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Cis-platinum (II) diaminedichloride: Another cause of bilateral small kidneys
CIS-PLATINUM ANOTHER
(II) DIAMINEDICHLORIDE:
CAUSE OF BILATERAL
A4RNOLD
C. FKIEDM.4N,
EVERETI’
14. I,.L\UTIN,
SMALL
KIDNEYS
M.D. M.D.
From the Department of Radiology, Albert Einstein College of Medicine. Montefiore Hospital and AMedical Center. Brour, New York
There are many causes of bilateral, small, smooth kidneys, the most comluon being renal vascular disease, chronic glomerulonephritides. renal papillary necrosis, and hereditary nephropathies. 1 Cis-platinum (II) cliaminedichloride (CPDD) is a recently introduced mtineoplastic drug whose limiting side effect is renal toxicity. ‘y3 We report the first case of bilateral renal atrophy due to CPDD therapy documented radiologically. Urologists must be aware of this entity in order to explain bilateral renal atrophy in this clinical context and to be able to elicit the history when it is not immediately forthcoming.
to the left reual vein necessitating an end-to-end repair. This was accompanied by a transient rise in serum creatinine (Table I); an isotope sca11 OII day 16 showed nonflmction of the left kidney. Chemotherapy was bqgm on day 33 using a protocol employing cyclophosphamide, vinhlastine, actinomycin D, bleomycin, and CPDD for induction and vinblastine, actinomycin D, and chlorambucil for maintenance. On day 42, 250 lug. of CPDD were given without apparent clxmge in renal function; the patient’s baseline creatiuine clearance was 86.2 ml./min. (Table 1).
Case Keport A twenty-one-year-old white Juan was admitted to the Montefiore Hospital and Medical Center (day 1) with a one-year history of ;I hard left testicular mass. A left orchiectomy (day 3) disclosed a11 embryonal cell carcinoula with small foci of syncytiotrophoblastic cells and teratoid elements. 411 excretory urogram (day 3) showed normal-sized kiclncys (left 1:3. O cm., right 12.6 cm.) and lateral deviation of the left kidney aud ureter by a retroperitoneal mass (Fig. 1A). A retroperitoneal lylnph;~de~lectonl~ was performed on day 15. complicated 1,~ injiq
S84
Creatininv jmg./dl. i 1 13
16 If-3 33 34 48 280 306 720
1’HoLo(:k-
11 10 I35 11 18 ,‘i 1:3 16 11 18
1.o 2.1 1 .3 1.2 1.1 i.0 1.-l 1.6
12.6 cm. I in length): note site retrq)eritoneal udenopnthy. (Bj After .surgery and CPDD therapy left kidney decreased to 9.7 cm. in length (less than 3 certebrul bodies) presuvnahly due to renal zrein thrombosis; right kidney unchunged with length 12.6 cm. (C) About one year ufter covupletion of (1 second course qf CPDD both kidneys decreased in length: /eft 8.8 cm., right 11 .O cm. (h&h
On day 280 a repeat creatinine clearance Id fallen to 59 ml./min. (Table I). ,4 repeat ltrogranl showed a small left kidney (9.7 cm .) and a normal right kidney (12.6 cm.) (Fig. 1B). On day 288, 228 mg. of CPDD was given. On day 306 the serum creatinine was 1.4. An excretory urograin about one year late1 showed a bilateral decrease in renal size, the left being smaller than the right (left 8.8 cm., right 11.0 cm.) (Fig. 1C). The creatinine rose slightly to 1.6 at about the same time. At no time was there ever any clinical evidence of infection. The patient received no radiation the].ap y
CPDD is the best known con~pountl among the platinum-coordination complexes, a new cl:iss of antitumor agents.’ It is most activr, against testicular and ovarian tumors and euhib its good activity in bladder carcinoma and heutl and neck malignancies. ’ Renal insrtf’ficienc\, is
0 cm. md right about 3.5 certehrul
kidney bodies
the major dose-limiting factor, occurring in 20 to 25 per cent of cases, usually mild and reversible, but becoming irreversible with high doses courses.’ Pathologic damage occurs or repeat primarily in distal convoluted tubules- and collecting ducts; acute tubular necrosis has been reported as well as chronic changes.” Otha nephrotoxic drugs and prior renal insufficiency augment the deleterious effects of CPDD.” Intravenous hydration along with mannitol infusion is reported to decrease CPDD nephrotoxicity without affecting antitumor activity allowing the use of higher doses (this was employed in this case). 01lr baseline excretory urogram showed normal-sized kidneys, and renal function was initially normal (Fig. 1‘4). Prior to the first course of CPDD creatinine clearance was only 86.2 tnl./mill. (nornlal 120 ml./min.). This was LIIIdoubteclly due to throlnbosis of the left renal L eill secondary to the surgical injury. The second urogrrun showed a small left kidney as a
result of the renal vein thrombosis and no significant change in the size of the right kidney (Fig. 1B). The creatinine clearance had dropped to 59 ml./min. due to CPDD toxicity in a patient with pre-existing renal impairment. Failure of the right kidney to hypertrophy was possibly due to CPDD toxicity. The final excretory urogram about one year after the second course of CPDD showed a decrease in the size of both kidneys due to CPDD (Fig. 1C). In a recent report Harmon et al. 4 described 8 cases of renal toxicity due to methylCCNU (a nitrosurea antineoplastic agent). As in our case, during the course of treatment there was no clinical evidence of renal deterioration by blood urea nitrogen or serum creatinine measurement (creatinine clearance not mentioned) nor by urinalysis. All patients had decreased renal size as measured by serial urography. In 3 cases the renal size continued to diminish even after treatment was completed; eventually in 4 cases renal function deteriorated progressively. Two patients showed decreased renal size and never had any other evidence of renal insufficiency. Urologists and radiologists should be aware that CPDD (or nitrosurea) therapy can cause
586
the urographic appearance of bilateral, small, smooth kidneys with or without concomitant clinical signs of decreasing renal function. It is suggested that in monitoring these patients radioisotope renal scanning might prove to be more sensitive to renal damage than either serial creatinine determinations or excretory urography, analogous to the situation in renal transplant patients.
Department of Radiology Walter Reed Army Medical Center Washington, D.C. 20012 (DR. FRIEDMAN) References 1. Davidson AJ: Radiologic Diagnosis of Renal Parenchymal Disease, Philadelphia, Saunders, 1977, pp. 96- 129. 2. Rozencweig M, VonHoff DD, Slavick M, and Muggia FM: Cis-diaminedichloroplatinum (II), Ann. Intern. Med. 86: 803 (1977). 3. Gonzalez-Vitale JC. Hayes DM, Cvitkovick E, and Sternberg SS: The renal pathology in clinical trials of cis-platinum (II) diaminedichloride, Cancer 39: 1362 (1977). 4. Harmon WE, Cohen HJ, Schneeberger EE, and Grope WE: Chronic renal failure in children treated with methylCCNU, N. Engl. J. Med. 300: 1200 (1979).
UROLOGY
/
DECEMBER
1980
/
VOLUME
XVI,
NUMBER
6
(II) DIAMINEDICHLORIDE:
CAUSE OF BILATERAL
A4RNOLD
C. FKIEDM.4N,
EVERETI’
14. I,.L\UTIN,
SMALL
KIDNEYS
M.D. M.D.
From the Department of Radiology, Albert Einstein College of Medicine. Montefiore Hospital and AMedical Center. Brour, New York
There are many causes of bilateral, small, smooth kidneys, the most comluon being renal vascular disease, chronic glomerulonephritides. renal papillary necrosis, and hereditary nephropathies. 1 Cis-platinum (II) cliaminedichloride (CPDD) is a recently introduced mtineoplastic drug whose limiting side effect is renal toxicity. ‘y3 We report the first case of bilateral renal atrophy due to CPDD therapy documented radiologically. Urologists must be aware of this entity in order to explain bilateral renal atrophy in this clinical context and to be able to elicit the history when it is not immediately forthcoming.
to the left reual vein necessitating an end-to-end repair. This was accompanied by a transient rise in serum creatinine (Table I); an isotope sca11 OII day 16 showed nonflmction of the left kidney. Chemotherapy was bqgm on day 33 using a protocol employing cyclophosphamide, vinhlastine, actinomycin D, bleomycin, and CPDD for induction and vinblastine, actinomycin D, and chlorambucil for maintenance. On day 42, 250 lug. of CPDD were given without apparent clxmge in renal function; the patient’s baseline creatiuine clearance was 86.2 ml./min. (Table 1).
Case Keport A twenty-one-year-old white Juan was admitted to the Montefiore Hospital and Medical Center (day 1) with a one-year history of ;I hard left testicular mass. A left orchiectomy (day 3) disclosed a11 embryonal cell carcinoula with small foci of syncytiotrophoblastic cells and teratoid elements. 411 excretory urogram (day 3) showed normal-sized kiclncys (left 1:3. O cm., right 12.6 cm.) and lateral deviation of the left kidney aud ureter by a retroperitoneal mass (Fig. 1A). A retroperitoneal lylnph;~de~lectonl~ was performed on day 15. complicated 1,~ injiq
S84
Creatininv jmg./dl. i 1 13
16 If-3 33 34 48 280 306 720
1’HoLo(:k-
11 10 I35 11 18 ,‘i 1:3 16 11 18
1.o 2.1 1 .3 1.2 1.1 i.0 1.-l 1.6
12.6 cm. I in length): note site retrq)eritoneal udenopnthy. (Bj After .surgery and CPDD therapy left kidney decreased to 9.7 cm. in length (less than 3 certebrul bodies) presuvnahly due to renal zrein thrombosis; right kidney unchunged with length 12.6 cm. (C) About one year ufter covupletion of (1 second course qf CPDD both kidneys decreased in length: /eft 8.8 cm., right 11 .O cm. (h&h
On day 280 a repeat creatinine clearance Id fallen to 59 ml./min. (Table I). ,4 repeat ltrogranl showed a small left kidney (9.7 cm .) and a normal right kidney (12.6 cm.) (Fig. 1B). On day 288, 228 mg. of CPDD was given. On day 306 the serum creatinine was 1.4. An excretory urograin about one year late1 showed a bilateral decrease in renal size, the left being smaller than the right (left 8.8 cm., right 11.0 cm.) (Fig. 1C). The creatinine rose slightly to 1.6 at about the same time. At no time was there ever any clinical evidence of infection. The patient received no radiation the].ap y
CPDD is the best known con~pountl among the platinum-coordination complexes, a new cl:iss of antitumor agents.’ It is most activr, against testicular and ovarian tumors and euhib its good activity in bladder carcinoma and heutl and neck malignancies. ’ Renal insrtf’ficienc\, is
0 cm. md right about 3.5 certehrul
kidney bodies
the major dose-limiting factor, occurring in 20 to 25 per cent of cases, usually mild and reversible, but becoming irreversible with high doses courses.’ Pathologic damage occurs or repeat primarily in distal convoluted tubules- and collecting ducts; acute tubular necrosis has been reported as well as chronic changes.” Otha nephrotoxic drugs and prior renal insufficiency augment the deleterious effects of CPDD.” Intravenous hydration along with mannitol infusion is reported to decrease CPDD nephrotoxicity without affecting antitumor activity allowing the use of higher doses (this was employed in this case). 01lr baseline excretory urogram showed normal-sized kidneys, and renal function was initially normal (Fig. 1‘4). Prior to the first course of CPDD creatinine clearance was only 86.2 tnl./mill. (nornlal 120 ml./min.). This was LIIIdoubteclly due to throlnbosis of the left renal L eill secondary to the surgical injury. The second urogrrun showed a small left kidney as a
result of the renal vein thrombosis and no significant change in the size of the right kidney (Fig. 1B). The creatinine clearance had dropped to 59 ml./min. due to CPDD toxicity in a patient with pre-existing renal impairment. Failure of the right kidney to hypertrophy was possibly due to CPDD toxicity. The final excretory urogram about one year after the second course of CPDD showed a decrease in the size of both kidneys due to CPDD (Fig. 1C). In a recent report Harmon et al. 4 described 8 cases of renal toxicity due to methylCCNU (a nitrosurea antineoplastic agent). As in our case, during the course of treatment there was no clinical evidence of renal deterioration by blood urea nitrogen or serum creatinine measurement (creatinine clearance not mentioned) nor by urinalysis. All patients had decreased renal size as measured by serial urography. In 3 cases the renal size continued to diminish even after treatment was completed; eventually in 4 cases renal function deteriorated progressively. Two patients showed decreased renal size and never had any other evidence of renal insufficiency. Urologists and radiologists should be aware that CPDD (or nitrosurea) therapy can cause
586
the urographic appearance of bilateral, small, smooth kidneys with or without concomitant clinical signs of decreasing renal function. It is suggested that in monitoring these patients radioisotope renal scanning might prove to be more sensitive to renal damage than either serial creatinine determinations or excretory urography, analogous to the situation in renal transplant patients.
Department of Radiology Walter Reed Army Medical Center Washington, D.C. 20012 (DR. FRIEDMAN) References 1. Davidson AJ: Radiologic Diagnosis of Renal Parenchymal Disease, Philadelphia, Saunders, 1977, pp. 96- 129. 2. Rozencweig M, VonHoff DD, Slavick M, and Muggia FM: Cis-diaminedichloroplatinum (II), Ann. Intern. Med. 86: 803 (1977). 3. Gonzalez-Vitale JC. Hayes DM, Cvitkovick E, and Sternberg SS: The renal pathology in clinical trials of cis-platinum (II) diaminedichloride, Cancer 39: 1362 (1977). 4. Harmon WE, Cohen HJ, Schneeberger EE, and Grope WE: Chronic renal failure in children treated with methylCCNU, N. Engl. J. Med. 300: 1200 (1979).
UROLOGY
/
DECEMBER
1980
/
VOLUME
XVI,
NUMBER
6