Introduction:
Autosomal Dominant Polycystic Kidney Disease(ADPKD) is the most common genetic kidney disease and also a significant cause of renal failure. Clinical and genetic information of ADPKD in Thailand is limited.
Methods:
We retrospectively analyzed ADPKD patients clinically diagnosed at Siriraj Hospital from 2001 to 2023. Inclusion criteria were at least one year of clinical, including renal function data and must be investigated for mutation analysis in PKD1 and PKD2 gene. Single nucleotide variations (SNVs) in the entire coding sequence of PKD1 and/or PKD2 gene was performed by Sanger sequencing analysis of both DNA strands and Multiplex ligation-dependent probe amplification (MLPA) for both genes were analyzed for detection of copy number variations (CNVs) (deletion/duplication).
Results:
We included 175 patients, with 80 (45.7%) males. The common comorbidities were hypertension (79%), dyslipidemia (35.1%), diabetes mellitus (4.7%). Mean age of ADPKD diagnosis was 43.2 years. Mutation analysis revealed pathogenic variants in the PKD1 gene in 113 patients (64.6%) and in the PKD2 gene in 26 patients (14.9%); no mutations were identified in 36 patients (20.6%). Protein-truncating (PT) variants accounted for 67% and 81% of pathogenic mutations in PKD1 and PKD2, respectively. There were no significant differences in gender, comorbidities (including hypertension), or renal complications among PKD1, PKD2, and patients without detectable mutations. Extrarenal manifestations were generally similar across groups, except for liver cysts, which were more frequent in PKD2 patients compared to PKD1 and patients without detectable mutations (73.1% vs. 61.9% vs. 47.2%, respectively, P=0.04). Within a median follow up age of 55.5 years, 9.4% develop coronary artery disease, 13.5% had stroke and 8.8% was diagnosed of malignancy, including one case of renal cell carcinoma. In terms of renal outcomes, 40.9% of patients progressed to end-stage kidney disease (ESRD), and 31.1% required initiation of renal replacement therapy (RRT). The median age at RRT initiation was 52.9 years, significantly varying across different patient groups: 51.9 years for those with PKD1-PT mutations, 54.2 years for PKD1-nonPT mutations, 74.7 years for PKD2 mutations, and 51.5 years for patients without detectable mutations (P=0.04). The PKD1-PT mutation significantly increased the risk of ESRD compared to the PKD2 mutation (HR 4.65, 95% CI 1.99–10.88, P<0.001). Among the 139 patients with either PKD1 or PKD2 mutations, the Predicting Renal Outcome in Polycystic Kidney Disease (PROPKD) score was calculated. High PROPKD score (>7) was strongly associated with an increased risk of RRT initiation (HR 12.09, 95% CI 3.95–37.01, P<0.001) compared to low PROPKD score (<3). During the follow-up period, 22 patients died, with infection being the most common cause of death.
Conclusions:
This study provides a detailed overview of the clinical features and genetic mutations in Thai ADPKD patients, with mutation distribution similar to other populations. PKD1-PT mutations were linked to the worst renal outcomes, followed by patients with no detectable mutations and PKD1-nonPT mutations. PROPKD score can also predict ESRD risk in our population. As the largest reported cohort of ADPKD patients in Thailand, this study underscores the need for further analysis and prospective studies to improve understanding and management of ADPKD in this population.
I have no potential conflict of interest to disclose.
I did not use generative AI and AI-assisted technologies in the writing process.