Background

1. 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 Background Results Summary 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). • The average age and nNO of the ARPKD patients (n=28) were 15±(SEM)2 years and 204±13 nL/min respectively compared to 32±2 years (p<0.0001) and 289±16 nL/min (p<0.0001) in the NIAID controls (n=25) and 14±1 years (p>0.7) and 272±11 nL/min (p<.0008) in the UNC controls (n=79). • Six ARPKD patients (21%) had a history of recurring respiratory tract infections including 3 out of 4 with otitis media requiring myringotomy tubes (nNO: 115, 132, 182 nL/min). • Air trapping on lung volume measurements was noted in 8 (n=22, 36%) and abnormal diffusion was noted in 16 (n=21, 76%) patients. • Three patients had available high resolution chest CT scans; no evidence of bronchiectasis was seen. Table 1. Respiratory Symptoms of ARPKD Patients Objectives To screen for respiratory ciliary dysfunction in ARPKD by assessing nNO production and to look for evidence of respiratory tract abnormalities in ARPKD patients. Conclusions Methods 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). • None of the ARPKD patients had nNO levels in the range seen with PCD (<100 nL/min). • However, the values were significantly lower than both older, same-site controls and age appropriate controls from UNC with lower levels in those with more respiratory problems. • Respiratory infections and respiratory tract abnormalities in ARPKD indicate further investigation of respiratory ciliary dysfunction is warranted. 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. References 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.