Clinical Investigation

Kidney International (1982) 21, 477–485; doi:10.1038/ki.1982.49

Distal nephron function in patients receiving chronic lithium therapy

Daniel Batlle1, Moises Gaviria1, Marlene Grupp1, Jose A L Arruda1, John Wynn1 and Neil A Kurtzman1

1Section of Nephrology and the Department of Psychiatry (Affective Disorders Clinic), University of Illinois Abraham Lincoln School of Medicine, Chicago, Illinois

Correspondence: Dr Daniel C Batlle, Section of Nephrology, University of Illinois Hospital, 840 South Wood Street, Chicago, Illinois 60612, USA

Received 6 May 1981; Revised 3 August 1981.

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Abstract

Distal nephron function in patients receiving chronic lithium therapy. Renal tubular function was studied in 14 patients chronically treated with lithium for affective disorders. Patients were separated into two groups according to the duration of lithium therapy: long-term (35 plusminus 7.0 months) and short-term (4.8 plusminus 0.8 months). At comparable urine lithium concentrations, patients on long-term therapy had a lower maximal urine osmolality (Umax) and free water reabsorption (TcH2O) than did patients on short-term therapy. The latter group achieved a Umax above 800 mOsm kg H2O. In contrast, both groups of patients failed to increase the urine-blood (U-B) PCO2 gradient normally during acute sodium bicarbonate loading. This low U-B PCO2 was observed at comparable urine bicarbonate concentrations between both groups of patients and controls, and thus was associated with a higher urine pH in patients. These findings indicate that the inability of these patients to achieve a normal U-B PCO2 in a maximally alkaline urine was the result of decreased distal hydrogen ion secretion rather than inability to raise urine bicarbonate concentrations as a result of a concentrating defect. Bicarbonate reabsorptive capacity was normal in our lithium-treated subjects. Both groups of patients achieved a normal U-B PCO2 gradient in response to sodium phosphate loading. They also were able to achieve a minimal urine pH and a maximal acid excretion similar to those of controls in response to a 3-day ammonium chloride loading test. Our data demonstrate that chronic lithium therapy is associated with a mild distal acidification defect disclosed only by the finding of a low U-B PCO2 gradient during sodium bicarbonate loading. This peculiar defect can be found in short-term lithium-treated patients in whom the concentrating capacity is relatively well preserved.

Fonction du néphron distal chez des malades recevant un traitement chronique par le lithium. La fonction tubulaire rénale a été étudiée chez 14 malades traités de façon chronique par le lithium pour des désordres affectifs. Les malades ont été séparés en deux groupes en fonction de la durée du traitement par le lithium: traitement à long terme (35 plusminus 7 mois) et à court terme (4,8 plusminus0,8 mois). Pour des concentrations urinaires de lithium comparables, les malades traités à long terme avaient une osmolalité urinaire maximale (Umax) inférieure et une réabsorption d'eau libre (TcH2O) inférieure à celle des malades à court terme. Les malades des deux groupes n'ont pas augmenté leur gradient urine-sang (U-B) de PCO2 de façon normale au cours d'une charge aiguë en bicarbonate de sodium. Ce gradient U-B PCO2 faible a été observé à des concentrations de bicarbonate dans l'urine comparables entre les deux groupes de malades et avec les contrôles, et par conséquent était associé à un pH urinaire plus élevé chez les malades que chez les contrôles. Ces constatations indiquent que l'incapacité de ces malades à réaliser un gradient normal dans une urine alcaline au maximum était la conséquence d'une diminution de la sécrétion distale d'ions hydrogènes plutôt que d'une incapacité à augmenter les concentrations de bicarbonate urinaire consécutive à un déficit de concentration. La capacité de réabsorption de bicarbonate était normale chez les sujets traités par le lithium. Les deux groupes de malades ont réalisé un gradient U-B PCO2 normal en réponse à une charge en phosphate de sodium. Dans les deux groupes on a obtenu un pH urinaire minimal et une excrétion d'acide maximale semblable à celle des contrôles en réponse à une charge de chlorure d'ammonium pendant trois jours. Ces observations démontrent que le traitement chronique par le lithium est associé à un déficit d'acidification distale modéré mis en évidence par la constatation d'un gradient faible de PCO2 entre l'urine et le sang au cours de la charge en bicarbonate de sodium. Ce déficit particulier peut être observé chez des malades traités à court terme par le lithium chez lesquels la capacité de concentration est relativement bien conservée.

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