A Multidisciplinary Nephrogenic Referral Clinic for Children and Adults- Diagnostic Achievements and Insights

Aviva Eliyahu ^1,5,12 Ben Pode-Shakked ^2,12 Yishay Ben-Moshe ^1,12 Ortal Barel ^3,4 Lilach C. Regev ^1,12 Maayan Kagan ^1,12 Dina Marek-Yagel ^6,12 Danit Atias-Varon ⁷ Einat Lahav ^7,12 Naomi Issler ^7,12 Omer Shlomovitz ^1,12 Nitzan Kol ³ Pazit Beckerman ^12,15 Meidad Greenberg ^10,12 Oded Volovelsky ^11,14 Yael Borovitz ^3,13 Miriam Davidovits ^12,13 Orly Haskin ¹³ Hadas Alfandary ^12,13 Shely Levi ^12,13 Maital Kaidar ^9,12 Zeev Katzir ¹⁷ Avital Angel-Korman ¹⁷ Rachel Becker-Cohen ¹⁸ Efrat Ben-Shalom ¹⁸ Adi Leiba ^19,20 Itai M Pessach ^12,16 Danny Lotan ^7,12 Moshe Shahar ^21,22 Yair Anikster ^4,6,12 Annick Raas-Rothschild ^2,12 Gideon Rechavi ^3,4,12 Benjamin Dekel ^7,8,12 Asaf Vivante ^1,7,12

¹Department of Pediatrics B, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel-Hashomer
²The Institute for Rare Diseases, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel-Hashomer
³Sheba Medical Center, Tel Hashomer, Sheba Medical Center, Tel Hashomer
⁴Sheba Medical Center, Tel Hashomer, The Wohl Institute for Translational Medicine
⁵The Danek Gertner Institute for Human Genetics, Sheba Medical Center, Tel Hashomer
⁶Metabolic Disease Unit, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel-Hashomer
⁷Pediatric Nephrology Unit, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel-Hashomer
⁸Pediatric Stem Cell Research Institute, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel-Hashomer
⁹Pediatric Nephrology Unit, Edith Wolfson Medical Center, Holon
¹¹Pediatric Nephrology Unit and Research Lab, Hadassah Medical Center and Faculty of Medicine, Hebrew University of Jerusalem
¹²Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv
¹³Institute of Nephrology, Schneider Children's Medical Center of Israel, Petach Tikva
¹⁴Wohl Translational Research Institute, Hadassah-Hebrew University Medical Center, Jerusalem
¹⁵Sheba Medical Center, Tel-Hashomer, Institute of Nephrology and Hypertension
¹⁶.Department of Pediatric Intensive Care, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel-Hashomer
¹⁷Nephrology and Hypertension Institute, Samson Assuta University Hospital, Ashdod; Ben Gurion University, Beer Sheva
¹⁸Institute of Pediatric Nephrology, Shaare Zedek Medical Center, Jerusalem, Israel and Faculty of Medicine, Hebrew University of Jerusalem
¹⁹Medical Corps, Israel Defense Forces
²⁰Department of Medicine, Mount Auburn Hospital, Harvard Medical School, Boston, Massachusetts, ארצות הברית
²¹Nephrology Section, Laniado Hospital, Netanya
²²Nephrology Section, the Ruth and Bruce Rappoport Faculty of Medicine, Technion, Haifa

Background: Genetic kidney diseases contribute a significant portion of kidney diseases in children and young adults. Nephrogenetics is a rapidly evolving subspecialty, however, in the clinical setting, increased use of genetic testing poses implementation challenges. Consequently, we established a national nephrogenetic clinic to apply a multidisciplinary model.

Methods: Patients were referred from different pediatric or adult nephrology units across the country, if their primary nephrologist suspected an undiagnosed genetic kidney disease. We determined the diagnostic rate and observed the effect of diagnosis on medical care. We also discuss the requirements of a nephrongenetic clinic in terms of logistics, recommended indications for referral and building a multidisciplinary team.

Results: Over 24 months, a total of 103 probands were evaluated, with an age range of 10 days to 72 years. The most common phenotypes included congenital anomalies of the kidneys and urinary tract, nephrotic syndrome or unexplained proteinuria, nephrocalcinosis/nephrolithiasis, tubulopathies and cryptogenic end-stage kidney disease. Over 90% of patients were referred due to clinical suspicion of an undetermined underlying genetic diagnosis. A molecular diagnosis was reached in 34/53 probands for whom genetic evaluation was completed, yielding a diagnostic rate of 64.2%. Of these, over 65% of diagnoses were made via next generation sequencing (gene panel- or exome sequencing).

Conclusions: We identified a significant fraction of genetics kidney etiologies among previously undiagnosed individuals which influenced subsequent clinical management. Our results support that nephrogenetics, a rapidly evolving field, may benefit from well-defined multidisciplinary co-management administered by a designated team of nephrologist, geneticist and bioinformatician.