Machine learning for prediction of chronic kidney disease progression: Validation of the Klinrisk model in the CANVAS Program and CREDENCE trial.

AIM: To validate the Klinrisk machine learning model for prediction of chronic kidney disease (CKD) progression in patients with type 2 diabetes in the pooled CANVAS/CREDENCE trials. MATERIALS AND METHODS: We externally validated the Klinrisk model for prediction of CKD progression, defined as 40% or higher decline in estimated glomerular filtration rate (eGFR) or kidney failure. Model performance was assessed for prediction up to 3 years with the area under the receiver operating characteristic curve (AUC), Brier scores and calibration plots of observed and predicted risks. We compared performance of the model with standard of care using eGFR (G1-G4) and urine albumin-creatinine ratio (A1-A3) Kidney Disease Improving Global Outcomes (KDIGO) heatmap categories. RESULTS: The Klinrisk model achieved an AUC of 0.81 (95% confidence interval [CI] 0.78-0.83) at 1 year, and 0.88 (95% CI 0.86-0.89) at 3 years. The Brier scores were 0.020 (0.018-0.022) and 0.056 (0.052-0.059) at 1 and 3 years, respectively. Compared with the KDIGO heatmap, the Klinrisk model had improved performance at every interval (P < .01). CONCLUSIONS: The Klinrisk machine learning model, using routinely collected laboratory data, was highly accurate in its prediction of CKD progression in the CANVAS/CREDENCE trials. Integration of the model in electronic medical records or laboratory information systems can facilitate risk-based care.

Expanding Access to High KDPI Kidney Transplant for Recipients Aged 60 y and Older: Cost Utility and Survival.

Background: Modern organ allocation systems are tasked with equitably maximizing the utility of transplanted organs. Increasing the use of deceased donor organs at risk of discard may be a cost-effective strategy to improve overall transplant benefit. We determined the survival implications and cost utility of increasing the use of marginal kidneys in an older adult Canadian population of patients with end-stage kidney disease. Methods: We constructed a cost-utility model with microsimulation from the perspective of the Canadian single-payer health system for incident transplant waitlisted patients aged 60 y and older. A kidney donor profile index score of ≥86 was considered a marginal kidney. Donor- and recipient-level characteristics encompassed in the kidney donor profile index and estimated posttransplant survival scores were used to derive survival posttransplant. Patients were followed up for 10 y from the date of waitlist initiation. Our analysis compared the routine use of marginal kidneys (marginal kidney scenario) with the current practice of limited use (status quo scenario). Results: The 10-y mean cost and quality-adjusted life-years per patient in the marginal kidney scenario were estimated at $379 485.33 (SD: $156 872.49) and 4.77 (SD: 1.87). In the status quo scenario, the mean cost and quality-adjusted life-years per patient were $402 937.68 (SD: $168 508.85) and 4.37 (SD: 1.87); thus, the intervention was considered dominant. At 10 y, 62.8% and 57.0% of the respective cohorts in the marginal kidney and status quo scenarios remained alive. Conclusions: Increasing the use of marginal kidneys in patients with end-stage kidney disease aged 60 y and older may offer cost savings, improved quality of life, and greater patient survival in comparison with usual care.

Association of body mass index with the development of metabolic acidosis in patients with chronic kidney disease.

Aims: Higher body mass index (BMI) is associated with higher bone mass and bone serves as a buffer during the development of metabolic acidosis. The authors sought to examine the relationship between BMI and metabolic acidosis in patients with chronic kidney disease (CKD). Materials and Methods: The study utilized a large US longitudinal data repository including over 103 million patients from healthcare provider organizations to evaluate the relationship between the exposure variable (BMI) and the prevalence and incidence of metabolic acidosis among patients with estimated glomerular filtration rate <60 ml/min/1.73 m2. Incident metabolic acidosis was identified at the first of two consecutive post-index serum bicarbonate values, 10-365 days apart, between 12 and <22 mEq/L in patients with normal index serum bicarbonate. Cox proportional hazard models were adjusted for multiple variables including demographics, comorbidities, income, education, and kidney function. Results: 103,766 patients qualified for this study; 6472 (6.2%) had metabolic acidosis at index. An inverse association between BMI category and metabolic acidosis was observed for both baseline (prevalence) and new-onset (incidence) metabolic acidosis. Compared to BMI category of 18.5 to <25 kg/m2, each category of incrementally higher BMI was associated with a decreasing risk of incident metabolic acidosis; the adjusted hazard ratios (95% confidence interval) were 0.866 (0.824-0.911), 0.770 (0.729-0.813), 0.664 (0.622-0.709), and 0.612 (0.571-0.655) for BMI 25 to <30, 30 to <35, 35 to <40, and 40+ kg/m2, respectively. Conclusions: Among patients with CKD, an incremental increase in BMI was inversely associated with both the prevalence and incidence of metabolic acidosis. These associations suggest that increased body weight may protect against the development of metabolic acidosis, a risk factor for progressive loss of kidney function.

A Predictive Model for Kidney Failure After Nephrectomy for Localized Kidney Cancer: The Kidney Cancer Risk Equation.

RATIONALE & OBJECTIVE: Nephrectomy is the mainstay of treatment for individuals with localized kidney cancer. However, surgery can potentially result in the loss of kidney function or in kidney failure requiring dialysis/kidney transplantation. There are currently no clinical tools available to preoperatively identify which patients are at risk of kidney failure over the long term. Our study developed and validated a prediction equation for kidney failure after nephrectomy for localized kidney cancer. STUDY DESIGN: Population-level cohort study. SETTING & PARTICIPANTS: Adults (n=1,026) from Manitoba, Canada, with non-metastatic kidney cancer diagnosed between January 1, 2004, and December 31, 2016, who were treated with either a partial or radical nephrectomy and had at least 1 estimated glomerular filtration rate (eGFR) measurement before and after nephrectomy. A validation cohort included individuals in Ontario (n=12,043) with a diagnosis of localized kidney cancer between October 1, 2008, and September 30, 2018, who received a partial or radical nephrectomy and had at least 1 eGFR measurement before and after surgery. NEW PREDICTORS & ESTABLISHED PREDICTORS: Age, sex, eGFR, urinary albumin-creatinine ratio, history of diabetes mellitus, and nephrectomy type (partial/radical). OUTCOME: The primary outcome was a composite of dialysis, transplantation, or an eGFR<15mL/min/1.73m2 during the follow-up period. ANALYTICAL APPROACH: Cox proportional hazards regression models evaluated for accuracy using area under the receiver operating characteristic curve (AUC), Brier scores, calibration plots, and continuous net reclassification improvement. We also implemented decision curve analysis. Models developed in the Manitoba cohort were validated in the Ontario cohort. RESULTS: In the development cohort, 10.3% reached kidney failure after nephrectomy. The final model resulted in a 5-year area under the curve of 0.85 (95% CI, 0.78-0.92) in the development cohort and 0.86 (95% CI, 0.84-0.88) in the validation cohort. LIMITATIONS: Further external validation needed in diverse cohorts. CONCLUSIONS: Our externally validated model can be easily applied in clinical practice to inform preoperative discussions about kidney failure risk in patients facing surgical options for localized kidney cancer. PLAIN-LANGUAGE SUMMARY: Patients with localized kidney cancer often experience a lot of worry about whether their kidney function will remain stable or will decline if they choose to undergo surgery for treatment. To help patients make an informed treatment decision, we developed a simple equation that incorporates 6 easily accessible pieces of patient information to predict the risk of reaching kidney failure 5 years after kidney cancer surgery. We expect that this tool has the potential to inform patient-centered discussions tailored around individualized risk, helping ensure that patients receive the most appropriate risk-based care.

Practical Utilization of Prediction Equations in Chronic Kidney Disease.

Chronic kidney disease (CKD) is common and can lead to kidney failure, cardiovascular complications, and early mortality. While nephrologists can provide valuable insights for patients at all stages of CKD, these scarce resources should be targeted at patients with the highest risk of progression and adverse outcomes. Prediction models are tools that can help providers risk stratify patients if they are effectively implemented into the clinical workflow. We believe these equations should demonstrate (1) clinical utility: where they can provide useful information to the physician and patients; and (2) clinical usability: where they are able to be easily integrated into clinical workflow and do not result in unnecessary costs or visits. CKD often remains unrecognized until later stages when a large window of opportunity to delay progression has already passed. Models to determine progression of CKD using thresholds such as a 40% decline in eGFR can provide clinical utility in risk stratifying patients at all stages of CKD, an endpoint that has been recommended by the FDA for the evaluation of drug approvals for disease-modifying therapies. For patients at more advanced stages of CKD with a greater risk of kidney failure, tools such as the kidney failure risk equation can be implemented to help guide most costly decisions, such as referral to multidisciplinary care, commencing dialysis modality education, or planning for vascular access placement surgery. In addition, models focused on determining outcomes following dialysis initiation can help inform shared decision-making between patient and provider to better inform decisions around conservative care. To ensure widespread adoption of these tools, it is important to ensure that they are broadly generalizable to many health settings and easily implemented into existing clinic workflows with minimum disruption.

Association of the Kidney Failure Risk Equation With High Health Care Costs.

Introduction: The Kidney Failure Risk Equations (KFRE) are accurate and validated to predict the risk of kidney failure in individuals with chronic kidney disease (CKD), but their potential to predict health care costs in the US health care system is unknown. We assessed the association of kidney failure risk from the 4-variable and 8-variable 2-year KFRE models with monthly health care costs in US patients with CKD stages G3 and G4. Methods: This was an ancillary study to a larger observational, retrospective cohort study examining the association between serum bicarbonate and adverse kidney outcomes. Monthly medical costs were calculated from individual health care insurance claims. Generalized linear regression models were used to examine the association of KFRE score with health care costs. Results: A total of 1721 patients qualified for the study (1475 and 246 with CKD stages G3 and G4, respectively). For 8-variable KFRE, each 1% (absolute) increase in risk was associated with 13.5% (P < 0.001) and 4.1% (P < 0.001) higher monthly costs for patients with CKD stage G3 and G4, respectively. For 4-variable KFRE, a 1% increase in risk was associated with 6.7% (P = 0.016) and 2.9% (P= 0.014) increase in monthly costs for patients with CKD stage G3 and G4, respectively. Conclusion: Higher risks of kidney failure as predicted by the 4-variable or 8-variable KFRE were associated with higher 2-year medical costs for patients with CKD stages G3 and G4. The KFRE may be a useful tool to anticipate medical costs and target cost-reducing interventions for patients at risk of kidney failure.

Increasing Serum Bicarbonate is Associated With Reduced Risk of Adverse Kidney Outcomes in Patients with CKD and Metabolic Acidosis.

Introduction: Low serum bicarbonate at a single point in time is associated with accelerated kidney decline in patients with chronic kidney disease (CKD). We modeled how changes in serum bicarbonate over time affect incidence of adverse kidney outcomes. Methods: We analyzed data from Optum's deidentified Integrated Claims-Clinical data set of US patients (2007-2019) with ≥1 year of prior medical record data, CKD stages G3 to G5, and metabolic acidosis (i.e., index serum bicarbonate 12 to <22 mmol/l). The primary predictor of interest was the change in serum bicarbonate, evaluated at each postindex outpatient serum bicarbonate test as a time-dependent continuous variable. The primary outcome was a composite of either a ≥40% decline in estimated glomerular filtration rate (eGFR) from index or evidence of dialysis or transplantation, evaluated using Cox proportional hazards models. Results: A total of 24,384 patients were included in the cohort with median follow-up of 3.7 years. A within-patient increase in serum bicarbonate over time was associated with a lower risk of the composite kidney outcome. The unadjusted hazard ratio (HR) per 1-mmol/l increase in serum bicarbonate was 0.911 (95% confidence interval [CI]: 0.905-0.917; P < 0.001). After adjustment for baseline eGFR and serum bicarbonate, the time-adjusted effect of baseline eGFR and other covariates, the HR per 1-mmol/l increase in serum bicarbonate was largely unchanged (0.916 [95% CI: 0.910-0.922; P < 0.001]). Conclusion: In a real-world population of US patients with CKD and metabolic acidosis, a within-patient increase in serum bicarbonate over time independent of changes in eGFR, was associated with a lower risk of CKD progression.

A Machine Learning Model to Predict Diuretic Resistance.

BACKGROUND: Volume overload is a common complication encountered in hospitalized patients, and the mainstay of therapy is diuresis. Unfortunately, the diuretic response in some individuals is inadequate despite a typical dose of loop diuretics, a phenomenon called diuretic resistance. An accurate prediction model that predicts diuretic resistance using predosing variables could inform the right diuretic dose for a prospective patient. METHODS: Two large, deidentified, publicly available, and independent intensive care unit (ICU) databases from the United States were used-the Medical Information Mart for Intensive Care III (MIMIC) and the Philips eICU databases. Loop diuretic resistance was defined as <1400 ml of urine per 40 mg of diuretic dose in 24 hours. Using 24-hour windows throughout admission, commonly accessible variables were obtained and incorporated into the model. Data imputation was performed using a highly accurate machine learning method. Using XGBoost, several models were created using train and test datasets from the eICU database. These were then combined into an ensemble model optimized for increased specificity and then externally validated on the MIMIC database. RESULTS: The final ensemble model was composed of four separate models, each using 21 commonly available variables. The ensemble model outperformed individual models during validation. Higher serum creatinine, lower systolic blood pressure, lower serum chloride, higher age, and female sex were the most important predictors of diuretic resistance (in that order). The specificity of the model on external validation was 92%, yielding a positive likelihood ratio of 3.46 while maintaining overall discrimination (C-statistic 0.69). CONCLUSIONS: A diuretic resistance prediction model was created using machine learning and was externally validated in ICU populations. The model is easy to use, would provide actionable information at the bedside, and would be ready for implementation in existing electronic medical records. This study also provides a framework for the development of future machine learning models.

Metabolic acidosis is undertreated and underdiagnosed: a retrospective cohort study.

BACKGROUND: Guidelines recommend treatment of metabolic acidosis (MA) in patients with chronic kidney disease (CKD), but the diagnosis and treatment rates in real-world settings are unknown. We investigated the frequency of MA treatment and diagnosis in patients with CKD. METHODS: In this retrospective cohort study, we examined administrative health data from two US databases [Optum's de-identified Integrated Claims + Clinical Electronic Health Record Database (US EMR cohort; 1 January 2007 to 30 June 2019) and Symphony Health Solutions IDV® (US claims cohort; 1 May 2016 to 30 April 2019)] and population-level databases from Manitoba, Canada (1 April 2006 to 31 March 2018). Patients who met laboratory criteria indicative of CKD and chronic MA were included: two consecutive estimated glomerular filtration results <60 mL/min/1.73 m2 and two serum bicarbonate results 12 to <22 mEq/L over 28-365 days. Outcomes included treatment of MA (defined as a prescription for oral sodium bicarbonate) and a diagnosis of MA (defined using administrative records). Outcomes were assessed over a 3-year period (1 year pre-index, 2 years post-index). RESULTS: A total of 96 184 patients were included: US EMR, 6179; Manitoba, 3223; US Claims, 86 782. Sodium bicarbonate treatment was prescribed for 17.6%, 8.7% and 15.3% of patients, and a diagnosis was found for 44.7%, 20.9% and 20.9% of patients, for the US EMR, Manitoba and US Claims cohorts, respectively. CONCLUSIONS: This analysis of 96 184 patients with laboratory-confirmed MA from three independent cohorts of patients with CKD and MA highlights an important diagnosis and treatment gap for this disease-modifying complication.

Metabolic Acidosis is Associated With Acute Kidney Injury in Patients With CKD.

Introduction: Metabolic acidosis in patients with chronic kidney disease (CKD) results from a loss of kidney function. It has been associated with CKD progression, all-cause mortality, and other adverse outcomes. We aimed to determine whether metabolic acidosis is associated with a higher risk of acute kidney injury (AKI). Methods: This was a retrospective cohort study. Using electronic health records and administrative data, we enrolled 2 North American cohorts of patients with CKD Stages G3-G5 as follows: (i) 136,067 patients in the US electronic medical record (EMR) based cohort; and (ii) 34,957 patients in the Manitoba claims-based cohort. The primary exposure was metabolic acidosis (serum bicarbonate between 12 mEq/l and <22 mEq/l). The primary outcome was the development of AKI (defined using ICD-9 and 10 codes at hospital admission or a laboratory-based definition based on Kidney Disease: Improving Global Outcomes guidelines). We applied Cox proportional hazards regression models adjusting for relevant demographic and clinical characteristics. Results: In both cohorts, metabolic acidosis was associated with AKI: hazard ratio (HR) 1.57 (95% confidence interval [CI] 1.52-1.61) in the US EMR cohort, and HR 1.65 (95% CI 1.58-1.73) in the Manitoba claims cohort. The association was consistent when serum bicarbonate was treated as a continuous variable, and in multiple subgroups, and sensitivity analyses including those adjusting for albuminuria. Conclusion: Metabolic acidosis is associated with a higher risk of AKI in patients with CKD. AKI should be considered as an outcome in studies of treatments for patients with metabolic acidosis.

Association of metabolic acidosis with fractures, falls, protein-calorie malnutrition and failure to thrive in patients with chronic kidney disease.

Background: The risk of adverse geriatric outcomes such as falls and fractures is high among patients with chronic kidney disease (CKD). Metabolic acidosis is associated with protein catabolism and bone loss in experimental animal and human studies. We sought to quantify the independent association of metabolic acidosis with adverse muscle, bone and functional outcomes in a large US community-based cohort. Methods: The Optum's de-identified Integrated Claims-Clinical dataset of US patients (2007-2017) was used to generate a cohort of patients with nondialysis-dependent CKD who had estimated glomerular filtration rate >10 to <60 mL/min/1.73 m2 and two serum bicarbonate values 12 to <22 mmol/L or 22-29 mmol/L. The primary outcomes were failure to thrive, protein-calorie malnutrition, and fall or fracture. Cox proportional hazards models were used for the primary outcomes for up to 10 years, while logistic regression models were used at 2 years. Results: A total of 51 558 patients qualified for the study, with a median [Interquartile Range (IQR)] follow-up time of 4.2 (2.5-5.8) years. Over a ≤10-year period, for each 1 mmol/L increase in serum bicarbonate, the hazard ratios (adjusted for age, sex, race, estimated glomerular filtration rate, serum albumin, hemoglobin, diabetes and cardiovascular comorbidities) for failure to thrive, protein-calorie malnutrition and fall or fracture were 0.91 [95% confidence interval (CI): 0.90-0.92], 0.91 (95% CI: 0.90-0.92) and 0.95 (95% CI: 0.95-0.96), all P < 0.001, respectively. Conclusions: The presence and severity of metabolic acidosis was a significant, independent risk factor for failure to thrive, protein-calorie malnutrition and fall or fracture in this large community cohort of patients with stage 3-5 CKD.

Role of artificial intelligence in the diagnosis and management of kidney disease: applications to chronic kidney disease and acute kidney injury.

PURPOSE OF REVIEW: Chronic kidney disease (CKD) and acute kidney injury (AKI) are global public health problems associated with a significant burden of morbidity, healthcare resource use, and all-cause mortality. This review explores recently published studies that take a machine learning approach to the diagnosis, management, and prognostication in patients with AKI or CKD. RECENT FINDINGS: The release of novel therapeutics for CKD has highlighted the importance of accurately identifying patients at the highest risk of progression. Many models have been constructed with reasonable predictive accuracy but have not been extensively externally validated and peer reviewed. Similarly, machine learning models have been developed for prediction of AKI and have found sufficient accuracy. There are issues to implementing these models, however, with conflicting results with respect to the relationship between prediction of an AKI outcome and improvements in the occurrence of other adverse events, and in some circumstances potential harm. SUMMARY: Artificial intelligence models can help guide management of CKD and AKI, but it is important to ensure that they are broadly applicable and generalizable to various settings and associated with improved clinical decision-making and outcomes.

Cost of the quanta SC+ hemodialysis system for self-care in the United Kingdom.

INTRODUCTION: New personal hemodialysis systems, such as the quanta SC+, are being developed; these systems are smaller and simpler to use while providing the clearances of conventional systems. Increasing the uptake of lower-intensity assistance and full self-care dialysis may provide economic benefits to the public health payer. In the United Kingdom, most hemodialysis patients currently receive facility-based dialysis costing more than £36,350 per year including patient transport. As such, we aimed to describe the annual costs of using the SC+ hemodialysis system in the United Kingdom for 3×-weekly and 3.5×-weekly dialysis regimens, for self-care hemodialysis provided both in-center and at home. METHODS: We applied a cost minimization approach. Costs for human resources, equipment, and consumables were sourced from the dialysis machine developer (Quanta Dialysis Technologies) based upon discussions with dialysis providers. Facility overhead expenses and transport costs were taken from a review of the literature. FINDINGS: Annual costs associated with the use of the SC+ hemodialysis system were estimated to be £26,642 for hemodialysis provided 3× weekly as home self-care; £30,235 for hemodialysis provided 3× weekly as self-care in-center; £29,866 for hemodialysis provided 3.5× weekly as home self-care; and £36,185 for hemodialysis provided 3.5× weekly as self-care in-center. DISCUSSION: We found that the SC+ hemodialysis system offers improved cost-effectiveness for both 3×-weekly and 3.5×-weekly self-care dialysis performed at home or as self-care in-center versus fully assisted dialysis provided 3× weekly with conventional machines in facilities.

Kidney Failure Risk Equation and Cost of Care in Patients with Chronic Kidney Disease.

BACKGROUND AND OBJECTIVES: Patients with CKD exhibit heterogeneity in their rates of progression to kidney failure. The kidney failure risk equation (KFRE) has been shown to accurately estimate progression to kidney failure in adults with CKD. Our objective was to determine health care utilization patterns of patients on the basis of their risk of progression. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We conducted a retrospective cohort study of adults with CKD and eGFR of 15-59 ml/min per 1.73 m2 enrolled in multidisciplinary CKD clinics in the province of Saskatchewan, Canada. Data were collected from January 1, 2004 to December 31, 2012 and followed for 5 years (December 31, 2017). We stratified patients by eGFR and risk of progression and compared the number and cost of hospital admissions, physician visits, and prescription drugs. RESULTS: In total, 1003 adults were included in the study. Within the eGFR of 15-29 ml/min per 1.73 m2 group, the costs of hospital admissions, physician visits, and drug dispensations over the 5-year study period comparing high-risk patients with low-risk patients were (Canadian dollars) $89,265 versus $48,374 (P=0.008), $23,423 versus $11,231 (P<0.001), and $21,853 versus $16,757 (P=0.01), respectively. Within the eGFR of 30-59 ml/min per 1.73 m2 group, the costs of hospital admissions, physician visits, and prescription drugs were $55,944 versus $36,740 (P=0.10), $13,414 versus $10,370 (P=0.08), and $20,394 versus $14,902 (P=0.02) in high-risk patients in comparison with low-risk patients, respectively, for progression to kidney failure. CONCLUSIONS: In patients with CKD and eGFR of 15-59 ml/min per 1.73 m2 followed in multidisciplinary clinics, the costs of hospital admissions, physician visits, and drugs were higher for patients at higher risk of progression to kidney failure by the KFRE compared with patients in the low-risk category. The high-risk group of patients with CKD and eGFR of 15-29 ml/min per 1.73 m2 had stronger association with hospitalizations costs, physician visits, and drug utilizations.

The Comparative Outcomes of Radical Prostatectomy versus Radiotherapy for Nonmetastatic Prostate Cancer: A Longitudinal, Population-Based Analysis.

PURPOSE: The comparative effectiveness of radical prostatectomy (RP) versus radiation therapy (RT) for prostate cancer remains a largely debated topic. Utilizing a provincial population-based linked data set from an equal-access, universal health care system, we sought to compare outcomes among patients treated with either radiation or prostatectomy for nonmetastatic prostate cancer. MATERIALS AND METHODS: We performed a retrospective cohort study by linking several administrative data sets to identify patients who were diagnosed with prostate cancer between 2004 and 2016 in Manitoba, Canada and who were subsequently treated with either RP or RT. Cox proportional hazard models with inverse probability of treatment weighting were used to compare rates of all-cause mortality, as well as prostate cancer specific mortality (PCSM) between patients who underwent RP vs RT. RESULTS: During the study period, 2,540 patients underwent RP and 1,895 underwent RT for prostate cancer. Unadjusted overall survival was higher for RP vs RT (5-year overall survival 95.52% for RP compared with 84.55% for RT, p <0.0001). In inverse probability of treatment weighting-adjusted Cox regression analysis, compared to patients in the RP groups, patients in the RT group had an increased rate of all-cause mortality (HR 1.93, 95% CI 1.65-2.26, p <0.0001), and PCSM (HR 3.98, 95% CI 2.89-5.49; p <0.0001). CONCLUSIONS: RT was associated with higher all-cause mortality and PCSM rates compared with RP. These findings highlight the importance of comparative effectiveness research to identify treatment disparities and warrant further investigation.

Costs of Assisted Home Dialysis: A Single-Payer Canadian Model From Manitoba.

RATIONALE & OBJECTIVE: The prevalence of kidney failure is increasing globally. Most of these patients will require life-sustaining dialysis at a substantial cost to the health care system. Assisted peritoneal dialysis (PD) and assisted home hemodialysis (HD) are potential alternatives to in-center HD and have demonstrated equivalent outcomes with respect to mortality and morbidity. We aim to describe the costs associated with assisted continuous cycling PD (CCPD) and assisted home HD. STUDY DESIGN: Cost minimization model. SETTING & POPULATION: Adult incident maintenance dialysis patients in Manitoba, Canada. INTERVENTION: Full- and partial-assist home HD and CCPD. Full-assist modalities were defined as nurse-assisted dialysis setup and takedown performed by a health care aide, whereas partial-assist modalities only included nurse-assisted setup. Additionally, full-assist home HD was evaluated under a complete care scenario with the inclusion of a health care aide remaining with the patient throughout the duration of treatment. OUTCOMES: Annual per-patient maintenance and training costs related to assisted and self-care home HD and CCPD, presented in 2019 Canadian dollars. MODEL PERSPECTIVE & TIME FRAME: This model took the perspective of the Canadian public health payer using a 1-year time frame. RESULTS: Annual total per-patient maintenance (and training) costs by modality were the following: full-assist CCPD, $75.717 (initial training costs, $301); partial-assist CCPD, $67,765 ($4,385); full-assist home HD, $47,862 ($301); partial-assist home HD, $44,650 ($14,813); and full-assist home HD (complete care), $64,659 ($301). LIMITATIONS: This model did not account for costs taken from the societal perspective or costs related to PD failure and modality switching. Additionally, this analysis reflects only costs experienced by a single center. CONCLUSIONS: Assisted home-based dialysis modalities are viable treatment options for patients from a cost perspective. Future studies to consider graduation rates to full self-care from assisted dialysis and the cost implications of respite care are needed.

Metabolic Acidosis and Cardiovascular Disease in CKD.

RATIONALE & OBJECTIVE: Metabolic acidosis related to chronic kidney disease (CKD) is associated with an accelerated decline in glomerular filtration rate (GFR) and the development of end-stage kidney disease. Whether metabolic acidosis is associated with cardiovascular (CV) events in patients with CKD is unclear. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: The Optum De-identified Electronic Health Records Dataset, 2007-2017, was used to generate a cohort of patients with non-dialysis-dependent CKD who had at least 3 estimated GFR < 60 mL/min/1.73 m2. Patients with metabolic acidosis (serum bicarbonate 12 to <22 mEq/L) or normal serum bicarbonate (22‒29 mEq/L) at baseline were identified by 2 consecutive measurements 28‒365 days apart. PREDICTOR: Serum bicarbonate as a continuous variable. OUTCOME: Primary outcome was a composite of major adverse cardiovascular events (MACE+). Secondary outcomes included individual components of the composite outcome. ANALYTICAL APPROACH: Cox proportional hazards models to evaluate the association between 1-mEq/L increments in serum bicarbonate and MACE+. RESULTS: A total of 51,558 patients were evaluated, 34% had metabolic acidosis. The median follow-up period was 3.9-4.5 years, depending on the outcome assessed. The adjusted hazard ratio (HR) for MACE+ was 0.964 (95% CI, 0.961-0.968). For the individual components of incident heart failure (HF), stroke, myocardial infarction (MI), and CV death, HRs were 0.98 (95% CI, 0.97-0.98), 0.98 (95% CI, 0.97-0.99), 0.96 (95% CI, 0.96-0.97), and 0.94 (95% CI, 0.93-0.94), respectively, for every 1-mEq/L increase in serum bicarbonate. LIMITATIONS: Possible residual confounding. CONCLUSIONS: Metabolic acidosis in CKD is associated with an increased risk of MACE+ as well as the individual components of incident HF, stroke, MI, and CV death. Randomized controlled trials evaluating treatments for the correction of metabolic acidosis in CKD to prevent CV events are needed.

Percutaneous Versus Surgical Insertion of Peritoneal Dialysis Catheters: A Systematic Review and Meta-Analysis.

BACKGROUND: Home-based peritoneal dialysis (PD) is an alternative to facility-based hemodialysis and has lower costs and greater freedom for patients with kidney failure. For a patient to undergo PD, a safe and reliable method of accessing the peritoneum is needed. However, different catheter insertion techniques may affect patient health outcomes. OBJECTIVE: To compare the risk of infectious and mechanical complications between surgical (open and laparoscopic) PD catheter insertion and percutaneous catheter insertion. DESIGN: Systematic review and meta-analysis. SETTING: We searched for observational studies and randomized controlled trials (RCTs) in CENTRAL, EMBASE, MEDLINE, PubMed, and SCOPUS from inception until June 2018. Data were extracted by 2 independent reviewers based on a preformed template. PATIENTS: Adult (aged 18+) patients with kidney failure who underwent a PD catheter insertion procedure. MEASUREMENTS: We analyzed leak, malfunction, and bleed as early complications (occurring within 1 month of catheter insertion). Infectious complications (exit-site infections, tunnel infections, and peritonitis) were presented as both early complications and with the longest duration of follow-up. METHODS: Random effects meta-analyses with the generic inverse variance method to estimate pooled rate ratios and 95% confidence intervals. We quantified heterogeneity by using the I2 statistic for inconsistency and assessed heterogeneity using the χ2 test. Sensitivity analysis was performed by removing studies at high risk of bias as measured with the Newcastle-Ottawa Scale and the Cochrane Risk of Bias tool. RESULTS: Twenty-four studies (22 observational, 2 RCTs) with 3108 patients and 3777 catheter insertions were selected. Data from 2 studies were unable to be extracted and were qualitatively assessed. In the remaining 22 studies, percutaneous insertion was associated with a lower risk of both exit-site infections (risk ratio [RR] = 0.36, 95% confidence interval [CI] = 0.24-0.53, I2 = 0%) and peritonitis (RR = 0.52, 95% CI = 0.36-0.77, I2 = 3%) within 1 month of the procedure. There was no difference in mechanical complication rates between the 2 techniques. LIMITATIONS: Lack of consistency in the time periods for the various outcomes reported, risk of bias concerns with respect to population comparability, and the inability to analyze individual component causes of primary nonfunction (catheter obstruction, catheter migration, and leak). CONCLUSIONS: Our meta-analysis suggests differences in early infectious complications in favor of percutaneous insertion and no significant differences in mechanical complications compared with surgical insertion. These findings have implications on the direction of PD programs in terms of maximizing operating room resources.

CONTEXTE: La dialyse péritonéale à domicile (DPD) est une alternative plus économique à l'hémodialyse en centre et offre une plus grande liberté aux patients atteints d'insuffisance rénale. Or, pour qu'un patient soit traité par DPD, il est essentiel de recourir à une méthode d'accès au péritoine qui soit fiable et sûre. Les techniques existantes pour l'insertion du cathéter sont toutefois susceptibles d'affecter les résultats de santé du patient. OBJECTIFS: Comparer le risque de complications mécaniques et infectieuses entre l'insertion chirurgicale (incision et laparoscopie) et percutanée d'un cathéter de DP. TYPE D'ÉTUDE: Revue systématique et méta-analyse. CADRE: Nous avons consulté les bases de données CENTRAL, EMBASE, MEDLINE, PubMed et SCOPUS à la recherche d'études observationnelles et d'essais contrôlés à répartition aléatoire (ECRA) de la création à juin 2018. Deux réviseurs indépendants ont procédé à l'extraction des données en suivant un modèle préformé. SUJETS: Des adultes atteints d'insuffisance rénale ayant subi une procédure d'insertion d'un cathéter de DP. MESURES: Nous avons analysé les fuites, le dysfonctionnement et les saignements comme des complications précoces (survenant dans le mois suivant l'insertion du cathéter). Les complications infectieuses (infections au point de sortie, infections des tunnels, péritonite) ont été présentées comme complications précoces et avec la plus longue durée de suivi. MÉTHODOLOGIE: Nous avons procédé à des méta-analyses selon la méthode générique de l'inverse de la variance avec effets aléatoires pour estimer les rapports des taux combinés et les intervalles de confiance à 95 %. L'hétérogénéité a été quantifiée en utilisant la statistique I2 pour l'incohérence et a été évaluée par le test du Chi-Deux. L'analyse de sensibilité a été réalisée en retirant les études présentant un risque élevé de biais, lesquelles ont été définies à l'aide de l'échelle Newcastle-Ottawa et de l'outil Cochrane sur le risque de biais. RÉSULTATS: En tout, 24 études (22 études observationnelles, 2 ECRA) ont été sélectionnées, ce qui représente 3 108 patients et 3 777 insertions de cathéters. Les données de deux études n'ont pu être extraites et ont été évaluées qualitativement. Dans les 22 autres études, l'insertion percutanée a été associée, dans le mois suivant la procédure, à un risque plus faible d'infections au site de sortie (RR = 0,36; IC à 95 %: 0,24-0,53; I2 = 0 %) et de péritonite (RR = 0,52; IC à 95 %: 0,36-0,77; I2 = 3 %). Aucune différence dans les taux de complications mécaniques n'a été observée entre les deux techniques. LIMITES: Les résultats sont limités par le manque de cohérence dans les périodes associées aux divers résultats signalés, le risque de biais quant à la comparabilité des populations et l'incapacité d'analyser les causes individuelles du non-fonctionnement primaire (obstruction du cathéter, migration du cathéter, fuite). CONCLUSION: Notre méta-analyse suggère des différences en faveur de l'insertion percutanée par rapport à l'insertion chirurgicale pour les complications infectieuses précoces, mais aucune différence significative en ce qui concerne les complications mécaniques. Ces résultats ont des implications sur l'orientation des programmes de DP relativement à l'optimisation des ressources du bloc opératoire.