Ambulatory Parathyroidectomy for Secondary Hyperparathyroidism at a Large Dialysis Program in Toronto: A Program Report.

Purpose of program: Operative wait times for non-oncology-related procedures continue to rise in Canada, and this was further exacerbated by the COVID-19 pandemic. These challenges will remain prevalent beyond the pandemic given the limited number of acute care beds and resources required to care for patients. As a result, the need for innovative approaches to optimize the utilization of health care resources while maintaining equitable and timely access is needed. In this report, we describe the development of a collaborative ambulatory parathyroidectomy program between two centers in Toronto, allowing for more expedient surgical treatment of secondary hyperparathyroidism among patients from a large dialysis program. Sources of information: The need for expanded access to surgical care for secondary hyperparathyroidism was identified through interdepartmental communication between referring nephrologists and surgeons at Sunnybrook Health Sciences Centre and Women's College Hospital, respectively. Methods: A multidisciplinary ambulatory parathyroidectomy planning team was formed that included nephrologists, endocrine surgeons, nurses, and patient care managers to conduct a needs assessment. It was identified that patients had long wait times, and to address that gap in care, a protocol was developed to identify suitable patients requiring treatment. The teams created a plan to coordinate patient care and transfers. A clinical tool and protocol for post-operative management of hypocalcemia was developed using a Delphi model, gathering input from many members of the care team. The Delphi process to finalize the protocol included a series of virtual meetings over a period of about 4 months with various stakeholders and included input from two departmental heads (medicine and surgery), three nephrologists, a nurse practitioner, a patient care manager, and two nurse educators. Meetings involved core members of the Nephrology Quality Improvement and Patient Safety at Sunnybrook Health Sciences Centre and finalized protocol was agreed upon by members of this group at a quarterly meeting. Key findings: In this article, we describe the development, initial deployment, and planned assessment of the ambulatory parathyroidectomy program at the Women's College Hospital and Sunnybrook Health Sciences Centre. The primary aim of the program is to increase accessibility to parathyroidectomy for secondary hyperparathyroidism. A secondary aim was to allow patients to have streamlined care with a team that is well versed with maintenance dialysis needs and optimizing treatment of post operative hypocalcemia through standardized protocols. Limitations: Ambulatory parathyroidectomy relies on effective communication, flow, and availability of acute care beds. It is anticipated that occasionally, unexpected hospital demands, and health care disruptions may occur, which can limit efficiency of the program. We will also need to examine the cost-effectiveness of this program as it may improve access but increase costs related to the procedure. As the program is implemented, useful adaptations and policies to our protocol to help mitigate these limitations will be documented and published in our outcomes report. Implications: Ontario residents with chronic kidney disease with secondary hyperparathyroidism who have failed medical management will have increased and timely access to parathyroidectomy.

Objectif du program: Les temps d'attente pour les interventions non oncologiques continuent d'augmenter au Canada, une situation qui s'est aggravée avec la pandémie de COVID-19. Ce problème persistera au-delà de la pandémie en raison du nombre limité de lits en soins aigus et de ressources pour soigner les patients. Par conséquent, l'adoption d'approches novatrices pour optimiser l'utilisation des ressources en santé, tout en maintenant un accès équitable et opportun, est nécessaire. Dans ce rapport, nous décrivons l'élaboration d'un programme collaboratif de parathyroïdectomie ambulatoire entre deux centres de Toronto, lequel permettra le traitement chirurgical plus rapide de l'hyperparathyroïdie secondaire chez les patients d'un important programme de dialyse. Sources: Le besoin d'élargir l'accès aux soins chirurgicaux pour l'hyperparathyroïdie secondaire a été révélé grâce à la communication interservices entre les néphrologues traitants du Sunnybrook Health Sciences Centre et les chirurgiens de l'Hôpital Women's College. Méthodologie: Une équipe multidisciplinaire de planification de la parathyroïdectomie ambulatoire composée de néphrologues, de chirurgiens-endocrinologues, d'infirmières et de gestionnaires de soins aux patients a été formée pour procéder à une évaluation des besoins. Il a été établi que les patients expérimentaient de longs temps d'attente et, pour combler cette lacune, un protocole a été mis au point pour identifier adéquatement les patients nécessitant un traitement. Les équipes ont créé un plan pour coordonner les soins aux patients et les transferts. Un outil clinique et un protocole de prise en charge postopératoire de l'hypocalcémie ont été mis au point à l'aide d'un modèle Delphi impliquant la participation plusieurs membres de l'équipe soignante. Le processus Delphi de finalisation du protocole a comporté, sur une période de quatre mois, une série de réunions virtuelles avec divers intervenants, ainsi que la participation de deux chefs de service (médecine et chirurgie), de trois néphrologues, d'une infirmière praticienne, d'un gestionnaire des soins aux patients et de deux formateurs en soins infirmiers. Ces rencontres ont réuni les principaux membres du Nephrology Quality Improvement and Patient Safety at Sunnybrook Health Sciences Centre, et ces derniers ont convenu d'un protocole finalisé lors d'une réunion trimestrielle. Principaux resultants: Cet article décrit l'élaboration, le déploiement initial et l'évaluation prévue du programme de parathyroïdectomie ambulatoire du Women's College Hospital et du Sunnybrook Health Sciences Centre. Le principal objectif du programme est d'accroître l'accessibilité à la parathyroïdectomie pour les patients souffrant d'hyperparathyroïdie secondaire. Les autres objectifs étaient de permettre aux patients de bénéficier de soins rationalisés, grâce à une équipe qui connaît parfaitement les besoins en dialyse d'entretien, et d'optimiser le traitement de l'hypocalcémie postopératoire grâce à des protocoles normalisés. Limites: La parathyroïdectomie ambulatoire repose sur l'efficacité du flux et de la communication, et sur la disponibilité des lits en soins aigus. Il est attendu que des demandes hospitalières inattendues et des perturbations se produiront de temps à autre, ce qui pourrait limiter l'efficacité du programme. Nous devrons également examiner la rentabilité du programme, car l'amélioration de l'accès pourrait se traduire par une augmentation des coûts liés à la procédure. Au fur et à mesure de la mise en œuvre du programme, des adaptations et politiques utiles à notre protocole seront documentées et publiées dans notre rapport sur les résultats, afin d'aider à atténuer ces limites. Conclusion: Les résidents de l'Ontario atteints d'insuffisance rénale chronique et d'hyperparathyroïdie secondaire dont la prise en charge médicale a échoué auront un accès accru et opportun à la parathyroïdectomie.

Nephrologist Follow-Up versus Usual Care after an Acute Kidney Injury Hospitalization (FUSION): A Randomized Controlled Trial.

BACKGROUND AND OBJECTIVES: Survivors of AKI are at higher risk of CKD and death, but few patients see a nephrologist after hospital discharge. Our objectives during this 2-year vanguard phase trial were to determine the feasibility of randomizing survivors of AKI to early follow-up with a nephrologist or usual care, and to collect data on care processes and outcomes. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We performed a randomized controlled trial in patients hospitalized with Kidney Disease Improving Global Outcomes (KDIGO) stage 2-3 AKI at four hospitals in Toronto, Canada. We randomized patients to early nephrologist follow-up (standardized basket of care that emphasized BP control, cardiovascular risk reduction, and medication safety) or usual care from July 2015 to June 2017. Feasibility outcomes included the proportion of eligible patients enrolled, seen by a nephrologist, and followed to 1 year. The primary clinical outcome was a major adverse kidney event at 1 year, defined as death, maintenance dialysis, or incident/progressive CKD. RESULTS: We screened 3687 participants from July 2015 to June 2017, of whom 269 were eligible. We randomized 71 (26%) patients (34 to nephrology follow-up and 37 to usual care). The primary reason stated for declining enrollment included hospitalization-related fatigue (n=65), reluctance to add more doctors to the health care team (n=59), and long travel times (n=40). Nephrologist visits occurred in 24 of 34 (71%) intervention participants, compared with three of 37 (8%) participants randomized to usual care. The primary clinical outcome occurred in 15 of 34 (44%) patients in the nephrologist follow-up arm, and 16 of 37 (43%) patients in the usual care arm (relative risk, 1.02; 95% confidence interval, 0.60 to 1.73). CONCLUSIONS: Major adverse kidney events are common in AKI survivors, but we found the in-person model of follow-up posed a variety of barriers that was not acceptable to many patients. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: Nephrologist Follow-up versus Usual Care after an Acute Kidney Injury Hospitalization (FUSION), NCT02483039 CJASN 16: 1005-1014, 2021. doi: https://doi.org/10.2215/CJN.17331120.

Maintained virological suppression and renal function with reduced dose tenofovir disoproxil fumarate in renally impaired chronic hepatitis B patients.

Tenofovir disoproxil fumarate (TDF) effectively suppresses viral replication in chronic hepatitis B (CHB), but occasionally leads to renal impairment. We evaluated the prevalence of viral and biochemical breakthrough and renal function kinetics in renally impaired patients with CHB on reduced and on full-dose TDF. This clinic-based longitudinal cohort study included patients receiving full and reduced dose TDF (due to eGFR [Cockcroft-Gault] <60 mL/min/1.73 m2 ). Viral and biochemical breakthroughs were assessed 1 month after starting full and reduced TDF dose until the end-of-follow-up. Breakthroughs were studied in full and reduced dose TDF, and renal function (MDRD) longitudinally before and after dose reduction within patients starting on full-dose TDF. Of 750 patients on TDF, 78 (10%) had reduced dose and 672 (90%) full dose. At the time of dose reduction, 36 (46%) patients had chronic kidney disease stage G3B. A viral breakthrough occurred in one cirrhotic dialysis-dependent patient (dosed 300 mg weekly) which resolved without signs of decompensation, and in one patient on full dose which resolved spontaneously. One biochemical breakthrough occurred during dose reduction and resolved naturally without viral breakthrough. The MDRD improved within the first year of dose reduction (+3.0 [2.5] mL/min per year; P < .005) and remained stable thereafter. Fifty-three (79%) patients reached an MDRD >50 mL/min during dose reduction. Low dose TDF maintains renal function and viral suppression in most renally impaired patients with CHB, even in those with advanced liver disease. This useful, yet simple strategy could be particularly viable in resource-constrained settings.

Major reductions in unnecessary aspartate aminotransferase and blood urea nitrogen tests with a quality improvement initiative.

BACKGROUND/CONTEXT: Unnecessary laboratory testing leads to considerable healthcare costs. Aspartate aminotransferase (AST), commonly ordered with alanine aminotransferase (ALT) and blood urea nitrogen (BUN), commonly ordered with creatinine (Cr), often add little value to patient management at significant cost. We undertook a choosing wisely based quality improvement initiative to reduce the frequency of testing. OBJECTIVES: To reduce the ratio of AST/ALT and BUN/Cr to less than 5% for all inpatient and outpatient test orders. MEASURES: Absolute number and ratio of AST/ALT and BUN/Cr; AST, ALT, BUN and Cr tests per 100 hospital days; projected annualised cost savings and monthly acute inpatient bed days. IMPROVEMENTS: We created guidelines for appropriate indications of AST and BUN testing, provided education with audit and feedback and removed AST and BUN from institutional order sets. IMPACT/RESULTS: The ratios of AST/ALT and BUN/Cr decreased significantly over the study period (0.37 to 0.14, 0.57 to 0.14, respectively), although the goal of 0.05 was not achieved due to a delay in adopting the choosing wisely strategies during the study time period by some inpatient units. The number of tests per 100 hospital days decreased from 20 to 7 AST (95% CI 19 to 20.5, 5.6 to 8.7, p<0.001) and from 72 to 17 BUN (95% CI 70 to 73.4, 16.6 to 22.9, p<0.001). The initiative resulted in a projected annualised cost savings of C$221 749. DISCUSSION: A significant decrease in the AST/ALT and BUN/Cr ratios can be achieved with a multimodal approach and will result in substantial healthcare savings.

A Challenging Diagnosis of IgG4-Related Disease When Understanding Limitations of Laboratory Testing Was Pivotal.

A 76-year-old man was incidentally found on a CT scan to have lymphadenopathy and bilateral kidney enlargement suggestive of infiltrative renal disease. He was largely asymptomatic but had bilateral salivary and lacrimal gland enlargement. A grossly elevated serum IgG (>70 g/L) with concomitant suppression of other immunoglobulins, a small IgG restriction, and a parotid biopsy revealing lymphoplasmacytic infiltrate with slight kappa light chain excess all suggested a lymphoproliferative disorder (LPD). The diagnostic workup was further confounded by a normal serum IgG4 concentration. Moreover, bone marrow and renal biopsies did not reveal evidence of LPD. Discussion with the laboratory not only clarified that the markedly increased total IgG could not be accounted for by the small IgG restriction, but also identified a discrepancy in the IgG4 measurement. Repeat analysis of a follow-up sample revealed an elevated IgG4 of 5.94 (reference interval: 0.039-0.864) g/L, which prompted a repeat parotid biopsy that showed predominant IgG4+ lymphocytic infiltrates. Despite the deluding presentations, a final diagnosis of IgG4-related disease (IgG4-RD) was made based on elevated serum IgG4 concentrations and histopathological findings. This case highlights the importance of recognizing limitations of laboratory testing and the benefit of close communications among clinical subspecialties and the laboratory.

Performance of Temporary Hemodialysis Catheter Insertion by Nephrology Fellows and Attending Nephrologists.

BACKGROUND AND OBJECTIVES: Concerns have been raised about nephrology fellows' skills in inserting temporary hemodialysis catheters. Less is known about temporary hemodialysis catheter insertion skills of attending nephrologists supervising these procedures. The aim of this study was to compare baseline temporary hemodialysis catheter insertion skills of attending nephrologists with the skills of nephrology fellows before and after a simulation-based mastery learning (SBML) intervention. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This pre- post-intervention study with a pretest-only comparison group was conducted at the University of Toronto in September of 2014. Participants were nephrology fellows and attending nephrologists from three university-affiliated academic hospitals who underwent baseline assessment of internal jugular temporary hemodialysis catheter insertion skills using a central venous catheter simulator. Fellows subsequently completed an SBML intervention, including deliberate practice with the central venous catheter simulator. Fellows were expected to meet or exceed a minimum passing score at post-test. Fellows who did not meet the minimum passing score completed additional deliberate practice. Attending nephrologist and fellow baseline performance on the temporary hemodialysis catheter skills assessment was compared. Fellows' pre- and post-test temporary hemodialysis catheter insertion performance was compared to assess the effectiveness of SBML. The skills assessment was scored using a previously published 28-item checklist. The minimum passing score was set at 79% of checklist items correct. RESULTS: In total, 19 attending nephrologists and 20 nephrology fellows participated in the study. Mean attending nephrologist checklist scores (46.1%; SD=29.5%) were similar to baseline scores of fellows (41.1% items correct; SD=21.4%; P=0.55). Only two of 19 attending nephrologists (11%) met the minimum passing score at baseline. After SBML, fellows' mean post-test score improved to 91.3% (SD=6.9%; P<0.001). Median time between pre- and post-test was 24 hours. CONCLUSIONS: Attending nephrologists' baseline temporary hemodialysis catheter insertion skills were highly variable and similar to nephrology fellows' skills, with only a small minority able to competently insert a temporary hemodialysis catheter. SBML was extremely effective for training fellows and should be considered for attending nephrologists who supervise temporary hemodialysis catheter insertions.

Molecular diagnostics in autosomal dominant polycystic kidney disease: utility and limitations.

BACKGROUND AND OBJECTIVES: Gene-based mutation screening is now available and has the potential to provide diagnostic confirmation or exclusion of autosomal dominant polycystic kidney disease. This study illustrates its utility and limitations in the clinical setting. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Using a molecular diagnostic service, genomic DNA of one affected individual from each study family was screened for pathologic PKD1 and PKD2 mutations. Bidirectional sequencing was performed to identify sequence variants in all exons and splice junctions of both genes and to confirm the specific mutations in other family members. In two multiplex families, microsatellite markers were genotyped at both PDK1 and PKD2 loci, and pair-wise and multipoint linkage analysis was performed. RESULTS: Three of five probands studied were referred for assessment of renal cystic disease without a family history of autosomal dominant polycystic kidney disease, and two others were younger at-risk members of families with autosomal dominant polycystic kidney disease being evaluated as living-related kidney donors. Gene-based mutation screening identified pathogenic mutations that provided confirmation or exclusion of disease in three probands, but in the other two, only unclassified variants were identified. In one proband in which mutation screening was indeterminate, DNA linkage studies provided strong evidence for disease exclusion. CONCLUSIONS: Gene-based mutation screening or DNA linkage analysis should be considered in individuals in whom the diagnosis of autosomal dominant polycystic kidney disease is uncertain because of a lack of family history or equivocal imaging results and in younger at-risk individuals who are being evaluated as living-related kidney donors.

Recessive NPHS2 (Podocin) mutations are rare in adult-onset idiopathic focal segmental glomerulosclerosis.

Recessive NPHS2 (podocin) mutations account for up to approximately 30% of steroid-resistant idiopathic FSGS in children and are associated with a reduced risk for disease recurrence after renal transplantation. R229Q, a missense variant that is present in 3.6% of the white population, has been implicated as a common disease-causing mutation. Given these clinical implications, we examined the role of NPHS2 mutations in a cohort of patients with adult-onset FSGS. We used denaturing HPLC to screen for heterozygous and homozygous gene variants in PCR-amplified DNA fragments that contained all exons and splice junctions of NPHS2. Bidirectional sequencing was performed to define all of the gene variants detected. With the use of the denaturing HPLC in a single-blind pilot study, 40 of 43 known NPHS2 mutations were detected from 22 pediatric patients with FSGS to establish a test sensitivity of 93%. This screen then was applied to 87 adult patients with idiopathic FSGS (15 steroid-sensitive, 63 steroid-resistant, and nine familial cases). In this latter cohort, compound heterozygous mutations were detected only in one patient with steroid-sensitive FSGS (R229Q and Q285fsX302) and no homozygous mutations. Overall, R229Q accounted for eight (80%) of ten of the putative mutant alleles that were detected in the study cohort. Contrary to the pediatric experience, recessive NPHS2 mutations are rare in this study population, suggesting that the pathogenesis of FSGS in adults may differ from that in children. These data do not support R229Q as a disease-causing mutation for steroid-resistant FSGS.

Real-time polymerase chain reaction assay for the rapid detection and characterization of chloroquine-resistant Plasmodium falciparum malaria in returned travelers.

BACKGROUND: Imported drug-resistant malaria is a growing problem in industrialized countries. Rapid and accurate diagnosis is essential to prevent malaria-associated mortality in returned travelers. However, outside of a limited number of specialized centers, the microscopic diagnosis of malaria is slow, unreliable, and provides little information about drug resistance. Molecular diagnostics have the potential to overcome these limitations. OBJECTIVE: We developed and evaluated a rapid, real-time polymerase chain reaction (PCR) assay to detect Plasmodium falciparum malaria and chloroquine (CQ)-resistance determinants in returned travelers who are febrile. METHODS: A real-time PCR assay based on detection of the K76T mutation in PfCRT (K76T) of P. falciparum was developed on a LightCycler platform (Roche). The performance characteristics of the real-time assay were compared with those of the nested PCR-restriction fragment-length polymorphism (RFLP) and the sequence analyses of samples obtained from 200 febrile returned travelers, who included 125 infected with P. falciparum (48 of whom were infected CQ-susceptible [K76] and 77 of whom were CQ-resistant [T76] P. falciparum), 22 infected with Plasmodium vivax, 10 infected with Plasmodium ovale, 3 infected with Plasmodium malariae malaria, and 40 infected with other febrile syndromes. All patient samples were coded, and all analyses were performed blindly. RESULTS: The real-time PCR assay detected multiple pfcrt haplotypes associated with CQ resistance in geographically diverse malaria isolates acquired by travelers. Compared with nested-PCR RFLP (the reference standard), the real-time assay was 100% sensitive and 96.2% specific for detection of the P. falciparum K76T mutation. CONCLUSION: This assay is rapid, sensitive, and specific for the detection and characterization of CQ-resistant P. falciparum malaria in returned travelers. This assay is automated, standardized, and suitable for routine use in clinical diagnostic laboratories.

Functional analysis of a novel GATA3 mutation in a family with the hypoparathyroidism, deafness, and renal dysplasia syndrome.

The hypoparathyroidism, deafness, and renal dysplasia (HDR) syndrome is an autosomal dominant disorder caused by mutations of a member of the GATA-binding family of transcription factors, GATA3. This dual zinc finger transcription factor binds DNA with its C-terminal zinc finger (ZnF2) and stabilizes this binding with its N-terminal zinc finger (ZnF1). ZnF1 also interacts with other zinc finger proteins, notably Friend of GATA (FOG). The HDR syndrome has been described in patients with mutations affecting both ZnF1 and ZnF2 domains; the former result in inefficient interaction with FOG, and the latter result in disruption of DNA binding. We report a patient with renal failure, hypoparathyroidism, and bilateral hearing loss. Assessment of family members indicated that the disease arose as a de novo mutation in her mother. Analysis of GATA3 in the family revealed a heterozygous missense mutation resulting in a nonconservative change of a single amino acid (R276P) in the ZnF1 domain. Functional analysis using dissociation electrophoretic mobility shift and yeast two-hybrid assays showed reduced binding affinity to the GATA motifs but normal interaction with FOG in vitro. These results are consistent with the predicted functions of human GATA3-ZnF1 from three-dimensional molecular modeling and with HDR being a result of GATA3 haploinsufficiency.