Clinical Outcomes and Vaccine Effectiveness for SARS-CoV-2 Infection in People Attending Advanced CKD Clinics: A Retrospective Provincial Cohort Study.

BACKGROUND: People with advanced CKD are at high risk of mortality and morbidity from coronavirus disease 2019 (COVID-19). We measured rates of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and severe outcomes in a large population attending advanced CKD clinics during the first 21 months of the pandemic. We examined risk factors for infection and case fatality, and we assessed vaccine effectiveness in this population. METHODS: In this retrospective cohort study, we analyzed data on demographics, diagnosed SARS-CoV-2 infection rates, outcomes, and associated risk factors, including vaccine effectiveness, for people attending a province-wide network of advanced CKD clinics during the first four waves of the pandemic in Ontario, Canada. RESULTS: In a population of 20,235 patients with advanced CKD, 607 were diagnosed with SARS-CoV-2 infection over 21 months. The case fatality rate at 30 days was 19% overall but declined from 29% in the first wave to 14% in the fourth. Hospitalization and intensive care unit (ICU) admission rates were 41% and 12%, respectively, and 4% started long-term dialysis within 90 days. Significant risk factors for diagnosed infection on multivariable analysis included lower eGFR, higher Charlson Comorbidity Index, attending advanced CKD clinics for more than 2 years, non-White ethnicity, lower income, living in the Greater Toronto Area, and long-term care home residency. Being doubly vaccinated was associated with lower 30-day case fatality rate (odds ratio [OR], 0.11; 95% confidence interval [CI], 0.03 to 0.52). Older age (OR, 1.06 per year; 95% CI, 1.04 to 1.08) and higher Charlson Comorbidity Index (OR, 1.11 per unit; 95% CI, 1.01 to 1.23) were associated with higher 30-day case fatality rate. CONCLUSIONS: People attending advanced CKD clinics and diagnosed with SARS-CoV-2 infection in the first 21 months of the pandemic had high case fatality and hospitalization rates. Fatality rates were significantly lower in those who were doubly vaccinated. PODCAST: This article contains a podcast at https://dts.podtrac.com/redirect.mp3/www.asn-online.org/media/podcast/CJASN/2023_04_10_CJN10560922.mp3.

Impact of quality improvement initiatives to improve CKD referral patterns: a systematic review protocol.

INTRODUCTION: Chronic kidney disease (CKD) is a global-health problem. A significant proportion of referrals to nephrologists for CKD management are early and guideline-discordant, which may lead to an excess number of referrals and increased wait-times. Various initiatives have been tested to increase the proportion of guideline-concordant referrals and decrease wait times. This paper describes the protocol for a systematic review to study the impacts of quality improvement initiatives aimed at decreasing the number of non-guideline concordant referrals, increasing the number of guideline-concordant referrals and decreasing wait times for patients to access a nephrologist. METHODS AND ANALYSIS: We developed this protocol by using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Protocols (2015). We will search the following empirical electronic databases: MEDLINE, Embase, Cochrane Library, CINAHL, Web of Science, PsycINFO and grey literature for studies designed to improve guideline-concordant referrals or to reduce unnecessary referrals of patients with CKD from primary care to nephrology. Our search will include all studies published from database inception to April 2021 with no language restrictions. The studies will be limited to referrals for adult patients to nephrologists. Referrals of patients with CKD from non-nephrology specialists (eg, general internal medicine) will be excluded. ETHICS AND DISSEMINATION: Ethics approval will not be required, as we will analyse data from studies that have already been published and are publicly accessible. We will share our findings using traditional approaches, including scientific presentations, open access peer-reviewed platforms, and appropriate government and public health agencies. PROSPERO REGISTRATION NUMBER: CRD42021247756.

Impact of the KidneyWise toolkit on chronic kidney disease referral practices in Ontario primary care: a prospective evaluation.

OBJECTIVES: Chronic kidney disease (CKD) is common; therefore, coordination of care between primary care and nephrology is important. Ontario Renal Network's KidneyWise toolkit was developed to provide guidance on the detection and management of people with CKD in primary care (www.kidneywise.ca). The aim of this study was to evaluate the impact of the April 2015 KidneyWise toolkit release on the characteristics of primary care referrals to nephrology. DESIGN AND SETTING: The study was a prospective pre-post design conducted at two nephrology sites (community site: Trillium Health Partners in Mississauga, Ontario, Canada, and academic site: St Joseph's Healthcare in Hamilton, Ontario, Canada). Referrals were compared during the 3-month time period immediately prior to, and during a 3-month period 1 year after, the toolkit release. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was the change in proportion of referrals for CKD that met the KidneyWise criteria. Additional secondary referral and quality of care outcomes were also evaluated. Multivariable logistic regression was used to evaluate preselected variables for their independent association with referrals that met the KidneyWise criteria. RESULTS: The proportion of referrals for CKD among people who met the KidneyWise referral criteria did not significantly change from pre-KidneyWise to post-KidneyWise implementation (44.7% vs 45.8%, respectively, adjusted OR 1.16, 95% CI 0.85 to 1.59, p=0.36). The proportion of referrals for CKD that provided a urine albumin-creatinine ratio significantly increased post-KidneyWise (25.8% vs 43.8%, adjusted OR 1.45, 95% CI 1.06 to 1.97, p=0.02). The significant independent predictors of meeting the KidneyWise referral criteria were academic site, increased age and use of the KidneyWise referral form. CONCLUSIONS: We did not observe any change in the proportion of appropriate referrals for CKD at two large nephrology centres 1 year after implementation of the KidneyWise toolkit.

Matrix metalloproteinase 9 is associated with peritoneal membrane solute transport and induces angiogenesis through ß-catenin signaling.

Background: For patients using peritoneal dialysis (PD), the peritoneal membrane can develop fibrosis and angiogenesis, leading to ultrafiltration failure, chronic hypervolemia and increased risk of technique failure and mortality. Matrix metalloproteinases (MMPs), and specifically the gelatinases (MMP2 and MMP9), may be involved in peritoneal membrane injury. Methods: From stable PD patients, mesothelial cells were assayed for MMP gene expression. MMP9 was overexpressed in mouse peritoneum by adenovirus, and MMP9 -/- mice were subjected to transforming growth factor ß (TGF-ß)-induced peritoneal fibrosis. Results: MMP9 mRNA expression correlated with peritoneal membrane solute transport properties. Overexpression of MMP9 in the mouse peritoneum induced submesothelial thickening and angiogenesis. MMP9 induced mesothelial cell transition to a myofibroblast phenotype measured by increased alpha smooth muscle actin and decreased E-cadherin expression. Angiogenesis was markedly reduced in MMP9 -/- mice treated with an adenovirus expressing active TGF-ß compared with wild-type mice. TGF-ß-mediated E-cadherin cleavage was MMP9 dependent, and E-cadherin cleavage led to ß-catenin-mediated signaling. A ß-catenin inhibitor blocked the angiogenic response induced by AdMMP9. Conclusions: Our data suggest that MMP9 is involved in peritoneal membrane injury possibly through cleavage of E-cadherin and induction of ß-catenin signaling. MMP9 is a potential biomarker for peritoneal membrane injury and is a therapeutic target to protect the peritoneal membrane in PD patients.

The impact of patient preference on dialysis modality and hemodialysis vascular access.

BACKGROUND: Home-based dialysis, including peritoneal dialysis (PD) and home hemodialysis (HHD), is associated with improved health related quality of life and reduced health resource costs. It is uncertain to what extent initial preferences for dialysis modality influence the first dialysis therapy actually utilized. We examined the relationship between initial dialysis modality choice and first dialysis therapy used. METHODS: Patients with chronic kidney disease (CKD) from a single centre who started dialysis after receiving modality education were included in this study. Multivariable logistic regression models were constructed to assess the independent association of patient characteristics and initial dialysis modality choice with actual dialysis therapy used and starting hemodialysis (HD) with a central venous catheter (CVC). RESULTS: Of 299 eligible patients, 175 (58.5%) initially chose a home-based therapy and 102 (58.3%) of these patients' first actual dialysis was a home-based therapy. Of the 89 patients that initially chose facility-based HD, 84 (94.4%) first actual dialysis was facility-based HD. The adjusted odds ratio (OR) for first actual dialysis as a home-based therapy was 29.0 for patients intending to perform PD (95% confidence interval [CI] 10.7-78.8; p < 0.001) and 12.4 for patients intending to perform HHD (95% CI 3.29-46.6; p < 0.001). Amongst patients whose first actual dialysis was HD, an initial choice of PD or not choosing a modality was associated with an increased risk of starting dialysis with a CVC (adjusted OR 3.73, 95% CI 1.51-9.21; p = 0.004 and 4.58, 95% CI 1.53-13.7; p = 0.007, respectively). CONCLUSIONS: Although initially choosing a home-based therapy substantially increases the probability of the first actual dialysis being home-based, many patients who initially prefer a home-based therapy start with facility-based HD. Programs that continually re-evaluate patient preferences and reinforce the values of home based therapies that led to the initial preference may improve home-based therapy uptake and improve preparedness for starting HD.

Management of hypophosphatemia in nocturnal hemodialysis with phosphate-containing enema: a technical study.

Hypophosphatemia is observed in patients undergoing nocturnal hemodialysis. Phosphate is commonly added to the dialysate acid bath, but systematic evaluation of the safety and reliability of this strategy is lacking. The objectives of this study were 4-fold. First, we determined whether predictable final dialysate phosphate concentrations could be achieved by adding varying amounts of Fleet® enema. Second, we assessed the stability of calcium (Ca) and phosphate dialysate levels under simulated nocturnal hemodialysis conditions. Third, we assessed for Ca-phosphate precipitate. Finally, we evaluated whether dialysate containing Fleet® enema met the current sterility standards. We added serial aliquots of enema to 4.5 L of dialysate acid concentrate and proportioned the solution on Gambro and Althin/Baxter dialysis machines for up to 8 hours. We measured dialysate phosphate, Ca, pH, and bicarbonate concentrations at baseline, and after simulated dialysis at 4 and 8 hours. We evaluated for precipitation visually and by assessing optical density at 620 nm. We used inoculation of agar to detect bacteria and Pyrotell reaction for endotoxin. For every 30 mL of Fleet® (1.38 mmol/mL of phosphate) enema added, the dialysate phosphate concentration increased by 0.2 mmol/L. There were no significant changes in dialysate phosphate, Ca, pH, and bicarbonate concentrations over 8 hours. No precipitate was observed in the dialysate by optical density measures at 620 nm for additions of up to 90 mL of enema. Bacterial and endotoxin testing met sterility standards. The addition of Fleet® enema to dialysate increases phosphate concentration in a predictable manner, and no safety problems were observed in our in vitro studies.

Comparison of volume of blood processed on haemodialysis adequacy measurement sessions vs regular non-adequacy sessions.

BACKGROUND: Knowledge that adequacy measures such as the urea reduction ratio (URR) or Kt/V(urea) are being measured on haemodialysis may influence the behaviour of patients or staff such that the treatment may be better on those days. This study therefore tested the hypothesis that mean volume of blood processed (VBP), utilized as a surrogate for adequacy, is higher on adequacy measurement days than non-measurement days. METHODS: Patients were identified who had been on haemodialysis over the preceding 8 months. Primary outcome was the difference in the mean VBP (in litres) on URR measurement compared with non-URR measurement days (DeltaVBP(U)(-N)). Univariate and multivariate correlates of mean VBP and DeltaVBP(U)(-N) were also determined. RESULTS: Eighty-nine patients were identified who met inclusion and exclusion criteria. Linear regression demonstrated a weak relationship between VBP and URR (r=0.24, P<0.02). This relationship was much stronger when VBP was adjusted for patient weight (mean VBP/weight; r=0.78, P<0.0001). The overall mean VBP was 87.4 l (+/-1.2 l) and the average DeltaVBP(U)(-N) was 1.1 l (+/-0.3 l) (P=0.001). Twenty per cent of patients had a clinically relevant DeltaVBP(U)(-N) of >3.6 l. Patients with a graft or fistula had a significantly higher DeltaVBP(U)(-N) than patients with a tunnelled catheter. CONCLUSIONS: This study demonstrates that the average VBP is less on non-URR than on URR measurement days; this difference was clinically important in >20% of patients. Univariate analysis indicated that the use of a fistula or graft correlated with a higher DeltaVBP(U)(-N). This implies that our current method of assessing dialysis adequacy does systematically overestimate the average delivered dose of dialysis in a subset of patients.