Canadian Journal of Kidney Health and Disease最新文献

Background: Older kidney transplant recipients have inferior outcomes compared to younger recipients, and this risk may be compounded by donor characteristics.

Objective: We applied an unsupervised machine learning clustering approach to group older recipients into similar phenotypes. We evaluated the association between each cluster and graft failure, and the impact of donor quality on outcomes.

Design: This is a nationally representative retrospective cohort study.

Setting and patients: Kidney transplant recipients aged ≥65 years identified from the Scientific Registry of Transplant Recipients (2000-2017).

Measurements and methods: We used unsupervised clustering to generate phenotypes using 16 recipient factors. Donor quality was evaluated using 2 approaches, including the Kidney Donor Risk Index (KDRI). All-cause graft failure was analyzed using multivariable Cox regression.

Results: Overall, 16 364 patients (mean age 69 years; 38% female) were separated into 3 clusters. Cluster 1 recipients were exclusively female; cluster 2 recipients were exclusively males without diabetes; and cluster 3 recipients were males with a higher burden of comorbidities. Compared to cluster 2, the risk of graft failure was higher for cluster 3 recipients (adjusted hazard ratio [aHR] = 1.25, 95% confidence interval [CI] = 1.19-1.32). Cluster 3 recipients of a lower quality (KDRI ≥1.45) kidney had the highest risk of graft failure (aHR = 1.74, 95% CI = 1.61-1.87) relative to cluster 2 recipients of a higher quality kidney.

Limitations: This study did not include an external validation cohort. The findings should be interpreted as exploratory and should not be used to inform individual risk prediction nor be applied to recipients <65 years of age.

Conclusions: In a national cohort of older kidney transplant recipients, unsupervised clustering generated 3 clinically distinct recipient phenotypes. These phenotypes may aid in complementing allocation decisions, providing prognostic information, and optimizing post-transplant care for older recipients.

Purpose of review: British Columbia (BC) has a robust provincial kidney care program emphasizing patient-centered and goal-oriented dialysis care. Despite maintaining a home dialysis prevalence of approximately 30%, consistently above the national average, a review was conducted to examine intake and attrition rates and optimize these outcomes within a learning health system context.

Sources of information: This review draws on published articles, program reports, and insights from the provincial kidney care program framework. Key components include funding models, multidisciplinary committees, administrative support, and comprehensive training resources for staff and patients.

Methods: A structured analysis was conducted to evaluate factors influencing home dialysis rates. The approach focused on health care system dynamics, professional practices, and patient characteristics, emphasizing identifying barriers and opportunities for program optimization.

Key findings: Challenges identified include ongoing biases among health care professionals and logistical barriers in remote areas. Future initiatives aim to standardize patient screening, promote home dialysis champions, adopt environmentally friendly practices, and expand peer support networks.

Limitations: The review is constrained by potential regional variability within BC and limited generalizability to other provinces or countries. In addition, patient preferences and broader societal influences require further exploration.

Implications: A systematic approach to assessing and optimizing home dialysis programs is essential. The findings highlight the need to address health care system barriers, improve professional education, and promote patient engagement to increase home dialysis uptake and sustainability.

Background: Quantifying the number and proportion of people with kidney failure (KF) who receive conservative kidney management is vital for health care system benchmarking and planning. It is not easy to ascertain this value precisely at the population level, but we can approximate it using information from different data sources to estimate the proportion of patients with advanced kidney disease who die without receiving dialysis or a transplant and should receive conservative kidney management.

Objective: To approximate the proportion of people with KF in Ontario, Canada, who die without receiving kidney replacement therapy.

Design: A review of unpublished provincial renal agency reports of 3 retrospective population-based cohorts combined with clinical interpretation.

Patients: The 3 cohorts of people were: 1. those who died between January 1, 2013 and December 31, 2017, with an estimated glomerular filtration rate (eGFR) <10 mL/min/1.73 m² and no evidence of receiving kidney replacement therapy; 2. those who initiated outpatient maintenance dialysis or received a preemptive transplant in the same period; and 3. those with a sustained low eGFR ≤ 10 mL/min/1.73 m² between April 1, 2015 and March 31, 2018, and were followed for 1 year to determine if they started dialysis. In this last cohort, patients whose kidney function improved (evidence of an eGFR > 10 mL/min/1.73 m²) or who received a transplant during follow-up were excluded from the analysis.

Measurements and methods: The 3 cohorts were derived at ICES and used linked health care databases for the province of Ontario, Canada. In 2016, Ontario had a population of about 14 million people. Two nephrologists reviewed the data to provide the clinical approximation.

Results: There were 1891 individuals with KF who died without kidney replacement (the no KRT cohort). The median (25th, 75th percentile) eGFR prior to death was 7 (5, 8) mL/min/1.73 m². During the same period, 13 511 individuals started dialysis or received a preemptive kidney transplant (the KRT cohort). There were 7259 individuals in the low eGFR cohort; over the following year, 66% started dialysis, 20% died without dialysis, and 14% were alive without starting dialysis. The clinical approximation is that between 13 and 16% of people with KF die without receiving kidney replacement therapy.

Limitations: The data reports lacked certain information to inform the clinical approximation. There was no information on the conversations health professionals had with people about kidney replacement therapy, any decisions made about receiving conservative care, or the circumstances that preceded death without kidney replacement therapy.

Conclusions: After reviewing data from the 3 cohorts, we clinically approximate

Background: Better data are necessary to determine whether baseline level of kidney function affects the rate of progressive kidney disease following pregnancy.

Objective: The objective was to determine whether the baseline (pre-pregnancy) estimated glomerular filtration rate (eGFR) modifies the association between becoming pregnant and the subsequent rate of progressive kidney disease.

Design: Population-based cohort study using provincial administrative health care databases in Ontario and Alberta, Canada.

Setting: The sample will be accrued from April 1, 2007, to March 31, 2023, in Ontario and from April 1, 2012, to March 31, 2023, in Alberta. Follow-up for study outcomes will occur until March 31, 2024.

Participants: The pregnant group will include adult female residents of Ontario or Alberta with a record of a pregnancy of 20 to 46 weeks' gestation during the accrual period, and the non-pregnant group will include adult female residents with no prior record of pregnancy. The cohort entry dates in those in the pregnant group will be the estimated date of conception; the entry dates for those in the non-pregnant group will be randomly assigned following the distribution of dates in the pregnant group. To be eligible, individuals must be between 18 and 45 years old at cohort entry. They require at least 1 serum creatinine measurement within 2 years before entry and should not have received maintenance dialysis or a prior kidney transplant. Both groups will be categorized into one of 3 levels of baseline eGFR (≥60, 45-59, and <45 mL/min per 1.73 m²). Inverse probability of treatment weighting on a propensity score will be used to balance the pregnant and non-pregnant groups on baseline characteristics (including age, proteinuria, hypertension, and diabetes) within the 3 categories of baseline eGFR.

Measurements: The primary outcome, progressive kidney disease, will be defined as a composite of a persistent ≥40% drop in eGFR from the baseline value, a new persistent eGFR <15 mL/min per 1.73 m², receipt of maintenance dialysis, or receipt of a kidney transplant. The secondary outcomes will be the components of the primary composite outcome examined separately and the annualized change in eGFR in mL/min per 1.73 m² from baseline.

Methods: We will test for statistical interaction to determine whether the baseline category of eGFR modifies the rate of long-term progressive kidney disease after pregnancy. We hypothesize that a statistical interaction will be present. We will present weighted cause-specific hazard ratios (HRs) and cumulative incidence function (CIF) curves for up to 10 years of follow-up for the pregnant and non-pregnant groups stratified by each eGFR category. We will perform additional pre-specified analyses to confirm whether the findings are ro

Objective: Monoclonal gammopathy of renal significance (MGRS) is a heterogeneous and relatively recently defined disorder that encompasses many kidney and hematologic pathologies. MGRS remains a rare disease and there is a need for more literature regarding its treatment and outcomes. In this study, we share our center's experience with MGRS including incidence of different kidney pathologies, clone type, kidney and hematologic response, and progression-free survival.

Methods: Data from 35 patients diagnosed with MGRS excluding light-chain amyloidosis between 2013 and 2022 at a single Canadian tertiary care center were retrospectively analyzed. All cases required kidney biopsy. Initial treatment included regimens containing bortezomib, rituximab, or cyclosporine, or steroids only. Parameters studied included incidence of different kidney pathologies, clone type, depth of hematologic response, kidney survival (KS), overall survival (OS), and progression-free survival (PFS).

Results: Out of 35 patients, there were 10 cases of monoclonal immunoglobulin deposition disease, 8 of proliferative glomerulonephritis with immune deposits, 5 of microtubular immune deposits including immunotactoid and types 1 and 2 cryoglobulinemic nephropathy, 3 of C3 glomerulonephritis, and 9 of other diagnoses. There were 21 cases with a plasma cell clone identified in bone marrow, 2 each of B cell and low-grade lymphoma, 1 atypical T cell clone, and 9 cases without an expanded clone on bone marrow biopsy. A total of 6 patients required kidney replacement therapy and 4 patients died; the median PFS was 59.3 months. Very good partial hematologic response or better was significantly associated with decreased proteinuria but not preserved eGFR. There was a non-significant trend toward better PFS with hematologic response.

Conclusion: Our experience confirms that MGRS is a heterogeneous disease and adds to the literature concerning the diagnosis and treatment of MGRS. Successful treatment of the underlying hematologic disorder with targeted therapy is more likely to lead to an improvement in kidney function.

Purpose of the conference: Hemodialysis is a life-sustaining treatment for patients with end-stage kidney disease. However, patients on dialysis continue to face poor quality of life and short life expectancies. Despite this, the nephrology community conducts the fewest randomized controlled trials of any medical discipline, relying instead on expert opinion to guide many aspects of hemodialysis care. There is a need to conduct high-quality pragmatic randomized controlled trials in hemodialysis to drive evidence-based practice. To this end, the Innovative Clinical Trials in Hemodialysis Centers initiative, with the support of the Canadian Institutes of Health Research and its Strategy for Patient-Oriented Research, funded the development of 6 pragmatic trial protocols. Gardener's Grove 2023 created a space to support the development of these trials and increase awareness and knowledge of past, ongoing, and future innovative, pragmatic, randomized controlled registry trials embedded in routine hemodialysis care. This report summarizes the proceedings of this conference.

Sources of information: The conference included 6 panel presentations, each featuring an overview of a new pragmatic trial followed by expert panel feedback from patient partners, nephrologists, researchers, and health care providers. The conference also included 10 educational sessions led by clinicians and researchers with experience in the fields of kidney medicine and clinical trials.

Methods: Gardener's Grove 2023 was a 4-day virtual conference held in March of 2023. Recordings of all the conference presentations were later published on the Gardener's Grove website and are summarized in the Supplemental Appendix of this report.

Key findings: The conference brought together 118 Canadian and international researchers, patients, and health care providers to collaborate on 6 pragmatic trials intended to test interventions to improve hemodialysis care. The proposed trials included (1) PREventing FracturEs in REnal Disease (PREFERRED), (2) DIALysis with EXpanded solute removal (DIALEX), (3) Sodium fOr diaLysis oUTcome rEduction (SOLUTE), (4) Finding the right blood pressure target for patients on dialysis, (5) DIuretic Use in patients with Residual renal function on hemodialysis (DIURESED), and (6) Lower vs higher dialysate bicarbonate concentration in patients receiving hemodialysis (Dial-Bicarb). All of these interventions were widely supported and received valuable feedback from panelists and conference attendees. The education sessions focused on various design and execution elements of pragmatic, randomized controlled registry trials embedded in routine care.

Limitations: The conference could have been improved by streamlining session topics and pacing, allowing additional time for discussions, strengthening online network opportunities, and improving survey response

Rationale: Albuminuria is a commonly used parameter for predicting decline in kidney filtration function. Cubilin, encoded by CUBN, is a critical protein involved in protein reabsorption in the proximal tubule. Mutations in CUBN lead to Imerslund-Gräsbeck syndrome (IGS), a disorder characterized by vitamin B12 deficiency (and consequences related to that) with or without albuminuria. Recent evidence suggests that C-terminal variants in CUBN may lead to albuminuria without other features of IGS.

Presenting concerns of the patient: Here, we report a case of a 52-year-old male with chronic, albumin-predominant, subnephrotic range proteinuria since his teenage years, but preserved estimated glomerular filtration rate (eGFR).

Interventions: Neither angiotensin-converting enzyme (ACE) inhibition nor angiotensin Type II (AT-II) receptor blockade reduced his degree of albuminuria.

Diagnosis: Genetic testing identified 3 distinct pathogenic variants in CUBN that were confirmed by segregation analysis to be a compound heterozygous mode of inheritance. All variants were downstream of the intrinsic factor-vitamin B12 binding domain of cubilin. The patient had normal vitamin B12 levels and did not exhibit any features of IGS.

Outcomes: Kidney biopsy was not pursued for this patient as diagnostic clarification was achieved by non-invasive genetic testing alone.

Novel findings: This case highlights several important lessons. First, not all albuminuria is made equal, and forms of tubular albuminuria can exist without compromising kidney filtration function. Second, identifying genetic forms of tubular albuminuria is key to avoiding ineffective interventions (eg, ACE inhibition, AT-II receptor blockade, sodium-glucose cotransporter-2 [SGLT2] inhibition) and unnecessary invasive procedures (eg, kidney biopsy). Third, the location of CUBN variants dictates phenotypic consequences, with C-terminal variants leading to albuminuria without vitamin B12 deficiency.

Background: The COVID-19 pandemic and its accompanying safeguards intensified many of the ongoing daily challenges faced by caregivers of young people with chronic kidney disease (CKD) both pre-transplant and post-transplant, and also created a variety of new and pressing concerns. Little is known about how these families managed this unexpected adversity in their lives.

Objective: To evaluate change in psychosocial risk for families of young people with CKD during the COVID-19 pandemic health emergency from the perspective of caregivers.

Design: A short-term longitudinal mixed-methods study with a convergent parallel design.

Setting: Manitoba, Canada.

Participants: Thirty-six caregivers of young people with CKD participated in a quantitative assessment prior to the pandemic; approximately half were transplant recipients. Thirteen were re-assessed during the pandemic (62% were caregivers of transplant recipients) using both qualitative and quantitative assessments.

Methods: First, caregivers completed the Psychosocial Assessment Tool (PAT) prior to the pandemic. Second, caregivers were re-assessed using the PAT during the pandemic. They were also interviewed about their experiences. Changes in PAT scores over time were evaluated, including an investigation of whether psychosocial risk was related to transplant status. Interviews were coded using thematic analysis. In the interpretation stage, the qualitative findings were combined with the quantitative results to help explain the latter and reach a more fulsome understanding of caregivers' experience.

Results: Quantitatively, overall family psychosocial risk scores increased significantly during the pandemic health emergency, as did the domain of Caregiver Problems. Families of transplant recipients were found to be at significantly lower psychosocial risk pre-pandemic than families of transplant candidates. Coding identified Negative Pandemic Experiences, Positive Pandemic Experiences, and Coping Mechanisms. Mixed-methods analyses revealed several areas of convergence and divergence between the quantitative and qualitative findings.

Limitations: Limitations included a small sample size that limited generalizability, single site data collection, and single caregiver report.

Conclusions: Although overall family psychosocial risk increased during the pandemic, caregivers described several resilience processes and characteristics. A mixed-method approach provided a unique perspective that highlighted the value of integrating quantitative and qualitative findings. Results were discussed within the pediatric psychosocial preventive health model framework.