Renal function lithium

Volume resuscitation is the cornerstone of management of lithium toxicity (Table 3) [124, 125]. Patients with underlying lithium-induced diabetes insipidus may initially present with volume depletion. It must be borne in mind, however, that hypernatremia [125] is a potential complication, especially in those with underlying diabetes insipidus. Forced saline diuresis is expected to increase lithium clearance by decreasing proximal tubular reabsorption. With normal renal function, lithium can be cleared at a rate of 10-40 mL/min [125]. The excretion of lithium can be further increased acutely by using acetazolamide and/or loop diuretics [124,125]. 

The antipsychotic dru are used cautiously in patients exposed to extreme heat or phosphorous insecticides and in those with respiratory disorders, glaucoma, prostatic hypertrophy, epilepsy, decreased renal function, lactation, or peptic ulcer. The antipsychotic drags are used cautiously in elderly and debilitated patients because these patients are more sensitive to the antipsychotic dragp. lithium is used cautiously in patients who are in situations in which they may sweat profusely and those who are suicidal, have diarrhea, or who have an infection or fever. 

Lithium is used in the prophylaxis and treatment of mania and in the prophylaxis of bipolar disorders and recurrent depression. Lithium should be stopped 24 hours before major surgery but the normal dose can be continued for minor surgery, with careful monitoring of fluids and electrolytes. After major surgery, renal function is reduced and this may compromise clearance of lithium. Lithium is a drug with a narrow therapeutic index and it should be avoided if possible in patients with renal impairment. Renal function should be tested before initiating treatment. If lithium is given to patients with renal impairment, a reduced dose should be used and serum lithium concentrations should be monitored closely. 

Renal function impairment Morphologic changes with glomerular and interstitial fibrosis and nephron atrophy have occurred in patients on chronic lithium therapy. The relationship between such changes and renal function has not been established. 

Lithium intoxication can be precipitated by the use of diuretics, particularly thiazides and metola-zone, and ACE inhibitors. NSAIDs can also precipitate lithium toxicity, mainly due to NSAID inhibition of prostaglandin-dependent renal excretion mechanisms. NSAIDs also impair renal function and cause sodium and water retention, effects which can predispose to interactions. Many case reports describe the antagonistic effects of NSAIDs on diuretics and antihypertensive drugs. The combination of triamterene and indomethacin appears particularly hazardous as it may result in acute renal failure. NSAIDs may also interfere with the beneficial effects of diuretics and ACE inhibitors in heart failure. It is not unusual to see patients whose heart failure has deteriorated in spite of increased doses of frusemide who are also concurrently taking an NSAID. 

Lithium is completely absorbed after oral administration reaching peak concentrations after 1-3 hours. Lithium is not metabolized and almost completely excreted unchanged in the urine with a half-life of on average 24 hours, but increasing to 40 hours or longer in the elderly and in patients with compromised renal function. After excretion 70-80% is reabsorbed by proximal renal tubule where it competes with sodium for reabsorption. Therefore low sodium levels decrease lithium excretion with consequent risks for lithium toxicity. 

CBC, BUN, creatinine (i.e., renal function), urinalysis, thyroid function tests EKG Serum lithium level (drawn 12 hours after dose) every 1-2 weeks until stable every 1—2 months during continuation phase Repeat thyroid function testast and urinalysis every 3-6 months... 

Polyuria, polydipsia, tremor, ataxia, nausea, diarrhea, weight gain, drowsiness, acne, hair loss Possible effects on thyroid and renal functioning with longterm administration Children prone to dehydration are at higher risk for acute lithium toxicity... 

Therapy requires monitoring of lithium levels, thyroid, and renal function... 

Lithium should not be administered to patients with fluctuating or unstable renal function. Because hthium may affect functioning of the cardiac sinus node, patients with sinus node dysfunction (e.g., sick sinus syndrome) should not receive hthium. Although hthium also has acute and chronic effects on the thyroid, patients with hypothyroidism may receive hthium if the thyroid disease is adequately treated and monitored. Laboratory tests that should be performed before initiation of hthium are listed in Table 5-1. 

As soon as possible, lithium and serum electrolyte levels should be measured, renal function tests performed, and an electrocardiogram obtained. 

A related issue is the patient s ability to metabolize and eliminate drugs adequately. For example, lithium is excreted entirely by the kidneys, and if a patient suffers from significantly impaired renal function, high, potentially toxic levels could develop on standard doses. Although the dose could be adjusted to compensate for the decrease in drug clearance, it might be more appropriate to choose another mood stabilizer such as valproate or carbamazepine, because they are primarily metabolized through the liver. 

In this context, the first role of the laboratory is to detect specific adverse effects to target organs (see Role of the Laboratory later in this chapter). Monitoring will generally be tailored to the specific therapy used because of its known potential for causing certain problems. Examples include periodic blood counts with carbamazepine or clozapine and thyroid and renal function studies with long-term maintenance lithium. 

After resolution of the acute phase, maintenance levels of at least 0.8 mEq/L are necessary for optimal efficacy and should be checked once every 6 to 12 months, or more often if clinically indicated. Other follow-up tests include periodic thyroid function tests, blood urea nitrogen, serum creatinine, serum calcium (because lithium may cause hypoparathyroidism), and an EGG. Thyroid function tests and renal function should be monitored approximately every 6 to 12 months (see the section Maintenance/Prophylaxis Treatment in Chapter 10). 

At one time, sustained-release preparations were thought to reduce renal toxicity, but more recent evidence has cast doubt on this assumption ( 313). A patient on long-term maintenance lithium should have renal function monitored periodically (i.e., every 12 months) with a urinalysis, BUN, and creatinine. If abnormal, a more intensive evaluation should include 24-hour urine osmolality and creatinine clearance. It is advisable to reduce maintenance lithium to optimal minimal dose-blood levels and, if possible, to avoid concomitant antipsychotics, which may enhance toxicity. Some data support the use of a once-a-day dose schedule to minimize peak lithium concentrations over a 24-hour period (314). 

Because no antidote is available, treatment is supportive. A patient s condition should be monitored closely, including fluid intake and output, mental status, and serum levels of lithium, creatinine, and electrolytes. Patients with normal renal function should be able to clear lithium unassisted. If necessary, attempts should be made to remove excess lithium from the body by gastric lavage and emesis. 

With normal renal function, all that may be necessary is watchful waiting, careful monitoring of the clinical status, and repeated serum lithium determinations. 

Coppen A, Bishop ME, Bailey JE, et al. Renal function in lithium and non-lithium treated patients with affective disorders. Acta Psychlatr Scand 1980 62 343-355. 

Hetmar O, Bolwig TG, Brun C, et al. Lithium long-term effects on the kidney I. Renal function in retrospect. Acta Psychiatr Scand 1986 73 574-581. 

The management of toxicity requires monitoring of electrolytes, regular CNS observations, use of anticonvulsants should seizures occur, increased fluid intake to promote excretion (unless renal function is impaired) and cardiac monitoring. Haemodialysis should be considered if conservative measures are ineffective or serum lithium is above 3.0 mmol L-l. However, it may be of limited additional value as the volume of distribution of lithium is high. 

Renal function was assessed in 10 patients taking longterm lithium (over 3 years, mean 80 months), 10 taking short-term lithium (3 years or less, mean 16 months), and 10 lithium-naive patients (250). Blood urea nitrogen and... 

In a historical cohort study, changes in renal function in 86 patients taking lithium were evaluated first after a median treatment duration of 5.8 years and again after 16 years (367). Maximum plasma osmolality was reduced in nine of 63 patients in the initial study and in 24 of 63 at follow-up. Other findings included increased serum... 

In a cross-sectional study of 12 octogenarians (average age 84 years) who had taken lithium for an average of 54 months (mean serum concentration 0.42 mmol/1), none became toxic and none had to stop treatment because of adverse effects. Transient renal function abnormalities were noted one patient developed nephrogenic diabetes insipidus and one became hypothyroidic (510). For lithium therapy in very old people, the authors advised close monitoring in a specialized setting. 

A five-year-old boy swallowed a button battery containing lithium (546). During the 4 days after ingestion, he developed a serum lithium concentration of 0.71 mmol/l without signs of lithium toxicity and with normal renal function. The battery was eventually retrieved by gastrotomy. 

A 56-year-old man with normal renal function and therapeutic lithium concentrations became toxic (serum concentration 2.53 mmol/1 24 hours after the last dose) with renal impairment (serum creatinine 141 gmol/l 1.6 mg/ dl) within days of starting levofloxacin. Both symptoms and laboratory abnormalities resolved with withdrawal of both lithium and levofloxacin (615). 

A review of the psychiatric effects of NSAIDs included a section on renal function and lithium clearance (666). 

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