Lithium toxicity and the kidney with special focus on nephrotic syndrome associated with the acute kidney injury: A case‐based systematic analysis

Abstract

Despite the progress made in treating bipolar and unipolar affective disorders, lithium carbonate is still a common drug in psychiatric practice. Lithium‐related renal side effects include nephrogenic diabetes insipidus, chronic tubulointerstitial nephropathy, and acute kidney injury (AKI). Nephrotic syndrome (NS) is an uncommon but severe complication of lithium treatment. We present a 49‐year‐old female treated with lithium carbonate due to a recurrent depressive disorder who developed NS during this therapy. NS spontaneously remitted after the drug withdrawal. Since her lithium serum levels were within the recommended values, we performed a retrospective analysis of lithium‐induced NS cases trying to determine causes predisposing to the NS development, underlying histopathology, and preservation or irreversible loss of kidney function. This analysis revealed that in lithium‐induced NS with AKI, lithium serum level was the key determinant of AKI development (the β coefficient = 0.8499 with a confidence interval ranging from 0.7452 to 0.9546 and p value < 0.0001). In these cases, the underlying pathology was mainly minimal change disease (MCD), which was quickly reversible upon the drug withdrawal. The development of chronic kidney disease (CKD) seemed to be associated with lithium therapy duration. However, the multiple regression analysis for CKD as the dependent variable showed that the decisive factor was focal segmental glomerulosclerosis (FSGS) as the underlying pathology (the β coefficient = 0.7866 with a confidence interval ranging from 0.600 to 0.9704 and the p value < 0.0001). Thus, we conclude that in lithium‐induced NS/AKI, serum lithium levels contribute to these complications, while FSGS lesions are responsible for CKD's disease progression.

Transition from minimal change disease to focal segmental glomerulosclerosis related to occupational exposure: A case report

“…Consequently, we suspect that his aggravated pathology and ESKD occurrence were related to metal nephrotoxicity. Nephrotoxicity induced by excess exposure to certain metals is well known, and lithium has been shown to cause MCD and FSGS[ 13 ]. Although there is not enough literature to confirm that lead and cadmium can cause FSGS, it has been proven that both of them induce podocytotoxicity and can even induce podocyte apoptosis[ 14 , 15 ].…”

A rare case of fatal poisoning during long-term therapy with lithium carbonate - chronic poisoning, suicide or psychiatric malpractice?

“…Zatrucia najczęściej mają charakter przypadkowy, ale opisano także próby samobójcze z wykorzystaniem tego leku [6]. Nerkowe działania niepożądane spowodowane przyjmowaniem soli litu obejmują nefrogenną moczówkę prostą, przewlekłą cewkowo-śródmiąższową nefropatię, ostre uszkodzenie nerek, ale też zespół nerczycowy [7].…”

Lithium therapy and parathyroid gland interaction

“…Both AKI and nephrotic syndrome improved with the withholding of lithium (8). Łukawska et al also presented a 49-year-old woman who developed nephrotic syndrome following lithium administration and spontaneously resolved following the drug discontinuation (9). The hypercalcemia right after lithium therapy has biochemical features like familial hypocalciuric hypercalcemia, while hypercalcemia of chronic Li therapy has the characteristics of primary hyperparathyroidism (3).…”