Heterocyclic dithiocarbamates have anti-inflammatory and anti-proliferative effects in rodent models of
chronic kidney disease. In this study, we tested the hypothesis that
pyrrolidine dithiocarbamate (
PDTC) reduces the progression of
polycystic kidney disease (PKD). Male Lewis
polycystic kidney (LPK) rats (an ortholog of Nek8/NPHP9) received
intraperitoneal injections of either saline vehicle or
PDTC (40 mg/kg once or twice daily) from postnatal weeks 4 until 11. By serial magnetic resonance imaging at weeks 5 and 10, the relative within-rat increase in total kidney volume and
cyst volume were 1.3-fold (P = 0.01) and 1.4-fold (P < 0.01) greater, respectively, in LPK + Vehicle compared to the LPK +
PDTC(40 mg/kg twice daily) group. At week 11 in LPK rats,
PDTC attenuated the increase in kidney weight to
body weight ratio by 25% (P < 0.01) and
proteinuria by 66% (P < 0.05 vs. LPK + Vehicle) but did not improve renal dysfunction. By quantitative whole-slide image analysis,
PDTC did not alter interstitial CD68+ cell accumulation, interstitial
fibrosis, or renal cell proliferation in LPK rats at week 11. The phosphorylated form of the nuclear factor (NF)-κB subunit, p105, was increased in cystic epithelial cells of LPK rats, but was not altered by
PDTC. Moreover,
PDTC did not significantly alter nuclear expression of the p50 subunit or NF-κB (p65)-DNA binding. Kidney enlargement in LPK rats was resistant to chronic treatment with a
proteasome inhibitor,
bortezomib. In conclusion,
PDTC reduced renal cystic enlargement and
proteinuria but lacked anti-inflammatory effects in LPK rats.