Clinical Investigation

Kidney International (1981) 20, 663–670; doi:10.1038/ki.1981.191

Renal function and biopsy findings in patients on long-term lithium treatment

Mattias Aurell1, Christian Svalander1, Leif Wallin1 and Christer Alling1

1Departments of Nephrology and Pathology, Sahlgrenska Hospital, and the Department of Psychiatry and Neurochemistry, St. Jörgens Hospital, University of Göteborg, Göteborg, Sweden

Correspondence: Dr M Aurell, Section of Nephrology, Department of Medicine I, Sahlgrenska Hospital, S-413 45 Göteborg, Sweden

Received 9 January 1981; Revised 20 March 1981.

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Abstract

Renal function and biopsy findings in patients on long-term lithium treatment. Nine patients on long-term lithium treatment (3 to 13 years) had abnormal renal function with a decreased GFR and/or a decreased maximal urinary concentration capacity. Four patients had received lithium as the only drug, whereas five patients had had concomitant treatment with neuroleptics. No patient had a history of nephrourological diseases. Abnormal renal morphology was present in the biopsy samples from all patients. Cortical fibrosis was found in a variable degree. Dilated tubules and microcysts in which the epithelial lining was clearly abnormal were found in the majority of samples. Electron micrographically, two types of abnormal epithelial cells were observed, one with small elongated mitochondria with dense matrix and the other with larger spherical and less dense mitochondria. In distal tubules, mitochondrial swelling, accumulation of cytosegrosomes, and nuclear pyknosis dominated the picture. These findings indicate a tubulointer-stitial nephropathy and support the hypothesis that long-term lithium treatment may cause renal damage in susceptible patients.

Fonction rénale et constatations biopsiques chez les malades soumis à un traitement au long cours par le lithium. Neuf malades soumis à un traitement au long cours par le lithium ont une modification de fonctionnement rénal sous la forme d'une diminution du débit de filtration glomérulaire et/ou de la capacité de concentration. Ces malades sont traités par le lithium depuis 3 à 13 ans. Quatre malades ont reçu du lithium seulement alors que les 5 autres avaient en même temps des neuroleptiques. Aucun d'entre eux n'a d'antécédent néphro-urologique. La morphologie rénale est anormale chez tous les malades. Des lésions de fibrose corticale d'intensité variable sont observées. Des dilatations tubulaires et des formations kystiques dont l'épithélium limitant est nettement anormal sont constatées dans la majorité des cas. En microscopic électronique deux types de cellules épithéliales anormales sont observés, l'un avec des mitochondries petites et allongées, avec une matrice dense, l'autre avec des mitochondries plus grandes, sphériques et moins denses. Dans les tubes distaux le gonflement mitochondrial, l'accumulation de cytosegrosomes et la pycnose nucléaire dominent. Ces constatations traduisent une néphropathie tubulo-interstitielle et sont en faveur de l'hypothèse selon laquelle le traitement au long cours par le lithium peut déterminer des lésions rénales chez certains malades.

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