Citrate therapy for polycystic kidney disease in rats.
BACKGROUND
Few treatments are available to slow the progression to renal failure in autosomal dominant polycystic kidney disease (PKD). In an animal model of PKD, the male heterozygous Han:SPRD rat, intake of a solution of potassium citrate plus citric acid (KCitr) from age one to three months prevented a decline in glomerular filtration rate (GFR). The present study tested whether this beneficial effect is sustained and explored handling of citrate and ammonia in normal and cystic kidneys.


METHODS
Rats were provided with tap water or citrate solutions to drink, and clearance and survival studies were performed.


RESULTS
The GFRs of rats with PKD that consumed KCitr from one month of age were normal at six months of age, while those of their counterparts on water were about one third of normal. Long-term KCitr treatment extended the average life span of rats with PKD from 10 to 17 months. Compared with normal rats, water-drinking rats with PKD had higher plasma [citrate], renal cortical [citrate], and fractional excretion of citrate, and lower rates of renal citrate consumption, ammonia synthesis, and ammonia excretion. Cortical PNH3 was not elevated in cystic kidneys. Intake of Na3 citrate/citric acid solution or K3 citrate solution, but not ammonium citrate/citric acid solution, prevented a decline in GFR in three-month-old rats with PKD.


CONCLUSIONS
Rats with PKD show abnormal renal handling of citrate and ammonia. Citrate salts that have an alkalinizing effect preserve GFR and extend survival.
Tanner
G A
GA
Department of Physiology and Biophysics, Indiana University School of Medicine, Indianapolis, Indiana, USA. gtanner@iupui.edu
Tanner
J A
JA
D000641:Ammonia / Q000378:metabolism; D000818:Animals; D002951:Citrates / Q000378:metabolism / Q000627:therapeutic use*; D004326:Drinking; D004573:Electrolytes / Q000378:metabolism; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007668:Kidney / Q000378:metabolism / Q000503:physiopathology; D007690:Polycystic Kidney Diseases / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D019357:Potassium Citrate / Q000627:therapeutic use; D051381:Rats; D011922:Rats, Mutant Strains; D012996:Solutions; D016019:Survival Analysis; D014867:Water
D002951:Citrates; D004573:Electrolytes; D012996:Solutions; D014867:Water; D000641:Ammonia; D019357:Potassium Citrate