Simultaneous renal arterial and venous thrombosis associated with idiopathic nephrotic syndrome: treatment with intra-arterial urokinase

BRIEFCLINICALOBSERVATIONS

ISOLATEDALDOSTERONE DEFICIENCYIN A PATIENT WITH AUTOIMMUNE ADRENALITIS

TABLE I Plasma Renin and Aldosterone Measurements

Isolated aldosterone deficiency is well recognized [ 11, but its association with autoimmune adrenalitis is not. We report a patient with autoimmune disease who initially presented with isolated aldosterone deficiency, prior to developing cortisol deficiency and typical Addison’s disease. A 20-year-old woman with a known history of familial autoimmune polyendocrinopathy [2] presented with a 2-month history of lethargy and postural lightheadedness. Examination demonstrated a marked postural reduction in blood pressure from 90/60 mm Hg with the patient supine to unrecordable when she was standing. There were no stigmata of Addison’s disease. Investigations revealed hyponatremia and a plasma sodium level of 126 mM/L, but normal plasma potassium (4.4 mM/L), normal renal function, and normal thyroid function. Twenty-four-hour urinary free cortisol excretion was 116 nM/L (normal 100 to 300 nM/L). Morning (9 AM) plasma cortisol levels were 766 and 721 nM/L. The result of autonomic function testing was also normal. Mineralocorticoid status was assessed by determination of plasma renin activity (PRA) and plasma aldosterone levels (Table I). These measurements demonstrated undetectable plasma aldosterone levels with the patient lying and standing, and correspondingly high PRA (more than 600 PM/L/minute, lying and standing), consistent with primary mineralocorticoid deficiency. Immunofluorescent studies of antibodies showed positive cytoplasmic staining to all three zones 124

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Plasma Renin Activity (PM/L/minute) Normal

ranges

Lying Standing Lying Standing Lying Standing Lying Standing

Presentation 1 month after treatment with fludrocortisone200~gdaily 2 months after treatment with fludrocortisone 2OOpg daily

of the adrenal cortex [3]. Treatment was commenced with fludrocortisone, increasing to a maintenance dose of 200 pg daily. The plasma sodium level rose into the normal range within 3 days, together with a correction of the postural decrease in blood pressure and of postural symptoms. There was a corresponding reduction in PRA (Table I). Two months later, the patient presented with a 24-hour history of weakness, vomiting, and diarrhea. Plasma cortisol failed to increase from a basal level of 176 nM/L in response to 250 pugtetracosactrin intramuscularly (normal response greater than 500 nM/L). The plasma ACTH level at 9 AM was elevated, 740 rig/L (normal less than 80 rig/L), confirming Addison’s disease. Isolated primary aldosterone deficiency may be a hitherto unrecognized early feature of autoimmune adrenalitis. It is suggested that mineralocorticoid status should be fully assessed in such patients with normal adrenal glucocorticoid status who present with hyperkalemia, hyponatremia, and/or postural hypotension. P.E.

HARRIS,

Ph.D.,

M.R.C.P.

Massachusetts General Hospital Boston, Massachusetts P. KENDALL-TAYLOR,

M.D.,

F.R.C.P.

Medical School University of Newcastle upon Tyne Newcastle upon Tyne, England of Medicine

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Plasma Aldosterone (PM/L)

0.8-14.5 1.1-42.2 >600 >600 86.6 156.1 20.4 80.3

Lying55.5-444 Standing 11 l-860 Lying <55.5 Standing <55.5 -

1. Lebel M, Gros JH. Angiotensin II effect on plasma steroids in selective hypoaldosteronism. Horm Metab Res 1982; 14: 432-6. 2. Doniach D, Bottazzo GF. Polyendocrine autoimmunity. In: Franklin EC, ed. Clinical immunology update. Amsterdam: Elsevier, 1981: 95-102. 3. Sotsiou F, Bottazzo GF, Doniach D. Immunofluorescent studies on autoantibodies to steroid producing cells and to germ line cells in endocrine disease and infertility. Clin Exp lmmunol 1980; 39: 97111. Submitted

March

2, 1990, and accepted in revised form July 12, 1990

SIMULTANEOUSRENAL ARTERIALAND VENOUS THROMBOSISASSOCIATED WITH IDIOPATHICNEPHROTIC SYNDROME:TREATMENT WITH INTRA-ARTERIAL UROKINASE The high incidence of renal vein thrombosis in the nephrotic syndrome, especially when associated with membranous glomerulonephropathy, is well known [ 11. Renal artery thrombosis is rare in these patients, and simultaneous renal artery and renal vein thrombosis, successfully treated with urokinase, is to our knowledge previously unreported [2,3]. A N-year-old man with nephrotic syndrome, diagnosed 12 months earlier, presented with right flank and right testicular pain. Physical examination revealed right costovertebral angle tenderness and right spermatic

BRIEF CLINICAL

cord swelling. The blood pressure was 150/100 mm Hg. Renal function was diminished (blood urea nitrogen 23 mg/dL, creatine 3 mg/dL, creatinine clearance 35 ml/minute), as were serum protein and albumin levels. Urinalysis revealed 100 mg/dL of protein and trace blood. Renal venography demonstrated a segmental thrombus as well as a 2.0 X 2.0-cm thrombus extending into the inferior vena cava from the right renal vein (Figure 1). The left renal vein was patent. Fluoroscopically observed slow flow from the right renal vein suggested a possible right renal artery lesion, and arteriography was performed. A partially obstructing thrombosis was identified in the main right renal artery, and two segmental branches were completely obstructed (Figure 2).

Figure 1. Segmental and main renal thrombi.

Administration of heparin was begun and the partial thromboplastin time was maintained at two times control. Urokinase was infused through the renal artery catheter at 80,000 IU/hour. After 24 hours, the patient’s blood pressure normalized. At 48 hours there was complete lysis of the venous thrombi (Figure 3). The renal arterial thrombi were more refractory to thrombolytic therapy. Nonetheless, the main renal artery thrombus completely lysed by 96 hours. The segmental occlusions never totally resolved, however, even after 144 hours of infusion (Figure 4). A renal scan revealed only a slight decrease in function of the right kidney compared to a baseline scan obtained a year prior to admission. Intra-arterial lytic therapy for both isolated renal arterial and renal venous thrombosis in the

OBSERVATIONS

nephrotic syndrome has been reported [4,5]. Both cases had a successful outcome, using streptokinase in one case and urokinase in the other. The case presented here is the first in which arterial infusion of urokinase was effective in treating combined arterial and venous thrombosis. The efficacy of lytic therapy in this setting is certainly of significance, but perhaps of greater significance is the finding of both arterial and venous involvement. Given the small number of reported cases of renal artery thrombosis in the nephrotic syndrome, it is interesting to speculate about the number of patients with possible undiagnosed renal artery thrombosis in a similar clinical setting. It may be that once renal vein thrombosis is diagnosed, the search for additional pathology is terminated.

renal vein (arrow) vein (arrowhead)

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OBSERVATIONS

Figure 2. Thrombi obstructing segmental renal arteries (arrows) and partially obstructing the main renal artery (arrowhead).

Figure 3. Normal renal vein or vena cava after urokinase. 126

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inferi-

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OBSERVATIONS

Figure 4. Normal main renal artery but persistent occlusion of segmental branches, especially to the lower pole (arrow).

J.S. KENNEDY

B.M.GERETY R. SILVERMAN M.E. PATTISON M.S. SISKIND G.D.PoND University

of Arizona

Health Sciences Center Tucson, Arizona

1. Llach F. Hypercoagulabrlrty, renal vein thrombosis and other complications of nephrotic syndrome. Kidney Int 1985; 28: 429-39. 2. Bryant MF. Kaufman JA, Fonter MF, Evans AR. Acute occlusions of the renal vasculature pedicle. South Med J 1957; 50: 1515-7. 3. Berlyne GM, Tavill AS, De Baker SB. Renal artery stenosis and the nephrotic syndrome. Q J Med 1964; 33: 325-35. 4. Monte XLT, Jimenez AA, Aguilar L, ei a/. Renal artery thrombosis occurring in an adult with the Idiopathic nephrotic syndrome: results of local treatment with streptokinase. Clin Nephrol 1979; 12: 90-2. 5. Vogelzang RL, Moe1 DI, Cohn RA, Donaldson JS, Langman CB, Nemcek AA Jr. Acute renal vein thrombosis: successful treatment with intraarterial urokinase. Radiology 1988; 169: 681-2. Submitted

May 17. 1990, and accepted in rewed form July 12, 1990

A SYNDROME RESEMBLING THROMBOTIC THROMBOCYTOPENIC PURPURAASSOCIATEDWITH CAPNOCYTOPHAGA CANlMORSUSSEPTICEMIA Thrombotic thrombocytopenic purpura (TTP) is a life-threaten-

ing disease of unknown cause, characterized by fever, thrombocytopenia, purpura, microangiopathic hemolysis, and microvascular thrombotic occlusions affecting the brain, kidneys, and other organs [l]. Capnocytophaga canimorsus, formerly dysgonic fermenter-2 (DF-2), is a fastidious, gram-negative bacillus that occurs in the mouths of dogs and cats, and can produce septicemia in humans [2]. The septicemia is frequently accompanied by disturbances of hemostasis that have been attributed to disseminated intravascular coagulation (DIC) [3]. We describe two cases of C. canimorsus septicemia in which there was severe thrombocytopenia with features of TTP, without the coagulopathy associated with DIC. Patient 1. A 72-year-old man was admitted to the Geelong Hospital with a history of 4 days of malaise, rigors, and dyspnea. Three days before admission he had developed blindness of the right eye, purpura, and melena. He had been well prior to this illness, with no history of alcoholism, splenectomy, or immunosuppression. Examination reJanuary

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vealed a pulse of 120/minute, blood pressure of 170/80 mm Hg, temperature of 39”C, tachypnea, widespread cutaneous petechiae and purpura, splinter hemorrhages, macroscopic hematuria, a right retinal artery occlusion with right retinal hemorrhages, and herpes simplex labialis. Blood cultures were taken and the patient received single intravenous doses of gentamicin 80 mg, flucloxacillin 1 g, and crystalline penicillin 1 X lo6 units. The hemoglobin level was 10.4 g/dL, white blood cell count 2.8 X log/L, and platelet count 8 X log/ L. Schistocytes were noted in the blood film. The serum urea level was 37.7 mmol/L, and the creatinine value 24 hmol/L. The prothrombin time (PT) and activated partial thromboplastin time (APTT) were normal. Fibrin degradation products were 20 pg/mL (normal, less than 10 pg/mL). A diagnosis of TTP was made and the patient was transferred to St. Vincent’s Hospital, Melbourne, for plasma exchange. At that hospital, the plasma fibrinogen was 6.0 g/L and lactate dehydrogenase 960 U/L (normal, less than 395 U/L). The bone marrow was Journal

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