis. RESULTS: We studied 634 participants, of whom approximately 24% had proteinuria, 35% had hematuria and 6.4% had an estimated glomerular filtration rate (eGFR) <60 ml/min per 1.73 m2. Overall, the number needed to screen (NNS) to detect 1 new case of eGFR <60 ml/min per 1.73 m2 was 16 (95% confidence interval [95% CI], 12-22), varying from as low as 5 (95% CI, 4-8) in participants >60 years of age, to as high as 84 (95% CI, 35 to >200) in people aged 18 to 40 years. CONCLUSIONS: Proteinuria and eGFR <60 ml/min per 1.73 m2 were frequently detected among participants in community-based screening carried out on World Kidney Day in the state of Jalisco, Mexico, especially in people over 40 years old. Our data indicate that screening on World Kidney Day may be useful for identifying Jalisco residents with CKD, and suggest that trials of targeted screening and intervention are feasible and warranted.

Benefits and harms of erythropoiesis-stimulating agents for anemia related to cancer: a meta-analysis.

BACKGROUND: Erythropoiesis-stimulating agents are used to treat anemia in patients with cancer. However, their safety and effectiveness is controversial. We did a systematic review of the clinical efficacy and harms of these agents in adults with anemia related to cancer or chemotherapy. METHODS: We conducted a systematic review of published and unpublished randomized controlled trials (RCTs) using accepted methods for literature searches, article selection, data extraction and quality assessment. We included RCTs involving anemic adults with cancer. We compared the use of erythropoiesis-stimulating agents with nonuse and assessed clinical outcomes (all-cause mortality, cardiovascular events and hypertension, health-related quality of life, blood transfusions and tumour response) and harms (serious adverse events) between groups. RESULTS: We identified 52 trials (n = 12 006) that met our selection criteria. The pooled all-cause mortality during treatment was significantly higher in the group receiving erythropoiesis-stimulating therapy than in the control group (relative risk [RR] 1.15, 95% confidence interval [CI] 1.03 to 1.29). Compared with no treatment, use of erythropoiesis-stimulating agents led to clinically detectable improvements in disease-specific measures of quality of life. It also reduced the use of blood transfusions (RR 0.64, 95% CI 0.56 to 0.73). However, it led to an increased risk of thrombotic events (RR 1.69, 95% CI 1.27 to 2.24) and serious adverse events (RR 1.16, 95% CI 1.08 to 1.25). INTERPRETATION: Use of erythropoiesis-stimulating agents in patients with cancer-related anemia improved some disease-specific measures of quality of life and decreased the use of blood transfusions. However, it increased the risk of death and serious adverse events. Our findings suggest that such therapy not be used routinely as an alternative to blood transfusion in patients with anemia related to cancer.

Screening for kidney disease in children on World Kidney Day in Jalisco, Mexico.

World Kidney Day (WKD) is intended to raise awareness and increase detection of chronic kidney disease (CKD), but most emphasis is placed on adults rather than children. We examined yield of screening for CKD and hypertension among poor children in Mexico. On WKD (2006, 2007), children (age < 18 years) without known CKD were invited to participate at two screening stations. We measured body mass index (BMI), blood pressure, and serum creatinine, and performed dipstick urinalysis. The Schwartz equation was used to estimate glomerular filtration rate (GFR; reduced GFR defined as < 60 ml/min per 1.73 m(2)). Proteinuria and hematuria were defined by a reading of >or= 1+ protein or blood on dipstick. Hypertension was defined by gender, age, and height-specific norms. In total, 240 children were screened (mean age 8.9 +/- 4.1 years; 44.2% male). Proteinuria and hematuria were detected in 38 (16.1%) and 41 (17.5%), respectively; 15% had BMI > 95th percentile for age. Reduced GFR was detected in four (1.7%) individuals. Systolic hypertension was more prevalent in younger children (age 0-8 years, 19.6%; age 9-13 years, 7.1%; age 14-17 years, 5.3%) suggesting a possible white-coat effect. Hematuria, proteinuria, hypertension and obesity were frequently detected among children in a community based screening program in Mexico. This form of screening might be useful in identifying children with CKD and hypertension in developing nations.