•
Osmotic Nephrosis Induced by Water-Soluble Triiodinated Contrast Media in Man
Diagnostic Radiology
A Retrospective Study of 47 Cases 1 Jean-Francois Moreau, M.D., A.I.H.P., Dominique Droz, I.H.P., Joseph Sabto, M.R.A.C.P., Paul Jungers, M.D., A.I.H.P., Dieter Kleinknecht, M.D., A.I.H.P., Nicole Hinglais, M.D., and Jean-Rene Michel, M.D., A.I.H.P. Renal biopsies were performed in 211 patients within 10 days of excretory urography or renal arteriography in which diatrizoate, iothalamate or ioxithalamate had been used. In 47 renal specimens, osmotic nephrosis of the proximal tubular cells was found. Previous renal function had been normal in 10 patients, moderately impaired in 19, and severely impaired in 18. Tubular atrophy and/or necrosis was associated with histological features in 29 of 47 patients. Diffuse osmotic nephrosis was more often found in patients biopsied soon after roentgenography and also with severe renal insufficiency, but was not necessarily associated with declining renal function. The mechanism(s) by which contrast media may induce osmotic nephrosis remains unclear. Contrast Media, toxicity. Kidneys, failure. Kidneys, necrosis. Kidneys, transplantation • Nephritis • Pyelonephritis
INDEX TERMS:
Radiology 115:329-336, May 1975 ATER-SOLUBLE triiodinated contrast media (WTCM), presently used for radiological examination of the urinary tract and vascular system, are usually considered safe and non-nephrotoxic (4, 12, 15, 20,39, 43). However, acute renal failure with or without anuria may follow excretory urography (IVP) or angiography, particularly when large doses of WTCM are used (2, 7, 8, 14,22,27,28,30,31,38). These complications reverse spontaneously but may require hemodialysis until recovery (27, 31). The pathophysiology of such accidents remains obscure (2, 22, 35). Until 1970, no pathological lesions were described which were specifically induced by WTCM in man and animals. Cortical necrosis in dogs (34) or medullary necrosis in infants (23) have been reported: these two lesions do not account for all of the renal accidents following IVP or renal angiography. Thrombotic or atheromatous embolizations of the renal vasculature (2, 37) are probably due to the traumatic effect of arterial catheterization. Glomerular, tubular and vascular lesions have been described (2), but are difficult to differentiate from changes caused by underlying nephropathy or artefacts. Several renal accidents after IVP or angiography have been observed at the Clinique Nephrologique of the Necker Hospital in Paris. In 1968, a first unpublished case of histological lesions of "osmotic nephrosis" was observed on renal biopsy of a young woman Who developed acute renal failure after high-dose IVP. These lesions are an intense vacuolization of the proximal tubular cells' cytoplasm. They were called "'osmotic nephrosis" by Allen (1) because the inducing agents are principally hyperosmolar solutions of sugars (19). Since 1970, some reports of WTCM-induced osmotic nephrosis (10, 23, 26, 32) led us to explore its relationship to the nephrotoxic effects of radiocontrast agents.
W
numbe r of cases
DELAY BETWEEN X-RAY EXAMINATION AND RENAL BIOPSY
20
10
23456789 days Chart I. Delay between x-ray examination and renal biopsy.
MATERIAL AND METHODS
Between 1 July 1971 and 1 July 1973, more than 12,500 IVPs and 700 renal angiographies were performed in the Service de Radiologie de I'Appareil Urinaire at the Necker Hospital. During the same period, 725 renal biopsies were carried out in the Departement d' Anatomie Pathologique of the Clinique Nephroloqlque (Prof. J. Hamburger). Of these, 211 renal biopsies were carried out less than 10 days after IVP or renal arteriography. Histological lesions of osmotic nephrosis were found in 47 patients ranging in age from 12 to 76 years
1 From the Service de Radiologie des Maladies de I'Appareil Urinaire (J. R. M., Chief), and Departement d' Anatomie Pathologique (N. H., Chief), and Unite de Recherches Nephroloqlques U 25 de I'lnserm (J. Hamburger, Chief), Hopital Necker, Paris, France. Presented at the XIII International Congress of Radiology, Madrid, October 20, 1973. Accepted for publication in November 1974. shan
329
330
May 1975
JEAN-FRANCOIS MOREAU AND OTHERS
Table I:
Anion
Iodine OsmoConcen- lalit Number tration I y of (gjl00 (mOsmj Patients ml) L)
Cation
Diatrizoate* lothalamatet loxithalamate**
Table IV:
Contrast Media Used in Patients with Osmotic Nephrosis
Sodium methylglucamine Sodium methylglucamine Sodium methylglucamine
37.6
2097
37
32
2150
2
38
2700
8
Extent of Osmotic Nephrosis in Proximal Tubules >90% 50-90%
Osmotic Nephrosis Induced by Water-Soluble Triiodinated Contrast Media in Man
Diagnostic Radiology
A Retrospective Study of 47 Cases 1 Jean-Francois Moreau, M.D., A.I.H.P., Dominique Droz, I.H.P., Joseph Sabto, M.R.A.C.P., Paul Jungers, M.D., A.I.H.P., Dieter Kleinknecht, M.D., A.I.H.P., Nicole Hinglais, M.D., and Jean-Rene Michel, M.D., A.I.H.P. Renal biopsies were performed in 211 patients within 10 days of excretory urography or renal arteriography in which diatrizoate, iothalamate or ioxithalamate had been used. In 47 renal specimens, osmotic nephrosis of the proximal tubular cells was found. Previous renal function had been normal in 10 patients, moderately impaired in 19, and severely impaired in 18. Tubular atrophy and/or necrosis was associated with histological features in 29 of 47 patients. Diffuse osmotic nephrosis was more often found in patients biopsied soon after roentgenography and also with severe renal insufficiency, but was not necessarily associated with declining renal function. The mechanism(s) by which contrast media may induce osmotic nephrosis remains unclear. Contrast Media, toxicity. Kidneys, failure. Kidneys, necrosis. Kidneys, transplantation • Nephritis • Pyelonephritis
INDEX TERMS:
Radiology 115:329-336, May 1975 ATER-SOLUBLE triiodinated contrast media (WTCM), presently used for radiological examination of the urinary tract and vascular system, are usually considered safe and non-nephrotoxic (4, 12, 15, 20,39, 43). However, acute renal failure with or without anuria may follow excretory urography (IVP) or angiography, particularly when large doses of WTCM are used (2, 7, 8, 14,22,27,28,30,31,38). These complications reverse spontaneously but may require hemodialysis until recovery (27, 31). The pathophysiology of such accidents remains obscure (2, 22, 35). Until 1970, no pathological lesions were described which were specifically induced by WTCM in man and animals. Cortical necrosis in dogs (34) or medullary necrosis in infants (23) have been reported: these two lesions do not account for all of the renal accidents following IVP or renal angiography. Thrombotic or atheromatous embolizations of the renal vasculature (2, 37) are probably due to the traumatic effect of arterial catheterization. Glomerular, tubular and vascular lesions have been described (2), but are difficult to differentiate from changes caused by underlying nephropathy or artefacts. Several renal accidents after IVP or angiography have been observed at the Clinique Nephrologique of the Necker Hospital in Paris. In 1968, a first unpublished case of histological lesions of "osmotic nephrosis" was observed on renal biopsy of a young woman Who developed acute renal failure after high-dose IVP. These lesions are an intense vacuolization of the proximal tubular cells' cytoplasm. They were called "'osmotic nephrosis" by Allen (1) because the inducing agents are principally hyperosmolar solutions of sugars (19). Since 1970, some reports of WTCM-induced osmotic nephrosis (10, 23, 26, 32) led us to explore its relationship to the nephrotoxic effects of radiocontrast agents.
W
numbe r of cases
DELAY BETWEEN X-RAY EXAMINATION AND RENAL BIOPSY
20
10
23456789 days Chart I. Delay between x-ray examination and renal biopsy.
MATERIAL AND METHODS
Between 1 July 1971 and 1 July 1973, more than 12,500 IVPs and 700 renal angiographies were performed in the Service de Radiologie de I'Appareil Urinaire at the Necker Hospital. During the same period, 725 renal biopsies were carried out in the Departement d' Anatomie Pathologique of the Clinique Nephroloqlque (Prof. J. Hamburger). Of these, 211 renal biopsies were carried out less than 10 days after IVP or renal arteriography. Histological lesions of osmotic nephrosis were found in 47 patients ranging in age from 12 to 76 years
1 From the Service de Radiologie des Maladies de I'Appareil Urinaire (J. R. M., Chief), and Departement d' Anatomie Pathologique (N. H., Chief), and Unite de Recherches Nephroloqlques U 25 de I'lnserm (J. Hamburger, Chief), Hopital Necker, Paris, France. Presented at the XIII International Congress of Radiology, Madrid, October 20, 1973. Accepted for publication in November 1974. shan
329
330
May 1975
JEAN-FRANCOIS MOREAU AND OTHERS
Table I:
Anion
Iodine OsmoConcen- lalit Number tration I y of (gjl00 (mOsmj Patients ml) L)
Cation
Diatrizoate* lothalamatet loxithalamate**
Table IV:
Contrast Media Used in Patients with Osmotic Nephrosis
Sodium methylglucamine Sodium methylglucamine Sodium methylglucamine
37.6
2097
37
32
2150
2
38
2700
8
Extent of Osmotic Nephrosis in Proximal Tubules >90% 50-90%
