Assessing ciliary function in polycystic kidney disease: beyond the kidney

An increased understanding of the genetic, molecular and cellular mechanisms responsible for the development of polycystic kidney disease has laid out the foundation for the development of rational therapies. Many animal models where these therapies can be tested are currently available. This review summarizes the rationale for these treatments, the results of preclinical trials and the prospects for clinical trials, some already in early phases of implementation.

Detection of autosomal dominant polycystic kidney disease by NMR spectroscopic fingerprinting of urine

Autosomal dominant polycystic kidney disease (ADPKD) is a renal disease with genetic transmisson. Mutations in the PKD1 and PKD2 genes, which encode integral membrane proteins of the cilia of primary renal tubule epithelial cells, are seen in ADPKD. The aim of this study was to evaluate the sinonasal epithelium, which is epithelium with cilia, by measuring the nasal mucociliary clearance time, and to investigate the effect of ADPKD on nasal mucociliary clearance. The study included 34 patients, selected from patients followed up in the Nephrology Clinic, and 34 age and gender-matched control group subjects. The nasal mucociliary clearance time (NMCT) was measured with the saccharin test. The mean age of the study subjects was 47.15 ± 14.16years in the patient group and 47.65 ± 13.85years in the control group. The eGFR rate was determined as mean 72.06 ± 34.26mL/min in the patient group and 99.79 ± 17.22mL/min in the control group (p < 0.001). The NMCT was determined to be statistically significantly longer in the patient group (903.6 ± 487.8s) than in the control group (580 ± 259s) (p = 0.006). The study results showed that the NMCT was statistically significantly longer in patients with ADPKD compared to the control group, but in the linear regression analysis results, no correlation was determined between eGFR and NMCT.

Short-term effects of tolvaptan on renal function and volume in patients with autosomal dominant polycystic kidney disease

Defining a Link with Autosomal-Dominant Polycystic Kidney Disease in Mice with Congenitally Low Expression of Pkd1

Overview of polycystic kidney disease in children.

Childhood ADPKD: Answers and more questions

Intermediate Volume on Computed Tomography Imaging Defines a Fibrotic Compartment that Predicts Glomerular Filtration Rate Decline in Autosomal Dominant Polycystic Kidney Disease Patients

Evaluation of urine biomarkers of kidney injury in polycystic kidney disease

Autosomal dominant (ADPKD) and autosomal recessive (ARPKD) polycystic kidney disease are caused by mutations in Pkd1/Pkd2 and Pkhd1, which encode polycystins (PCs) and fibrocystin/polyductin (FPC). Our recent study reported that a deficiency in FPC increases the severity of cystic disease in Pkd2 mutants and down-regulates PC2 in vivo, but the precise molecular mechanism of these effects is unknown (Kim, I., Fu, Y., Hui, K., Moeckel, G., Mai, W., Li, C., Liang, D., Zhao, P., Ma, J., Chen, X.-Z., George, A. L., Jr., Coffey, R. J., Feng, Z. P., and Wu, G. (2008) J. Am. Soc. Nephrol. 19, 455-468). In this study, through the use of deletion and mutagenesis strategies, we identified a PC2-binding domain in the intracellular C terminus of FPC and an FPC-binding domain in the intracellular N terminus of PC2. These binding domains provide a molecular basis for the physical interaction between PC2 and FPC. In addition, we also found that physical interaction between the binding domains of PC2 and FPC is able to prevent down-regulation of PC2 induced by loss of FPC. In vivo, we generated a mouse model of ADPKD with hypomorphic Pkd2 alleles (Pkd2nf3/nf3) and show that PC2 down-regulation is accompanied by a phenotype similar to that of Pkhd1(-/-) mice. These findings demonstrate a common mechanism underlying cystogenesis in ADPKD and ARPKD and provide insight into the molecular relationship between PC2 and FPC.

Informatics-guided drug repurposing for Autosomal Dominant Polycystic Kidney Disease (ADPKD).

Anoctamin 1 induces calcium-activated chloride secretion and proliferation of renal cyst–forming epithelial cells

Polycystic Liver Disease: The Benefits of Targeting cAMP.

Phenotypic variability in PKD1: The family as a starting point

The vasculopathy of autosomal dominant polycystic kidney disease: Insights from animal models