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Conclusions from a Kidney Disease: Improving Global Outcomes

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Conclusions from a Kidney Disease: Improving Global Outcomes KDIGO executive conclusions www.kidney-international.org Common Elements in Rare Kidney Diseases: Conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies OPEN Conference Se´gole`ne Ayme´1, Detlef Bockenhauer2, Simon Day3, Olivier Devuyst4,16, Lisa M. Guay-Woodford5,16, Julie R. Ingelfinger6, Jon B. Klein7, Nine V.A.M. Knoers8, Ronald D. Perrone9, Julia Roberts10, Franz Schaefer11, Vicente E. Torres12, Michael Cheung13, David C. Wheeler14 and Wolfgang C. Winkelmayer15; for Conference Participants17 1Institut du Cerveau et de la Moelle Épinière, Centre National de la Recherche Scientifique Unite Mixte de Recherche 7225, Institut National de la Santé et de la Recherche Médicale U 1127, Université Pierre et Marie Curie-P6 Unite Mixte de Recherche S 1127, Paris, France; 2University College of London Centre for Nephrology, Great Ormond Street Hospital for Children National Health Service Foundation Trust, London, UK; 3Clinical Trials Consulting and Training Limited, Buckingham, UK; 4Institute of Physiology, University of Zurich, Zurich, Switzerland; 5Center for Translational Science, Children’s National Health System, Washington, DC, USA; 6MassGeneral Hospital for Children at Massachusetts General Hospital, Harvard University, Boston, Massachusetts, USA; 7Division of Nephrology and Hypertension, The University of Louisville School of Medicine, Louisville, Kentucky, USA; 8Department of Genetics, Center for Molecular Medicine, University Medical Center Utrecht, Utrecht, The Netherlands; 9Department of Medicine, Division of Nephrology, Tufts Medical Center, Tufts University School of Medicine, Boston, Massachusetts, USA; 10Polycystic Kidney Disease Foundation, Kansas City, Missouri, USA; 11Division of Pediatric Nephrology, Centre for Pediatrics and Adolescent Medicine, Heidelberg University Medical Centre, Heidelberg, Germany; 12Division of Nephrology and Hypertension, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota, USA; 13Kidney Disease: Improving Global Outcomes, Brussels, Belgium; 14University College London, London, UK; and 15Selzman Institute for Kidney Health, Section of Nephrology, Department of Medicine, Baylor College of Medicine, Houston, Texas, USA Rare kidney diseases encompass at least 150 different addressing these challenges was developed and is conditions, most of which are inherited. Although presented here. individual rare kidney diseases raise specific issues, as a Kidney International (2017) 92, 796–808; http://dx.doi.org/10.1016/ group these rare diseases can have overlapping challenges j.kint.2017.06.018 in diagnosis and treatment. These challenges include small KEYWORDS: chronic kidney disease progression; clinical trials; diagnostics; numbers of affected patients, unidentified causes of genetic kidney diseases; practical and integrated patient support; transla- disease, lack of biomarkers for monitoring disease tional care ª progression, and need for complex care. To address Copyright 2017, International Society of Nephrology. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license common clinical and patient issues among rare kidney (http://creativecommons.org/licenses/by-nc-nd/4.0/). diseases, the KDIGO Controversies Conference entitled, Common Elements in Rare Kidney Diseases, brought together a panel of multidisciplinary clinical providers and he definition of rare diseases varies across the world. In patient advocates to address five central issues for rare Europe, a disease or disorder is defined as rare when the T < kidney diseases. These issues encompassed diagnostic prevalence is 1 in 2000 individuals; whereas in the challenges, management of kidney functional decline and USA, the designation of rare disorder applies when <200,000 progression of chronic kidney disease, challenges in clinical Americans are affected. Rare kidney diseases encompass $ 150 study design, translation of advances in research to clinical different conditions. The majority are inherited,1 while others, care, and provision of practical and integrated patient such as the primary glomerulonephritides, have complex eti- support. Thus, by a process of consensus, guidance for ologies. For inherited kidney disorders, diagnosis, manage- ment, and treatment are complex, especially when they are Correspondence: Olivier Devuyst, Institute of Physiology, University of associated with multisystem complications. Patients often Zurich, Winterthurerstrasse 190, CH-8057, Zurich, Switzerland. E-mail: spend years visiting multiple health care providers before [email protected], or Lisa M. Guay-Woodford, Children’s National receiving an accurate diagnosis. Advances in kidney replace- Health System, 6th Floor Main Hospital, Center 6, 111 Michigan Avenue NW, ment therapy and its increased access allow prolonged patient Washington, DC 20010, USA. E-mail: [email protected] survival, yet often with a poor quality of life. In particular, 16 The conference was co-chaired by OD and LMGW. children born with severe congenital nephropathies face a high 17See Appendix for list of other conference participants. likelihood of altered physical, cognitive, and psychosocial Received 21 February 2017; revised 22 May 2017; accepted 8 June 2017 development.2 796 Kidney International (2017) 92, 796–808 S Aymé et al.: Common elements in rare kidney diseases: KDIGO conference report KDIGO executive conclusions Therapeutic advances in rare kidney diseases have been for recurrence in kidney transplantation, evaluating family hindered by several factors, including unresolved genetic de- members’ suitability for kidney donation, and prompting – fects, lack of biomarkers to monitor disease progression, evaluation for extrarenal features (Table 1).10 12 heterogeneous clinical phenotypes, and outdated diagnostic Genetic testing can play an essential role in evaluating classifications that do not reflect underlying pathophysiolog- children and young adults and thus should be considered when ical mechanisms.1,3 Many initiatives have focused on rare the clinical phenotype does not suggest a clear diagnosis.9 kidney diseases, and regulations have been created to promote The role of genetic testing in adults is generally more limited. the development of therapies, organize optimal health care However, for those suspected to have a genetic disease, such as systems, and encourage research. Patient organizations have X-linked Alport syndrome, testing can confirm diagnosis and also taken a leading role in these matters. Together, techno- establish inheritance patterns.13 In addition, some patients logical advances and organized advocacy have helped enhance view genetic testing as important for family planning, under- understanding of the clinical, genetic, and mechanistic issues standing their disease, and contributing personally to disease in many inherited kidney disorders. research. Therefore, practitioners who treat adults with rare To address common clinical and patient issues among rare kidney diseases should be knowledgeable about the modalities kidney diseases, Kidney Disease: Improving Global Outcomes of genetic testing, and all patients should be informed that (KDIGO) convened a global, multidisciplinary Controversies genetic testing is available when applicable. Conference to address 5 central issues in rare kidney diseases: For some patients, such as those with nephrotic syndrome diagnostic challenges, management of kidney functional and urogenital malformations, genetic testing can be justified decline and progression of chronic kidney disease (CKD), based on minimal phenotypic information. Testing should be challenges in clinical study design, translation of advances in considered when the index of suspicion for a given disease is research to clinical care, and provision of practical and inte- high and the patient would otherwise be exposed to invasive grated patient support. The deliberations from this confer- procedures, or to ineffective or costly treatment with side effects ence are now summarized here with additional ancillary (e.g., children with steroid-resistant nephrotic syndrome).14 information available online at http://kdigo.org/conferences/ The decision to perform genetic testing should be collabora- common-elements/. tive, with input from the nephrologist, clinical geneticist, genetic counselor, genetic lab specialist, the primary care physician, the DIAGNOSTIC CHALLENGES patient, and his or her caregivers. With decreasing turnaround The growing use of next-generation sequencing techniques is times, genetic testing is increasingly becoming an important expected to increase diagnostic accuracy for rare kidney dis- contributor to clinical decision making.9 eases, help decipher the molecular mechanism of disease, facilitate genetic counseling, and offer possibilities for carrier Presymptomatic genetic screening testing.4 The burgeoning wealth of genetic and molecular In the context of genetic disorders, nephrologists should serve information has evoked new challenges, such as the need for as advocates for patients and their children, always respecting more sophisticated bioinformatic analytic tools and algo- each patient’s religious beliefs, cultural perspectives, and au- rithms. Additionally, the changes in molecular techniques and tonomy in decision making. Patients with any genetic diagnosis interpretations are creating novel ethical, legal, and social should be counseled about reproductive options, including challenges.5,6 Even for well-defined disorders, barriers to
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