Scandinavian Journal of Clinical and Laboratory Investigation

ISSN: 0036-5513 (Print) 1502-7686 (Online) Journal homepage: http://www.tandfonline.com/loi/iclb20

Urinary excretion of albumin β2-microglobulin and free light chains during lithium treatment E. B. Pedersen, C. E. Mogensen, K. Sølling, A. Amdisen & S. Darling To cite this article: E. B. Pedersen, C. E. Mogensen, K. Sølling, A. Amdisen & S. Darling (1978) Urinary excretion of albumin β2-microglobulin and free light chains during lithium treatment, Scandinavian Journal of Clinical and Laboratory Investigation, 38:3, 269-272, DOI: 10.1080/00365517809108422 To link to this article: http://dx.doi.org/10.1080/00365517809108422

Published online: 14 Feb 2011.

Submit your article to this journal

View related articles

Citing articles: 1 View citing articles

Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=iclb20 Download by: [Australian National University]

Date: 05 June 2016, At: 18:27

Scand J. clin. Lab. Invest. 38, 269-272, 1978.

Urinary excretion of albumin s,-microglobulin and free light chains during lithium treatment

Downloaded by [Australian National University] at 18:27 05 June 2016

E. B. P E D E R S E N , C. E . M O G E N S E N , K . S 0 L L I N G , A. A M D I S E N & S. D A R L I N G Department of Medicine C and M, Aarhus Kommunehospital and Aarhus University, Psychopharmacology Research Unit and Clinical Departments, Psychiatric Hospital in Aarhus, DK-8240 Risskov, Denmark

Pedersen, G.B., Mogensen, C.E., Sralling, K.,Amdisen, A. & Darling, S. Urinary excretion of albumin, B2-microglobulin and free light chains during lithium treatment. Scand. J. din. Lab. Invest. 38,269-272, 1978. Albumin, Bz-microglobulin and free light chains were determined in urine in nine manic-depressive patients before and at intervals during three months of lithium treatment (longitudinal study). The same determinations were carried out in twenty-seven manic-depressive patients who had been treated with lithium for 3 months to 20 years and also in a control group (transversal study). There were no statistically significant changes in urinary excretions of albumin, B2microglobulin and free light chains during the longitudinal study. In one patient albumin excretion gradually increased during the study and remained elevated on reexamination 1 year later. No significant differences were found between the lithium treated patients and control subjects in the transversal study in either albumin, /12-microglobulin or free light chain excretion. It is not clear whether the increased and sustained albumin excretion in one of the patients was due to lithium or was coincidental. The study shows that in most patients lithium treatment does not affect renal protein excretion. Key-words: B2-microgIobulin; lithium; manic-depressive patients; albumin; light chains of immunoglobulins; proteinuria.

E. B. Pedersen, M.D., Department of Medicine C, Aarhus Kommunehospital, DK-8000 Aarhus, C Denmark

Lithium therapy occasionally affects kidney function and structure. Maximum concentrating ability after dehydration and vasopressin was markedly impaired in ten patients during lithium treatment [5]. Recently chronic interstitial nephritis was demonstrated in renal biopsies from patients who had been treated with lithium [6]. Proteinuria is not found when tested by conventional urine stix methods. 0036-55 13/78/05004269502.00

01978 Medisinsk Fysiologisk Forenings Forlag

However, the development of sensitive radioimmunoassays has made it possible to measure urinary excretion of plasma proteins even when no proteinuria can be detected by standard clinical methods. In early stages lithium induced damage of the kidneys might be reflected by changes in urinary plasma proteins. The aim of the present study has been to examine the effect of lithium on urinary excretion of albumin, Bz-microglobulin and free light chains. In a longitudinal study determinations

270

E. B. Pedersen et al.

were performed in patients before and at intervals during three months of lithium. In a transversal study determinations were performed in patients who had been given lithium treatment for a long time and in a control group.

Downloaded by [Australian National University] at 18:27 05 June 2016

MATERIAL A N D METHODS

Patients. Two different groups of patients suffering from recurrent manic-depressive disorder were studied; the latter term is here used synonymously with endogenous affective disorder [2]. None of the patients had arterial hypertension or renal disease. The longitudinal study comprised nine subjects, seven male and two female, mean age 45 years (range 27-56 years). All were examined on eight occasions: before lithium and after 1, 6, 8, 13, 30, 60 and 90 days of lithium treatment. Some patients received additional psychopharmacological medication, which was unchanged during the study period. Lithium treatment was instituted with sustained release tablets (Litarex@)one tablet (6 mmol lithium) twice daily from the day after pre-treatment examination; the dose was adjusted after 6 days to maintain a lithium concentration of 0.7-1.2 mmol/l in blood samples drawn in the morning 12 h after the evening dose of lithium [I]. The transversal study comprised twenty-seven subjects, twelve male and fifteen female, mean age 45 years (range 23-69 year). Lithium was the only drug used; the patients had been treated for periods of 3 months to 20 years, median 4 years. Examinations were further performed in twelve healthy control subjects,

seven male and five female, mean age 42 years (range 28-65 years).

Procedure. The subjects arrived at the laboratory at 08.00 hours after a fasting period of approximately 8 h. Urine was collected from 08.00 to 12.00 hours and analysed for albumin, B2microglobulin and free light chains. Blood samples for determination of creatinine and lithium were drawn at 09.00 hours. Methods. Albumin, µglobulin and free light chains in urine were determined by radioimmunoassays [4, 7, 81. Free light chains are given as concentrations of lambda kappa chains. Mann-Whitney’s test was used for unpaired comparison between two groups, and Friedman’s test for paired comparison between several groups [31.

+

RESULTS

Longitudinal study. Table 1 shows urinary excretion of albumin, µglobulin, free light chains, serum creatinine and serum lithium before and at intervals during 3 months of lithium treatment. No significant changes were found in protein excretions or serum creatinine during the study (Friedman’s test). In one patient albumin excretion gradually increased from initially normal levels to clearly elevated values during the last three examinations (16.3; 10.4; 13.4; 14.6; 24.5; 36.5; 60.8; 42.3 pglmin). The patient continued on lithium; on reexamination 1 year later albumin excretion remained high (85 pglmin), but creatinine

TABLE I. Longitudinal study: Means f 1 SEM of urinary excretion of albumin, /&-microglobulin, free light chains serum creatinine and serum lithium in nine manic-depressive patients Examination No.

2

1

3

4

5

6

7

8

~ _ _ _ _ _ _

Albumin (pglrnin) µ globulin (Amin) Free light chains Wmin) Serum creatinine (pmol/l) Serum lithium (mmol/l)

6.6 6.6 k 1.6 1.4 0.080 0.067 f0.014 +0.015 3.9 3.4 f 0.6 f0.6 86 82 6.6 f 6.3 0.20 0.00 0.00 0.01

+

*

7.7 f 1.4

0.094 kO.018 3.5 k0.5

87 k 5.7 0.49 - 0.08

+

6.4 k 1.4 0.065 +0.010

3.3 0.6 87 k6.1 0.13 k 0.05

8.3

f2.2 0.096 k 0.032 4.0 f 0.8 86 + 5.3 0.82 f0.03

9.1 f 3.5 0.080 fO.018 4.7 f 1.1 89 f 4.7 0.83 k 0.05

12.7 f 6.1 0.074 f0.014 3.4 & 0.6 87 5.5 0.79 f0.07

*

*16.6 5.5 0.060 k0.013

3.3 f0.9 84 + 4.2 0.94 kO.11

Renal protein excretion during lithium treatment

271

TABLE 11. Transversal study: means 1 SEM of urinary excretion of albumin, B2-microglobulin and light chains, and creatinin clearance in lithium treated patients and control subjects Lithium treated Control patients (n = 27) subjects (n = 12)

Downloaded by [Australian National University] at 18:27 05 June 2016

Albumin (pg/min) 8,-microglobulin (,ug/min) Light chains (pglmin) Creatinine clearance (mlimin)

clearance was unchanged and normal. No significant bacteriuria was found in this patient. In two patients an increased albumin excretion was found on day 90 (1.9; 3.4; 3.8; 3.3; 2.8; 3.9; 1.5; 24.5 pg/min and 7.1 ; 4.1 ; 5.1 ;4.6; 6.9; 4.6; 6.6; 43.7 pg/min, respectively). The first committed suicide in a depressive episode some months after the study and was not reexamined. The latter had had influenza with fever during the days prior to the last examination. Lithium treatment was continued, and reexamination 1 year later showed normal albumin excretion (6.5 pg/min). Transversal study. The results from the transversal study are given in Table 11. No significant differences were found between urinary excretions of albumin, /32-microglobulin and free light chains in the lithium treated patients and the control subjects, and creatinine clearances were the same in the two groups. The patients’ average serum concentration of lithium was 0.84 mmol/l.

DISCUSSION Conventional lithium therapy has been shown to affect renal structure and function [5,6]. Early changes might be detected as increase in urinary protein excretion, e.g. by measuring the effect of lithium on albumin, /&-microglobulin and free light chains excretion in urine by sensitive radioimmunologic methods. In the present study, however, no significant changes were found in urinary excretion of albumin, B2-microglobulin and free light chains during 3 months of lithium treatment, and there were no significant differences in urinary excretion of these proteins between a group of patients who had received lithium for a long time and a control group.

12.1*2.2 0.090+ 0.008 5.16f 1.10

9.1 k2.6 0.085k0.031 4.91f1.20

102f4.1

104k 3.9

In the kidneys albumin, ~2-microglobulinand free light chains are handled by glomerular filtration and subsequent tubular reabsorption. Increased urinary excretion of B2-microglobulin and to lesser degree of free light chains associated with unchanged or slightly increased albumin excretion indicates predominantly tubular damages; on the other hand increased albumin excretion and unchanged µglobulin and free light chain excretion suggests glomerular lesions. The decreased concentrating ability during lithium therapy most likely is caused by an effect of the lithium ion on the distal tubules and collecting ducts [S]. The absence of signs of tubular dysfunction in the present study, when estimated by urinary excretion of µglobulin and free light chains, could be attributed to the fact that reabsorption of these proteins takes place in the proximal tubules. The present results thus indicate that as far as reabsorption of proteins is concerned proximal tubular function is unaffected by lithium treatment. In one patient in the longitudinal study urinary albumin excretion gradually increased during 3 months of lithium treatment and remained elevated when control measurement was performed 1 year later. The unchanged normal excretion of /32-microglobulin and free light chains associated with gradually increasing albumin excretion suggests that glomerular permeability was increased. It is not clear whether this change was caused by lithium treatment or was coincidental. REFERENCES 1 Amdisen, A. Serum level monitoring and clinical pharmacokinetics of lithium. Clin. Pharmacokinet

.

2, 73, 1971.

272

E. B. Pedersen et al.

2 Bastrup, P.C. Lithium in prophylaxis. Curr. Psychiat. Ther. 9, 125, 1971 3 Bradley, J.V. Distribution-free Srarisrical Tests. Prentice-Hall, Englewood Cliffs, New Jersey, 1968. 4 Evrin, P.E., Petersen, P.A., Wide, L. & Berggird, 1. Radioimmunoassay of beta-2-microglobulin in human biological fluids. Srand. J. cfin. Lab. Invest. 28, 439. 1971.

Downloaded by [Australian National University] at 18:27 05 June 2016

5 Forest, N.J., Cohem, A.D., Torretti, J., Himmelhoch, J.M. & Epstein, F.H. On the mechanism of Lithiuminduced diabetes insipidus in man and rat. J. din. Invest. 53, 1115, 1974. 6 Hestbech, J., Hansen, H.E., Amidsen, A. & Olsen, S.

Chronic renal lesions following long-term treatment with lithium. Kidnet Int. 12, 205, 1917. 7 Miles, D.W., Mogensen, C.E. & Gundersen, H.J.G. Radioimmunoassay for urinary albumin using a single antibody. Scand. J. din. Lab. I n w s t . 26, 5, 1970. 8 Sslling, K. Free light chains of immunoglobulins in

normal serum and urine determined by radioimmunoassay. Scand. J. cfin. Lab. Invest. 35, 407, 1975.

Received 19 September 1977 Accepted 24 December 1977

Urinary excretion of albumin beta2-microglobulin and free light chains during lithium treatment.

Scandinavian Journal of Clinical and Laboratory Investigation ISSN: 0036-5513 (Print) 1502-7686 (Online) Journal homepage: http://www.tandfonline.com...
395KB Sizes 0 Downloads 0 Views