Diagnostic Radiology
Renal Vein Thrombosis: An Underdiagnosed Complication of Multiple Renal Abnormalities 1 Robert A. Clark, M.D., George M. Wyatt, M.D., and David P. Colley, M.D.
Thirty-one cases of renal vein thrombosis (RVT) were reviewed retrospectively for clinical, laboratory, and radiographic findings. An underlying renal disorder was present in 28 cases, absent in only 3. This supports other evidence that RVT is usually a complication of renal disease rather than a primary event, and that nephrotic syndrome may be due to renal disease rather than RVT. The findings also confirmed the large spectrum of urographic appearances in RVT, and were used as a basis for developing specific and liberal indications for renal venography. INDEX TERMS: Thrombosis, renal. (GU system, venous disorder, 8[0] .750). (Other GU structure, renal vein thrombosis, 8[9] .751). (Renal veins , thrombosis, 9[66].751)
Radiology 132:43-50, July 1979
ENAL VEIN thrombosis (RVT) has been considered
R
an unusual clinical entity. We have recognized this lesion with increasing frequency, however, and believe that it may be underdiagnosed because of its variable clinical and radiographic presentations. We therefore reviewed 31 cases of RVT documented by renal venography at the University of Cincinnati Medical Center in the past 6 years. Seventeen of these cases were seen in the last 2 years since we have become more aware of the relatively frequent occurrence of this complication of numerous renal disorders. Evidence now exists that RVT is a complication of the underlying renal abnormality in most cases, rather than the primary process (3, 7, 9, 10). Primary RVT, i.e., RVT without a known renal disease, is probably rare in adults, although it occurs in infants with dehydration and diarrhea or in those having diabetic mothers. Physicians in the past have not usually considered the diagnosis of RVT unless the patient had massive proteinuria or nephrotic syndrome. RVT can occur, however, in the absence of either of these clinical conditions (6, 10). There are no diagnostic laboratory tests for RVT and often the pathologist has difficulty making the diagnosis from renal biopsy. The findings on excretory urography (EU) are variable (4, 11). In early RVT the kidney may be enlarged, the calyces compressed by edema, and renal function impaired. In the more chronic phase the kidney may be normal to small in size, with normal renal excretion of contrast material and occasional ureteral notching due to collateral vessels. Any combination of these findings can occur in RVT, and urograms are not always recognized as abnormal.
Fig. 1. Normal selective renal venogram. The intrarenal interlobar veins are completely visualized to the level of the arcuate veins (arrow). The extraparenchymal veins are normally opacified.
1 From the Department of Radiology, Cincinnati General Hospital, Cincinnati, Ohio. Received Nov. 21, 1978; accepted and revision requested Jan. 31,1979; revision received Mar. 9. Presented at the Sixty-fourth Scientific Assembly and Annual Meeting of the Radiolog ical Society of North America, Chicago, III., Nov. 26-Dec. 1,1978. as
43
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Fig. 2. Normal selective renal transplant venogram. a. Without intra-arterial epinephrine to inhibit arterial flow, the resultant incomplete retrograde venous opacification mimics RVT. b. With selective intra-arterial epinephrine, the intrarenal venous opacification is complete and normal.
We believe that our study establishes criteria for the selection of patients at risk for RVT. From these criteria we have developed indications beyond the classic urographic signs for selective renal venography in the diagnos is of RVT. MATERIAL AND METHOD
All cases of RVT documented by renal venography from 1973 to 1978 were reviewed retrospectively. The clinical and pathologic records were reviewed, as well as the radiographs. All patients had had excretory urograms and inferior cavagrams . Those without inferior vena cava (IVC) occlusion or tumor invasion had had selective venography. Each case was evaluated for the following criteria: (a) clinical-laboratory: having known underlying renal disease, i.e., proteinuria or nephrotic syndrome, with abnormal serum urea nitrogen (BUN) and serum creatinine (function arbitrarily classified as normal if BUN was less than 15 mg/100 ml and serum creatinine less than 1.2 mg/100 ml; as renal insufficiency if BUN was greater than 15 mg/100 ml but less than 100 mg/100 ml and serum creatinine greater than 1.2 mg/100 ml but less than 10 mg/100 ml; or as renal fai lure if BUN was greater than 100 mg/1 00 ml and serum creatinine greater than 10 mg/100 ml); (b)
pathologic: i.e., renal biopsy or autopsy tissue diagnosis; and (c) radiographic: i.e., size, excretion (arbitrarily graded as normal , impaired, or nonvisualizable), laterality of involvement, and findings of IVC and renal venography. Using the above criteria, cases were then compared both inter- and intra-group according to the following categories: Group A (RVT associated with medical renal disease); Group B (RVT not associated with underlying renal disease); Group C (RVT associated with trauma); Group 0 (RVT associated with renal transplantation); and Group E (RVT associated with renal tumor). Inferior vena cavography was performed via the femoral vein using the Seldinger technique. Forty-five ml of 60 % methylglucamine diatrizoate was injected over a 3-sec. interval while the patient performed a Valsalva maneuver. Films were exposed at a rate of 1/sec. Cavograms were then evaluated for the presence of thrombus or tumor. In transplanted kidneys the patency of the appropriate iliac vein was evaluated in a similar manner using 30 ml of contrast material injected over 3 sec. The presence or absence of retrograde opacification of the renal veins varied both in normal patients and in those with RVT. Therefore it could not be used as a valid diagnostic sign. Similarly, "wash-in" or flow effects of
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RENAL VEIN THROMBOSIS
TABLE I:
CLINICAL-LABORATORY FINDINGS IN RVT (31 PATIENTS)
A Group Proteinuria Nephrotic syndrome Renal function Normal Insufficiency Failure
Medical Renal Disease (15)
Group
IVC Normal Diagnostic Side involved with RVT Left Right Bilateral
C Trauma (1)
D Renal Transplant (4)
E Tumor (8)
3/3 1/3
1/1
3/4
0/1
1/4
0/8 0/8
1/1 0/1 0/1
0/4 3/4 4/4
11/15
0/3 1/3
5/15
7/15 3/15
2/3
TABLE II:
Renal size on EU Normal Large Small Renal visualization on EU Normal Impaired Nonvisualization
B No Renal Disease (3)
10/15
A Medical Renal Disease (15)
Diagnostic Radiology
8/8
0/8 0/8
RADIOGRAPHIC FINDINGS IN RVT (31 PATIENTS)
B
C Trauma (1)
No Renal Disease (3)
E Tumor (8)
D Renal Transplant (4)
0/1 0/1 1/1
0/0 4/4 0/0
8/8 (Renal mass) 0/8 0/8
0/3 0/3 3/3
0/1 1/1
0/4 2/4 2/4
0/8 0/8
313 0/3
1/1 0/1
0 0
1/1 0/1 0/1
6/15 7/15 2/15
0/3
8/15 6/15 1/15 12/15 3/15
3/3 0/3
0/1
8/8
(Iliac vein)
8/15 2/15 5/15
3/3
nonopacified blood from the renal veins into the contrast-filled vena cava was seen in patients with and without RVT.
When the inferior cavagram was nondiagnostic, selective catheterization of the renal veins was performed. A catheter was placed for the intra-arterial injection of at least 10 J.Lg of epinephrine 20 to 30 sec. prior to the venous injection of 40 ml of contrast material over a 4 sec. interval. Films were again exposed at a rate of 1/sec. The normal selective renal venogram demonstrated the entire interlobar venous system to the level of the arcuate veins (Fig. 1). Incomplete vascular opacification occurred frequently, with better filling of vessels in one renal segment than in another. This may have been due either to nonuniform distribution of epinephrine within the kidney or to improper catheter position. The former effect is illustrated in Figure 1, with slightly better filling of upper than lower pole veins. The right kidney commonly exhibited the latter effect, since the more vertical right renal vein and caudally directed catheter tended to promote selectively better retrograde filling of veins in the lower pole (14). In both instances, repeat injections of contrast material, using a larger dose of intra-arterial epinephrine and redirected catheter placement, were sometimes necessary. Intraarterial epinephrine was required to diminish arterial flow, since "wash-in" of unopacified blood from the arterial bed
TABLE III:
4/4 0/4
5/8 3/8 3/8 2/8
3/8
RVT ASSOCIATED WITH MEDICAL RENAL DISEASE (15 PATIENTS)
MGN or MPGN (13/15 cases) Idiopathic etiology (6 cases) Drug abuse nephropathy (3 cases) Diabetic nephropathy (1 case) Streptococcal glomerulonephropathy (1 case) * SLE nephropathy (1 case) (Ref. 2) Diabetes and papillary necrosis (1 case) Hypertensive nephrosclerosis (1 case) Malakoplakia (1 case) * SLE
= systemic lupus erythematosis
sometimes simulated RVT on the venogram (1, 5, 12) (Fig. 2). The abnormal renal venogram demonstrated thrombus within the lumen as a filling defect surrounded by contrast material. Alternatively, occlusion of the main renal vein or interlobar veins resulted in nonfilling. In the chronic phase, venous synechiae or fenestration could be seen. Varices and collateral channels were also frequently present in chronic renal vein thrombosis. There were no complications as a result of venography in our series of patients. RESULTS
The clinical and radiographic findings are summarized
46
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3,a,b
c.d
Fig . 3. RVT associated with MGN. a. Urogram demonstra ting bilateral large kidneys with splayed compressed calyces. b. Selective right renal venogram showing a characteristic pattern of chronic RVT with varicosities , venous synech iae (open arrows), and collateral channels (curved arrows). c. Selective left renal venogram showing nonfilling of the inter lobar veins with extensive collateral opacification (curved arrows). d. Repeat selective left renal venogram five months after c at the time of increasing renal insufficiency, show ing further occlusion of the renal venous collaterals and increased adrenal capsular vein fill ing.
in TABLES I and II. TABLE III lists the various etiologies of medical renal disease. RVT was associated with medical renal disease in 15 cases (Group A) (Figs . 3-5); no known renal disease in 3 cases (Group B) (Fig. 6); trauma in 1 case (Group C) (Fig. 7, a girl with traumatic renal arterial thrombosis referred for evaluation of hypertension 2 months following an automobile accident); renal transplantation in 4 cases, 3 acute and 1 chronic, all associated with transplant rejection (Group 0 ; the initial renal disease
leading to transplantation was membranous glomerulonephropathy [MGN] in 2 cases, membranoproliferative glomerulonephropathy [MPGN] in 1 case, and hypertensive nephrosclerosis in 1 case) (Fig . 8); and renal tumor in 8 cases, all unilateral renal cell carcinoma (Group E). DISCUSSION
We believe that RVT is a relatively common compll-
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cation of multiple renal abnormalities, underdiagnosed because the clinical appearance, laboratory studies, and radiographic findings of excretory urography are nonspecific. The most interesting and as yet undefined relationship identified in our series was that between RVT and various medical renal diseases (Group A). MGN and MPGN in particular are commonly associated with RVT; in 3 of our cases of transplanted kidneys with RVT (Group D), MGN or MPGN was the original renal disease. Several investigators (9, 10) have estimated that 30-50% of patients with MGN develop RVT. There is also an association of MGN with a variety of solid tumors (3). Additionally, in patients with MGN or MPGN, nephrotic syndrome is common (2, 3, 7,9, 10, 13). The association of nephrotic syndrome with RVT has been well documented (9,10,13). There is somecontroversy as to whether nephrotic syndrome or RVT is primary , but most of the evidence points to the former, with RVT as a complication. In experimental studies and in humans without renal disease, occlusion of the IVC or the renal veins results in only slight proteinuria without nephrotic syndrome (6). In our 8 cases of RVT associated with tumor (Group E), none had proteinuria or nephrotic syndrome, including 3 patients with bilateral RVT or caval occlusion. Furthermore , of our 15 cases of RVT associated with medical renal disease, only 11 had proteinuria. The evidence therefore suggests that in most cases RVT may be secondary either to nephrotic syndrome or its underlying renal disorder. This sequence appears to be related to a hypercoagulable state: an increase in platelets , fibrinogen, and clotting factors has been observed in patients with nephrotic syndrome (8). Low serum antithrombin levels have also been demonstrated in nephrotic syndrome due to the loss of this substance in the urine (7). Under this circumstance, the renal venous blood would be most deficient in serum antithrombin and thus most coagulable, and could explain the increased frequency of RVT. The 3 patients with RVT and no known renal disease (Group B) displayed striking similarities. Each was a man between 40 and 46 years old who was entirely well until the onset of viral-type illness with fever, diarrhea, and upper respiratory symptoms. This subsided completely, only to be followed 3 to 6 weeks later with acute severe flank pain, oliguria or anuria, and renal failure. In all 3 patients, the kidneys were unable to be visualized on excretory urography, and each patient had bilateral RVT; in all 3 cases, our nephrologists decided that renal biopsy was contraindicated. Two men are currently alive with chronic renal failure; the third died but autopsy was not performed. Although we can only speculate, these cases may represent primary RVT in the adult. The radiographic appearances of RVT have been well catalogued (4, 11). Our review confirms the large spectrum of findings. Therefore we do not feel confident in limiting renal venography to those patients with a defined set of radiographic criteria for RVT .
Diagnostic Radiology
.. Fig. 4. RVT in MPGN. Selective renal venogram, subtraction view. shows venous synechiae or fenestration in the proximal renal vein (arrow) due to recanalization of previous thrombus.
We disagree with previous investigators (4, 11, 15) that renal venography is hazardous and that renal arteriography should be performed as the initial angiographic study . In our series there were no venographic complications and venograms were definitive. Consequently, except in the
Fig. 5. RVT in diabetic nephropathy. The venous thrombus is visualized (open arrow) , as well as nonfilling of most intrarenal branches. Additionally, a circumaortic renal vein is present (curved arrow).
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evaluation of coincident renal trauma, tumor, or renal arterial stenosis, we do not routinely perform renal arteriography as the first study. Moreover, selective renal venography is mandatory since in only 6 of our cases (3 in Group A and 3 in Group E, TABLE II) was the inferior cavagram sufficient for diagnosis. CONCLUSION
Fig. 6. RVT with no known renal disease. Selective left renal venogram shows extensive venous thrombus (open arrow), incomplete intrarenal venous filling, and collateral channels (curved arrow) .
Fig. 7. RVT associated with trauma . The aortogram (not shown) revealed typical traumatic renal artery thrombosis with abrupt occulsion of the left renal artery. The selective left renal venogram shows nonfilling of intrarenal veins and organized thrombus in the main renal vein (arrow).
Based on our experience and review we have developed the following indications for renal venography in the diagnosis of RVT: (a) Any patient with MGN, MPGN, or other nephropathy, with an unexplained deterioration of renal function. The estimated frequency of RVT in these disorders and our demonstrated high frequency of these entities with RVT warrant renal venography. (b) Acute idiopathic nonobstructive renal failure. Regardless of whether this entity is primary RVT, the early diagnosis can be made only by renal venography. (c) Unexplained deterioration in renal function following transplantation, particularly if the original renal disease was MGN or MPGN. (d) Renal arterial trauma. Examination both of arteries and veins is important in light of recent reports of successful repair of traumatic vascular occlusions. (e) Renal tumor in which the renal vein is not seen in the venous phase of the arteriogram, or in which neovascularity is seen in the area of the renal vein or the in-
Fig. 8. RVT with renal transplantation. Selective renal transplant venogram shows occlusion of most intrarenal branches with thrombosis.
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THROMBOSIS
Diagnostic Radiology
9,a,b
c
Fig. 9. Progressive improvement of RVT with long-term heparin therapy. a. Initial selective left renal venogram showing a clot (open arrow s) and poor intrarenal venous filling . b. Repeat venogram 13 months after a shows improvement but is still abnormal. c. Venogram 4 months after band 17 months after the original venogram is essentially normal. RVT has resolved with long-term heparin therapy and renal function has improved.
ferior cava. The propensity of renal cell carcinoma to invade and grow along the renal vein is well known. The importance of the diagnosis of RVT cannot be overstressed. RVT is a treatable condition which often complicates poorly understood renal diseases that have no definitive therapy. We have observed several cases of resolution of RVT with long-term heparin therapy, and a resultant improvement of renal function (Fig. 9). We have found selective renal venography to be a safe, definitive diagnostic procedure. For these reasons we
advocate these aggressive, liberal indications for its use.
REFERENCES 1. Abrams HL, Boijsen E, Borgstrom KE: Effect of epinephrine on the renal circulation . Angiographic observations. Radiology 79: 911-922. Dec 1962 2. Appel GB, Williams GS, Meltzer JI. et al: Renal vein thrombos is, nephrotic syndrome, and systemic lupus erythematosus: an association in four cases. Ann Intern Med 85:310-317, Sep 1976
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Case Records of the Massachusetts General Hospital, Case
28-1978. N Engl J Med 299:136-145,20 Jul 1978 4. Chait A, Stoane L, Moskowitz H, et al: Renal vein thrombosis. Radiology 90:886-896, May 1968 5. Gyepes MT, Desilets DT, Gray RK, et al: Epinephrine-assisted renal venography in renal vein thrombosis: report of two adolescents with nephrotic syndrome. Radiology 93:793-797, Oct 1969 6. Jackson BT, Thomas ML: Post-thrombotic inferior vena caval obstruction: a review of 24 patients. Br Med J 1:18-22, 3 Jan 1970 7. Kauffmann RH, de Graeff J, de la Riviere GB, et al: Unilateral renal vein thrombosis and nephrotic syndrome. Report of a case with protein selectivity and antithrombin III clearance studies. Am J Med 60: 1048-1054, Jun 1976 8. Kendall AG, Lohmann RC, Dossetor JB: Nephrotic syndrome. A hypercoagulable state. Arch Intern Med 127:1021-1027, Jun
11. Mulhern CB, Arger RH, Miller WT, et al: The specificity of renal vein thrombosis. Am J Roentgenol 125:291-299, Oct 1975 12. Olin TB, Reuter SR: A pharmacoangiographic method for improving nephrophlebography. Radiology 85: 1036-1042, Dec 1965 13.
Rosenmann E, Pollak VE, Pirani CL: Renal vein thrombosis in the adult: a clinical and pathologic study based on renal biopsies. Medicine 47:269-335, Jul 1968 14. Smith JC Jr, Rosch J, Athanasoulis CA, et al: Renal venography in the evaluation of poorly vascularized neoplasms of the kidney. Am J Roentgenol 123:552-556, Mar 1975 15. Wegner GP, Crummy AB, Flaherty TT, et al: Renal vein thrombosis. A roentgenographic diagnosis. JAMA 209: 1661-1667, 15 Sep 1969
1971 9. Uach F, Arieff AI, Massry SG: Renal vein thrombosis and nephrotic syndrome. A prospective study of 36 adult patients. Ann Intern Med 83:8-14, Jul 1975 10. Uach F, Koffler A, Finck E, et al: On the incidence of renal vein thrombosis in the nephrotic syndrome. Arch Intern Med 137: 333-336, Mar 1977
July 1979
Department of Radiology Cincinnati General Hospital 234 Goodman St. Cincinnati, Ohio 45267
Renal Vein Thrombosis: An Underdiagnosed Complication of Multiple Renal Abnormalities 1 Robert A. Clark, M.D., George M. Wyatt, M.D., and David P. Colley, M.D.
Thirty-one cases of renal vein thrombosis (RVT) were reviewed retrospectively for clinical, laboratory, and radiographic findings. An underlying renal disorder was present in 28 cases, absent in only 3. This supports other evidence that RVT is usually a complication of renal disease rather than a primary event, and that nephrotic syndrome may be due to renal disease rather than RVT. The findings also confirmed the large spectrum of urographic appearances in RVT, and were used as a basis for developing specific and liberal indications for renal venography. INDEX TERMS: Thrombosis, renal. (GU system, venous disorder, 8[0] .750). (Other GU structure, renal vein thrombosis, 8[9] .751). (Renal veins , thrombosis, 9[66].751)
Radiology 132:43-50, July 1979
ENAL VEIN thrombosis (RVT) has been considered
R
an unusual clinical entity. We have recognized this lesion with increasing frequency, however, and believe that it may be underdiagnosed because of its variable clinical and radiographic presentations. We therefore reviewed 31 cases of RVT documented by renal venography at the University of Cincinnati Medical Center in the past 6 years. Seventeen of these cases were seen in the last 2 years since we have become more aware of the relatively frequent occurrence of this complication of numerous renal disorders. Evidence now exists that RVT is a complication of the underlying renal abnormality in most cases, rather than the primary process (3, 7, 9, 10). Primary RVT, i.e., RVT without a known renal disease, is probably rare in adults, although it occurs in infants with dehydration and diarrhea or in those having diabetic mothers. Physicians in the past have not usually considered the diagnosis of RVT unless the patient had massive proteinuria or nephrotic syndrome. RVT can occur, however, in the absence of either of these clinical conditions (6, 10). There are no diagnostic laboratory tests for RVT and often the pathologist has difficulty making the diagnosis from renal biopsy. The findings on excretory urography (EU) are variable (4, 11). In early RVT the kidney may be enlarged, the calyces compressed by edema, and renal function impaired. In the more chronic phase the kidney may be normal to small in size, with normal renal excretion of contrast material and occasional ureteral notching due to collateral vessels. Any combination of these findings can occur in RVT, and urograms are not always recognized as abnormal.
Fig. 1. Normal selective renal venogram. The intrarenal interlobar veins are completely visualized to the level of the arcuate veins (arrow). The extraparenchymal veins are normally opacified.
1 From the Department of Radiology, Cincinnati General Hospital, Cincinnati, Ohio. Received Nov. 21, 1978; accepted and revision requested Jan. 31,1979; revision received Mar. 9. Presented at the Sixty-fourth Scientific Assembly and Annual Meeting of the Radiolog ical Society of North America, Chicago, III., Nov. 26-Dec. 1,1978. as
43
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Fig. 2. Normal selective renal transplant venogram. a. Without intra-arterial epinephrine to inhibit arterial flow, the resultant incomplete retrograde venous opacification mimics RVT. b. With selective intra-arterial epinephrine, the intrarenal venous opacification is complete and normal.
We believe that our study establishes criteria for the selection of patients at risk for RVT. From these criteria we have developed indications beyond the classic urographic signs for selective renal venography in the diagnos is of RVT. MATERIAL AND METHOD
All cases of RVT documented by renal venography from 1973 to 1978 were reviewed retrospectively. The clinical and pathologic records were reviewed, as well as the radiographs. All patients had had excretory urograms and inferior cavagrams . Those without inferior vena cava (IVC) occlusion or tumor invasion had had selective venography. Each case was evaluated for the following criteria: (a) clinical-laboratory: having known underlying renal disease, i.e., proteinuria or nephrotic syndrome, with abnormal serum urea nitrogen (BUN) and serum creatinine (function arbitrarily classified as normal if BUN was less than 15 mg/100 ml and serum creatinine less than 1.2 mg/100 ml; as renal insufficiency if BUN was greater than 15 mg/100 ml but less than 100 mg/100 ml and serum creatinine greater than 1.2 mg/100 ml but less than 10 mg/100 ml; or as renal fai lure if BUN was greater than 100 mg/1 00 ml and serum creatinine greater than 10 mg/100 ml); (b)
pathologic: i.e., renal biopsy or autopsy tissue diagnosis; and (c) radiographic: i.e., size, excretion (arbitrarily graded as normal , impaired, or nonvisualizable), laterality of involvement, and findings of IVC and renal venography. Using the above criteria, cases were then compared both inter- and intra-group according to the following categories: Group A (RVT associated with medical renal disease); Group B (RVT not associated with underlying renal disease); Group C (RVT associated with trauma); Group 0 (RVT associated with renal transplantation); and Group E (RVT associated with renal tumor). Inferior vena cavography was performed via the femoral vein using the Seldinger technique. Forty-five ml of 60 % methylglucamine diatrizoate was injected over a 3-sec. interval while the patient performed a Valsalva maneuver. Films were exposed at a rate of 1/sec. Cavograms were then evaluated for the presence of thrombus or tumor. In transplanted kidneys the patency of the appropriate iliac vein was evaluated in a similar manner using 30 ml of contrast material injected over 3 sec. The presence or absence of retrograde opacification of the renal veins varied both in normal patients and in those with RVT. Therefore it could not be used as a valid diagnostic sign. Similarly, "wash-in" or flow effects of
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TABLE I:
CLINICAL-LABORATORY FINDINGS IN RVT (31 PATIENTS)
A Group Proteinuria Nephrotic syndrome Renal function Normal Insufficiency Failure
Medical Renal Disease (15)
Group
IVC Normal Diagnostic Side involved with RVT Left Right Bilateral
C Trauma (1)
D Renal Transplant (4)
E Tumor (8)
3/3 1/3
1/1
3/4
0/1
1/4
0/8 0/8
1/1 0/1 0/1
0/4 3/4 4/4
11/15
0/3 1/3
5/15
7/15 3/15
2/3
TABLE II:
Renal size on EU Normal Large Small Renal visualization on EU Normal Impaired Nonvisualization
B No Renal Disease (3)
10/15
A Medical Renal Disease (15)
Diagnostic Radiology
8/8
0/8 0/8
RADIOGRAPHIC FINDINGS IN RVT (31 PATIENTS)
B
C Trauma (1)
No Renal Disease (3)
E Tumor (8)
D Renal Transplant (4)
0/1 0/1 1/1
0/0 4/4 0/0
8/8 (Renal mass) 0/8 0/8
0/3 0/3 3/3
0/1 1/1
0/4 2/4 2/4
0/8 0/8
313 0/3
1/1 0/1
0 0
1/1 0/1 0/1
6/15 7/15 2/15
0/3
8/15 6/15 1/15 12/15 3/15
3/3 0/3
0/1
8/8
(Iliac vein)
8/15 2/15 5/15
3/3
nonopacified blood from the renal veins into the contrast-filled vena cava was seen in patients with and without RVT.
When the inferior cavagram was nondiagnostic, selective catheterization of the renal veins was performed. A catheter was placed for the intra-arterial injection of at least 10 J.Lg of epinephrine 20 to 30 sec. prior to the venous injection of 40 ml of contrast material over a 4 sec. interval. Films were again exposed at a rate of 1/sec. The normal selective renal venogram demonstrated the entire interlobar venous system to the level of the arcuate veins (Fig. 1). Incomplete vascular opacification occurred frequently, with better filling of vessels in one renal segment than in another. This may have been due either to nonuniform distribution of epinephrine within the kidney or to improper catheter position. The former effect is illustrated in Figure 1, with slightly better filling of upper than lower pole veins. The right kidney commonly exhibited the latter effect, since the more vertical right renal vein and caudally directed catheter tended to promote selectively better retrograde filling of veins in the lower pole (14). In both instances, repeat injections of contrast material, using a larger dose of intra-arterial epinephrine and redirected catheter placement, were sometimes necessary. Intraarterial epinephrine was required to diminish arterial flow, since "wash-in" of unopacified blood from the arterial bed
TABLE III:
4/4 0/4
5/8 3/8 3/8 2/8
3/8
RVT ASSOCIATED WITH MEDICAL RENAL DISEASE (15 PATIENTS)
MGN or MPGN (13/15 cases) Idiopathic etiology (6 cases) Drug abuse nephropathy (3 cases) Diabetic nephropathy (1 case) Streptococcal glomerulonephropathy (1 case) * SLE nephropathy (1 case) (Ref. 2) Diabetes and papillary necrosis (1 case) Hypertensive nephrosclerosis (1 case) Malakoplakia (1 case) * SLE
= systemic lupus erythematosis
sometimes simulated RVT on the venogram (1, 5, 12) (Fig. 2). The abnormal renal venogram demonstrated thrombus within the lumen as a filling defect surrounded by contrast material. Alternatively, occlusion of the main renal vein or interlobar veins resulted in nonfilling. In the chronic phase, venous synechiae or fenestration could be seen. Varices and collateral channels were also frequently present in chronic renal vein thrombosis. There were no complications as a result of venography in our series of patients. RESULTS
The clinical and radiographic findings are summarized
46
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July 1979
3,a,b
c.d
Fig . 3. RVT associated with MGN. a. Urogram demonstra ting bilateral large kidneys with splayed compressed calyces. b. Selective right renal venogram showing a characteristic pattern of chronic RVT with varicosities , venous synech iae (open arrows), and collateral channels (curved arrows). c. Selective left renal venogram showing nonfilling of the inter lobar veins with extensive collateral opacification (curved arrows). d. Repeat selective left renal venogram five months after c at the time of increasing renal insufficiency, show ing further occlusion of the renal venous collaterals and increased adrenal capsular vein fill ing.
in TABLES I and II. TABLE III lists the various etiologies of medical renal disease. RVT was associated with medical renal disease in 15 cases (Group A) (Figs . 3-5); no known renal disease in 3 cases (Group B) (Fig. 6); trauma in 1 case (Group C) (Fig. 7, a girl with traumatic renal arterial thrombosis referred for evaluation of hypertension 2 months following an automobile accident); renal transplantation in 4 cases, 3 acute and 1 chronic, all associated with transplant rejection (Group 0 ; the initial renal disease
leading to transplantation was membranous glomerulonephropathy [MGN] in 2 cases, membranoproliferative glomerulonephropathy [MPGN] in 1 case, and hypertensive nephrosclerosis in 1 case) (Fig . 8); and renal tumor in 8 cases, all unilateral renal cell carcinoma (Group E). DISCUSSION
We believe that RVT is a relatively common compll-
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cation of multiple renal abnormalities, underdiagnosed because the clinical appearance, laboratory studies, and radiographic findings of excretory urography are nonspecific. The most interesting and as yet undefined relationship identified in our series was that between RVT and various medical renal diseases (Group A). MGN and MPGN in particular are commonly associated with RVT; in 3 of our cases of transplanted kidneys with RVT (Group D), MGN or MPGN was the original renal disease. Several investigators (9, 10) have estimated that 30-50% of patients with MGN develop RVT. There is also an association of MGN with a variety of solid tumors (3). Additionally, in patients with MGN or MPGN, nephrotic syndrome is common (2, 3, 7,9, 10, 13). The association of nephrotic syndrome with RVT has been well documented (9,10,13). There is somecontroversy as to whether nephrotic syndrome or RVT is primary , but most of the evidence points to the former, with RVT as a complication. In experimental studies and in humans without renal disease, occlusion of the IVC or the renal veins results in only slight proteinuria without nephrotic syndrome (6). In our 8 cases of RVT associated with tumor (Group E), none had proteinuria or nephrotic syndrome, including 3 patients with bilateral RVT or caval occlusion. Furthermore , of our 15 cases of RVT associated with medical renal disease, only 11 had proteinuria. The evidence therefore suggests that in most cases RVT may be secondary either to nephrotic syndrome or its underlying renal disorder. This sequence appears to be related to a hypercoagulable state: an increase in platelets , fibrinogen, and clotting factors has been observed in patients with nephrotic syndrome (8). Low serum antithrombin levels have also been demonstrated in nephrotic syndrome due to the loss of this substance in the urine (7). Under this circumstance, the renal venous blood would be most deficient in serum antithrombin and thus most coagulable, and could explain the increased frequency of RVT. The 3 patients with RVT and no known renal disease (Group B) displayed striking similarities. Each was a man between 40 and 46 years old who was entirely well until the onset of viral-type illness with fever, diarrhea, and upper respiratory symptoms. This subsided completely, only to be followed 3 to 6 weeks later with acute severe flank pain, oliguria or anuria, and renal failure. In all 3 patients, the kidneys were unable to be visualized on excretory urography, and each patient had bilateral RVT; in all 3 cases, our nephrologists decided that renal biopsy was contraindicated. Two men are currently alive with chronic renal failure; the third died but autopsy was not performed. Although we can only speculate, these cases may represent primary RVT in the adult. The radiographic appearances of RVT have been well catalogued (4, 11). Our review confirms the large spectrum of findings. Therefore we do not feel confident in limiting renal venography to those patients with a defined set of radiographic criteria for RVT .
Diagnostic Radiology
.. Fig. 4. RVT in MPGN. Selective renal venogram, subtraction view. shows venous synechiae or fenestration in the proximal renal vein (arrow) due to recanalization of previous thrombus.
We disagree with previous investigators (4, 11, 15) that renal venography is hazardous and that renal arteriography should be performed as the initial angiographic study . In our series there were no venographic complications and venograms were definitive. Consequently, except in the
Fig. 5. RVT in diabetic nephropathy. The venous thrombus is visualized (open arrow) , as well as nonfilling of most intrarenal branches. Additionally, a circumaortic renal vein is present (curved arrow).
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evaluation of coincident renal trauma, tumor, or renal arterial stenosis, we do not routinely perform renal arteriography as the first study. Moreover, selective renal venography is mandatory since in only 6 of our cases (3 in Group A and 3 in Group E, TABLE II) was the inferior cavagram sufficient for diagnosis. CONCLUSION
Fig. 6. RVT with no known renal disease. Selective left renal venogram shows extensive venous thrombus (open arrow), incomplete intrarenal venous filling, and collateral channels (curved arrow) .
Fig. 7. RVT associated with trauma . The aortogram (not shown) revealed typical traumatic renal artery thrombosis with abrupt occulsion of the left renal artery. The selective left renal venogram shows nonfilling of intrarenal veins and organized thrombus in the main renal vein (arrow).
Based on our experience and review we have developed the following indications for renal venography in the diagnosis of RVT: (a) Any patient with MGN, MPGN, or other nephropathy, with an unexplained deterioration of renal function. The estimated frequency of RVT in these disorders and our demonstrated high frequency of these entities with RVT warrant renal venography. (b) Acute idiopathic nonobstructive renal failure. Regardless of whether this entity is primary RVT, the early diagnosis can be made only by renal venography. (c) Unexplained deterioration in renal function following transplantation, particularly if the original renal disease was MGN or MPGN. (d) Renal arterial trauma. Examination both of arteries and veins is important in light of recent reports of successful repair of traumatic vascular occlusions. (e) Renal tumor in which the renal vein is not seen in the venous phase of the arteriogram, or in which neovascularity is seen in the area of the renal vein or the in-
Fig. 8. RVT with renal transplantation. Selective renal transplant venogram shows occlusion of most intrarenal branches with thrombosis.
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Diagnostic Radiology
9,a,b
c
Fig. 9. Progressive improvement of RVT with long-term heparin therapy. a. Initial selective left renal venogram showing a clot (open arrow s) and poor intrarenal venous filling . b. Repeat venogram 13 months after a shows improvement but is still abnormal. c. Venogram 4 months after band 17 months after the original venogram is essentially normal. RVT has resolved with long-term heparin therapy and renal function has improved.
ferior cava. The propensity of renal cell carcinoma to invade and grow along the renal vein is well known. The importance of the diagnosis of RVT cannot be overstressed. RVT is a treatable condition which often complicates poorly understood renal diseases that have no definitive therapy. We have observed several cases of resolution of RVT with long-term heparin therapy, and a resultant improvement of renal function (Fig. 9). We have found selective renal venography to be a safe, definitive diagnostic procedure. For these reasons we
advocate these aggressive, liberal indications for its use.
REFERENCES 1. Abrams HL, Boijsen E, Borgstrom KE: Effect of epinephrine on the renal circulation . Angiographic observations. Radiology 79: 911-922. Dec 1962 2. Appel GB, Williams GS, Meltzer JI. et al: Renal vein thrombos is, nephrotic syndrome, and systemic lupus erythematosus: an association in four cases. Ann Intern Med 85:310-317, Sep 1976
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Case Records of the Massachusetts General Hospital, Case
28-1978. N Engl J Med 299:136-145,20 Jul 1978 4. Chait A, Stoane L, Moskowitz H, et al: Renal vein thrombosis. Radiology 90:886-896, May 1968 5. Gyepes MT, Desilets DT, Gray RK, et al: Epinephrine-assisted renal venography in renal vein thrombosis: report of two adolescents with nephrotic syndrome. Radiology 93:793-797, Oct 1969 6. Jackson BT, Thomas ML: Post-thrombotic inferior vena caval obstruction: a review of 24 patients. Br Med J 1:18-22, 3 Jan 1970 7. Kauffmann RH, de Graeff J, de la Riviere GB, et al: Unilateral renal vein thrombosis and nephrotic syndrome. Report of a case with protein selectivity and antithrombin III clearance studies. Am J Med 60: 1048-1054, Jun 1976 8. Kendall AG, Lohmann RC, Dossetor JB: Nephrotic syndrome. A hypercoagulable state. Arch Intern Med 127:1021-1027, Jun
11. Mulhern CB, Arger RH, Miller WT, et al: The specificity of renal vein thrombosis. Am J Roentgenol 125:291-299, Oct 1975 12. Olin TB, Reuter SR: A pharmacoangiographic method for improving nephrophlebography. Radiology 85: 1036-1042, Dec 1965 13.
Rosenmann E, Pollak VE, Pirani CL: Renal vein thrombosis in the adult: a clinical and pathologic study based on renal biopsies. Medicine 47:269-335, Jul 1968 14. Smith JC Jr, Rosch J, Athanasoulis CA, et al: Renal venography in the evaluation of poorly vascularized neoplasms of the kidney. Am J Roentgenol 123:552-556, Mar 1975 15. Wegner GP, Crummy AB, Flaherty TT, et al: Renal vein thrombosis. A roentgenographic diagnosis. JAMA 209: 1661-1667, 15 Sep 1969
1971 9. Uach F, Arieff AI, Massry SG: Renal vein thrombosis and nephrotic syndrome. A prospective study of 36 adult patients. Ann Intern Med 83:8-14, Jul 1975 10. Uach F, Koffler A, Finck E, et al: On the incidence of renal vein thrombosis in the nephrotic syndrome. Arch Intern Med 137: 333-336, Mar 1977
July 1979
Department of Radiology Cincinnati General Hospital 234 Goodman St. Cincinnati, Ohio 45267
