Total Kidney Volume in Autosomal Dominant Polycystic Kidney Disease: A Biomarker of Disease Progression and Therapeutic Efficacy.

Autosomal dominant polycystic kidney disease (ADPKD) is the most common potentially life-threatening monogenic disorder in humans, characterized by progressive development and expansion of fluid-filled cysts in the kidneys and other organs. Ongoing cyst growth leads to progressive kidney enlargement, whereas kidney function remains stable for decades as a result of hyperfiltration and compensation by unaffected nephrons. Kidney function irreversibly declines only in the late stages of the disease, when most of the parenchyma is lost to cystic and fibrotic tissue and the remaining compensatory capacity is overwhelmed. Hence, conventional kidney function measures, such as glomerular filtration rate, do not adequately assess disease progression in ADPKD, especially in its early stages. Given the recent development of potential targeted therapies in ADPKD, it has become critically important to identify relevant biomarkers that can be used to determine the degree of disease progression and evaluate the effects of therapeutic interventions on the course of the disease. We review the current evidence to provide an informed perspective on whether total kidney volume (TKV) is a suitable biomarker for disease progression and whether TKV can be used as an efficacy end point in clinical trials. We conclude that because cystogenesis is the central factor leading to kidney enlargement, TKV appears to be an appropriate biomarker and is gaining wider acceptance. Several studies have identified TKV as a relevant imaging biomarker for monitoring and predicting disease progression and support its use as a prognostic end point in clinical trials.

Proceedings From a Canadian Nephrology Forum: Nephrology Is Back.

PURPOSE OF CONFERENCE: On January 18, 2020, the Nephrology is Back learning day forum was held in Toronto, ON, Canada. The objectives of the meeting were to describe recent advances in nephrology for community and academic nephrologists and patients, and to define challenges and opportunities for integration of new data into clinical practice. The intent was to test a unique forum for continuing medical education integrating physician and patient experiences with the goal of encouraging change in practice. SOURCES OF INFORMATION: Program content was based on current literature and clinical experience. Additional information was provided by patient partners who attended the meeting to provide their perspective on current issues in nephrology. METHODS: A steering committee (A.L., A.S., and D.S.) developed goals and an outline for the content to be covered over the course of the meeting and led the recruitment of speakers. Speakers were asked to develop their presentations independently following direction by the committee, based on primary sources, including their own experiences. Presentations were followed by discussion including both physicians and patients, and participants had an opportunity to evaluate the conference and its outcomes. KEY FINDINGS: We present a unique approach to providing continuing medical education by including both physicians and patients in the learning process. Patient perspectives accompanying presentations around data and other clinical topics provided a much different environment from other knowledge translation exercises. We believe this represents an innovative approach for knowledge translation that allows physicians to address clinical topics in a novel manner, including the integration of new findings into practice and the need to cascade this education to their peers. LIMITATIONS: Because the conference was a one-time event, it has been difficult to assess the actual clinical impact of the knowledge translation exercise and whether physician behaviors have changed as a result of the activity. The conference could also have included broader representation from across Canada. IMPLICATIONS: The success of this test forum among both physicians and patient partners suggests that the inclusion of patient partners in learning could have an important role in future educational initiatives.

OBJECTIF DE LA CONFÉRENCE: La journée d'apprentissage Nephrology is Back s'est tenue à Toronto (Ontario) au Canada le 18 janvier 2020. Cette réunion visait à décrire les plus récentes avancées de la néphrologie pour les néphrologues des centres communautaires et universitaires, de même que pour les patients, et à cerner les occasions d'intégrer ces nouvelles données dans la pratique clinique et les défis rencontrés. L'intention était de tester un forum de formation médicale continue intégrant les expériences des médecins et des patients afin d'entraîner des changements dans la pratique. SOURCES: Le contenu du programme s'inspirait de la documentation actuelle et de l'expérience clinique. L'invitation de patients partenaires à donner leur point de vue sur les enjeux actuels en néphrologie a fourni des informations supplémentaires. MÉTHODOLOGIE: Le comité directeur (AL, AS et DS) a élaboré les objectifs de la réunion et un plan du contenu à couvrir, en plus de diriger le recrutement des intervenants. Ces derniers ont été invités à préparer leur présentation de façon indépendante en suivant les directives du comité, en se basant sur des sources primaires et en intégrant leurs expériences personnelles. Ces présentations ont été suivies de discussions impliquant tant des médecins que des patients, et les participants ont évalué la conférence et ses issues. PRINCIPAUX RÉSULTATS: Nous présentons une approche de formation médicale continue unique qui intègre à la fois l'avis des médecins et de patients partenaires au processus d'apprentissage. Le point de vue des patients sur les données et les autres sujets abordés pendant les présentations a fourni un environnement très différent des exercices d'application des connaissances habituels. Nous sommes d'avis qu'il s'agit d'une approche innovante pour l'application des connaissances et qu'elle offre aux médecins une nouvelle façon d'aborder certains sujets, notamment l'intégration des plus récentes découvertes à la pratique et la nécessité de transmettre ces apprentissages aux pairs. LIMITES: Il s'agissait d'un événement ponctuel. Il est donc difficile d'évaluer l'impact clinique réel de cette conférence sur la transmission des connaissances et de déterminer si les comportements des médecins ont changé à la suite de l'activité. La conférence aurait également bénéficié d'une meilleure représentation au niveau national. CONCLUSION: Le succès de cette conférence rassemblant à la fois des médecins et des patients partenaires suggère que l'inclusion de ces derniers au processus d'apprentissage pourrait jouer un rôle de premier plan dans les futures activités d'apprentissage.

A cross-sectional immunosurveillance study of anti-EPO antibody levels in CRF patients receiving epoetin alfa in 5 Ontario Renal Centers.

BACKGROUND: Epoetin alfa (Eprex*; Johnson & Johnson, Manati, PR) has been used successfully to correct the anemia of chronic renal failure for more than 12 years. Anti-erythropoietin (anti-EPO) antibodies have been reported in a small number of patients, resulting in a blood disorder, pure red cell aplasia (PRCA). To evaluate the utility of a large-scale anti-EPO antibody screening program in patients with chronic kidney disease (CKD) administered epoetin alfa, a study involving 5 large renal centers in southern Ontario, Canada, was conducted. METHODS: More than 1,500 hemodialysis, peritoneal dialysis, and predialysis patients were screened for the prevalence of anti-EPO antibodies by means of a radioimmunoprecipitation (RIP) assay. Serum samples were drawn and shipped to PPD Development (Richmond, VA) for the immunoprecipitation assay. Serum EPO levels also were measured. All samples that tested positive or borderline for antibodies were sent to MDS Pharma Services (Montreal, Canada) for the neutralization assay. RESULTS: Of 1,531 samples tested, 1 patient tested low-positive and 3 borderline results were detected by means of RIP. PRCA previously was diagnosed in the patient with the low-positive antibody level; the patient was treated with cyclosporine and currently is being administered epoetin alfa with good response. The 3 patients with borderline antibody results manifested no clinical signs of PRCA. Neutralization assays performed on all 4 serum samples were negative for anti-EPO antibodies. CONCLUSION: Results from this surveillance study show that the prevalence of antibody to EPO in patients with CKD administered epoetin alfa in 5 Canadian renal centers is low, and the value of a large-scale antibody screening program for PRCA cannot be justified.