Renal Toxicity of Lithium

3/9/2020 Renal toxicity of lithium - UpToDate
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Renal toxicity of lithium

Author: Edgar V Lerma, MD, FACP, FASN, FAHA
Section Editor: Richard H Sterns, MD
Deputy Editor: John P Forman, MD, MSc
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Aug 2020. | This topic last updated: Apr 21, 2020.
INTRODUCTION
Chronic lithium ingestion in patients with bipolar (manic depressive) illness has been associated with
several different forms of kidney injury [1]. Nephrogenic diabetes insipidus (NDI) is the most common
renal side effect of lithium therapy [2,3].
The predominant form of chronic kidney disease associated with lithium therapy is a chronic
tubulointerstitial nephropathy [4]. Although the majority of studies show infrequent and relatively mild
renal insufficiency attributable to lithium therapy, end-stage kidney disease (ESKD) secondary to
lithium-associated chronic tubulointerstitial nephropathy does occur in a small percentage of patients
[3,5-8]. Relatively less is known about potential glomerular toxicity of lithium, particularly the nephrotic
syndrome. Additional kidney manifestations of lithium exposure include renal tubular acidosis and
hypercalcemia. (See "Lithium poisoning".)
NEPHROGENIC DIABETES INSIPIDUS
Normally, water permeability of principal cells in the collecting tubule is regulated by antidiuretic
hormone (ADH). Aquaporin-2 water channels (AQP2), which normally reside in the endosomes of
principal cells, move to and fuse with the luminal membrane under the influence of ADH, thereby
allowing water to be reabsorbed down the favorable concentration gradient. (See "General principles
of disorders of water balance (hyponatremia and hypernatremia) and sodium balance (hypovolemia
and edema)", section on 'Regulation of plasma tonicity'.)
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Chronic lithium ingestion can lead to resistance to ADH, resulting in polyuria and polydipsia in up to
20 to 40 percent of patients [4,9]. Lithium enters the principal cells of the collecting duct through
epithelial sodium channels in the luminal membrane [9,10]. It then accumulates in these cells and
interferes with the ability of ADH to increase water permeability. Several possible mechanisms may
be involved [2,9,11-14].
Lithium may increase expression of cyclooxygenase-2 and therefore increase urinary prostaglandin
E2 excretion by medullary interstitial cells [13]. These prostaglandins then act on principal cells to
induce lysosomal degradation of AQP2 water channels and a decline in urine concentrating ability:
Lithium may reduce AQP2 gene transcription, an effect that is prostaglandin

independent, ●
leading to a further decrease in concentrating ability [13].
Lithium induces collecting duct remodeling characterized by a decreased population of

principal ●
cells relative to the number of intercalated cells, a phenomenon that was previously presumed to
be due to apoptosis [11,12]. However, lithium may actually lead to proliferation of principal cells,
which then undergo cell cycle arrest [15]. This may also be responsible for the development of
interstitial nephritis and renal fibrosis.
With chronic use in humans, nephrogenic diabetes insipidus (NDI) often becomes irreversible. In one
study, patients who had been on the drug for more than 18 years invariably had an irreversible defect
[12].
Acute onset of nocturia is an important clue to the presence of NDI. The urine is normally most
concentrated in the morning due to lack of fluid ingestion overnight; as a result, the first manifestation
of a loss of concentrating ability is often nocturia.
It should not be assumed that polyuria in a patient taking lithium is due to NDI. Both central diabetes
insipidus (CDI) and primary polydipsia have also been described in patients treated with lithium; they
may be induced by lithium or reflect underlying psychiatric disease, particularly the use of
psychotropic medications, which induce a dry mouth, thereby stimulating thirst and producing a
picture of primary polydipsia [4,16,17].
Thus, a water restriction test may be helpful in establishing the correct diagnosis since the treatment
of these disorders is different. (See "Evaluation of patients with polyuria" and "Causes of hypotonic
hyponatremia in adults", section on 'Primary polydipsia due to psychosis'.)
Treatment — Although usually at least partially reversible [18], the lithium-induced concentrating
defect may be permanent after prolonged therapy [4,19]. When lithium-induced NDI is diagnosed,
discontinuation of the drug may be appropriate. However, in many cases, the benefits of lithium on
mood stabilization and suicide prevention outweigh the risks [20,21]. For those patients who continue
lithium therapy, we recommend the concomitant use of the potassium-sparing diuretic, amiloride.
Amiloride inhibits the epithelial sodium channels in collecting tubule cells (figure 1) and therefore
should minimize further accumulation of lithium (if lithium therapy is continued). The following data
support the use of amiloride in patients with NDI who continue to use lithium:
Amiloride was given to nine patients who continued to take lithium despite the development of
●
NDI [10]. After three to four weeks of therapy, mean urine volume fell significantly (from 4.7 to
3.1 liters per day), and urine osmolality increased significantly (from 228 to 331 mosm/kg). This
effect persisted for at least six months.
In a placebo-controlled crossover study, 11 patients with lithium-induced NDI were treated

with ●
10 mg/day of amiloride or placebo in random order for six weeks [22]. Amiloride therapy
significantly increased the responsiveness of the urine osmolality to exogenous arginine
vasopressin (165 percent increase in urine osmolality); no change in responsiveness to arginine
vasopressin was seen with placebo.
However, amiloride is likely to be effective only when there is a mild to moderate concentrating defect
that is potentially reversible. The experience with amiloride has been disappointing in patients with
severe disease (maximum urine osmolality below 200 mosmol/kg). In these patients, the tubular
damage is often permanent, even if lithium is discontinued [4,19]; as a result, diminishing lithium entry
into the collecting tubular cells cannot improve concentrating ability.
If amiloride therapy is given, serum lithium concentrations must be carefully monitored since diuretic
induced volume depletion may increase proximal sodium and lithium reabsorption. The ensuing fall in
lithium excretion may then require a reduction in drug dose.
Other therapeutic options to manage polyuria in lithium-induced NDI are similar to those in other
causes of NDI: a thiazide diuretic (to diminish distal water delivery or upregulate aquaporin receptors
[23]) and a nonsteroidal antiinflammatory drug (NSAID; to decrease the synthesis of prostaglandins)
[16]. (See "Treatment of nephrogenic diabetes insipidus".)
Another well-accepted regimen is the use of the combination of low-sodium diet and thiazide diuretics.
Thiazides decrease urine volume and increase urine osmolality by producing a state of mild sodium
depletion; this reduces distal tubule delivery of sodium and increases fractional water reabsorption in
the collecting duct. As with the use of amiloride, serum lithium concentrations must be closely
monitored after initiation of therapy with a thiazide diuretic. (See "Treatment of nephrogenic diabetes
insipidus".)
Since most patients have only partial resistance to ADH, it is also possible that attaining
supraphysiologic levels of ADH (by administering desmopressin [1-deamino,8-D arginine
vasopressin; dDAVP]) will attenuate the polyuria. The likelihood of success may be increased by
combining desmopressin with an NSAID [24]. NSAID therapy alone also may be effective in selected
patients [25]. (See "Treatment of nephrogenic diabetes insipidus".)
The risk of hypernatremia and its complications is also considerable in these patients. This is
particularly true in settings in which fluid intake is curtailed, during an acute illness, or when
inadequate fluid resuscitation is given in those undergoing surgery.
RENAL TUBULAR ACIDOSIS
The tubular defect in the distal nephron can also impair the ability to maximally acidify the urine. This
is most often manifested as the incomplete form of type 1 (distal) renal tubular acidosis, in which the
urine pH is persistently above 5.3 but the extracellular pH and bicarbonate concentration are within
the normal range [4]. (See "Etiology and diagnosis of distal (type 1) and proximal (type 2) renal
tubular acidosis" and "Overview and pathophysiology of renal tubular acidosis and the effect on
potassium balance".)
NEPHROTIC SYNDROME
Lithium has infrequently been associated with the nephrotic syndrome. Most cases are due to
minimal change disease [26,27], but focal segmental glomerulosclerosis (FSGS) has also been
described (picture 1 and picture 2) [6,28].
The mechanism by which lithium leads to glomerular injury is not completely understood, but the
course is highly suggestive of an etiologic role for lithium (ie, epithelial toxicity). Proteinuria generally
begins within 1.5 to 10 months after the onset of therapy and, in minimal change disease, completely
or partially resolves in most patients one to four weeks after lithium is discontinued [26]. In several
patients, reinstitution of lithium led to recurrent nephrosis [26,27]. Corticosteroids have occasionally
been required to induce remission; it is possible that the minimal change disease in such cases was
unrelated to lithium [26].
The relationship to FSGS is less clear. In three patients, for example, cessation of lithium did not lead
to resolution of the disease [28], suggesting either no relation to lithium or possible secondary FSGS
due to tubular injury induced by chronic lithium therapy. (See "Focal segmental glomerulosclerosis:
Pathogenesis", section on 'Drugs and toxins'.)
Edema during the manic phase — Occasionally, lithium-treated patients become edematous in the
absence of overt kidney, hepatic, or cardiac disease [29-31]. How this occurs is not well understood,
but two factors may contribute: a marked increase in sodium intake that may be induced in part by
mania and perhaps a lithium-induced reduction in maximum sodium excretory capacity that is of no
importance when sodium intake is relatively normal. Affected patients present with the unusual
combination of edema plus high rates of urinary sodium excretion that can exceed 200 mEq/day
[30,31]. Serum lithium concentrations may also fall below the therapeutic range at this time due to
enhanced urinary lithium excretion. Volume expansion appropriately decreases the proximal
reabsorption of sodium; lithium reabsorption also falls since it is reabsorbed via the same transporters
as sodium [4].
CHRONIC INTERSTITIAL NEPHRITIS AND KIDNEY FUNCTION IMPAIRMENT
Long-term lithium use is associated with chronic kidney disease that occasionally progresses to end
stage kidney disease (ESKD) [6-8,32-37]. As an example, in a large, retrospective, case-control study
of Swedish adults, 1.8 percent of patients receiving renal replacement therapy (RRT) for ESKD had a
history of lithium exposure compared with 0.2 percent of patients without ESKD (odds ratio 7.8, 95%
CI 5.4-11.1) [38].
Major risk factors for nephrotoxicity appear to be the duration of lithium exposure and the cumulative
dose [7,39]. Other risk factors include episodes of acute intoxication, increased age [34,39], other
comorbid illnesses (eg, hypertension, diabetes mellitus, hyperparathyroidism, and hyperuricemia),
and concomitant use of other antipsychotic medications. The degree of kidney function impairment is
variable [16,34,35,39,40].
Chronic interstitial nephritis usually presents as the insidious development of renal insufficiency, with
normal to only a mild degree of proteinuria, often in the setting of nephrogenic diabetes insipidus
(NDI). The degree of interstitial fibrosis on kidney biopsy may be directly related to the duration and
cumulative dose of lithium [7,39]. Additional histologic lesions may be suggestive of chronic interstitial
nephritis due to lithium:
In experimental animals fed with lithium, there is a predominance of tubular lesions (ie, dilatation
●
of tubules in the distal segments and collecting ducts); glomerulosclerosis tends to be a late
event [41].
In humans, the presence of tubular cysts, which have been demonstrated to be of distal and
●
collecting tubular origin, probably correspond to these tubular lesions [6,42].
Such microcysts have also been demonstrated on magnetic resonance imaging and ultrasonographic
studies [43,44].
It has been suggested that 15 to 20 percent of patients develop a slowly progressive decline in
glomerular filtration rate, which usually does not fall below 40 to 60 mL/min [4,7,16]. Progressive
kidney failure with a serum creatinine concentration above 2 mg/dL (176 micromol/L) due solely to
lithium is uncommon [40] but can occur if lithium is continued after otherwise unexplained kidney
function impairment has developed [34,35]. In a review of 74 patients with lithium-induced renal
insufficiency from France, the mean loss of creatinine clearance was 2.3 mL/min per year, and, by
age 65 years, 12 reached ESKD [7]. The average latent period between the onset of lithium therapy
and ESKD was 20 years.
The course of the kidney disease after discontinuation of lithium is unpredictable. There may be some
recovery of kidney function, particularly with correction of hypovolemia. Progressive kidney failure can
occur among patients with significant renal insufficiency as is shown in the following studies:
In one study, seven out of nine patients with lithium nephrotoxicity and a serum creatinine
●
concentration of >2.5 mg/dL (221 micromol/L) progressed to ESKD even after stopping lithium
[6]. Among 10 patients who had an initial serum creatinine less than 2.5 mg/dL (221 micromol/L),
only one developed ESKD.
Another study identified 18 patients with ESKD among 3369 lithium-treated patients in two
●
regions of Sweden, a sixfold higher prevalence of disease than in the general population [8]. Of
these, 13 had discontinued lithium for at least two years prior to starting dialysis. Eleven patients
had serum creatinine concentrations greater than 1.4 mg/dL (125 micromol/L) at the time that
lithium was discontinued; two patients had initial serum creatinine concentrations less than 1.1
mg/dL (100 micromol/L). However, both patients had even lower creatinine concentrations (less
than 0.7 mg/dL [65 micromol/L]) when lithium was started, suggesting that a decline in kidney
function had occurred with lithium.
Progressive renal insufficiency after cessation of lithium may be due to secondary factors, such as
systemic and intraglomerular hypertension, possibly resulting in secondary glomerulosclerosis [6].
(See "Secondary factors and progression of chronic kidney disease".)
HYPERPARATHYROIDISM AND HYPERCALCEMIA
Another complication of long-term therapy with lithium carbonate is hyperparathyroidism, with

associated hypercalcemia and hypocalciuria [45].
There are several mechanisms by which lithium may increase serum calcium levels:
Increasing the threshold for the calcium-sensing mechanism within the parathyroid gland
[46]. ●
Thus, parathyroid hormone (PTH) secretion continues despite the presence of hypercalcemia.
●
Inducing PTH overproduction via inhibiting the action of glycogen synthase kinase 3b (GSK-3b).
●
Inhibiting calcium transport (influx) across cell membranes.
As hypercalcemia develops, it is further confounded by kidney failure and its progression, which leads
to decreased urinary calcium excretion (hypocalciuria). Other findings associated with lithium-induced
hypercalcemia/hyperparathyroidism include a normal serum phosphorus level and an elevated serum
magnesium level.
There is a higher proportion of patients (33 percent) who develop parathyroid hyperplasia in those
with lithium-induced hyperparathyroidism compared with the proportion of hyperparathyroidism
affecting the general population [45]. This is probably the reason why acute withdrawal of lithium does
not necessarily translate into any significant change in serum calcium levels [47]. Because simple
discontinuation of lithium carbonate therapy does not always lead to normalization of serum-intact
PTH and calcium levels, surgical parathyroidectomy has been a common option in those patients.
Case reports have been published in which the use of cinacalcet [45], a calcimimetic, decreased or
normalized the serum calcium, with some reduction of serum-intact PTH levels, similar to its effect in
patients with primary hyperparathyroidism [48,49], thereby averting the need for surgical treatment. It
is believed that cinacalcet can neutralize the effects of lithium on the calcium-sensing receptor of the
parathyroid gland. However, the mechanisms that underlie this effect remain undefined.
POSSIBLE INTERACTION WITH ANGIOTENSIN-CONVERTING ENZYME

INHIBITORS
Some evidence suggests that there may be an adverse interaction between lithium and angiotensin
converting enzyme (ACE) inhibitors, leading to renal insufficiency that may be associated with lithium
accumulation toxicity [50,51]. Although it is unclear whether this interaction is real, the serum
creatinine concentration and lithium levels must be closely monitored if a patient on lithium is begun
on an ACE inhibitor.
EXPERIMENTAL INVESTIGATIONS OF ALTERNATIVE TREATMENT OPTIONS
Caffeic acid phenethyl ester (CAPE), a known component of honeybee propolis, was protective
against oxidative stress induced by reactive oxygen species (ROS), commonly observed in ischemia
reperfusion and toxic injuries. Used in experimental rat models, CAPE was shown to be protective
against lithium-induced tubular damage and oxidative stress [52].
N-acetylcysteine (NAC) has been demonstrated to be renoprotective and effective in preventing

hypoperfusion and radiocontrast-induced nephropathy. Experimental Sprague-Dawley rats given NAC
with lithium had significantly lower percentages of tubular necrosis and tubular lumen obstruction [53].
SOCIETY GUIDELINE LINKS
Links to society and government-sponsored guidelines from selected countries and regions around
the world are provided separately. (See "Society guideline links: Chronic kidney disease in
adults".)
SUMMARY AND RECOMMENDATIONS
Chronic lithium ingestion in patients with bipolar (manic depressive) illness has been associated
●
with a variety of kidney diseases, particularly nephrogenic diabetes insipidus (NDI) and, less
frequently, chronic tubulointerstitial nephropathy. (See 'Introduction' above.)
Approximately 20 to 40 percent of patients who chronically take lithium develop polyuria and
●
polydipsia. In such patients, a water restriction test should be performed to establish the
presence of NDI since patients with bipolar illness may also develop central diabetes insipidus
(CDI) and primary polydipsia. NDI appears to result from lithium accumulation in collecting tubule
cells, which interferes with the ability of antidiuretic hormone (ADH) to increase water
permeability. (See 'Nephrogenic diabetes insipidus' above.)
In patients who develop NDI, lithium therapy should be discontinued, if possible. However,
for ●
those patients in whom lithium therapy is absolutely necessary despite its renal effects,
concomitant amiloride therapy to minimize lithium accumulation in collecting tubule cells is
recommended. Amiloride is likely to be effective only when there is a mild to moderate
concentrating defect that is potentially reversible. (See 'Treatment' above.)
Therapy of the polyuria in lithium-induced disease is similar to that in other causes of NDI: a
●
thiazide diuretic (to diminish distal water delivery or upregulate aquaporin receptors), a
nonsteroidal antiinflammatory drug (NSAID; to decrease the synthesis of prostaglandins)
provided kidney function is preserved, and a low-sodium diet. (See 'Treatment' above.)
Since most patients have only partial resistance to ADH, it is also possible that attaining
●
supraphysiologic levels of ADH (by administering desmopressin [1-deamino,8-D arginine

vasopressin; dDAVP]) will attenuate the polyuria. (See 'Treatment' above.)
Long-term lithium use is associated with the insidious onset of chronic kidney disease due to
●
chronic interstitial nephritis in up to 15 to 20 percent of patients. Major risk factors for

nephrotoxicity appear to be the duration of lithium exposure, the cumulative dose, and advanced
age. The degree of renal insufficiency is generally relatively mild but may occasionally progress
to end-stage kidney disease (ESKD). (See 'Chronic interstitial nephritis and kidney function
impairment' above.)
The course of the kidney disease after discontinuation of lithium is unpredictable. There may be
●
some recovery of kidney function, particularly with correction of hypovolemia. However,

progression of chronic kidney disease can occur. (See 'Chronic interstitial nephritis and kidney
function impairment' above.)
Long-term therapy with lithium may lead to hyperparathyroidism, hypercalcemia, and

●
hypocalciuria. Discontinuation of lithium therapy does not always lead to normalization of

parathyroid hormone (PTH) and calcium levels; thus, surgical parathyroidectomy is a common
option in such patients. Cinacalcet, a calcimimetic, may also reduce PTH levels and a return the
serum calcium to normal, thereby averting the need for surgical treatment. (See
'Hyperparathyroidism and hypercalcemia' above.)
Less commonly, lithium therapy can be associated with distal renal tubular acidosis,
minimal ●
change disease, focal segmental glomerulosclerosis (FSGS), and edema during episodes of
mania. (See 'Renal tubular acidosis' above and 'Nephrotic syndrome' above and 'Edema during
the manic phase' above.)
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Topic 2358 Version 27.0

GRAPHICS
Ion transport in collecting tubule principal cells
Schematic representation of sodium (Na) and potassium (K) transport in the sodium-reabsorbing
principal cells in the collecting tubules. The entry of filtered sodium into these cells is mediated by
selective sodium channels in the apical (luminal) membrane (ENaC); the energy for this process is
provided by the favorable electrochemical gradient for sodium (cell interior electronegative and low
cell sodium concentration). Reabsorbed sodium is pumped out of the cell by the Na-K-ATPase pump
in the basolateral (peritubular) membrane. The reabsorption of cationic sodium makes the lumen
electronegative, thereby creating a favorable gradient for the secretion of potassium into the lumen
via potassium channels (ROMK and BK) in the apical membrane. Aldosterone (Aldo), after combining
with the cytosolic mineralocorticoid receptor (Aldo-R), leads to enhanced sodium reabsorption and
potassium secretion by increasing both the number of open sodium channels and the number of Na
K-ATPase pumps. The potassium-sparing diuretics (amiloride and triamterene) act by directly
inhibiting the epithelial sodium channel; spironolactone acts by competing with aldosterone for
binding to the mineralocorticoid receptor.
Graphic 60693 Version 15.0

Lithium nephrotoxicity with microcytic dilation at the corticomedullary junction

with interstitial lymphocytic infiltrate associated with tubulointerstitial fibrosis
and global glomerulosclerosis (Jones silver stain)
Reproduced from: Fogo AB, Lusco MA, Andeen NK, et al. AJKD atlas of renal pathology: Lithium nephrotoxicity.
Am J Kidney Dis 2017; 69:e1. Illustration used with the permission of Elsevier Inc. All rights reserved.
Lithium nephrotoxicity with microcystic tubular dilation and interstitial lymphocytic

infiltrate associated with tubulointerstitial fibrosis and segmental glomerulosclerosis
(Masson trichrome stain)
Reproduced from: Fogo AB, Lusco MA, Andeen NK, et al. AJKD atlas of renal pathology: Lithium nephrotoxicity. Am J
Kidney Dis 2017; 69:e1. Illustration used with the permission of Elsevier Inc. All rights reserved.
Contributor Disclosures
Edgar V Lerma, MD, FACP, FASN, FAHA Employment: Associates in Nephrology. Equity Ownership/Stock
Options: Fresenius [Dialysis]. Grant/Research/Clinical Trial Support: AstraZeneca [Hyperkalemia].
Consultant/Advisory Boards: Tricida [Metabolic acidosis]. Richard H Sterns, MD Nothing to disclose John P
Forman, MD, MSc Nothing to disclose
Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are
addressed by vetting through a multi-level review process, and through requirements for references to be
provided to support the content. Appropriately referenced content is required of all authors and must conform to
UpToDate standards of evidence.
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3/9/2020 Renal toxicity of lithium - UpToDate

NEPHROGENIC DIABETES INSIPIDUS

Lithium​ ​may reduce ​AQP2 ​gene transcription, an effect that is prostaglandin

Lithium​ ​induces collecting duct remodeling characterized by a decreased population of

In a placebo-controlled crossover study, 11 patients with lithium-induced NDI were treated

RENAL TUBULAR ACIDOSIS

CHRONIC INTERSTITIAL NEPHRITIS AND KIDNEY FUNCTION IMPAIRMENT

collecting tubular origin, probably correspond to these tubular lesions [​6,42​].

HYPERPARATHYROIDISM AND HYPERCALCEMIA

Another complication of long-term therapy with ​lithium​ ​carbonate is hyperparathyroidism, with

POSSIBLE INTERACTION WITH ANGIOTENSIN-CONVERTING ENZYME

EXPERIMENTAL INVESTIGATIONS OF ALTERNATIVE TREATMENT OPTIONS

N-acetylcysteine (NAC) has been demonstrated to be renoprotective and effective in preventing

SOCIETY GUIDELINE LINKS

supraphysiologic levels of ADH (by administering ​desmopressin ​[1-deamino,8-D arginine

chronic interstitial nephritis in up to 15 to 20 percent of patients. Major risk factors for

some recovery of kidney function, particularly with correction of hypovolemia. However,

Long-term therapy with ​lithium ​may lead to hyperparathyroidism, hypercalcemia, and

hypocalciuria. Discontinuation of lithium therapy does not always lead to normalization of

Use of UpToDate is subject to the ​Subscription and License Agreement​.

2. ​Trepiccione F, Christensen BM. Lithium-induced nephrogenic diabetes insipidus: new clinical

5. ​Aurell M, Hestbech J. Lithium-induced uraemia. Lancet 1979; 1:882.

6. ​Markowitz GS, Radhakrishnan J, Kambham N, et al. Lithium nephrotoxicity: a progressive

53. ​Efrati S, Averbukh M, Berman S, et al. N-Acetylcysteine ameliorates lithium-induced renal

Topic 2358 Version 27.0

Ion transport in collecting tubule principal cells

Graphic 60693 Version 15.0

Lithium nephrotoxicity with microcytic dilation at the corticomedullary junction

Graphic 115166 Version 1.0

Lithium nephrotoxicity with microcystic tubular dilation and interstitial lymphocytic

Graphic 115167 Version 1.0

Conflict of interest policy

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Lithium may reduce AQP2 gene transcription, an effect that is prostaglandin

Lithium induces collecting duct remodeling characterized by a decreased population of

collecting tubular origin, probably correspond to these tubular lesions [6,42].

Another complication of long-term therapy with lithium carbonate is hyperparathyroidism, with

supraphysiologic levels of ADH (by administering desmopressin [1-deamino,8-D arginine

Long-term therapy with lithium may lead to hyperparathyroidism, hypercalcemia, and

Use of UpToDate is subject to the Subscription and License Agreement.

2. Trepiccione F, Christensen BM. Lithium-induced nephrogenic diabetes insipidus: new clinical

5. Aurell M, Hestbech J. Lithium-induced uraemia. Lancet 1979; 1:882.

6. Markowitz GS, Radhakrishnan J, Kambham N, et al. Lithium nephrotoxicity: a progressive

53. Efrati S, Averbukh M, Berman S, et al. N-Acetylcysteine ameliorates lithium-induced renal