Kidney and inferior vena cava abnormalities with leg thromboses (KILT) syndrome: A case report and literature review

Abstract

Venous thromboembolism (VTE) is now increasingly recognized within paediatrics. A Canadian VTE registry has estimated the incidence as 0.7 to 1.0 per 100,000 population, with a peak in infancy and adolescence. Congenital inferior vena cava agenesis (IVCA) is an important risk factor that may be unfamiliar to paediatricians. Several case reports have since described an association between IVCA, VTE, and renal hypoplasia, which has been referred to as KILT syndrome (Kidney and IVC abnormalities with Leg Thromboses). We describe the first reported paediatric case of KILT syndrome in Canada. In any young patient presenting with a spontaneous DVT, particularly, if it is bilateral in nature with no co-existing risk factors for thrombus formation, we recommend investigating for the possibility of an underlying congenital vena cava anomaly. The use of prolonged anticoagulant therapy is supported by the inherent life-long risk of recurrent thrombosis associated with IVC anomalies.

INTRODUCTION

Since 2001 (1–3), several case reports have described an association between inferior vena cava agenesis (IVCA), venous thromboembolism (VTE), and renal hypoplasia, collectively referred to as KILT syndrome (Kidney and IVC abnormalities with Leg Thromboses) (4, 5). This is a rare phenomenon with a varying clinical presentation. Often the diagnosis is subsequent to incidental identification of the triad of anomalies on imaging studies. This is very important to recognize in clinical practice as it predisposes young individuals to the development of recurrent venous thromboembolism. We describe the first reported paediatric case of KILT syndrome in Canada.

CASE

A 17-year-old male presented to hospital with a 4-week history of lower back pain and increasing bilateral lower limb pain. Prior to admission he had difficulty in ambulation and rapidly increasing leg swelling (Figure 1), with a 1-month history of intermittent breathlessness when mobilising. Otherwise he had no significant medical history, with no relevant risk factors or family history of VTE. On examination, his lower limbs were warm, edematous, and extremely tender to palpation, with palpable peripheral pulses. The remainder of his physical examination was normal.

Figure 1.

Photograph of the lower limbs, demonstrating significant swelling; right leg worse than the left leg.

A Doppler ultrasound and computerized tomography (CT) angiogram demonstrated occlusive thrombus in the major portion of the distal Inferior vena cava (IVC) (Figure 2); extensive thrombi in the associated venous system; multiple collaterals in the peritoneal and pelvic cavities, an acute right renal vein thrombosis with renal enlargement; left renal atrophy with scarring of the parenchyma indicative of chronic changes; and possible subsegmental pulmonary emboli (PE). Further investigations including a chest CT scan did not demonstrate evidence of a PE. An extensive thrombophilia workup was unremarkable apart from a mildly elevated factor VIII level. A nuclear scan of his kidneys demonstrated 85% function on the right with 15% function on the left. His renal function was normal with a creatinine of 75 µmol/L.

Figure 2.

Computerized tomography angiogram of the abdomen demonstrating occlusive thrombus in the distal inferior vena cava (indicated by the red arrow).

Management focussed on both anticoagulation and analgesia. Given the extent and chronicity of the Deep vein thrombosis (DVTs), the patient was not eligible for thrombolysis. A heparin infusion was initiated, and then transitioned to low-molecular weight heparin (LMWH) for long-term anticoagulation. His anti-Xa levels were monitored regularly and dose adjustment performed as required. A continuous opioid infusion was required for pain control, with subsequent conversion to oral analgesics as required. Upon discharge, he was able to walk short distances independently, requiring aids for longer distances. Follow-up with several disciplines, including paediatrics, haematology, nephrology, pain team, physiotherapy, and occupational therapy were arranged.

At his 6-month follow-up, a Doppler ultrasound demonstrated an interval improvement involving most areas of the abdomen, pelvis, and proximal lower extremity veins. He received treatment with enoxaparin for 3 months after which he was transitioned to tinzaparin, which he continues on in the long-term.

DISCUSSION

We report the case of a 17-year-old male with extensive DVTs due to an underlying IVCA, with azygous continuation. IVCA is recognized as an independent risk factor for DVTs in the paediatric population with a reported male preponderance (6) and an estimated incidence of five per cent of the cases (4–6). IVCA is invariably subclinical in nature and tends to present after 30 years of age with spontaneous lower limb DVT (7).

The mechanism of thrombus formation is attributable to venous stasis and inadequate drainage of the lower limbs by the azygous vein, despite its structural enlargement (4,5). This phenomenon has been reported in 20 per cent of similar cases in the literature to date (5,6). It is hypothesized that emboli from a DVT may travel via the azygous system into the pulmonary circulation, increasing the risk of potentially fatal embolization (4).

The phenomenon known as KILT syndrome arises from the theory that during embryological development, the right metanephrons drain into the IVC. As such, the absence of the IVC may impact upon right kidney development. The left metanephrons are protected due to their alternate path of venous drainage (8). The presence of left renal hypoplasia in several case reports indicates that other factors contribute to the development of renal hypoplasia, such as renal vein thrombosis, which is comparable to the findings in our patient.

When a DVT is suspected in practice, ultrasound is the imaging modality of choice, although it is not sufficient to identify underlying IVCA, thereby underestimating its prevalence. The gold standard for diagnosis is abdominal and pulmonary CT with contrast angiography (5,9,14).

Management of children with VTE in the context of IVCA is not yet standardized given the paucity of evidence in the literature. Consequently, treatment strategies are based upon the management of VTE in general paediatrics and adult patients. The aim is to treat and prevent local extension of existing thrombi, reduce the risk of recurrence, and prevent potentially fatal embolization.

Data from the Canadian VTE Registry demonstrate that most paediatricians opt to use LMWH in the long-term (1). This is supported by the REVIVE study (10), which randomized children following their first presentation of VTE to either LMWH or unfractionated heparin (UFH) followed by oral anticoagulation. Results revealed LMWH was an effective treatment with lower risks of bleeding, and this is supported by other observational studies (11). Consideration should be given to the use of direct oral anticoagulants, given the minimal drug interactions and infrequent laboratory monitoring required, however, clinical evidence to support their use in paediatrics is limited at present (12).

Patients with severe or extensive VTE may require mechanical thrombolysis or surgical intervention, including IVC reconstruction in severe and chronic cases; however, there is a lack of evidence to support this currently (6,13).

Overall, there is no clear consensus with regards to the most efficacious approach; however, long-term anticoagulation is indicated, given the inherent life-long risk of recurrent thrombosis associated with IVC anomalies. We advocate a holistic approach to the management of these patients, including a focus on physical rehabilitation and analgesia.

In any patient presenting with a spontaneous DVT, particularly, if it is bilateral in nature with no co-existing risk factors for thrombus formation, we recommend investigating for a potential underlying congenital IVC anomaly (15). Identification of any associated anomalies, with input from relevant specialist services, is key in order to minimize morbidity.

Informed consent was obtained for this case

Funding Information: There are no funders to report for this submission.

Potential Conflicts of Interest: All authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.