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A broad clinical spectrum of PLCε1-related kidney disease and intrafamilial variability

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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.

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Funding

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

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Authors and Affiliations

  1. Department of Pediatric Nephrology, Faculty of Medicine, Istanbul University-Cerrahpaşa, Istanbul, Turkey

    Esra Karabağ Yılmaz, Seha Saygili, Nur Canpolat, Ayse Agbas & Salim Caliskan

  2. Department of Pediatric Nephrology, Faculty of Medicine, Hacettepe University, Sihhiye, 06100, Ankara, Turkey

    Bora Gulhan, Rezan Topaloglu & Fatih Ozaltin

  3. Department of Pediatric Nephrology, Faculty of Medicine, Cukurova University, Adana, Turkey

    Aysun Karabay Bayazıt

  4. Department of Pediatric Nephrology, Faculty of Medicine, Gaziantep University, Gaziantep, Turkey

    Beltinge Demircioglu Kilic

  5. Department of Pediatric Nephrology, Faculty of Medicine, Koc University, Istanbul, Turkey

    Nurver Akıncı

  6. Department of Pediatric Nephrology, Faculty of Medicine, Yeni Yuzyil University, Istanbul, Turkey

    Meryem Benzer

  7. Department of Pediatric Nephrology, Faculty of Medicine, Istanbul Medeniyet University, Istanbul, Turkey

    Nilufer Goknar

  8. Department of Pediatric Nephrology, Faculty of Medicine, Eskisehir Osmangazi University, Eskisehir, Turkey

    Asli Kavaz Tufan

  9. Department of Pediatric Nephrology, Faculty of Medicine, Karadeniz Technical University, Trabzon, Turkey

    Mukaddes Kalyoncu

  10. Department of Pediatric Nephrology, Faculty of Medicine, Ondokuz Mayıs University, Samsun, Turkey

    Hulya Nalcacioglu & Demet Tekcan

  11. Department of Pediatric Nephrology, Faculty of Medicine, Dokuz Eylül University, Izmir, Turkey

    Gizem Yıldız

  12. Department of Pediatric Nephrology, Faculty of Medicine, Istanbul University, Istanbul, Turkey

    Ahmet Nayır

  13. Nephrogenetics Laboratory, Department of Pediatric Nephrology, Faculty of Medicine, Hacettepe University, Ankara, Turkey

    Fatih Ozaltin

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  1. Esra Karabağ Yılmaz
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Correspondence to Fatih Ozaltin.

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Yılmaz, E.K., Saygili, S., Gulhan, B. et al. A broad clinical spectrum of PLCε1-related kidney disease and intrafamilial variability. Pediatr Nephrol 37, 1855–1866 (2022). https://doi.org/10.1007/s00467-021-05371-7

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  • DOI: https://doi.org/10.1007/s00467-021-05371-7

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