Decline in renal concentration ability in lithium treated patients

Lithium is a common therapeutic agent used to treat patients with various mood
disorders. In Western countries about 0.1% of humans are being treated with
lithium. However, its use has been associated with several forms of renal
injury. The most common presentation of lithium-induced nephrotoxicity is
nephrogenic diabetes insipidus (NDI), characterized by resistance to
vasopressin, polyuria, and polydipsia. Slightly impaired renal concentrating
ability is found in about 50% of patients. Initially, the decreased urinary
concentrating ability is largely reversible after cessation of lithium.
However, continued treatment ultimately results in polyuria due to nephrogenic
diabetes insipidus (NDI) in about 20% of patients. Nephrogenic diabetes
insipidus induced by lithium may even persist despite the cessation of
treatment, indicating irreversible renal damage. This functional lesion is
associated with chronic focal interstitial fibrosis predominantly in the
medullary region of the kidney which may be progressive, leading to end-stage
renal failure.
Lithium-induced nephrogenic diabetes insipidus results from accumulation of
lithium in the collecting tubular cells after entry into these cells through
the epithelial sodium channels (ENaC) in the luminal membrane. Lithium blocks
vasopressin-induced reabsorption by inhibiting adenylate cyclase activity, and
hence cyclic adenosine monophosphate production, and also by decreasing the
apical membrane expression of aquaporin 2, the collecting tubule water channel.
Besides polyuria due to nephrogenic diabetes insipidus, however, both central
diabetes insipidus (CDI) and primary polydipsia have also been described in
patients treated with lithium. Therefore, a dDAVP test should be performed to
establish the correct diagnosis.
Lithium induced defects in urinary concentration can frequently be ameliorated
by treatment with diuretics (thiazide, amiloride). In addition, early treatment
with amiloride is thought to prevent the development of renal insufficiency.
However, most patients with lithium induced nephrogenic diabetes insipidus only
present with complaints in an advanced stage of the disease. Early recognition
of an impaired urinary concentration may be helpful in selecting lithium
treated patients at risk of severe nephrogenic diabetes insipidus and allow
increased surveillance and an earlier start of treatment. In the current study
we aim to explore the decline in renal concentration ability and nephrogenic
diabetes insipidus in a Dutch population of lithium treated patients.

- to explore the decline in renal concentration ability (RCA) in a Dutch
population of lithium treated patient
- to explore the decline in kidney function

This is a retrospective cross-sectional study.

Patients may be exposed to the risk of adverse effects as a consequence of
their participation in this study. Adverse reactions occurring most often (but
still infrequently) include transient headache, nausea, nasal congestion,
rhinitis nosebleed, sore throat, cough, upper respiratory infections and
flushing occasionally along with mild abdominal cramps. In addition, intranasal
DDAVP at high dosage infrequently produce a slight elevation of blood pressure.
Since dDAVP is administered only once, there is no prolonged action and
development of severe adverse reactions is thus unlikely. Furthermore, many of
these risks are substantially minimized by increased subject monitoring before,
during, and after treatment.
Early recognition of an impaired urinary concentration may be helpful in
selecting lithium treated patients at risk of severe nephrogenic diabetes
insipidus and allow increased surveillance and an earlier start of treatment.
Finally, information obtained from this study may improve the evaluation and
care for patients with lithium induced NDI in the future.