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Renal biopsy studies of lithium and prelithium patients and comparison with cadaver transplant kidneys
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Ncurr,phorm~l‘,,k,y?. Vol IX. pp 1001 to 1002 Perpamon Prers Ltd lY7Y. Printed I” Great Bntain
RENAL BIOPSY STUDIES OF LITHIUM AND PRELIT~IUM PATIENTS AND COMPARISON WITH CADAVER TRANSPLANT KIDNEYS B. DAVIES and PRISCILLA KINCAID-SMITI-I Departments of Psychiatry and Medicine, University of Melbourne, Royal Melbourne Hospital. Victoria 3050, Australia
Ultrastructural studies showed an apparent swelling of the cytoplasm and mitochondria and other intracellular organelles were distributed at the periphery of the cells. This gave rise to the PAS positive granular appearance described on light microscopy. No evidence of actual cell necrosis was seen. These changes were found in the distal convoluted tubules and collecting ducts. (B) Non-specific changes were found in the renal biopsy material from all three groups of patients. A comparison of the graded severity of these lesions showed: 1. Transplant vs biopsies 2 = - 2.41. P = 0.01. 2. Transplant vs lithium biopsies 2 = -2.92, P = 0.003. 3. Prelithium vs lithium biopsies 2 = -0.52, P > 0.05 NS. Thus, the transplant kidneys differed significantly from both the lithium and prelithium patients in regard to these non-specific renal changes.
Hestbech, Hansen, Amdisen and Ohen (1977) described a cleariy irreversible morphological lesion, thought to be progressive in the kidneys of patients receiving lithium. The widespread use of lithium in preventing recurrences of affective illness has made the renal effects of lithium an important area of study. This investigation describes a renal biopsy study of lithium and prelithium patients and an age-matched sample of cadaver kidneys.
METHODS Renal biopsies were obtained from two groups of patients: (1) Sixteen patients who had been taking lithium regularly for a mean of 5.5 years. None had been clinically “Iithium toxic”. (2) Nine patients about to start lithium prophylaxis. Biopsies from an age-matched sample of cadaver donor kidneys were also studied. Biopsy results were classed as: (1) Specific tubular lesion. (2) Non specific changes which were assessed as: (a) percentage glomeruli sclerosed (b) degree of tubular atrophy (c) interstitial fibrosis (d) cast formation. These last three were graded on a O-3 scale. The prelithium and transplant biopsies were assessed blindly and were presented in a random order. The specific tubular lesion, was found only in the patients on lithium, so that the observer (PIG) was not blind in this regard.
DlSCUSSlON
RESULTS (A) The specific tubular lesion was found only in the 16 patients being treated with lithium. It has been described elsewhere (Burrows, Davies and KincaidSmith, 1978). Key patients,
words: cadaver
renal biopsy, controls.
lithium
and
prelithium
These results confirm the unique and specific tubular lesion in patients on lithium. The present studies show that they develop within a few days of starting lithium and appear to be reversible. Their location is where the vasopressin receptors are thought to be, and the changes may be the pathological basis of the vasopressin-resistant diabetes insipidus syndrome seen in patients on lithium. At this time the relationship of this lesion to the non-specific changes of nephron atrophy are unclear. With regard to the non-specific lesions described by Hestbech ttr uf. (1977). we have found them equally in patients about to start lithium. Only one of the patients had never received major tranquillisers or antidepressants for his illnesses of mood, and his was the only normal prelithium biopsy. We are therefore investigating the possible nephrotoxic effects of both antidepressants and major tranquillisers. These findings and a comparative study of renal function tests of the two groups of patients will be reported elsewhere (Kincaid-Smith, unpublished).
1001
B. DAVIES and PRISCILLAKINCAID-SMITH
1002
Fig. 1. Electron
microscopy
of renal tubular cell. showing swelling tion of mitochondria.
REFERENCES
Burrows, G. D., Davies, B. and Kincaid-Smith, P. (1978). Unique tubular lesion after lithium. Lancer I: 1310. Hestbech, J., Hansen, A. E.. Amdisen, A. and Ohen, S.
of cytoplasm
(1977). Chronic
and peripheral
distribu-
renal lesions following long term treatment with lithium. Kiciner inr. t2: 205-213. Kincaid-Smith, P., Burrows. G., Holwill, B., Walter, M. and Davies, B. (1979). Renal studies in lithium and prelithium patients, and biopsy comparisons with transplant donor kidneys. In press.
Ncurr,phorm~l‘,,k,y?. Vol IX. pp 1001 to 1002 Perpamon Prers Ltd lY7Y. Printed I” Great Bntain
RENAL BIOPSY STUDIES OF LITHIUM AND PRELIT~IUM PATIENTS AND COMPARISON WITH CADAVER TRANSPLANT KIDNEYS B. DAVIES and PRISCILLA KINCAID-SMITI-I Departments of Psychiatry and Medicine, University of Melbourne, Royal Melbourne Hospital. Victoria 3050, Australia
Ultrastructural studies showed an apparent swelling of the cytoplasm and mitochondria and other intracellular organelles were distributed at the periphery of the cells. This gave rise to the PAS positive granular appearance described on light microscopy. No evidence of actual cell necrosis was seen. These changes were found in the distal convoluted tubules and collecting ducts. (B) Non-specific changes were found in the renal biopsy material from all three groups of patients. A comparison of the graded severity of these lesions showed: 1. Transplant vs biopsies 2 = - 2.41. P = 0.01. 2. Transplant vs lithium biopsies 2 = -2.92, P = 0.003. 3. Prelithium vs lithium biopsies 2 = -0.52, P > 0.05 NS. Thus, the transplant kidneys differed significantly from both the lithium and prelithium patients in regard to these non-specific renal changes.
Hestbech, Hansen, Amdisen and Ohen (1977) described a cleariy irreversible morphological lesion, thought to be progressive in the kidneys of patients receiving lithium. The widespread use of lithium in preventing recurrences of affective illness has made the renal effects of lithium an important area of study. This investigation describes a renal biopsy study of lithium and prelithium patients and an age-matched sample of cadaver kidneys.
METHODS Renal biopsies were obtained from two groups of patients: (1) Sixteen patients who had been taking lithium regularly for a mean of 5.5 years. None had been clinically “Iithium toxic”. (2) Nine patients about to start lithium prophylaxis. Biopsies from an age-matched sample of cadaver donor kidneys were also studied. Biopsy results were classed as: (1) Specific tubular lesion. (2) Non specific changes which were assessed as: (a) percentage glomeruli sclerosed (b) degree of tubular atrophy (c) interstitial fibrosis (d) cast formation. These last three were graded on a O-3 scale. The prelithium and transplant biopsies were assessed blindly and were presented in a random order. The specific tubular lesion, was found only in the patients on lithium, so that the observer (PIG) was not blind in this regard.
DlSCUSSlON
RESULTS (A) The specific tubular lesion was found only in the 16 patients being treated with lithium. It has been described elsewhere (Burrows, Davies and KincaidSmith, 1978). Key patients,
words: cadaver
renal biopsy, controls.
lithium
and
prelithium
These results confirm the unique and specific tubular lesion in patients on lithium. The present studies show that they develop within a few days of starting lithium and appear to be reversible. Their location is where the vasopressin receptors are thought to be, and the changes may be the pathological basis of the vasopressin-resistant diabetes insipidus syndrome seen in patients on lithium. At this time the relationship of this lesion to the non-specific changes of nephron atrophy are unclear. With regard to the non-specific lesions described by Hestbech ttr uf. (1977). we have found them equally in patients about to start lithium. Only one of the patients had never received major tranquillisers or antidepressants for his illnesses of mood, and his was the only normal prelithium biopsy. We are therefore investigating the possible nephrotoxic effects of both antidepressants and major tranquillisers. These findings and a comparative study of renal function tests of the two groups of patients will be reported elsewhere (Kincaid-Smith, unpublished).
1001
B. DAVIES and PRISCILLAKINCAID-SMITH
1002
Fig. 1. Electron
microscopy
of renal tubular cell. showing swelling tion of mitochondria.
REFERENCES
Burrows, G. D., Davies, B. and Kincaid-Smith, P. (1978). Unique tubular lesion after lithium. Lancer I: 1310. Hestbech, J., Hansen, A. E.. Amdisen, A. and Ohen, S.
of cytoplasm
(1977). Chronic
and peripheral
distribu-
renal lesions following long term treatment with lithium. Kiciner inr. t2: 205-213. Kincaid-Smith, P., Burrows. G., Holwill, B., Walter, M. and Davies, B. (1979). Renal studies in lithium and prelithium patients, and biopsy comparisons with transplant donor kidneys. In press.