#3773 Exploring prognostic markers in autosomal dominant polycystic kidney disease
Background and Aims Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disease and one of the most common causes of end-stage kidney disease (ESRD). The major ADPKD genes are PKD1 and PKD2, accounting for >90% of diagnosed families. The causal gene (PKD1>PKD2 or minor genes), type of PKD1 mutation, sex (male>female), environmental factors (obesity, salt intake), and total kidney volume (TKV), among others, are associated with severity and risk of progression to ESRD in ADPKD. TKV may be associated with intrarenal vascular involvement by kidney cysts. The best way to estimate TKV is by magnetic resonance imaging (MRI). Mutational analysis and MRI are expensive techniques, require expertise, and they are not always available in all centers. An increase in renal resistive index (RRI) assessed by ultrasonography (US) reflects intrarenal vascular involvement and has been related to a decrease in glomerular filtration rate (GFR) in other nephropathies. Gut microbiome has not been explored in ADPKD patients, but it has been demonstrated its relevance in other kidney diseases. Therefore, our aim was to explore the gut microbiome, and the RRI in ADPKD patients and to investigate their link with prognostic markers, such as causal gene, sex, obesity, and TKV. Method A cross-sectional observational study was performed including patients diagnosed with ADPKD. Relevant clinical, demographic, and analytical information were gathered for each participant. Mutational analysis was performed. TKV was measured by MRI. RRI was assessed by US. Gut microbiome profile was obtained by Shotgun. Results This study included 50 ADPKD patients with a median age of 44.5 years old (IR: 34.8–57.5). Men presented higher TKV compared to women (1786.8 vs 943, P = 0.007). TKV was positively correlated with RRI, and body mass index (BMI) and inversely correlated with GFR, and 1.25 dihydroxyvitamin D. BMI was positively correlated with hemoglobin and inversely correlated with 1.25 dihydroxyvitamin, and GFR. In the multivariate analysis, TKV, GFR, and sex were independent predictors of RRI, with statistical significance. The gut microbiome was compared between ADPKD patients according to GFR, using ANCOM-BC methodology adjusted by age, sex, and BMI. A statistically significant higher prevalence of species from the phylum Actinomycetota was observed in ADPKD patients with GFR≥60ml/min/1.73 m2, and a higher prevalence of species from the phylum Bacteroidota and Bacillota was found in ADPKD patients with GFR <60ml/min/1.73 m2. The taxonomic profiles when comparing between ADPKD patients with RRI <0.65 to ADPKD patients with RRI≥0.65 were distinct at species level, observing a predominance of Streptococcus genus in the group RRI ≥0.65. Analyzing RRI as a continuous variable, an increase in Streptococcus genus was confirmed while RRI rises. Moreover, higher RRI levels were associated to an increase in Pseudomonadota and Thermodesulfobacteriota and lower RRI levels were associated to an increase in Bacteroidota. Comparing taxonomic profiles in ADPKD patients according to the presence of PKD1 or PKD2 mutations, an increase in Actinomycetota, and Bacteroidota at phylum level, and Bacilalles, and Veionella at order level was observed in PKD1 group. Conclusion TKV, GFR, and sex are independent predictors of RRI in ADPKD, which implies a link between these factors and renal macro and microvascular involvement. Regarding the gut microbiome in our ADPKD patients, some specific taxa have been shown to be associated to well-stablished prognostic markers. Future studies may explore the role of these bacterial groups as potential biomarkers in ADPKD.
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