The Clinical and Mutational Spectrum of 69 Turkish Children with Autosomal Recessive or Autosomal Dominant Polycystic Kidney Disease: A Multicenter Retrospective Cohort Study

Ozum Tutal; Bora Gulhan; Emine Atayar; Selcuk Yuksel; Z Birsin Ozcakar; Oguz Soylemezoglu; Seha Saygili; Salim Caliskan; Mihriban Inozu; Esra Baskin; Ali Duzova; Mutlu Hayran; Rezan Topaloglu; Fatih Ozaltin

doi:10.1159/000528258

The Clinical and Mutational Spectrum of 69 Turkish Children with Autosomal Recessive or Autosomal Dominant Polycystic Kidney Disease: A Multicenter Retrospective Cohort Study

Nephron. 2023 Jan 19:1-14. doi: 10.1159/000528258. Online ahead of print.

Authors

Ozum Tutal¹, Bora Gulhan², Emine Atayar³, Selcuk Yuksel⁴, Z Birsin Ozcakar⁵, Oguz Soylemezoglu⁶, Seha Saygili⁷, Salim Caliskan⁷, Mihriban Inozu⁸, Esra Baskin⁹, Ali Duzova², Mutlu Hayran¹⁰, Rezan Topaloglu², Fatih Ozaltin^{2

3}

Affiliations

¹ Department of Pediatrics, Hacettepe University, Ankara, Turkey.
² Division of Pediatric Nephrology, Department of Pediatrics, Hacettepe University, Ankara, Turkey.
³ Nephrogenetics Laboratory, Division of Pediatric Nephrology, Department of Pediatrics Hacettepe University, Ankara, Turkey.
⁴ Division of Pediatric Nephrology, Department of Pediatrics, Pamukkale University, Denizli, Turkey.
⁵ Division of Pediatric Nephrology, Department of Pediatrics, Ankara University, Ankara, Turkey.
⁶ Division of Pediatric Nephrology, Department of Pediatrics, Gazi University, Ankara, Turkey.
⁷ Division of Pediatric Nephrology, Department of Pediatrics, Istanbul University-Cerrahpaşa, Istanbul, Turkey.
⁸ Department of Pediatric Nephrology, Ankara City Hospital, Bilkent, Ankara, Turkey.
⁹ Division of Pediatric Nephrology, Department of Pediatrics, Baskent University, Ankara, Turkey.
¹⁰ Department of Preventive Oncology, Hacettepe University, Ankara, Turkey.

PMID: 36657418
DOI: 10.1159/000528258

Abstract

Introduction: Autosomal recessive polycystic kidney disease (ARPKD) is associated with pathogenic variants in the PKHD1 gene. Autosomal dominant polycystic kidney disease (ADPKD) is mainly associated with pathogenic variants in PKD1 or PKD2. The present study aimed to identify the clinical and genetic features of Turkish pediatric ARPKD and ADPKD patients.

Methods: This multicenter, retrospective cohort study included 21 genetically confirmed ARPKD and 48 genetically confirmed ADPKD patients from 7 pediatric nephrology centers. Demographic features, clinical, and laboratory findings at presentation and during 12-month intervals were recorded.

Results: The median age of the ARPKD patients at diagnosis was lower than the median age of ADPKD patients (10.5 months [range: 0-15 years] vs. 5.2 years [range: 0.1-16 years], respectively, [p = 0.014]). At the time of diagnosis, the median eGFR in the ARPKD patients was lower compared to that of ADPKD patients (81.6 [IQR: 28.7-110.5] mL/min/1.73 m2 and 118 [IQR: 91.2-139.8] mL/min/1.73 m2, respectively, [p = 0.0001]). In total, 11 (52.4%) ARPKD patients had malnutrition; 7 (33.3%) patients had growth retardation at presentation; and 4 (19%) patients had both malnutrition and growth retardation. At diagnosis, 8 (16.7%) of the ADPKD patients had malnutrition, and 5 (10.4%) patients had growth retardation. The malnutrition, growth retardation, and hypertension rates at diagnosis were higher in the ARPKD patients than the ADPKD patients (p = 0.002, p = 0.02, and p = 0.0001, respectively). ARPKD patients with malnutrition and growth retardation had worse renal survival compared to the patients without (p = 0.03 and p = 0.01). Similarly, ADPKD patients with malnutrition had worse renal survival compared to the patients without (p = 0.002). ARPKD patients with truncating variants had poorer 3- and 6-year renal outcome than those carrying non-truncating variants (p = 0.017).

Conclusion: Based on renal survival analysis, type of genetic variant, growth retardation, and/or malnutrition at presentation were observed to be factors associated with progression to chronic kidney disease (CKD). Differentiation of ARPKD and ADPKD, and identification of the predictors of the development of CKD are vital for optimal management of patients with ARPKD or ADPKD.

Keywords: Autosomal dominant polycystic kidney disease; Autosomal recessive polycystic kidney disease; Chronic kidney disease; PKD1; PKD2; PKHD1; Prognosis.