Lithium treatment reduces the renal kallikrein excretion rate

Lithium treatment reduces the renal kallikrein excretion rate.
Lithium salts are widely used agents for the prophylactic treatment
of affective disorders. Lithium salts may be associated with distal
nephron dysfunction. Kallikrein is a protease which is generated by
the distal nephron. We used an amidolytic assay of
chromatographically purified enzyme to determine the urinary
excretion rate of active kallikrein in relation to lithium
treatment. All plasma lithium concentrations were within the
therapeutic range (0.4 to 0.9 mmol/liter). In 15 patients the
urinary excretion rate of active kallikrein was 267.4 65.6 mU/24
hrs before lithium treatment, and fell to 117.8 39.6 mU/24 hrs (P
< 0.05) on day 14 of lithium treatment. This reduction was
associated with a decrease of immunoreactive kallikrein in the same
urines by 66%. In another 15 patients who had undergone lithium
therapy for an average period of 5.6 years, the urinary excretion
rate of active kallikrein was 86.1 14.5 mU/24 hrs, while 21
age-matched healthy controls had an excretion rate of 364.1 58.4
mU/24 hrs (P < 0.05). Measurements of immunoreactive kallikrein
in the same urine samples demonstrated a reduction of kallikrein
after long-term lithium treatment by 78%. These observations could
not be attributed to changes in creatinine clearance, renal sodium
or potassium excretion rates or plasma concentrations of
aldosterone and vasopressin. Addition of lithium to the urine in
vitro had no demonstrable effect on kallikrein measurement by
amidolytic assay. We conclude that lithium in therapeutic plasma
concentrations may directly suppress the secretion of kallikrein by
renal connecting tubule cells.