Clinical Significance of Low BUN in Patients on Lithium
A low BUN in a patient on lithium therapy is generally not clinically significant and does not indicate renal dysfunction; it more commonly reflects dietary factors, hydration status, or reduced protein intake rather than lithium-related kidney damage.
Understanding BUN in the Context of Lithium Therapy
Why Low BUN is Not a Concern
BUN is an unreliable marker for monitoring lithium-induced renal effects because it can be low due to decreased dietary protein intake, overhydration, or malnutrition—factors unrelated to kidney function 1.
Serum creatinine and estimated glomerular filtration rate (eGFR) are the appropriate markers for assessing renal function in lithium-treated patients, not BUN 2, 3, 4.
In psychiatric patients, BUN may be particularly low if protein intake is reduced, which is common in patients with mood disorders 1.
What Actually Matters: Monitoring Renal Function on Lithium
The critical renal parameters to monitor in lithium patients are:
Serum creatinine levels should be checked at baseline and every 3-6 months, with concern arising when creatinine consistently rises above 1.6 mg/dL (140 μmol/L) 2, 5.
Estimated GFR (eGFR) declines by approximately 0.92% per year of lithium treatment (compared to 0.71% per year from aging alone), with 29.5% of patients experiencing at least one low eGFR value (<60 mL/min/1.73 m²) after ≥15 years of treatment 4.
Creatinine clearance may show significant decline in long-term lithium users (>10 years), though this is typically a gradual process 3, 6.
Clinical Algorithm for Interpreting Low BUN on Lithium
Step 1: Assess the Clinical Context
Check serum creatinine and calculate eGFR—if these are normal, the low BUN is not indicative of renal dysfunction 2, 4.
Evaluate dietary protein intake—low BUN often reflects inadequate protein consumption rather than kidney disease 1.
Assess hydration status—overhydration dilutes BUN and is common in patients with lithium-induced polyuria 2, 7.
Step 2: Rule Out Lithium-Related Renal Issues
Lithium primarily affects tubular function (causing polyuria and reduced urine concentrating ability) rather than glomerular function in most patients 2, 3, 7.
Glomerular function (measured by creatinine and eGFR) is not progressive in the majority of patients, though a very small subset may develop interstitial nephritis 2.
Serum BUN and creatinine levels remain within normal limits in most lithium-treated patients, even after years of therapy 3, 6.
Step 3: Appropriate Monitoring Strategy
Baseline assessment should include complete blood count, thyroid function tests, urinalysis, BUN, creatinine, serum calcium, and pregnancy test in females 5.
Ongoing monitoring should include lithium levels, renal function (creatinine), and thyroid function every 3-6 months 5, 2.
Annual creatinine monitoring is sufficient for most stable patients, with more frequent testing if creatinine begins to rise 2.
Common Pitfalls to Avoid
Do not use BUN alone to assess renal function in lithium patients—it is influenced by too many non-renal factors to be reliable 1.
Do not discontinue lithium based solely on low BUN—this would deprive patients of effective mood stabilization without valid medical justification 5, 2.
Do not overlook the real renal concern with lithium, which is progressive decline in urine concentrating ability and potential for nephrogenic diabetes insipidus, not low BUN 2, 3, 7.
Avoid confusing low BUN with renal failure—end-stage renal failure from lithium is extremely rare, with no cases reported even in cohorts followed for decades 4.
When to Investigate Further
If creatinine is elevated (>1.6 mg/dL) or eGFR is declining, obtain nephrology consultation regardless of BUN level 2, 4.
If polyuria is severe (>3.5 L/day), evaluate for nephrogenic diabetes insipidus with urine osmolality testing after water deprivation 3, 7.
If the patient has medical comorbidities (hypertension, diabetes), monitor renal function more closely as these are additional risk factors for declining eGFR 4.
Risk Factors for Actual Lithium-Induced Renal Dysfunction
Longer duration of lithium treatment (>15-17 years) is associated with measurable decline in GFR 4, 6.
Higher serum lithium concentrations increase risk of renal impairment more than duration alone 4.
Lower lithium doses paradoxically correlate with worse renal outcomes, possibly due to more frequent dosing causing higher peak levels 4.
Female sex is associated with 19% greater decline in eGFR compared to males 4.
Starting lithium at age ≥40 years predicts higher risk of later low eGFR 4.