491
worth, happiness, and self-esteem, only
to
find that the
D.D.A.V.P. TEST IN ASSESSMENT OF RENAL FUNCTION DURING LITHIUM THERAPY
cur-
rency debases. Lordswood House,
Harborne, Birmingham B17 9DB
ANTON R. DEWSBURY
LITHIUM-INDUCED URÆMIA?
SIR,-Dr Hestbech and Dr Aurell (Jan. 27, p. 212) report of uraemia in a patient on lithium and conclude that
a case
"lithium treatment, even when well controlled, may cause renal damage". Poorly controlled lithium treatment to toxicity with disturbance of renal function, and lead may even well-controlled treatment may be associated with inhibition of tubular water reabsorption, resulting in polyuria and thirst. However, severe disturbance of glomerular filtration with uraemia had not been described before, so how well controlled was the lithium treatment in Hestbech and Avrell’s patient ? Their patient twice had raised serum-lithium values (1-4 mmol/1 in December, 1975, and 2.1mmol/1 in September, 1977, on the second occasion accompanied by tiredness). In November, 1977, the patient was given antihypertensive treatment (unspecified) which could have led to loss of sodium, lowered lithium excretion, and a rise in the serum-lithium concentration. This patient thus had one or more mild lithium intoxications, and since he also had severe lithium-induced’ polyuria, it is not surprising that his kidney showed morphological changes which resembled those observed previously by Hestbech and colleagues in lithium-treated patients selected for having polyuria or having had lithium poisoning. The history of nephrolithiasis and the development of hypertension with renal arteriosclerosis may or may not have played a role in this case. Hestbech and Aurell state that the "the rapid progression of renal insufficiency stopped when lithium treatment was withdrawn." Their data, however, show the opposite. Apart from a serum-creatinine of 152 umol/l (1-69 mg/dl) shortly before lithium treatment was stopped there is no indication of kidney malfunction during lithium therapy. It was not until 1-3 months after discontinuation of lithium that severe renal deterioration developed-namely, a rise in serum-creatinine to 500 umol/1 (5-66 mg/dl) in February, 1978, and a fall in glomerular filtration-rate from 38 ml/min in January, 1978, to 13 ml/min in March. This pattern differs from that seen in Hestbech’s earlier study, where seven patients had reduced creatinine clearance due to lithium poisoning; after elimination of lithium from the body the creatinine clearance remained moderately low in three patients and rose to normal in four. No patient showed progressive deterioration of renal function with development of uraemia. In Hestbech and Aurell’s case lithium probably was responsible for the morphological kidney changes, but whether the fall in G.F.R. was an after-effect of treatment, whether the urxmia was caused by kidney disease that was independent of lithium (the patient had proteinuria, renal arteriosclerosis, hypertension, aneemia, and a raised E.S.R.), or whether kidney disease led to uraemia because the patient’s kidneys had become vulnerable as a result of lithium intoxications due to inadequately controlled treatment remain open questions. Many patients are on long-term lithium for affective disorder, and in some serious organic illness may develop at some time. Such cases should be assessed carefully to determine whether the treatment caused the illness, and disturbed kidney function calls for special attention. Large-scale investigations of the effects of lithium on renal function which are under way may help the doctor to weigh the benefits and hazards of lithsevere
lum
treatment.
SIR,-Lithium treatment impaires tubular function’ and is associated with morphological kidney lesions.2 Dehydration has been used to assess the urinary concentrating capacity. This procedure is very uncomfortable for the polyuric patient, it may be hazardous, and it is impossible in some poorly cooperating psychotic patients. We have therefore been testing a D.D.A.V.P. (1-desamino-8-arginine vasopressin) test instead. Urinary osmolality was measured 3 h after 40 fLg D.D.A.V.P. (’Minirin’, Ferring AB, Sweden) administered intranasally. The result was compared with that of a 14 h period of total
UTNYUKAIIUN
Comparison
]t:1
UKINAK1’
UbMULALIIYimosm/Kgm2u
of D.D.A.V.P. and
dehydration
tests.
restriction of fluid intake. Eighteen inpatients on lithium were studied. The D.D.A.V.P. test could readily be performed in all of them, but five patients refused, or were too psychotic to participate in, the dehydration test. The results in the remaining thirteen patients showed a satisfactory correlation between the two tests over a wide range of urinary concentrating capacities (see figure). No sideeffects during the D.D.A.V.P. test were reported. Seven patients. agreed to prolong the dehydration period to 18 h, but there was little further increase in urinary osmolality (9 + 35 mosmol/kg water ; mean ± s.E.M.). We consider the D.D.A.V.P. test to be a safe, convenient, and reliable measure to estimate renal concentrating capacity in patients treated with lithium. Unlike the dehydration test, it can readily be done in psychotic patients. We now include it as a routine method in our regular assessment of tubular function in these patients. Department of Medicine, University Hospital, S-901 85 Umeå, Sweden
KJELL ASPLUND
ANDERS WAHLIN WALTER RAPP
Umedalen Hospital, Umeå
COMPLICATIONS OF DISOPYRAMIDE
SIR,-Dr Nies and co-workers (Feb. 10, p. 330) report due
to
Psychopharmacology
Research Unit, Aarhus University Institute of Psychiatry
Psychiatric Hospital, DK-8240 Risskov, Denmark
Bucht, G., Wahlin, A. Lancet, 1978, i, 779. Hestbech, J., and others. Kidney Int. 1977, 12, 205. 3. Hayler, AM., Flanagan, R. J. J. Chromatogr 1978, 153, 461.
1. 2.
PER VESTERGAARD
an
disopyramide involving complications interesting therapy. Whilst disopyramide was prescribed at a dose within the recommended range, the toxicity is hardly surprising in view of the high plasma concentrations of the drug: On the basis of the 13 - 8 h half-life of disopyramide elimination in this patient even the "trough" plasma-disopyramide concentration during therapy would have been above 6.00 mg/l. Our experience of measuring plasma-disopyramide concentrations by specific gas-liquid chromatography3suggests that case
worth, happiness, and self-esteem, only
to
find that the
D.D.A.V.P. TEST IN ASSESSMENT OF RENAL FUNCTION DURING LITHIUM THERAPY
cur-
rency debases. Lordswood House,
Harborne, Birmingham B17 9DB
ANTON R. DEWSBURY
LITHIUM-INDUCED URÆMIA?
SIR,-Dr Hestbech and Dr Aurell (Jan. 27, p. 212) report of uraemia in a patient on lithium and conclude that
a case
"lithium treatment, even when well controlled, may cause renal damage". Poorly controlled lithium treatment to toxicity with disturbance of renal function, and lead may even well-controlled treatment may be associated with inhibition of tubular water reabsorption, resulting in polyuria and thirst. However, severe disturbance of glomerular filtration with uraemia had not been described before, so how well controlled was the lithium treatment in Hestbech and Avrell’s patient ? Their patient twice had raised serum-lithium values (1-4 mmol/1 in December, 1975, and 2.1mmol/1 in September, 1977, on the second occasion accompanied by tiredness). In November, 1977, the patient was given antihypertensive treatment (unspecified) which could have led to loss of sodium, lowered lithium excretion, and a rise in the serum-lithium concentration. This patient thus had one or more mild lithium intoxications, and since he also had severe lithium-induced’ polyuria, it is not surprising that his kidney showed morphological changes which resembled those observed previously by Hestbech and colleagues in lithium-treated patients selected for having polyuria or having had lithium poisoning. The history of nephrolithiasis and the development of hypertension with renal arteriosclerosis may or may not have played a role in this case. Hestbech and Aurell state that the "the rapid progression of renal insufficiency stopped when lithium treatment was withdrawn." Their data, however, show the opposite. Apart from a serum-creatinine of 152 umol/l (1-69 mg/dl) shortly before lithium treatment was stopped there is no indication of kidney malfunction during lithium therapy. It was not until 1-3 months after discontinuation of lithium that severe renal deterioration developed-namely, a rise in serum-creatinine to 500 umol/1 (5-66 mg/dl) in February, 1978, and a fall in glomerular filtration-rate from 38 ml/min in January, 1978, to 13 ml/min in March. This pattern differs from that seen in Hestbech’s earlier study, where seven patients had reduced creatinine clearance due to lithium poisoning; after elimination of lithium from the body the creatinine clearance remained moderately low in three patients and rose to normal in four. No patient showed progressive deterioration of renal function with development of uraemia. In Hestbech and Aurell’s case lithium probably was responsible for the morphological kidney changes, but whether the fall in G.F.R. was an after-effect of treatment, whether the urxmia was caused by kidney disease that was independent of lithium (the patient had proteinuria, renal arteriosclerosis, hypertension, aneemia, and a raised E.S.R.), or whether kidney disease led to uraemia because the patient’s kidneys had become vulnerable as a result of lithium intoxications due to inadequately controlled treatment remain open questions. Many patients are on long-term lithium for affective disorder, and in some serious organic illness may develop at some time. Such cases should be assessed carefully to determine whether the treatment caused the illness, and disturbed kidney function calls for special attention. Large-scale investigations of the effects of lithium on renal function which are under way may help the doctor to weigh the benefits and hazards of lithsevere
lum
treatment.
SIR,-Lithium treatment impaires tubular function’ and is associated with morphological kidney lesions.2 Dehydration has been used to assess the urinary concentrating capacity. This procedure is very uncomfortable for the polyuric patient, it may be hazardous, and it is impossible in some poorly cooperating psychotic patients. We have therefore been testing a D.D.A.V.P. (1-desamino-8-arginine vasopressin) test instead. Urinary osmolality was measured 3 h after 40 fLg D.D.A.V.P. (’Minirin’, Ferring AB, Sweden) administered intranasally. The result was compared with that of a 14 h period of total
UTNYUKAIIUN
Comparison
]t:1
UKINAK1’
UbMULALIIYimosm/Kgm2u
of D.D.A.V.P. and
dehydration
tests.
restriction of fluid intake. Eighteen inpatients on lithium were studied. The D.D.A.V.P. test could readily be performed in all of them, but five patients refused, or were too psychotic to participate in, the dehydration test. The results in the remaining thirteen patients showed a satisfactory correlation between the two tests over a wide range of urinary concentrating capacities (see figure). No sideeffects during the D.D.A.V.P. test were reported. Seven patients. agreed to prolong the dehydration period to 18 h, but there was little further increase in urinary osmolality (9 + 35 mosmol/kg water ; mean ± s.E.M.). We consider the D.D.A.V.P. test to be a safe, convenient, and reliable measure to estimate renal concentrating capacity in patients treated with lithium. Unlike the dehydration test, it can readily be done in psychotic patients. We now include it as a routine method in our regular assessment of tubular function in these patients. Department of Medicine, University Hospital, S-901 85 Umeå, Sweden
KJELL ASPLUND
ANDERS WAHLIN WALTER RAPP
Umedalen Hospital, Umeå
COMPLICATIONS OF DISOPYRAMIDE
SIR,-Dr Nies and co-workers (Feb. 10, p. 330) report due
to
Psychopharmacology
Research Unit, Aarhus University Institute of Psychiatry
Psychiatric Hospital, DK-8240 Risskov, Denmark
Bucht, G., Wahlin, A. Lancet, 1978, i, 779. Hestbech, J., and others. Kidney Int. 1977, 12, 205. 3. Hayler, AM., Flanagan, R. J. J. Chromatogr 1978, 153, 461.
1. 2.
PER VESTERGAARD
an
disopyramide involving complications interesting therapy. Whilst disopyramide was prescribed at a dose within the recommended range, the toxicity is hardly surprising in view of the high plasma concentrations of the drug: On the basis of the 13 - 8 h half-life of disopyramide elimination in this patient even the "trough" plasma-disopyramide concentration during therapy would have been above 6.00 mg/l. Our experience of measuring plasma-disopyramide concentrations by specific gas-liquid chromatography3suggests that case
