Esra Karabağ Yılmaz1, Seha Saygili1, Bora Gulhan2, Nur Canpolat1, Aysun Karabay Bayazıt3, Beltinge Demircioglu Kilic4, Nurver Akıncı5, Meryem Benzer6, Nilufer Goknar7, Asli Kavaz Tufan8, Mukaddes Kalyoncu9, Hulya Nalcacioglu10, Demet Tekcan10, Gizem Yıldız11, Ayse Agbas1, Ahmet Nayır12, Rezan Topaloglu2, Salim Caliskan1, Fatih Ozaltin13,14. 1. Department of Pediatric Nephrology, Faculty of Medicine, Istanbul University-Cerrahpaşa, Istanbul, Turkey. 2. Department of Pediatric Nephrology, Faculty of Medicine, Hacettepe University, Sihhiye, 06100, Ankara, Turkey. 3. Department of Pediatric Nephrology, Faculty of Medicine, Cukurova University, Adana, Turkey. 4. Department of Pediatric Nephrology, Faculty of Medicine, Gaziantep University, Gaziantep, Turkey. 5. Department of Pediatric Nephrology, Faculty of Medicine, Koc University, Istanbul, Turkey. 6. Department of Pediatric Nephrology, Faculty of Medicine, Yeni Yuzyil University, Istanbul, Turkey. 7. Department of Pediatric Nephrology, Faculty of Medicine, Istanbul Medeniyet University, Istanbul, Turkey. 8. Department of Pediatric Nephrology, Faculty of Medicine, Eskisehir Osmangazi University, Eskisehir, Turkey. 9. Department of Pediatric Nephrology, Faculty of Medicine, Karadeniz Technical University, Trabzon, Turkey. 10. Department of Pediatric Nephrology, Faculty of Medicine, Ondokuz Mayıs University, Samsun, Turkey. 11. Department of Pediatric Nephrology, Faculty of Medicine, Dokuz Eylül University, Izmir, Turkey. 12. Department of Pediatric Nephrology, Faculty of Medicine, Istanbul University, Istanbul, Turkey. 13. Department of Pediatric Nephrology, Faculty of Medicine, Hacettepe University, Sihhiye, 06100, Ankara, Turkey. fozaltin@hacettepe.edu.tr. 14. Nephrogenetics Laboratory, Department of Pediatric Nephrology, Faculty of Medicine, Hacettepe University, Ankara, Turkey. fozaltin@hacettepe.edu.tr.
Abstract
BACKGROUND: The phenotypic and genotypic spectrum and kidney outcome of PLCε1-related kidney disease are not well known. We attempted to study 25 genetically confirmed cases of PLCε1-related kidney disease from 11 centers to expand the clinical spectrum and to determine the relationship between phenotypic and genotypic features, kidney outcome, and the impact of treatment on outcome. METHODS: Data regarding demographics, clinical and laboratory characteristics, histopathological and genetic test results, and treatments were evaluated retrospectively. RESULTS: Of 25 patients, 36% presented with isolated proteinuria, 28% with nephrotic syndrome, and 36% with chronic kidney disease stage 5. Twenty patients underwent kidney biopsy, 13 (65%) showed focal segmental glomerulosclerosis (FSGS), and 7 (35%) showed diffuse mesangial sclerosis (DMS). Of the mutations identified, 80% had non-missense, and 20% had missense; ten were novel. No clear genotype-phenotype correlation was observed; however, significant intrafamilial variations were observed in three families. Patients with isolated proteinuria had significantly better kidney survival than patients with nephrotic syndrome at onset (p = 0.0004). Patients with FSGS had significantly better kidney survival than patients with DMS (p = 0.007). Patients who presented with nephrotic syndrome did not respond to any immunosuppressive therapy; however, 4/9 children who presented with isolated proteinuria showed a decrease in proteinuria with steroids and/or calcineurin inhibitors. CONCLUSION: PLCε1-related kidney disease may occur in a wide clinical spectrum, and genetic variations are not associated with clinical presentation or disease course. However, clinical presentation and histopathology appear to be important determinants for prognosis. Immunosuppressive medications in addition to angiotensin-converting enzyme inhibitors may be beneficial for selected patients. "A higher resolution version of the Graphical abstract is available as Supplementary information".
BACKGROUND: The phenotypic and genotypic spectrum and kidney outcome of PLCε1-related kidney disease are not well known. We attempted to study 25 genetically confirmed cases of PLCε1-related kidney disease from 11 centers to expand the clinical spectrum and to determine the relationship between phenotypic and genotypic features, kidney outcome, and the impact of treatment on outcome. METHODS: Data regarding demographics, clinical and laboratory characteristics, histopathological and genetic test results, and treatments were evaluated retrospectively. RESULTS: Of 25 patients, 36% presented with isolated proteinuria, 28% with nephrotic syndrome, and 36% with chronic kidney disease stage 5. Twenty patients underwent kidney biopsy, 13 (65%) showed focal segmental glomerulosclerosis (FSGS), and 7 (35%) showed diffuse mesangial sclerosis (DMS). Of the mutations identified, 80% had non-missense, and 20% had missense; ten were novel. No clear genotype-phenotype correlation was observed; however, significant intrafamilial variations were observed in three families. Patients with isolated proteinuria had significantly better kidney survival than patients with nephrotic syndrome at onset (p = 0.0004). Patients with FSGS had significantly better kidney survival than patients with DMS (p = 0.007). Patients who presented with nephrotic syndrome did not respond to any immunosuppressive therapy; however, 4/9 children who presented with isolated proteinuria showed a decrease in proteinuria with steroids and/or calcineurin inhibitors. CONCLUSION: PLCε1-related kidney disease may occur in a wide clinical spectrum, and genetic variations are not associated with clinical presentation or disease course. However, clinical presentation and histopathology appear to be important determinants for prognosis. Immunosuppressive medications in addition to angiotensin-converting enzyme inhibitors may be beneficial for selected patients. "A higher resolution version of the Graphical abstract is available as Supplementary information".
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