ASN's Mission

ASN leads the fight to prevent, treat, and cure kidney diseases throughout the world by educating health professionals and scientists, advancing research and innovation, communicating new knowledge, and advocating for the highest quality care for patients.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005


The Latest on Twitter

Kidney Week

Abstract: TH-PO593

Lack of Alpha-Intercalated Cells Links Autosomal Dominant Polycystic Kidney Disease to Urinary Tract Infection in Mice and Humans

Session Information

Category: Developmental Biology and Inherited Kidney Diseases

  • 402 Stem Cells


  • Gao, Chao, Albany medical college, Albany, New York, United States
  • Zhang, Long, Albany medical college, Albany, New York, United States
  • Chen, Lihe, NIH, Bethesda, Maryland, United States
  • Zhang, Ye, AMC, Albany, New York, United States
  • Chen, Enuo, Albany Medical College, Albany, New York, United States
  • Wallace, Darren P., University of Kansas Medical Center, Kansas City, Kansas, United States
  • Zhou, Qiaoling, Xiangya Hospital, Changsha, China
  • Higgins, Paul J., Albany Medical College, Albany, New York, United States
  • Zhang, Wenzheng, Albany Medical College, Albany, New York, United States

Urinary tract infection (UTI) is a common feature of autosomal dominant polycystic kidney disease (ADPKD) with ~30-50% of ADPKD patients having at least one UTI during their lifetime. However, the underlying cellular and molecular mechanisms linking ADPKD to UTI remain unaddressed.


Hence, Pkd2f/f Aqp2Cre mice were generated to disrupt Pkd2 in Aqp2+ progenitor cells, which give rise to all known cell types of the connecting tubule/collecting duct (CNT/CD).


Pkd2f/f Aqp2Cre mice developed severe PKD and died by P17. Double and triple immunofluorescence (IF) staining for various segment- and/or cell-specific markers were conducted. At least 1000 CNT/CD cells from 3 Pkd2f/f Aqp2Cre and 3 WT mice for each IF combination were categorized and counted based on the marker expression. Using Aqp2, V-ATPase B1B2 and AE1 as markers for principal cells (PC), intercalated cells (IC) and a-IC, respectively, we found that Pkd2f/f Aqp2Cre mice had a reduced IC/PC ratio from 37.61±1.23% in WT to 7.45±1.08% and completely lost a-IC at P17. Neutralized urine from Pkd2f/f Aqp2Cre mice is significantly less inhibitory for bacterial growth than that from WT mice. In P6 Pkd2f/f Aqp2Cre mice, cysts began to be detectable with occasional presence of a-IC. TUNEL assay showed that IC, particular a-IC, were more apoptotic than PC. We conducted the same IF with kidneys from ADPKD patients (n=27) and minimal change disease patients (MCD) as normal control (n=5). While all PC and IC markers were readily detectable in each of MCD samples, cysts containing AQP2+ cells were found only in 13 ADPKD samples. Among these 13 ADPKD samples, we counted >4000 CNT/CD cells and found that ADPKD diminished the IC/PC ratio from 26.07±6.19% in MCD to 10.12±6.53%. None of the ADPKD kidneys had AE1+ cells in Aqp2+ labeled cystic structure. Seldom AE1+ cells were observed in apparently normal CNT/CD of some ADPKD kidneys.


Our data suggest that Pkd2 deletion in Aqp2+ progenitor cells is sufficient for PKD development, and a-IC are selectively depleted with the disease development in both mice and human. The lack of a-IC to acidify urine and secret neutrophil gelatinase-associated lipocalin (NGAL) that chelates siderophore-containing iron may link ADPKD to UTI.


  • NIDDK Support