Why is a urinalysis (UA) recommended before starting lithium therapy in a patient with bipolar disorder?

Why Urinalysis is Required Before Starting Lithium

Urinalysis is mandatory before initiating lithium therapy to establish baseline renal tubular function, as lithium commonly causes nephrogenic diabetes insipidus and can lead to chronic kidney disease, making baseline assessment essential for detecting future deterioration.

Baseline Renal Function Assessment

• The FDA requires baseline urinalysis along with BUN, creatinine, and serum calcium before starting lithium to evaluate both tubular function (via urine specific gravity or osmolality) and glomerular function (via serum creatinine or creatinine clearance). 1

• The American Academy of Child and Adolescent Psychiatry recommends baseline laboratory assessment including urinalysis, complete blood cell counts, thyroid function tests, blood urea nitrogen, creatinine, and serum calcium levels before initiating lithium therapy. 2

• Baseline urinalysis specifically evaluates tubular concentrating ability, which lithium frequently impairs, and establishes a reference point for monitoring progressive renal changes. 1

Lithium's Renal Toxicity Profile

Nephrogenic Diabetes Insipidus

• Chronic lithium therapy is commonly associated with diminished renal concentrating ability, occasionally presenting as nephrogenic diabetes insipidus with polyuria and polydipsia, requiring careful management to avoid dehydration with resulting lithium retention and toxicity. 1

• Lithium-treated patients demonstrate significantly greater urinary excretion of arginine vasopressin (AVP) compared to controls, indicating diminished tubular responsiveness to AVP even when creatinine clearance remains normal. 3

• Beta-2-microglobulin excretion rates are significantly higher in lithium patients with manifest polyuria and severe concentration defects, serving as an early marker of tubular dysfunction. 4

Chronic Kidney Disease Risk

• Morphologic changes with glomerular and interstitial fibrosis and nephron atrophy have been reported in patients on chronic lithium therapy, though the relationship between renal functional and morphologic changes and their association with lithium therapy has not been definitively established. 1

• Ever use of lithium is associated with a hazard ratio for renal failure of 2.5 (95% CI: 1.6-4.0) adjusted for known renal risk factors, with absolute risk being age-dependent and patients 50 years or older at particular risk (NNH = 44). 5

• Lithium has been implicated in inducing chronic tubulointerstitial nephropathy, acute tubular necrosis, and rarely minimal change disease with nephrotic syndrome. 6

Monitoring Algorithm

Initial Assessment

• Obtain baseline urinalysis including specific gravity, protein, glucose, and microscopic examination before the first lithium dose. 2, 1

• Measure baseline 24-hour urine volume if polyuria symptoms are present or if more detailed tubular function assessment is needed. 1

• Assess urine osmolality following a period of water deprivation to establish baseline concentrating capacity. 1

Ongoing Surveillance

• The American Academy of Child and Adolescent Psychiatry recommends regular monitoring of lithium levels, renal function (including urinalysis), and thyroid function every 3-6 months during maintenance therapy. 7, 2

• Progressive or sudden changes in renal function, even within the normal range, indicate the need for reevaluation of treatment. 1

• Patients on lithium therapy may benefit from monitoring of glomerular function via urinalysis to prevent the onset of nephrotic syndrome. 6

Critical Clinical Considerations

Contraindications Based on Renal Status

• Lithium should generally not be given to patients with significant renal disease, as the risk of lithium toxicity is very high in such patients. 1

• If the psychiatric indication is life-threatening and the patient has renal impairment, lithium treatment may be undertaken with extreme caution, including daily serum lithium determinations, adjustment to usually low doses, and hospitalization. 1

Urinary Tract Pathology

• Urinary tract imaging should be part of the routine work-up in patients presenting with symptoms and signs of lithium intoxication, since concomitant urinary tract lesions (such as glandular cystitis causing bladder outlet obstruction) might occasionally cause renal impairment leading to reduced lithium excretion. 8

Common Pitfalls to Avoid

• Never initiate lithium without baseline urinalysis, as you will have no reference point to detect the common complication of nephrogenic diabetes insipidus or progressive renal impairment. 2, 1

• Do not assume normal serum creatinine indicates normal renal function—tubular dysfunction (detected by urinalysis and concentrating ability) often precedes changes in creatinine clearance. 3, 4

• Avoid attributing polyuria solely to psychiatric polydipsia without first ruling out lithium-induced nephrogenic diabetes insipidus through urinalysis and urine osmolality testing. 1, 8

• Treatment with lithium should be initiated only where personnel and facilities for close clinical and laboratory monitoring are available, due to its narrow therapeutic window and renal toxicity risk. 2