Trajectories of Nutritional Parameters Before and After Prescribed Oral Nutritional Supplements: A Longitudinal Cohort Study of Patients With Chronic Kidney Disease Not Requiring Dialysis

Background: The association between oral nutritional supplement use and nutritional parameters among patients with nondialysis chronic kidney disease (CKD-ND) with or at high risk of undernutrition/protein-energy wasting has not been previously studied. The definition of patient subgroups most likely to benefit from oral nutritional supplementation (ONS) is also an area where more research is needed. Objective: To assess nutritional parameter trajectories among patients with CKD-ND prescribed oral nutritional supplements in British Columbia, and to compare trajectories by nutritional phenotype. Design: Longitudinal cohort study, pre-post design. Setting: Multidisciplinary CKD clinics across British Columbia. Patients: A total of 3957 adult patients with CKD-ND, who entered multidisciplinary CKD clinics during 2010 to 2019, met criteria for oral nutritional supplement prescription based on dietitian assessment, and received ≥1 oral nutritional supplement prescription. Measurements: Longitudinal nutritional parameters, including body mass index (BMI), serum albumin, serum bicarbonate, serum phosphate, and neutrophil-to-lymphocyte ratio (NLR). Methods: Using linear mixed models, slopes for nutritional and inflammation parameters were assessed in the 2-year periods before and after the first oral nutritional supplement prescription. Hierarchical cluster analysis was applied to identify nutritional phenotypes using baseline data, and slope analysis was repeated by cluster. Results: In the pre-oral-nutritional-supplement period, declines in BMI (−0.87 kg/m2/year, 95% confidence interval [CI]: −0.99 to −0.75), albumin (−1.11 g/L/year, 95% CI: −1.27 to −0.95), and bicarbonate (−0.49 mmol/L/year; 95% CI: −0.59 to −0.39), and increases in NLR (+0.79/year; 95% CI: 0.60 to 0.98) and phosphate (+0.05 mmol/L/year; 95% CI: 0.04 to 0.06) were observed. Following oral nutritional supplement prescription, there were statistically significant increases in BMI slope (+0.91 kg/m2/year, P < .0001), albumin slope (+0.82 g/L/year, P < .0001), and phosphate slope (+0.02 mmol/L/year, P = .005), as well as a decline in NLR slope of −0.55/year ( P < .0001). There was no significant change in bicarbonate slope. Cluster analysis identified 5 distinct phenotypes. The cluster with the highest mean baseline NLR and lowest mean BMI demonstrated the greatest number of improvements in nutritional parameter slopes in the post-oral-nutritional-supplement period. Limitations: Possibility of residual confounding. Data on dietary intake, muscle mass, and nutritional scoring systems were not available in the registry. Conclusions: Among patients with CKD-ND prescribed oral nutritional supplements, there were improvements in nutrition/inflammation parameters over time following the first ONS prescription. The heterogeneity in response to ONS by cluster subgroup suggests an individualized approach to nutritional management may be beneficial.

Effect of a Perioperative Hypotension-Avoidance Strategy Versus a Hypertension-Avoidance Strategy on the Risk of Acute Kidney Injury: A Clinical Research Protocol for a Substudy of the POISE-3 Randomized Clinical Trial

Background: Most patients who take antihypertensive medications continue taking them on the morning of surgery and during the perioperative period. However, growing evidence suggests this practice may contribute to perioperative hypotension and a higher risk of complications. This protocol describes an acute kidney injury substudy of the Perioperative Ischemic Evaluation-3 (POISE-3) trial, which is testing the effect of a perioperative hypotension-avoidance strategy versus a hypertension-avoidance strategy in patients undergoing noncardiac surgery. Objective: To conduct a substudy of POISE-3 to determine whether a perioperative hypotension-avoidance strategy reduces the risk of acute kidney injury compared with a hypertension-avoidance strategy. Design: Randomized clinical trial with 1:1 randomization to the intervention (a perioperative hypotension-avoidance strategy) or control (a hypertension-avoidance strategy). Intervention: If the presurgery systolic blood pressure (SBP) is <130 mmHg, all antihypertensive medications are withheld on the morning of surgery. If the SBP is ≥130 mmHg, some medications (but not angiotensin receptor blockers [ACEIs], angiotensin receptor blockers [ARBs], or renin inhibitors) may be continued in a stepwise manner. During surgery, the patients’ mean arterial pressure (MAP) is maintained at ≥80 mmHg. During the first 48 hours after surgery, some antihypertensive medications (but not ACEIs, ARBs, or renin inhibitors) may be restarted in a stepwise manner if the SBP is ≥130 mmHg. Control: Patients receive their usual antihypertensive medications before and after surgery. The patients’ MAP is maintained at ≥60 mmHg from anesthetic induction until the end of surgery. Setting: Recruitment from 108 centers in 22 countries from 2018 to 2021. Patients: Patients (~6800) aged ≥45 years having noncardiac surgery who have or are at risk of atherosclerotic disease and who routinely take antihypertensive medications. Measurements: The primary outcome of the substudy is postoperative acute kidney injury, defined as an increase in serum creatinine concentration of either ≥26.5 μmol/L (≥0.3 mg/dL) within 48 hours of randomization or ≥50% within 7 days of randomization. Methods: The primary analysis (intention-to-treat) will examine the relative risk and 95% confidence interval of acute kidney injury in the intervention versus control group. We will repeat the primary analysis using alternative definitions of acute kidney injury and examine effect modification by preexisting chronic kidney disease, defined as a prerandomization estimated glomerular filtration rate <60 mL/min/1.73 m2. Results: Substudy results will be analyzed in 2022. Limitations: It is not possible to mask patients or providers to the intervention; however, objective measures will be used to assess acute kidney injury. Conclusions: This substudy will provide generalizable estimates of the effect of a perioperative hypotension-avoidance strategy on the risk of acute kidney injury.

Synthetic ACTH for Treatment of Glomerular Diseases: A Case Series

Rationale: Synthetic adrenocorticotropic hormone (Tetracosactide) has been used in the treatment of refractory glomerular diseases. Literature surrounding the use of this medication is limited to small case series and there is conflicting data on the rate of adverse events associated with this medication. Presenting concerns of the patient: Glomerulonephritis not in remission after at least 6 months of treatment with conservative care. Stable doses of concurrent immunosuppression were permitted. Diagnoses: Membranous nephropathy, IgA nephropathy, minimal change disease, and focal and segmental glomerulosclerosis. Intervention: Intramuscular synthetic adrenocorticotropic hormone (Tetracosactide, Synacthen Depot) with doses of either 1 mg weekly or 1 mg twice weekly. Outcomes: Five of 12 patients had at least a partial remission with Tetracosactide. Median time to response was 6 months for responders. Five of the 12 patients had adverse events documented, 2 of which led to treatment discontinuation. No patients with focal and segmental glomerulosclerosis responded to treatment. Lessons Learned: Higher rate of adverse events than previously reported with synthetic adrenocorticotropic hormone and uncertain treatment efficacy.

A Quantitative and Qualitative Study on Patient and Physician Perceptions of Nephrology Telephone Consultation During COVID-19

Background: COVID-19 required rapid adoption of virtual modalities to provide care for patients with a chronic disease. Care was initially provided by telephone, which has not been evaluated for its effectiveness by patients and providers. This study reports patients’ and nephrologists’ perceptions and preferences surrounding telephone consultation in a chronic kidney disease (CKD) clinic. Objective: To evaluate patient and physician perspectives on the key advantages and disadvantages of telephone consultations in a nephrology out-patient clinic setting. Design: Cross-sectional observational survey study. Setting: General nephrology clinic and a multidisciplinary kidney care clinic in London, Ontario, Canada. Participants: Patients with CKD who were fluent in English and participated in at least one telephone consultation with a nephrologist during the COVID-19 pandemic. Methods and measurements: Nephrologists’ and participants’ input facilitated the development of both patient and nephrologist surveys. Participants provided self-reported measures in 5 domains of satisfaction: user experience, technical quality, perceived effectiveness on well-being, perceived usefulness, and effect on interaction. Nephrologists provided self-reported measures within 6 categories: general experience, time management, medication changes, quality of care, job satisfaction, and challenges/strengths. Descriptive statistics were used to present data. Content analysis was performed on 2 open-ended responses. Results: Of the 372 participants recruited, 235 participated in the survey (63% response). In all, 79% of the participants were ≥65 years old and 91% were white. Telephone consultation was a comfortable experience for 68%, and 73% felt it to be a safer alternative during the pandemic. Although 65% perceived no changes to health care access, most reported spending less time and fewer resources on transit and parking. Disadvantages to telephone consultation included a lack of physical examination and reduced patient-physician rapport. Eleven of 14 nephrologists were surveyed, with most reporting confidence in the use of telephone consultation. Physician barriers to telephone consultation included challenges with communications and lack of technology to support telephone clinics. Limitations: Our survey included a majority of older, white participants, which may not be generalizable to other participants particularly those of other ages and ethnicity. Conclusion: Although both patients and nephrologists adapted to telephone consultations, there remain opportunities to further explore populations and situations that would be better facilitated with an in-person visit. Future research in virtual care will require measurement of health care outcomes and economics. Trial registration: Not applicable as this was a survey.

Program Report: Nîsohkamâtowak—Helping Patients and Families Living With Kidney Disease in Northern Saskatchewan

Purpose of the Program: Nîsohkamâtowak, the Cree word for Helping Each Other, is an initiative to close gaps in kidney health care for First Nations and Métis patients, their families, and communities in northern Saskatchewan. Nîsohkamâtowak emerged from a collaboration between the Kidney Health Community Program and First Nations and Métis Health Services to find ways to deliver better care and education to First Nations and Métis people living with kidney disease while acknowledging Truth and Reconciliation and the Calls to Action. Sources of Information: This article describes how traditional Indigenous protocols and storytelling were woven into the Nîsohkamâtowak events, gathering of patient and family voices in writing and video format, and how this work led to a collaborative co-designed process that incorporates the Truth and Reconciliation: Calls to Action into kidney care and the benefits we have seen so far. The teachings of the 4 Rs—respect, reciprocity, responsibility, and relevance, were critical to ensuring that Nîsohkamâtowak reports and learning were shared with participants and the communities represented in this initiative. Methods: Group discussions and sharing circles were facilitated in several locations throughout northern and central Saskatchewan. Main topics of discussion were traditional medicines, residential schools impact, community and peer supports for kidney disease patients, and cultural safety education for health care providers. Key Findings: The general themes selected for improvement were education, support within the local community, traditional practices and cultural competency, and delivery of services. To address these gaps in kidney care, the following objectives were co-created with First Nations and Métis patients, families, and communities for Kidney Health to provide culturally appropriate education and resources, to ensure appropriate follow-up support to include strengthening connections to communities and other health authorities, to incorporate traditional practices into program design, and to ensure appropriate service delivery across the spectrum of care with a focus on screening and referral, which is strongly linked to coordination of care with local health centers. Implications: As a result of this work, the Kidney Health Community Program restructured the delivery of services and continues to work with Nîsohkamâtowak advisors on safety initiatives and chronic kidney disease awareness, prevention, and management in their respective communities. The Truth and Reconciliation and Calls to Action are honored to close the gaps in kidney care. Limitations: Nîsohkamâtowak is a local Kidney Health initiative that has the good fortune of having dedicated funding and staff to carry out this work. The findings may be unique to the First Nations and Métis communities and people who shared their stories. Truth and Reconciliation is an ongoing commitment that must be nurtured. Although not part of this publication, the effects of COVID-19 have made it difficult to further advance the Calls to Action, with more limited staff resources and the inability to meet in person as in the past.

T Scores, FRAX, Frailty Phenotype, Falls, and Its Relationship to Fractures in Patients on Maintenance Hemodialysis

Background: Despite the magnitude of fracture and the consequences in patients receiving hemodialysis, optimal risk assessment tools in this population are not well explored. Frailty and falls—known risk factors for fracture in chronic kidney disease (CKD) and non-CKD populations—are common in patients receiving hemodialysis (HD) therapy. While the relationship between T scores in relation to fractures in patients receiving HD is recognized, there is a paucity of data to the additional contributions of fracture assessment tool (FRAX), frailty status, and falls in its relationship with fracture. Objectives: To evaluate the clinical utility of adding FRAX, frailty status, and falls to T scores at the femoral neck to determine whether it enhances fracture discrimination in patients on maintenance HD. Design: A cross-sectional observational study. Setting: Two main dialysis units in Regina, Saskatchewan, Canada. Patients: A total of 109 patients on maintenance HD at two dialysis units from January 1, 2017, to December 31, 2018, were included in the study. Measurements: Fracture (the main outcome) was documented based on the review of medical charts, self-recall, and additionally vertebral fractures were identified by an x-ray. Areal bone mineral density (BMD) was measured by dual-energy x-ray absorptiometry (DXA). FRAX score was calculated using an online algorithm based on 11 clinical risk factors. We calculated the FRAX score for hip fracture and major osteoprotoic fracture with and without the inclusion of BMD. Frailty was assessed using the Fried criteria, which included assessments of unintentional weight loss, weakness (handgrip strength), slowness (walking speed), and questionnaires for physical activity and self-perceived exhaustion. Patients were enquired about the history and frequency of falls. Methods: A total of 131 patients underwent frailty assessments at the two dialysis units during the dialysis treatment. Following frailty assessments, they were referred for DXA scans and upon receipt of the results undertook FRAX questionnaires. They were additionally sent for lumbar x-rays and contacted for a history of falls. Association between the BMD-T score, FRAX, frailty status, falls, with fracture were examined with sequential multivariable logistic regression models. Differences were considered statistically significant at P values <.05. Results: A total of 109 patients were included in the data analysis. The composite of fracture occurred in 37.6% of patients. About 59.3% were identified as frail, and 29% of the participants had at least one fall in the last year. On multivariate regression analysis, each lower standard deviation (SD) in femoral neck T score was associated with 48% higher odds of fracture (odds ratio [OR] = 1.48; 95% confidence interval [CI] 1.20-1.68, P = .005). With the inclusion for FRAX scores (hip), the OR for fracture remained significant at 1.38 (OR = 1.38, 95% CI 1.04-1.63, P = .043). The addition of frailty status and history of falls did not further improve the model. Low T score and FRAX were both independent risk factors in patients on HD therapy. Limitations: This is a single-center study with a small sample size which limits the generalizability of the findings. Due to the cross-sectional study, associations identified may be difficult to interpret. Conclusions: Both BMD measurements by DXA and FRAX are useful tools to assess fracture in patients receiving HD. The addition of frailty status and history of falls is not associated with fractures in this population. Larger prospective studies are needed to determine whether the inclusion of frailty and falls to the conventional models will improve fracture assessment in the population receiving HD. Trial Registration: The study was not registered on a publicly accessible registry as it did not involve health care intervention on human participants.

A Canadian Study of Cisplatin Metabolomics and Nephrotoxicity (ACCENT): A Clinical Research Protocol

Background: Cisplatin, a chemotherapy used to treat solid tumors, causes acute kidney injury (AKI), a known risk factor for chronic kidney disease and mortality. AKI diagnosis relies on biomarkers which are only measurable after kidney damage has occurred and functional impairment is apparent; this prevents timely AKI diagnosis and treatment. Metabolomics seeks to identify metabolite patterns involved in cell tissue metabolism related to disease or patient factors. The A Canadian study of Cisplatin mEtabolomics and NephroToxicity (ACCENT) team was established to harness the power of metabolomics to identify novel biomarkers that predict risk and discriminate for presence of cisplatin nephrotoxicity, so that early intervention strategies to mitigate onset and severity of AKI can be implemented. Objective: Describe the design and methods of the ACCENT study which aims to identify and validate metabolomic profiles in urine and serum associated with risk for cisplatin-mediated nephrotoxicity in children and adults. Design: Observational prospective cohort study. Setting: Six Canadian oncology centers (3 pediatric, 1 adult and 2 both). Patients: Three hundred adults and 300 children planned to receive cisplatin therapy. Measurements: During two cisplatin infusion cycles, serum and urine will be measured for creatinine and electrolytes to ascertain AKI. Many patient and disease variables will be collected prospectively at baseline and throughout therapy. Metabolomic analyses of serum and urine will be done using mass spectrometry. An untargeted metabolomics approach will be used to analyze serum and urine samples before and after cisplatin infusions to identify candidate biomarkers of cisplatin AKI. Candidate metabolites will be validated using an independent cohort. Methods: Patients will be recruited before their first cycle of cisplatin. Blood and urine will be collected at specified time points before and after cisplatin during the first infusion and an infusion later during cancer treatment. The primary outcome is AKI, defined using a traditional serum creatinine-based definition and an electrolyte abnormality-based definition. Chart review 3 months after cisplatin therapy end will be conducted to document kidney health and survival. Limitations: It may not be possible to adjust for all measured and unmeasured confounders when evaluating prediction of AKI using metabolite profiles. Collection of data across multiple sites will be a challenge. Conclusions: ACCENT is the largest study of children and adults treated with cisplatin and aims to reimagine the current model for AKI diagnoses using metabolomics. The identification of biomarkers predicting and detecting AKI in children and adults treated with cisplatin can greatly inform future clinical investigations and practices.

Quality of Life and Hemodynamic Effects of Switching From Hemodialysis to Hemodiafiltration: A Canadian Controlled Cohort Study

Background: Recent randomized clinical trials have demonstrated beneficial effects of hemodiafiltration (HDF) compared with hemodialysis (HD) on mortality and hemodynamic stability. Data on quality of life in HDF compared with HD is limited. Objective: This study aimed to determine whether patients receiving HD experience improvements in quality of life, hemodynamic and laboratory parameters after switching to HDF. Design: Observational controlled cohort study. Setting & Patients: Adult patients receiving maintenance dialysis were followed for 3 months both before and after transfer to a new unit, where they received HDF. Prior to transfer, control patients were already treated by HDF. Methods: Quality of life at baseline and follow-up was measured using the validated minutes to recovery (MR) question. Dialysis data were collected for 3 consecutive sessions monthly; laboratory values were collected monthly. Wilcoxon signed rank test and repeated measures analysis of covariance were used to evaluate pre/post transfer changes and quantile regression to identify predictors of change in recovery time. Results: Of 227 patients, 82 died, were transplanted, were hospitalized or did not transfer, leaving 123 subjects and 22 controls for analysis. MR did not improve with switching to HDF, although patients with MR > 60 min before transfer experienced a significant decrease in their MR, compared with controls. There was no improvement in intradialytic hypotension with HDF. There were no differences in laboratory values before vs after switch. Limitations: Nonrandomized single-center study, including only small numbers of patients and covering a short follow-up period; hemodynamic values only evaluated over 1 week per month; residual kidney function not recorded. Conclusions: In this Canadian experience of HDF, patients remained stable with respect to several laboratory and dialysis related parameters. Switch to HDF was associated with substantially reduced recovery time in patients with MR > 60 minutes at baseline.

Incidence and Outcomes of Acute Kidney Injury in Patients Admitted to Hospital With COVID-19: A Retrospective Cohort Study

Background: The incidence of acute kidney injury (AKI) in patients with COVID-19 and its association with mortality and disease severity is understudied in the Canadian population. Objective: To determine the incidence of AKI in a cohort of patients with COVID-19 admitted to medicine and intensive care unit (ICU) wards, its association with in-hospital mortality, and disease severity. Our aim was to stratify these outcomes by out-of-hospital AKI and in-hospital AKI. Design: Retrospective cohort study from a registry of patients with COVID-19. Setting: Three community and 3 academic hospitals. Patients: A total of 815 patients admitted to hospital with COVID-19 between March 4, 2020, and April 23, 2021. Measurements: Stage of AKI, ICU admission, mechanical ventilation, and in-hospital mortality. Methods: We classified AKI by comparing highest to lowest recorded serum creatinine in hospital and staged AKI based on the Kidney Disease: Improving Global Outcomes (KDIGO) system. We calculated the unadjusted and adjusted odds ratio for the stage of AKI and the outcomes of ICU admission, mechanical ventilation, and in-hospital mortality. Results: Of the 815 patients registered, 439 (53.9%) developed AKI, 253 (57.6%) presented with AKI, and 186 (42.4%) developed AKI in-hospital. The odds of ICU admission, mechanical ventilation, and death increased as the AKI stage worsened. Stage 3 AKI that occurred during hospitalization increased the odds of death (odds ratio [OR] = 7.87 [4.35, 14.23]). Stage 3 AKI that occurred prior to hospitalization carried an increased odds of death (OR = 5.28 [2.60, 10.73]). Limitations: Observational study with small sample size limits precision of estimates. Lack of nonhospitalized patients with COVID-19 and hospitalized patients without COVID-19 as controls limits causal inferences. Conclusions: Acute kidney injury, whether it occurs prior to or after hospitalization, is associated with a high risk of poor outcomes in patients with COVID-19. Routine assessment of kidney function in patients with COVID-19 may improve risk stratification. Trial registration: The study was not registered on a publicly accessible registry because it did not involve any health care intervention on human participants.