#5983 PULMONARY INVOLVEMENT IN AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE

Abstract

Abstract Background and Aims Autosomal dominant policystic kidney disease (ADPKD) is the most common genetic kidney disease. It is caused by mutations in PKD1 and PKD2 genes, which encode for polycystin-1 (PC-1) and polycystin-2 (PC-2), two proteins localized in the primary cilia which regulate calcium permeability and cellular signaling pathways. The major phenotype of the disease is the formation of multiple cysts in the kidneys but in many cases it also involves other organs like heart, brain and lungs. The latters are not yet well studied; some papers report a higher prevalence of bronchiectasis in ADPKD patients compared to the general population; morover, one work describes the absence of PC-1 in motile cilia of ADPKD pts compared to controls, who actually do express the protein. Based on available literature, we hypothesized that the PC-1 and PC-2 could have a role also in motile cilia. Exaled nasal nitric oxide (nNO) is an indirect marker of cilia dysfunction, standardized for the screening of primary ciliary dyskinesia, a motile ciliopathy, in which very low levels of nNO are found because of the entrapment of NO in the abundant stagnant mucus. Method We recruited 27 patients with ADPKD and 25 randomly selected controls. We compared nNO measurements between the two groups, stratifying for truncated mutations and eGFR. After stratification according to ADPKD genetic mutation, we analyzed separately each of the two subgroups with the control group. Results nNO levels were no different in ADPKD patients compared with healthy controls (mean ± standard deviation: 850±240 vs 923±290; P = .3). However in sub-group analysis, lower nNO measurements were found in patients with truncated mutation (769±164) compared to the control group (924±290, P = .05). No association was observed between renal functions expressed as eGFR and nNO levels. Discussion Overall nNO levels did not differ in ADPKD individuals compared to controls, although lower nNO measurements were observed in ADPKD patients exhibiting a truncated mutation. Conclusion Even at the edge of the statistical significance (P = .05), given it's confirmed in a wider population, this finding could signify that pts who carry a more aggressive genotype (PKD-1 truncated mutation) may not express polycystins in motile cilia; this aspect is in line with the verified knowledge that this kind of mutation ends up in the total absence of the protein. On the other hand, pts with a missense mutation may still express the protein in motile cilia, therefore without any functional impairment.