The current study was undertaken to investigate the presence of CNP im
munoreactivity in both human kidney and urine. Immunohistochemical sta
ining with an indirect immunoperoxidase method utilizing an antibody w
hich is 100% cross-reactive to both CNP-53 and CNP-22 was performed on
five human kidney specimens (three biopsies of normal cadaveric donor
kidneys and two of normal autopsy specimens). CNP immunoreactivity wa
s positive in proximal, distal and medullary collecting duct tubular c
ells in a cytoplasmic and granular staining pattern. CNP immunoreactiv
ity was also determined in the urine of five healthy volunteers utiliz
ing a sensitive and specific double-antibody radioimmunoassay with a m
ean concentration of 10.8 +/- 1.0 pg/ml. With the utilization of high
pressure liquid chromatography, this immunoreactivity proved to be con
sistent with both the low molecular weight form, CNP-22, as well as th
e high molecular weight form, CNP-53. Urinary excretion of CNP was als
o measured in normal subjects (N = 5) and in patients with congestive
heart failure (CHF, N = 6). CHF patients excreted over three times mor
e CNP than normals (27.2 +/- 2.8 vs. 8.7 +/- 0.81 pg/min, P < 0.004) d
espite no difference between the two groups in plasma CNP concentratio
ns (6.97 +/- 0.28 vs. 8.08 +/- 1.52 pg/ml, P = NS). This study demonst
rates for the first time the presence of CNP immunoreactivity in human
kidney and suggests that renal tubular cells may be an additional non
-vascular site of synthesis for this cardiorenal acting peptide. This
study also demonstrates an increase in urinary CNP excretion in conges
tive heart failure.