Screening for Respiratory Ciliary Dysfunction in Autosomal Recessive Polycystic Kidney DiseaseRoot H1, Gunay-Aygun M2, Holland SM1, Olivier KN11Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases and 2Medical Genetics Branch, National Human Genome Research Institute, Bethesda, MD
Autosomal recessive polycystic kidney disease (ARPKD) is a rare sensory ciliopathy characterized by enlarged kidneys due to renal cysts and associated congenital hepatic fibrosis (CHF).1 Recent data have suggested a possible connection between sensory ciliopathies and respiratory ciliary dysmotility. Bronchiectasis was seen on chest CT scans in 37% of autosomal dominant polycystic kidney disease patients vs. 12% of control chronic kidney disease patients suggesting possible respiratory ciliary abnormalities.2 In vivo measurement of nasal nitric oxide (nNO) production has been used as an easily performed, sensitive screen for primary ciliary dyskinesia (PCD).
Table 1. Respiratory Symptoms of ARPKD Patients
To screen for respiratory ciliary dysfunction in ARPKD by assessing nNO production and to look for evidence of respiratory tract abnormalities in ARPKD patients.
Figure 1. Nasal Nitric Oxide Levels in ARPKD patients and 2 sets of controls: healthy volunteers from NIAID (age 32±2 years) and from UNC (age 14±1).
Records of patients enrolled in a natural history study of ARPKD/CHF at the NIH were reviewed for a history of respiratory symptoms for a history of respiratory symptoms and/or respiratory tract infections, prior pulmonary function test results, and chest imaging. Sampling of nNO was performed through a foam nasal probe during exhalation through a resistor and was measured in real-time via a NiOx (Aerocrine) chemiluminescense analyzer. Values from ARPKD patients were compared to the nNO measurements from healthy volunteers.
1. Harris PC, Torres VE. Polycistic Kidney Disease. Annu. Rev. Med. 2009. 60:321-37.
2. Driscoll JA, Bhalla S, Liapis H, Ibricevic A, Brody SL. Autosomal Dominant Polycistic Kidney Disease is Associated with an Increased Prevalence of Radiographic Bronchiectasis. 2008. Chest. 133:1181-1188.
Figure 2. Lung Function Tests results of ARPKD patients. These are the % predicted values of Forced Expiratory Volume in 1 second (FEV1), Total Lung Capacity (TLC) and Diffusing Capacity of the Lung for Carbon Monoxide (DLCO).
*PET = Pressure Equalization Tubes
Supported in part by intramural funds of the NIAID and NHGRI and by the Genetic Diseases of Mucociliary Clearance Consortium, NIH 9 U54 HL096458-06 funded by Office of the Director, and supported by ORDR and NHLBI, NIH.