NEFROLOGÍA. Vol. XXV. Número 2. 2005 Left renal vein hypertension syndrome S. Mendizábal, E. Román*, A. Serrano**, O. Berbel and J. Simón Pediatric Nephrology Department. La Fe Children's Hospital. Valencia. *Pediatrics Department. Orihuela Hospital. Alicante. **Pediatric Urology Department. La Fe Chidren's Hospital. Valencia. SUMMARY Introduction: Left renal vein compression, causing retrograde hypertension, determines a syndrome characterized by the presence of hematuria, gonadal vein dilatation and varicocele. Being a rare cause of hematuria its aetiology is diverse but of precise characteristics. Diagnosis is not easy and treatment requires to rule out its precise aetiology and consider the intensity of the compression phenomenon because of interventionist attitudes have important implications and are not risk free. Material y methods: We report nine children, aged 8-15 years, presenting with hematuria of urologic characteristics. Diagnosis of left renal vein hypertension or nutcracker phenomenon was established through ultrasound (regular and doppler-ultrasound) and helical-TC performed in all, and left renal venography performed in six of them. Results: Retroaortic renal vein was present in two cases, a varicose accessorial renal vein due to anomalous drainage in one and compression at the aortomesenteric space in six. Because of the symptoms severity therapeutic attitude was interventionist in two cases, performing an auto-transplantation in one, and endovascular stent placement al the level of the left renal vein compression in other. Conclusions: Diagnosis of this syndrome is not always easy because less invasive explorations usually show parameters that are difficult to distinguish from normality. Severity of clinical manifestations and therapeutic attitude are related with the presence of renal vein hyperpressure and collateral varicose circulation indicating the lack of compensation of a difficult drainage. Key words: Hematuria. Left renal vein hypertension. Renal autotransplantation. Nutcracker syndrome. Retroaortic renal vein. SINDROME DE HIPERTENSION VENA RENAL IZQUIERDA RESUMEN Introducción: La compresión de la vena renal izquierda (VRI), a partir de la hiperpresión retrógrada que provoca, define un síndrome caracterizado por hematuria, dilatación de vena gonadal y varicocele. De etiología variada pero de características concretas, es una causa infrecuente de hematuria, de diagnóstico difícil y cuyo trata- Correspondence: Dr. Santiago Mendizábal Oteiza Servicio de Nefrología Pediátrica. Hospital Infantil La Fe Avda. de Campanar, 21 46009 Valencia E-mail: mendizabal­san@gva.es 141 S. MENDIZÁBAL y cols. miento requiere tanto una concreción etiológica como la valoración de la intensidad del fenómeno de compresión. Todo ello, por las imbricaciones que pueden suponer en actitudes intervencionistas no siempre exentas de riesgos. Material y métodos: Se aportan nueve niños, con hematuria de características urológicas y de edad al inicio de la sintomatología de 8-15 años. En todos se realizó ecografía modo B y doppler color en siete, con TAC helicoidal en todos y en seis de ellos venografia renal selectiva, estableciendo el diagnóstico de síndrome de hipertensión de vena renal izquierda (HVRI) o fenómeno de «cascanueces». Resultados: El diagnóstico fue de vena renal retroaórtica en dos casos, vena renal accesoria varicosa por drenaje anómalo en uno y de compresión a nivel del espacio aorto-mesentérico en los seis restantes. La actitud terapéutica, intervencionista en dos casos ante su importante repercusión clínica, consistió en un autotrasplante renal y la colocación de un stent a nivel de la zona de compresión en la VRI. Conclusiones: El diagnóstico del síndrome no siempre es fácil ya que las exploraciones menos invasivas reflejan con frecuencia patrones en los que es difícil precisar el límite de normalidad. La intensidad de las manifestaciones clínicas y con ello la actitud terapéutica está en relación a la existencia de circulación colateral varicosa y a la hiperpresión venosa renal, como indicadores de una falta de compensación de la dificultad de drenaje. Palabras clave: Hematuria. Síndrome hipertensión vena renal izquierda. Autotrasplante renal. Fenómeno de cascanueces. Vena renal retroaórtica. INTRODUCTION The LRVH syndrome defines the compression of the left renal vein with the development of renal venous hypertension that transmitted backwards to the parenchyma may lead to unilateral hematuria, gonadal vein syndrome and varicocele. The compression mechanism, the nutcracker phenomenon, is diverse, the most frequent type being vein trapping in the aortic-mesenteric space, although it has been described in the retro-aortic space due to the abnormality of the renal vein path, which is trapped between the aortic artery and the lumbar spine1-5. Less frequent are the cases of compression exerted by aberrant nerves6, cysts7, retroperitoneal fibrosis secondary to surgeries or radiotherapy8, or due to aberrant renal veins with an abnormal dreinage2. Occasionally, diagnosis is made during abdominal examinations done for trauma9 or in combination with IgA nephropathy10. The consequence in all the cases is a backwards venous renal hypertension because of vena cava drainage impairment and the development of compensating collateral circulation. Unilateral hematuria would result in direct hemorrhage into the urinary tract by rupture of the thin walls of these peripelvic and periuretheral dilated veins. Backwards hyperpressure would lead to the gonadal vein syndrome and varicocele11. 142 A great variety of manifestations related to this syndrome has been described such as proteinuria, occasionally orthostatic5,12,13, nocturnal by the lying position7 or by gestation14,15. Less frequently, it is accompanied by arterial hypertension16 and other more unspecific manifestations such as breathlessness, fatigue, back pain and even severe hematuria that produces anemia and requires transfusion. MATERIAL AND METHODS Nine male children aged 8-15 years (Table I) are presented, which chief complaint was reddish urine, occasionally accompanied by clots. The constitutional habit was normal and they lacked a history of renal disease. Two patients had severe kyphoscoliosis, and one of them had spastic quadriplegia due to connatal hypoxia. The main predominant manifestation was macroscopic hematuria in eight children, in seven being recurrent with normal urine between crises and manifested after sports physical activity and, in the other case (case #8), presented constantly for 9 months. Only in one child, hematuria manifested as persistent microscopic hematuria for one year. Other manifestations were breathlessness and nonjustifiable fatigue, recurrent testicular pain for a varicocele in two cases, and acute anemia requiring LEFT RENAL VEIN HYPERTENSION Table I. Patients characteristics Case Age at symptoms beginning (years) 9 Current age (years) 14 Clinical symptoms at diagnosis Red hematuria with clots after sports (biking, football). Anemia and transfusion requirement. Retro-aortic left renal vein. Persistent microhematuria for one year. Retro-aortic left renal vein. Red hematuria with clots after sports (golf). Breathlessness. Fatigue. Left lumbar pain. Accessory renal vein with abnormal drainage. Red hematuria after sports (football/biking). Recurrent testicular pain (left varicocele). Left lumbar pain Trapping at the aorto-mesenteric space. Recurrent red hematuria after sports (football). Trapping at the aorto-mesenteric space. Recurrent red hematuria after sports (gymnastics). Trapping at the aorto-mesenteric space. Recurrent red hematuria after sports (football/gymnastics). Trapping at the aorto-mesenteric space. Constant red hematuria. Anemia. Transfusion. Proteinuria. Left lumbar pain. Trapping at the aorto-mesenteric space. Recurrent red hematuria after sports. Recurrent testicular pain (left varicocele). Left lumbar pain. Right renal stones. Trapping at the aorto-mesenteric space. Conservative Treatment 1 Auto-transplantation 2 3 8 12 12 15 4 10 15 Conservative 5 6 7 8 12 9 12 15 20 15 17 18 Conservative Conservative Conservative Stent placement Conservative 9 9 14 blood transfusion in other two cases. In one case, there was severe proteinuria. One patient associated right renal stones. The radiological study comprised a B-mode ultrasound in all cases, and color Doppler ultrasound in seven, with a helicoidal CT scan in all cases and selective left renal venography in six measuring venous flow velocity, the anatomic path of LRV and measures of intravenous pressure for both LRV and the vena cava. In one patient an MRI was performed and in another direct visualization by cytoscopy. RESULTS The hematuria characteristics are suggestive of an urological origin, with absence of dysmorphic red blood cells. In 7 cases with gross recurrent hematuria, it was associated to performing physical activity in sports that obliges to intense movements of the lumbar area, especially golf, biking and gymnastics. In the patient with constant hematuria and proteinuria, there was an association with severe kyphoscoliosis and spastic quadriplegia. The only case with isolated persistent microscopic hematuria had a retro-aortic left renal vein being diagnosed by means of a radiological examination done after an abdominal trauma after a motor vehicle accident. The LRVH suspicion diagnosis done based on symptoms and the ultrasound findings was confirmed by helicoidal CT scan and selective renal venography. The low velocity values and diameters of LRV at the previous and posterior regions to the aorto-mesenteric space, the aorto-mesenteric distance, the angle formed by the aortic and mesenteric arteries, and the LRV pressure gradient in relation to the vena cava are shown in Table II. In two patients (cases #1 and #2) a left renal vein can be observed in the retro-aortic path, with a compression between the aortic artery and the lumbar spine (Fig. 1), and in one of them, there is collateral varicose circulation around the kidney pelvis (Fig. 2). In one patient (case #3) with an accessory varicose renal vein, with an abnormal drainage to the lumbar vein, diagnosed by magnetic resonance imaging (Fig. 3) in the presence of normal findings in other examinations, and in the remaining 6 patients compression takes place a the aorto-mesenteric 143 S. MENDIZÁBAL y cols. Table II. Findings of examinations performed Case LRV Echo-Doppler Flow velocity Relationship between Ao-Me region/ distal region 1 2 3 4 5 6 7 8 9 Normal V (17-24) LRVH V (17-24) 5.4 2 1.5 4.5 2.57 ± 0.7 2.8 ± 1.5 5.21 ± 2.55 7.9 ± 2.7 Diameter, Pre-space (mm) LVR LVR 3,5 LVR 9 8.1 5.6 8.2 5 8.3 7.7 ± 1.8 (3.2-10.5) 9.5 ± 2.6 (5.9-18) Helicoidal CT scan LVR and Aorto-mesenteric (Ao-Me) space characteristics * Relationship Pre/Post Retro-aortic Retro-aortic 1.75 Accessory 3.6 2.7 2.7 2.7 2.5 3.8 1.2 ± 0.1 (1.1-1.4) 4.6 ± 1.6 (1.9-8) Ao-Me distance (mm) Ao-Me angle 25° 28° 45° 15° 23° 26° 26° 24° 19° 40º-90º < 40º Selective left renal venography LVR compression imaging Positive Negative Positive Positive Positive Positive Pressure gradient LVR/ VC (mmHg) 4 1 4 3 2 3 Normal < 1 Borderline 1 - 3 3 9 Varicose 3 2.1 2.7 4.3 2.9 5.7 6 ± 1.5 4.5 ± 0.6 LVR: left renal vein. VC: vena cava. Ao-Me: aorto-mesenteric. Normal V: normal values. LRVH V: left renal vein hypertension values. space level (Fig. 4). One patient (case #8) was examined by cytoscopy because of persistent gross hematuria, observing the outflow of hematuric urine solely through the left ureteric meatus. The minimum follow-up time in all cases was two years (range 2-8 years). In two patients, interventional therapy is performed in the face of severe clinical manifestations, with severe hemorrhages that for- Fig. 1.--Compression of left renal vein with a retro-aortic path. Fig. 2.--Peripelvic varicosities due to retro-aortic vein. 144 LEFT RENAL VEIN HYPERTENSION number of hematuria episodes throughout the follow-up period. DISCUSSION Considering that the etiologic evaluation of hematuria is sometimes complex, to specify the diagnosis of LRV trapping syndrome is difficult and cannot be established with routine methods17-24. Therefore, as important is clinical suspicion as are initial examinations aimed at pointing out at the possible etiology of this hematuria with vascular origin. The diagnosis should be suspected in the case of gross hematuria with urologic characteristics or microhematuria with non-dysmorphic red blood cells, in relation to physical exercise and sports that condition postures with a greater risk of compression on LRV, with unspecific symptoms of fatigue, and of course the detection of varicocele. Performing noninvasive radiological examinations such as color Doppler ultrasound may represent the intermediate step before undertaking other studies such as helicoidal CT scan, three-dimensional helicoidal CT scan25 or magnetic resonance imaging26. Finally, in the face of a strong suspicion, performing a cytoscopy in the acute phase with visualization of unilateral left hematuria would oblige to invasive diagnostic procedures with therapeutic capabilities such as selective renal venography. In general, moderate manifestations may be controlled with conservative methods27. However, when symptoms are severe and the risks are important, acting is necessary. Different therapeutic methodologies have been used such as renal vein transposition surgeries28, renal auto-transplantation29, stent placement19,30-32, and instillation through ureteroscopy of silver nitrate solutions directly to the pelvic wall21. In five of our eight patients, a non-interventional attitude was kept, with periodic monitoring, and postural hygiene and physical exercise guidelines, observing a reduction in the number of hematuria episodes. Among the remaining three, two were subsidiary of correcting surgical intervention due to the magnitude of hematuria episodes, the third having kidney annulment because of abdominal trauma. In conclusion, considering that renal hypertension is a rare cause of hematuria, its features are particular and allow clinical suspicion that justifies the confirmatory examinations. The indicative data that will allow to adopt a conservative or surgical attitude, not always free of risks, are the magnitude of hematuria, its clinical repercussion and the exploratory findings with presence of renal venous hypertension and varicose collateral circulation. 145 Fig. 3.--Varicose accessory left renal vein draining to the ascending lumbar vein. ced to blood transfusion, one case showing an important compensating peripelvic varicose circulation (Fig. 2). In one case with retro-aortic renal vein, an auto-transplantation was performed, and in the other case, a stent was placed at the site of the aorto-mesenteric compression. Auto-transplantation is followed by thrombosis and renal ischemic infarction with annulment and nephrectomy. 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