Lithium-induced nephropathy usually manifests in adulthood as it develops slowly after many years of cumulative exposure. There is very limited information available in pediatric patients. Renal function monitoring and timely intervention is the key in preventing lithium-induced chronic kidney disease in these patients. We report a case of a 14-year-old boy who was on lithium for almost 9 years for his complex psychiatric illness. He presented with increased urinary frequency and nocturia. His serum creatinine increased to 1.15 mg/dL (estimated glomerular filtration rate or eGFR 53 ml/min/1.73 m2) from a baseline of 0.78 mg/dL (eGFR 86 ml/min/1.73 m2) a year prior to this presentation. Results of the imaging study were consistent with lithium-induced nephropathy. He was managed conservatively. His serum creatinine returned to baseline of 0.78 mg/dL after a year of discontinuation of lithium, consistent with mild chronic kidney disease. This case highlights the fact that lithium-induced chronic kidney disease can present in pediatric age group when lithium is initiated at a young age in children and that timely intervention may prevent further progression of renal damage. In addition to drug levels, routine monitoring of renal function during lithium therapy is essential.
Lithium is a mood stabilizing agent which is used for the treatment of bipolar disorder. Clinical manifestations of lithium nephrotoxicity include acute kidney injury, chronic kidney disease (CKD), impaired urinary concentrating ability (nephrogenic diabetes insipidus), renal tubular acidosis, and nephrotic syndrome. CKD is commonly due to chronic tubulointerstitial nephropathy (CTIN) [
A 14-year-old male with multiple psychiatric conditions, including bipolar disorder, attention deficit hyperactivity disorder, oppositional defiant disorder, posttraumatic stress disorder, and poor impulse control, presented to the primary care physician (PCP) with urinary frequency and nocturia of a month’s duration. His medications included clonidine 0.1 mg three times daily, guanfacine 4 mg daily, bupropion sustained-release 150 mg daily, quetiapine 200 mg twice daily, and lithium 450 mg three times daily. Lithium was started when he was 5 years old. A year prior to his presentation, the lithium level was in the range of 0.9–1.1 mmol/L and serum creatinine was 0.78 mg/dL (estimated glomerular filtration rate or eGFR 86 ml/min/1.73 m2 based on the bedside Schwartz formula) [
Time course of serum creatinine and lithium level.
Renal ultrasound. (a) Sagittal left kidney: echogenic pyramids, punctuate hyperechoic foci in cortex, comet tail artifact (black arrow outlined in white), and small cyst with through transmission (white arrow with black outline). (b) Sagittal left kidney: echogenic pyramids with many punctuate hyperechogenicities. Two tiny sonolucent cysts with through transmission (black arrows with white outlines). (c) Sagittal right kidney: many punctuate cortical hyperechogenicities. (d) Transverse right kidney: generally increased cortical echogenicity (star) relative to adjacent liver (triangle).
The patient was managed conservatively with hydration and avoidance of nephrotoxic agents. His serum creatinine peaked at 1.6 mg/dL (eGFR 38 ml/min/1.73 m2) followed by a gradual return to baseline of 0.78 mg/dL (eGFR 86 ml/min/1.73 m2) at one year. Hypercalcemia and hypercalciuria also resolved with a serum calcium of 9.6 mg/dL, a PTH of 32 pg/mL, and a urine calcium to creatinine ratio of 55 mg/g Cr. Polyuria and nocturia persisted.
Several studies have established the long-term risk of CKD in adult patients on lithium [
Clinical manifestations of lithium nephrotoxicity could be due to either chronic tubulointerstitial or glomerular injury or both. The most common finding on renal biopsy is CTIN in the form of interstitial fibrosis, dilated tubules, and microcysts. The clinical manifestations of lithium-induced CKD develop after 10–20 years of treatment; however, subclinical interstitial fibrosis can be seen on biopsy as early as 2 years [
Several pathophysiologic mechanisms of lithium-induced nephropathy have been proposed. Lithium substitutes for sodium at epithelial sodium channels (ENaC) on the apical membrane of the collecting duct and gets transported into tubular cells and remains trapped, as it is a poor substrate for the sodium-potassium-ATPase pump on the basolateral membrane, leading to cytotoxic lithium concentrations [
The few pediatric case reports of lithium-induced nephropathy have shown nephrotic syndrome (glomerular injury) due to minimal change disease, focal segmental glomerulosclerosis, and membranous nephropathy [
Our patient’s low baseline eGFR prior to and after resolution of the acute component confirmed concurrent CKD. Renal ultrasound showed echogenic punctate foci and additional findings of microcysts with widespread involvement of the cortex and medulla. This pattern is most consistent with lithium-induced CKD. These punctate foci are thought to represent smaller microcysts [
Studies in adults show that the rate of progression of lithium-induced CKD correlates with the duration of treatment [
Lithium-induced CKD patients may have some improvement in eGFR after stopping lithium [
Lithium is the most effective agent for bipolar disorder and may have to be continued in some patients if interruption of lithium results in detrimental psychiatric consequences. A close collaboration among PCP, psychiatrists, and nephrologists should help in balancing the risk of suicide, psychiatric relapses, and progressive renal damage, especially in patients who have already developed CKD [
All of the professional guidelines agree on the need to monitor kidney function periodically, although the recommendations vary [
Lithiumeter (adapted from Malhi G. S. et al, Journal of Affective Disorders, 2017; 217–266).
Our patient also had hypercalcemia with suppressed PTH. We excluded common causes based on lack of exogenous intake and lab findings. Hypercalcemia resolved after stopping lithium. Lithium-induced hypercalcemia has usually been attributed to hyperparathyroidism. However, in published studies, the prevalence of hypercalcemia is much higher than the prevalence of hyperparathyroidism in such patients which suggests that mechanisms other than hyperparathyroidism may be involved [
To summarize, this case report shows that lithium-induced CKD can develop in a pediatric patient. Providers should vigilantly monitor renal function in children on lithium therapy.
Estimated glomerular filtration rate
Chronic kidney disease
Chronic tubulointerstitial nephropathy
Primary care physician
Parathyroid hormone
Thyroid-stimulating hormone
Epithelial sodium channels
Aquaporin 2
Glycogen synthase kinase type 3
The authors declare that there are no conflicts of interest.
Neena Gupta contributed to conception, design, interpretation, and literature search and critically revised manuscript to its final version. Gibson Meghan contributed to initial drafting of the paper and literature search. Ellen C. Wallace contributed to conception, design, and interpretation of images and critically revised manuscript.