Vol. 115, June Printed in U.S.A.
THE JOURNAL OF UROLOGY
Copyright© 1976 by The Williams & Wilkins Co.
THE PROTEAN MANIFESTATIONS OF RENAL VEIN THROMBOSIS IN THE ADULT H. G. KIRULUTA, A. W. BRUCE, S. V. JARZYLO
AND
P. A. F. MORRIN
From the Division of Nephrology, Department of Medicine and the Departments of Urology and Diagnostic Radiology, Queen's University and the Kingston General Hospital, Kingston, Ontario, Canada
ABSTRACT
We reviewed 8 cases of renal vein thrombosis, 4 of which were detected at autopsy, 1 by laparotomy and the remaining 3 by venography. In 4 cases malignancy also was found and in 2 membranous glomerulonephritis was noted. In 1 patient the thrombosis occurred in a solitary kidney, while it was bilateral in 3. The 4 patients in whom the diagnosis was made during life were treated with anticoagulants alone and 3 are alive with stable renal function 3, 4 and 7 ½ years after diagnosis. Renal vein thrombosis was first diagnosed by Rayer in 1837 on the basis of autopsy findings in 7 patients. 1 In 1963 Kowal and associates were able to find only 65 cases in the literature, in most of which the diagnosis had been made post mortem. 2 In 1968 Rosenmann and associates reported a detailed study on 15 patients and reviewed the clinical, radiological and pathological findings. 3 Since that time there have been numerous reports on the etiology, pathophysiology, treatment and prognosis.•·• During the last 5 years we have encountered 4 cases of renal vein and/or vena caval thrombosis that were diagnosed while the patient was living and we were able to collect 4 cases in which the diagnosis was unsuspected and only established at autopsy. Herein we describe the protean manifestations of this syndrome as it presented in these patients. The relevant clinical features of the patients are shown in the table. Cases 6 and 8 had extensive carcinoma and the renal vein thrombosis was probably a pre-terminal event. In cases 5 and 7 the thrombosis was an unanticipated finding at autopsy. Case 4 was diagnosed at laparotomy, which was performed prior to transfer to our center because of abdominal pain, increasing abdominal distension associated with deteriorating renal function and severe edema. The patient had renal cell carcinoma invading the left renal vein and vena cava. In this instance the thrombosis was also a pre-terminal event associated with the malignancy. The first 3 cases are of particular interest and are described in more detail. CASE REPORTS
Case 1. J. B., a 32-year-old man, underwent right radical nephrectomy for stage 1 renal cell carcinoma. A preoperative excretory urogram (IVP) revealed normal function in both kidneys. The blood pressure was 110/65, serum creatinine 1.2 mg. per cent and blood urea nitrogen (BUN) 15 mg. per cent. The operation was uneventful but 1 day postoperatively there was a short period of anuria and the patient's temperature was 39.8C. By 2 days postoperatively the BUN was 44 mg. per cent and the creatinine was 4.8 mg. per cent. These values increased during the next few days to 140 and 13.4 mg. per cent, respectively (fig. 1). The 24-hour urine protein excretion ranged between 0.3 and 3.0 gm. An infusion IVP subsequently revealed a functioning left kidney, which had enlarged significantly from the preoperative examination. A left testicular venogram showed thrombosis of the left renal vein (fig. 2). The patient was treated with continuous intravenous infusion of heparin for 2 weeks and oral anticoagulation was Accepted for publication August 15, 1975.
maintained with sodium warfarin for 4 months. The BUN was 20 mg. per cent and the creatinine was 1.8 mg. per cent 30 days postoperatively. After 6 months the blood pressure was 120/80, BUN 33 mg. per cent, serum creatinine 0.6 mg. per cent and the urine contained only a trace of protein. The patient was in good health 4 years later, with a blood pressure of 130/78, normal BUN and urine free of protein. Case 2. T. S., a 24-year-old man, had a 4-month history of bilateral, intermittent flank pain and ankle edema. He had received a football injury to the back 2 years previously, after which he experienced intermittent left flank pain associated with hematuria. These symptoms subsided spontaneously without further investigation. Examination revealed a well built, young man with a blood pressure of 130/80. There was mild ankle edema and slight tenderness in the upper left quadrant. The BUN was 11 and the creatinine was 1.1 mg. per cent. The total serum protein was 4.5 and the albumin was 2.9 gm. per cent. Urinalysis revealed 3 plus protein and 24-hour protein excretion ranged from 2 to 14 gm. (fig. 3). An IVP revealed bilateral, enlarged kidneys with poor excretion. A percutaneous, left renal biopsy showed changes of membranous glomerulonephritis (fig. 4), and immunofluorescent staining was positive for lgG but not for BlC. The histology was considered to be compatible with renal vein thrombosis. A venacavogram showed a shaggy, intraluminal filling defect above both renal veins (fig. 5). Anticoagulation was commenced with heparin given intravenously for 2 weeks and then continued with oral sodium warfarin. During the next 3 months the patient continued to excrete large amounts of protein. Treatment with 60 mg. prednisone on alternate days was given for 21 months. Steroid therapy was followed by a prompt decrease in protein excretion. The blood pressure was 120/80, BUN 17 mg. per cent and the creatinine 1.1 mg. per cent 1 year later. The 24-hour protein excretion was 0.9 gm. The patient has been followed for 90 months. The blood pressure was normal and the 24-hour urine protein excretion was 200 mg. when he was last seen. Case 3. K. C., a 41-year-old man, had the nephrotic syndrome in October 1970. The BUN at that time was 12 mg. per cent, the creatinine 1.1 mg. per cent and the 24-hour urine protein excretion ranged from 11.2 to 17.9 gm. A renal biopsy showed the characteristic histology of membranous glomerulonephritis but immunofluorescent staining was negative for lgG and BlC. The patient was treated with 60 mg. prednisone on alternate days for 16 months without apparent benefit. In March 1972, 150 mg. azathioprine was instituted daily and was followed by a decrease in protein excretion (fig. 6). In May the patient suffered chest pain on the left side and shortness of
634
635
RENAL VEIN THROMBOSIS IN ADULT
Clinical features of 8 patients with renal vein or vena caval thrombosis Case No. - Age-S ex
Protein Excretion (gm./24 hrs.)
Site of Thrombosis
Associated Disease
1-32-M
Ca rt. kidney
Lt. renal vein
1.5-3.2
2-21-M
Membranous glomerulopathy
Bilat. renal veins and
2.0-14.0
inferior vena cava
Anticoagulants for 4 mos. Anticoagulants and prednisone
3-41-M
Membranous glomerulopathy
Rt. renal vein initially and subsequently It. renal vein as well
Tuberous sclerosis, Ca It. kidney with invasion of renal vein Chronic renal failure owing to phenacetin nephropathy Cholangiocellular Ca liver with extrinsic compression of inferior vena cava Dementia and acute pyelonephritis (bilat.) Squamous cell Ca rt. lung with metastases to both kidneys
4-47-F 5-56-F* 6-69-F* 7-66-F* 8-44-F*
11.2-17.9
Current Status
Followup (yrs.)
Asymptomatic, creatinine 0.6 Asymptomatic, no protein uria, creatinine 1.1 Persistent nephrotic syn-
4
Treatment
Anticoagulants
drome,
0.5
Lt. renal vein
0.5-0.6
Dead
Inferior vena cava and bilat. renal veins
0.1-0.4
Dead
Trace of protein on urinalysis Trace of protein on urinalysis
Lt. renal vein
3
creati-
nine 1.9 Dead
Lt. renal vein
Lt. renal vein
Anticoagulants
7½
Dead Dead
• Diagnosis made at autopsy. HEPARIN
COUMAOIN
mg/lOOml
....z z ~.... a:
4
U)
','O
60 ~
-i
50 ~
z
0
8 6
....
//o-r:/
10
u
a:
:,;,
o}~, .......o
12
::. ::,
ml./min.
70 (')
14
,f I
o-0
m (')
30 rm l>
20
:,;,
l>
z
10 m Oi-'--2-4--6-8--10_1_2_14_1_6_18_2_0_22_2_4_2_6_2_8_3_0_~ 0 (')
2
t
DAYS POST OP.
24hr. urine protein
':,l~-------------------ML Urine/24hrs.
:~ 2000
FIG. 2. Case 1. Testicular venogram demonstrates left renal vein occlusion with collateral circulation.
1000
2
4
6
8
10 12 14
16 18 20 22 24 26 28 30
DAYS POST OP.
change in his general condition and nephrotic rate of protein excretion 4 months later.
FIG. 1. Case 1. Clinical course
DISCUSSION
breath. A lung scan demonstrated multiple pulmonary emboli. A venacavogram revealed complete occlusion of the right renal vein (fig. 7, A). Intravenous heparin was given for 2 weeks and oral anticoagulation with sodium warfarin was continued for 5 months and then discontinued by the patient against medical advice. In January 1975 blood pressure was 190/110, BUN 30.6 mg. per cent, creatinine 2.8 mg. per cent and the 24-hour urine protein excretion had risen to 4.6 gm. An IVP showed large kidneys with poor excretion. A repeat venogram revealed bilateral renal vein occlusions and a large mass on the right side of the vena cava (fig. 7, B). Renal arteriography subsequently showed this mass to be caused by collateral veins that had formed after thrombosis of the right renal vein (fig. 8). The patient was started on long-term anticoagulants. There was no
A review of the literature would suggest that renal vein thrombosis in the adult is relatively uncommon. The exact incidence is unknown because the condition may be completely asymptomatic and only discovered at autopsy, as illustrated by cases 4 to 6. In this hospital the condition was found in 0.4 per cent of all autopsies performed during a 7-year period. However, the true frequency is probably greater because the disease in the adult is not necessarily fatal and many cases are undoubtedly missed. There are no pathognomonic clinical features but a history of back pain followed by proteinuria may suggest the diagnosis, as in case 2. Proteinuria appears to be a constant finding in clinical and experimental renal vein thrombosis"· 10 and the condition is accepted generally as one of the causes of the
636
KIRULUTA AND ASSOCIATES mgm HEPARIN/24hrs.
COUMADIN
HEPARIN
PREDNISONE
~ mg./lOOml ~ 2 . 0 ~ "' 1.5 a:
u
! -~
I
2
3
4
5
6
7
8
9
10 II
12
13 14
/:: 19
26
Gm/24hr. 14 12 C
!
0
.
ct .:
::5
FIG. 5. Case 2. Venacavogram demonstrates bilateral renal vein occlusions and right caval thrombus.
10
8 6 4
......__,,__
"'
2
"'
0 -....--..,--,---r-,-....---,--r--r-.--.--,--,--,--1 ,.,_, - - , I 19 26 2 3 4 5 6 7 8 9 10 II 12 13 14
,::
THE JOURNAL OF UROLOGY
Copyright© 1976 by The Williams & Wilkins Co.
THE PROTEAN MANIFESTATIONS OF RENAL VEIN THROMBOSIS IN THE ADULT H. G. KIRULUTA, A. W. BRUCE, S. V. JARZYLO
AND
P. A. F. MORRIN
From the Division of Nephrology, Department of Medicine and the Departments of Urology and Diagnostic Radiology, Queen's University and the Kingston General Hospital, Kingston, Ontario, Canada
ABSTRACT
We reviewed 8 cases of renal vein thrombosis, 4 of which were detected at autopsy, 1 by laparotomy and the remaining 3 by venography. In 4 cases malignancy also was found and in 2 membranous glomerulonephritis was noted. In 1 patient the thrombosis occurred in a solitary kidney, while it was bilateral in 3. The 4 patients in whom the diagnosis was made during life were treated with anticoagulants alone and 3 are alive with stable renal function 3, 4 and 7 ½ years after diagnosis. Renal vein thrombosis was first diagnosed by Rayer in 1837 on the basis of autopsy findings in 7 patients. 1 In 1963 Kowal and associates were able to find only 65 cases in the literature, in most of which the diagnosis had been made post mortem. 2 In 1968 Rosenmann and associates reported a detailed study on 15 patients and reviewed the clinical, radiological and pathological findings. 3 Since that time there have been numerous reports on the etiology, pathophysiology, treatment and prognosis.•·• During the last 5 years we have encountered 4 cases of renal vein and/or vena caval thrombosis that were diagnosed while the patient was living and we were able to collect 4 cases in which the diagnosis was unsuspected and only established at autopsy. Herein we describe the protean manifestations of this syndrome as it presented in these patients. The relevant clinical features of the patients are shown in the table. Cases 6 and 8 had extensive carcinoma and the renal vein thrombosis was probably a pre-terminal event. In cases 5 and 7 the thrombosis was an unanticipated finding at autopsy. Case 4 was diagnosed at laparotomy, which was performed prior to transfer to our center because of abdominal pain, increasing abdominal distension associated with deteriorating renal function and severe edema. The patient had renal cell carcinoma invading the left renal vein and vena cava. In this instance the thrombosis was also a pre-terminal event associated with the malignancy. The first 3 cases are of particular interest and are described in more detail. CASE REPORTS
Case 1. J. B., a 32-year-old man, underwent right radical nephrectomy for stage 1 renal cell carcinoma. A preoperative excretory urogram (IVP) revealed normal function in both kidneys. The blood pressure was 110/65, serum creatinine 1.2 mg. per cent and blood urea nitrogen (BUN) 15 mg. per cent. The operation was uneventful but 1 day postoperatively there was a short period of anuria and the patient's temperature was 39.8C. By 2 days postoperatively the BUN was 44 mg. per cent and the creatinine was 4.8 mg. per cent. These values increased during the next few days to 140 and 13.4 mg. per cent, respectively (fig. 1). The 24-hour urine protein excretion ranged between 0.3 and 3.0 gm. An infusion IVP subsequently revealed a functioning left kidney, which had enlarged significantly from the preoperative examination. A left testicular venogram showed thrombosis of the left renal vein (fig. 2). The patient was treated with continuous intravenous infusion of heparin for 2 weeks and oral anticoagulation was Accepted for publication August 15, 1975.
maintained with sodium warfarin for 4 months. The BUN was 20 mg. per cent and the creatinine was 1.8 mg. per cent 30 days postoperatively. After 6 months the blood pressure was 120/80, BUN 33 mg. per cent, serum creatinine 0.6 mg. per cent and the urine contained only a trace of protein. The patient was in good health 4 years later, with a blood pressure of 130/78, normal BUN and urine free of protein. Case 2. T. S., a 24-year-old man, had a 4-month history of bilateral, intermittent flank pain and ankle edema. He had received a football injury to the back 2 years previously, after which he experienced intermittent left flank pain associated with hematuria. These symptoms subsided spontaneously without further investigation. Examination revealed a well built, young man with a blood pressure of 130/80. There was mild ankle edema and slight tenderness in the upper left quadrant. The BUN was 11 and the creatinine was 1.1 mg. per cent. The total serum protein was 4.5 and the albumin was 2.9 gm. per cent. Urinalysis revealed 3 plus protein and 24-hour protein excretion ranged from 2 to 14 gm. (fig. 3). An IVP revealed bilateral, enlarged kidneys with poor excretion. A percutaneous, left renal biopsy showed changes of membranous glomerulonephritis (fig. 4), and immunofluorescent staining was positive for lgG but not for BlC. The histology was considered to be compatible with renal vein thrombosis. A venacavogram showed a shaggy, intraluminal filling defect above both renal veins (fig. 5). Anticoagulation was commenced with heparin given intravenously for 2 weeks and then continued with oral sodium warfarin. During the next 3 months the patient continued to excrete large amounts of protein. Treatment with 60 mg. prednisone on alternate days was given for 21 months. Steroid therapy was followed by a prompt decrease in protein excretion. The blood pressure was 120/80, BUN 17 mg. per cent and the creatinine 1.1 mg. per cent 1 year later. The 24-hour protein excretion was 0.9 gm. The patient has been followed for 90 months. The blood pressure was normal and the 24-hour urine protein excretion was 200 mg. when he was last seen. Case 3. K. C., a 41-year-old man, had the nephrotic syndrome in October 1970. The BUN at that time was 12 mg. per cent, the creatinine 1.1 mg. per cent and the 24-hour urine protein excretion ranged from 11.2 to 17.9 gm. A renal biopsy showed the characteristic histology of membranous glomerulonephritis but immunofluorescent staining was negative for lgG and BlC. The patient was treated with 60 mg. prednisone on alternate days for 16 months without apparent benefit. In March 1972, 150 mg. azathioprine was instituted daily and was followed by a decrease in protein excretion (fig. 6). In May the patient suffered chest pain on the left side and shortness of
634
635
RENAL VEIN THROMBOSIS IN ADULT
Clinical features of 8 patients with renal vein or vena caval thrombosis Case No. - Age-S ex
Protein Excretion (gm./24 hrs.)
Site of Thrombosis
Associated Disease
1-32-M
Ca rt. kidney
Lt. renal vein
1.5-3.2
2-21-M
Membranous glomerulopathy
Bilat. renal veins and
2.0-14.0
inferior vena cava
Anticoagulants for 4 mos. Anticoagulants and prednisone
3-41-M
Membranous glomerulopathy
Rt. renal vein initially and subsequently It. renal vein as well
Tuberous sclerosis, Ca It. kidney with invasion of renal vein Chronic renal failure owing to phenacetin nephropathy Cholangiocellular Ca liver with extrinsic compression of inferior vena cava Dementia and acute pyelonephritis (bilat.) Squamous cell Ca rt. lung with metastases to both kidneys
4-47-F 5-56-F* 6-69-F* 7-66-F* 8-44-F*
11.2-17.9
Current Status
Followup (yrs.)
Asymptomatic, creatinine 0.6 Asymptomatic, no protein uria, creatinine 1.1 Persistent nephrotic syn-
4
Treatment
Anticoagulants
drome,
0.5
Lt. renal vein
0.5-0.6
Dead
Inferior vena cava and bilat. renal veins
0.1-0.4
Dead
Trace of protein on urinalysis Trace of protein on urinalysis
Lt. renal vein
3
creati-
nine 1.9 Dead
Lt. renal vein
Lt. renal vein
Anticoagulants
7½
Dead Dead
• Diagnosis made at autopsy. HEPARIN
COUMAOIN
mg/lOOml
....z z ~.... a:
4
U)
','O
60 ~
-i
50 ~
z
0
8 6
....
//o-r:/
10
u
a:
:,;,
o}~, .......o
12
::. ::,
ml./min.
70 (')
14
,f I
o-0
m (')
30 rm l>
20
:,;,
l>
z
10 m Oi-'--2-4--6-8--10_1_2_14_1_6_18_2_0_22_2_4_2_6_2_8_3_0_~ 0 (')
2
t
DAYS POST OP.
24hr. urine protein
':,l~-------------------ML Urine/24hrs.
:~ 2000
FIG. 2. Case 1. Testicular venogram demonstrates left renal vein occlusion with collateral circulation.
1000
2
4
6
8
10 12 14
16 18 20 22 24 26 28 30
DAYS POST OP.
change in his general condition and nephrotic rate of protein excretion 4 months later.
FIG. 1. Case 1. Clinical course
DISCUSSION
breath. A lung scan demonstrated multiple pulmonary emboli. A venacavogram revealed complete occlusion of the right renal vein (fig. 7, A). Intravenous heparin was given for 2 weeks and oral anticoagulation with sodium warfarin was continued for 5 months and then discontinued by the patient against medical advice. In January 1975 blood pressure was 190/110, BUN 30.6 mg. per cent, creatinine 2.8 mg. per cent and the 24-hour urine protein excretion had risen to 4.6 gm. An IVP showed large kidneys with poor excretion. A repeat venogram revealed bilateral renal vein occlusions and a large mass on the right side of the vena cava (fig. 7, B). Renal arteriography subsequently showed this mass to be caused by collateral veins that had formed after thrombosis of the right renal vein (fig. 8). The patient was started on long-term anticoagulants. There was no
A review of the literature would suggest that renal vein thrombosis in the adult is relatively uncommon. The exact incidence is unknown because the condition may be completely asymptomatic and only discovered at autopsy, as illustrated by cases 4 to 6. In this hospital the condition was found in 0.4 per cent of all autopsies performed during a 7-year period. However, the true frequency is probably greater because the disease in the adult is not necessarily fatal and many cases are undoubtedly missed. There are no pathognomonic clinical features but a history of back pain followed by proteinuria may suggest the diagnosis, as in case 2. Proteinuria appears to be a constant finding in clinical and experimental renal vein thrombosis"· 10 and the condition is accepted generally as one of the causes of the
636
KIRULUTA AND ASSOCIATES mgm HEPARIN/24hrs.
COUMADIN
HEPARIN
PREDNISONE
~ mg./lOOml ~ 2 . 0 ~ "' 1.5 a:
u
! -~
I
2
3
4
5
6
7
8
9
10 II
12
13 14
/:: 19
26
Gm/24hr. 14 12 C
!
0
.
ct .:
::5
FIG. 5. Case 2. Venacavogram demonstrates bilateral renal vein occlusions and right caval thrombus.
10
8 6 4
......__,,__
"'
2
"'
0 -....--..,--,---r-,-....---,--r--r-.--.--,--,--,--1 ,.,_, - - , I 19 26 2 3 4 5 6 7 8 9 10 II 12 13 14
,::
