Varicose vein surgery after acute isolated superficial vein thrombosis in daily practice: INSIGHTS-SVT study.

OBJECTIVE: The aim of this study was to assess the utilization of surgical interventions in patients diagnosed with superficial vein thrombosis (SVT) and its potential association with the occurrence of venous thromboembolism (VTE) and bleeding events. METHODS: INSIGHTS-SVT, a prospective, non-interventional, multicenter study in Germany, investigated the management and outcomes of patients with acute SVT who received conservative and/or invasive treatments at the discretion of the treating physician. RESULTS: Among the 872 patients with 12-month data, 657 had medical therapy only, and 215 patients underwent vascular surgery (70 within 3 months of SVT diagnosis, 136 between months 4 and 12, and nine had an intervention in both periods). The most commonly performed procedures included endovenous thermal ablation, ligation of the saphenofemoral or saphenopopliteal junction, and vein stripping. The primary outcome of symptomatic VTE was observed in 5.8% of conservatively treated patients and 6.3% of those who underwent surgical intervention. Additionally, the secondary outcome of recurrent or extended SVT was documented in 4.7% of conservatively treated patients and 5.3% of invasively treated patients. Bleeding events occurred in 1.4% of conservatively treated patients and 2.1% of surgically treated patients. These differences were statistically not significant. Furthermore, our analysis indicated a potential protective effect associated with surgical treatments, such as ligation of the saphenofemoral or saphenopopliteal junction, stripping and endovenous thermal ablation, concerning the endpoint of VTE for patients when applied after 3 months from the index SVT event. CONCLUSIONS: In line with previous research, our study suggests that surgical interventions are not frequently employed in the management of SVT, although they may be warranted in select cases. Nevertheless, additional research is essential to gain a deeper understanding of the indications, criteria, and benefit of surgical interventions in the treatment of SVT.

Determinants of Late Venous Thromboembolic Events After Acute Isolated Superficial Vein Thrombosis in Daily Practice: 12 Month Results of the INSIGHTS-SVT Study.

OBJECTIVE: Long term incidence of symptomatic venous thromboembolism (VTE) and bleeding events in patients with superficial vein thrombosis (SVT) was investigated. METHODS: In this prospective, observational study, patients with acute SVT were treated at the discretion of the responsible physician. The primary efficacy outcome was symptomatic VTE including deep vein thrombosis (DVT), pulmonary embolism (PE), and recurrent or extending SVT. The primary safety outcome was clinically relevant bleeding, recorded at periodic clinic visits over a 12 month period. RESULTS: The mean age of 872 patients with 12 month follow up was 60.6 ± 14.5 years, 64.5% were female, 80.1% had chronic venous disease (defined as chronic venous insufficiency and or varicose veins), and 41.9% had a history of VTE. They were receiving fondaparinux in 62.1% (mean duration 34.9 ± 15.7 days), low molecular weight heparin (LMWH) in 25.0% (mean duration 26.2 ± 23.2 days), any other anticoagulants in 6.2%, and no anticoagulant in 6.7%. At 12 months, 108 patients (14.3%) achieved the primary efficacy outcome. The most common VTE event was recurrent or extending SVT in 11.0%, followed by symptomatic DVT in 2.7%, symptomatic PE in 2.4%, hospitalisation due to VTE in 1.8%, and death in 1.1%. Clinically relevant bleeding events occurred in 2.1% of patients, and major bleedings in 0.3%. By drug, the rate of the primary efficacy outcome was highest in the LMWH group (22.4%) and lowest in the fondaparinux group (10.4%). In a multivariable model, patients with events between three months and 12 months were significantly more likely to have higher BMI (hazard ratio [HR] 1.06; p = .002), history of VTE (HR 2.89; p = .002), and severe systemic infections (HR 7.59; p = .006). CONCLUSION: The risk of symptomatic VTE remained elevated over 12 months of follow up. Therefore, anticoagulation beyond 45 days may be considered in patients with risk factors. [ClinicalTrials.gov identifier: NCT02699151.].

Clinical Characteristics and Current Practice of Endovascular Revascularization in Aorto-Iliac, Femoropopliteal and Infra-Popliteal Lower Extremity Artery Disease-Insights from the RECCORD Registry.

BACKGROUND: Endovascular revascularization (EVR) is a pillar of therapeutic management in patients with symptomatic lower extremity artery disease (LEAD). Due to lack of scientific evidence, the approach of EVR type and the devices used at the different anatomic vascular segments of the lower limbs vary substantially between operators and centers. We analyzed data from the RECcording COurses of vasculaR Diseases (RECCORD) registry to assess the current real-world EVR treatment patterns in relation to anatomic vascular segments in symptomatic LEAD patients in Germany. PATIENTS AND METHODS: RECCORD is an ongoing, prospective, multicenter, all-comers and entirely web-based registry platform. Baseline demographic and periprocedural data of patients undergoing EVR for symptomatic LEAD were assessed and performed EVRs were grouped according to the intervened anatomic vascular segment. We analyzed four EVR groups comprising either the aorto-iliac, femoropopliteal, or infrapopliteal segments (all these EVRs with or without a further intervention in another anatomic segment) or the infrapopliteal segment alone. RESULTS: A total of 2210 EVR segments (in 1639 patients) were analyzed. Of those 616 (27.9%) were aorto-iliacal, 1346 (60.9%) femoropopliteal, 248 (11.2%) infrapopliteal and 104 (4.7%) only infrapopliteal segments. Aorto-iliac EVR was associated with younger age, smoking, claudication and simple lesions, while the distal infrapopliteal EVRs were related to advanced age, diabetes, multiple comorbidities, limb threatening ischemia and complex lesions. The use of different EVR devices at the aorto-iliac, femoropopliteal, infrapopliteal and only infrapopliteal segments were: only ballon-angioplasty: 8.3%, 12.9%, 58.1% and 63.5%; stenting: 82.3%, 45.3%, 16.9% and 12.5%; drug-coated balloon: 11.2%, 55.0%, 19.4% and 19.2%. CONCLUSION: The RECCORD registry data demonstrate that in LEAD clinical and lesion characteristics are related to anatomic vascular segments. Despite the clear relationship between vascular segments and the current use of device types, prospective, segment-specific clinical studies are warranted to establish a consistent, evidence-based path for EVR in LEAD.

Management and Outcomes of Patients with Isolated Superficial Vein Thrombosis under Real Life Conditions (INSIGHTS-SVT).

OBJECTIVE: Management and outcomes of superficial vein thrombosis (SVT) are highly variable and not well described. Therefore, the INvestigating SIGnificant Health TrendS in the management of SVT (INSIGHTS-SVT) study collected prospective data under real life conditions. METHODS: Prospective observational study of objectively confirmed acute isolated SVT. The primary outcome was a composite of symptomatic deep vein thrombosis (DVT), pulmonary embolism (PE), and extension or recurrence of SVT at three months. The primary safety outcome was clinically relevant bleeding. RESULTS: A total of 1 150 patients were included (mean age 60.2 ± 14.7 years; 64.9% women; mean BMI 29.4 ± 6.3 kg/m2). SVT was below the knee in 54.5%, above the knee in 26.7%, above and below the knee in 18.8%. At baseline, 93.6% received pharmacological treatment (65.7% fondaparinux, 23.2% heparins, 4.3% direct oral anticoagulants [DOACs], 14.5% analgesics), 77.0% compression treatment, and 1.9% surgery; 6.4% did not receive any anticoagulation. The primary outcome occurred in 5.8%; 4.7% had recurrent or extended SVT, 1.7% DVT, and 0.8% PE. Clinically relevant non-major bleeding occurred in 1.2% and major bleeding in 0.3%. Complete clinical recovery of SVT was reported in 708 patients (62.4%). Primary outcome adjusted by propensity score and for treatment duration was lower with fondaparinux compared with low molecular weight heparin (4.4% vs. 9.6%; hazard ratio [HR] 0.51; 95% confidence interval [CI] 0.3 - 0.9; p = .017). On multivariable analysis, associated factors for primary outcome included another SVT prior to the present SVT event (HR 2.3), age per year (HR 0.97), duration of drug treatment per week (HR 0.92), and thrombus length (HR 1.03). CONCLUSION: At three month follow up, patients with isolated SVT are at risk of thromboembolic complications (mainly recurrent or extended SVT), despite anticoagulation. In this real life study, about one third had received either heparins, oral anticoagulants, or no anticoagulation.

ETNA-VTE Europe: Benefits and risks of venous thromboembolism treatment using edoxaban in the first 3 months.

INTRODUCTION: Edoxaban had a positive risk-benefit ratio for the treatment of venous thromboembolism (VTE) compared to conventional therapy with warfarin. The objective of this analysis of the ongoing ETNA-VTE Europe study was to assess the real-world benefits and risks of edoxaban during the first 3 months of treatment, the highest risk period for further VTE events. METHODS: ETNA-VTE Europe is a prospective, non-interventional, post-authorization study, conducted in eight European countries. Participants had initial or recurrent acute VTE (deep vein thrombosis [DVT] and/or pulmonary embolism [PE]) that occurred ≤2 weeks prior to enrolment and received edoxaban therapy. RESULTS: The analysis set included 2672 patients (PE ± DVT, n = 1117; DVT only, n = 1555); mean age 62.9 ± 16.0 years, bodyweight 81.9 ± 17.4 kg, estimated glomerular filtration rate 95.4 ± 42.8 mL/min; 46.4% were female. Overall, 66.4% of patients (PE ± DVT, 68.5%; DVT-only, 64.8%) received heparin lead-in treatment for at least 5 days. Most patients (87.7%) received edoxaban at a dose of 60 mg once daily. Event rates at 3 months were: recurrent VTE 0.34% (n = 9), major bleeding 0.97% (n = 26), all-cause mortality 0.79% (n = 21). Rates were numerically higher in the PE ± DVT group compared with the DVT-only group (recurrent VTE, 0.45% (n = 5) versus 0.26% (n = 4); major bleeding, 1.34% (n = 15) versus 0.71% (n = 11); and all-cause mortality 1.16% (n = 13) versus 0.51% (n = 8)). CONCLUSIONS: The results support the safety and effectiveness of edoxaban in a general VTE population during the most critical time period, the first 3 months. The outcomes of this study extend the principal efficacy and safety data on edoxaban into the routine clinical practice setting.

Current evidence on aortic remodeling after endovascular repair.

Anatomical changes after endovascular repair (EVAR) of abdominal aortic aneurysms (AAAs) are thoroughly studied as they could affect the long-term postoperative outcome. The aim of the present study was to review the literature and summarize the recent data regarding the aortic remodeling and its clinical significance. A continuous aortic neck expansion is observed after EVAR and is more rapid at the first month and during the third postoperative year. This aortic neck dilation is not influenced by the type of proximal stent-graft fixation, is comparable to open surgical aneurysm repair and is most probably related with the natural progression of aneurismal disease. Aortic neck angulation reduces significantly immediately after EVAR and then continues to reduce slowly and gradually. Neck angulations ≥60° have a greater reduction compared to neck angulations <60°. An expansion of the common iliac arteries at the distal landing zone is also observed after EVAR and is more prominent in the first six postoperative months. A postoperative increase of the distance between superior mesenteric artery and iliac bifurcations (aortoiliac elongation) is described and is associated with increased type I endoleaks and reinterventions. The aneurysm sac diameter most frequently reduces after EVAR in absence of an endoleak and this aneurysm sac regression has been associated with the stent-graft type.

Rationale, design, and methodology of the observational INSIGHTS-SVT study on the current state of care and outcomes of patients with superficial vein thrombosis.

OBJECTIVE: Superficial vein thrombosis (SVT) is a common disease in clinical practice. In terms of pathophysiology and outcomes, the condition is related to venous thromboembolism, bearing a potential for severe thromboembolic complications if it is not treated adequately. A wide range of treatment approaches (including oral and injectable anticoagulants, pain medication, nondrug therapy including compression therapy, and no treatment at all) are applied in clinical practice, but there is sparse information about selection of patients for therapies, current treatment pathways, and drug use as well as outcomes. The INvestigating SIGnificant Health TrendS in the management of Superficial Vein Thrombosis (INSIGHTS-SVT) study aims to close this gap by collecting representative data on the current treatment of SVT. METHODS: The observational prospective study of about 1200 patients is carried out by up to 120 clinical and office-based physicians who regularly treat patients with SVT and are capable of conducting appropriate compression ultrasound diagnostics, such as vascular physicians, phlebologists, internists, vascular surgeons, and general practitioners. Patients are eligible for inclusion if they have ultrasound-confirmed acute, isolated SVT of the lower extremities. Documentation about the characteristics of the patients, diagnostics, comorbidities, and medical and nonmedical treatment is collected at baseline, at 10 ± 3 days or at approximately 45 days (depending on treatment), at approximately 3 months, and at approximately 12 months. Patients are requested to fill in quality of life questionnaires (on pain, Venous Insufficiency Epidemiological and Economic Study on Quality of Life/Symptoms [VEINES-QOL/Sym], EuroQol-5 Dimension 5-Level [EQ-5D-5L]) at baseline and at approximately 3 months. Interventions are not stipulated by the trial protocol. RESULTS: The primary efficacy outcome is the incidence of venous thromboembolism at 3 months; the primary safety outcome is the combined incidence of major and clinically relevant bleeding events at 3 months. As quality measures, plausibility checks at data entry, queries based on statistical analyses that focus on outliers and distribution of values, monitoring visits, and adjudication procedures will be applied. CONCLUSIONS: This large study is expected to provide a comprehensive picture of patients with SVT under clinical practice conditions in Germany.

Ultrasound imaging in the diagnosis of large vessel vasculitis.

Nowadays noninvasive vascular imaging has an important role in the diagnostic work-up of the large vessel vasculitides (LVV), most importantly giant cell arteritis (GCA) and Takayasu arteritis. Among the imaging modalities available, ultrasound (US) has several important advantages, including low costs, rapid and repetitive availability without exposure to radiation, and high spatial resolution for assessment of large and medium-sized arteries. Therefore, US can be regarded the first line imaging method in suspected LVV. In patients with suspected GCA, US can replace temporal artery biopsy in certain clinical scenarios, and the application of US early in the diagnostic work-up of suspected GCA in specialized fast track clinics has been suggested to reduce the rate of visual ischaemic complications and associated costs. In other LVV such as Takayasu arteritis and chronic periaortitis, the diagnostic accuracy in comparison to other noninvasive imaging methods has not been formally tested but can be considered to be excellent. However, quality of US is highly dependent on the operator's experience, and assessment of the thoracic aorta which is frequently involved in GCA and TA is limited. The role of US in the follow-up of LVV under treatment is unclear. In view of the promising data supporting its value on the one hand and several uncertainties and controversies on the other hand, the present review article provides a comprehensive overview on current evidence for the application of US in the diagnosis and follow up of LVV. Recent multicentre study results and emerging trends such as the application of compression sonography in the diagnosis of GCA and the use of contrast enhanced ultrasound in disease activity assessment in Takayasu arteritis are discussed.

Hypothenar hammer syndrome.

The diagnosis of hypothenar hammer syndrome (HHS) should be considered in the case of hand ischemia in people who occupationally or recreationally use the hypothenar region literally as a “hammer”. Routine diagnostics should consist of physical examination including Allen’s test, acral plethysmography and duplex sonography. According to the prevailing opinion angiography remains the «gold standard test¼ for establishing the diagnosis of HHS. Early diagnosis allows more effective therapeutic strategies and is important to prevent long-term negative medical sequelae. Several basic principles apply to all patients, for example hand protection and smoking cessation. The optimal treatment options, particularly the indication for surgery, remain controversial due to a lack of sound data from case series or prospective randomized trials.

Impact of cranial and axillary/subclavian artery involvement by color duplex sonography on response to treatment in giant cell arteritis.

OBJECTIVE: Color duplex sonography (CDS) today is broadly used in the diagnostic workup of patients with suspected cranial or extracranial giant cell arteritis (GCA). This study aimed to determine the prognostic impact of the disease pattern assessed by CDS on the treatment response in GCA. METHODS: This was a retrospective, longitudinal follow-up study of 43 patients who were diagnosed with GCA at our institution between 2002 and 2010. All patients underwent CDS of the temporal and subclavian/axillary arteries at baseline and were observed for at least 6 months. Vasculitis was sonographically characterized by a circumferential, hypoechogenic wall thickening. According to the CDS findings, patients were categorized into patients with involvement of the subclavian/axillary arteries only (group A1, n = 17), patients with involvement of both the subclavian/axillary arteries and the temporal arteries (group A2, n = 9), and patients with isolated cranial GCA (group B, n = 17). Data on recurrences, corticosteroid doses, and steroid-sparing agents were extracted from the medical records. Treatment response over time was analyzed by Kaplan-Meier curves with log-rank testing. RESULTS: The mean follow-up time was 25.4 months and did not differ between groups (P = .4). Patients in group A1 were significantly younger than patients in groups A2 and B (P < .01). The interval between symptom onset and diagnosis was significantly longer in groups A1 and A2 compared with group B (P < .01). The number of recurrences per month was significantly higher in group A2 compared with group A1 and group B (A1, 0.07; A2, 0.13; B, 0.03; P < .01). Whereas there were no significant differences in the mean time until a daily prednisolone dose <10 mg was reached, patients in group A2 more frequently required steroid-sparing agents (A1, 24%; A2, 56%; B, 24%; P = .04). CONCLUSIONS: Extensive vascular involvement of both the temporal and subclavian/axillary arteries, as depicted by CDS, may be associated with a poor treatment response in GCA.

Reduced intraepidermal nerve fiber density in patients with chronic ischemic pain in peripheral arterial disease.

Chronic ischemic pain in peripheral arterial disease (PAD) is a leading cause of pain in the lower extremities. A neuropathic component of chronic ischemic pain has been shown independent of coexisting diabetes. We aimed to identify a morphological correlate potentially associated with pain and sensory deficits in PAD. Forty patients with symptomatic PAD (Fontaine stages II-IV), 20 with intermittent claudication (CI), and 20 with critical limb ischemia (CLI) were enrolled; 12 volunteers served as healthy controls. All patients were examined using pain scales and questionnaires. All study participants underwent quantitative sensory testing (QST) at the distal calf and skin punch biopsy at the distal leg for determination of intraepidermal nerve fiber density (IENFD). Additionally, S100 beta serum levels were measured as a potential marker for ischemic nerve damage. Neuropathic pain questionnaires revealed slightly higher scores and more pronounced pain-induced disability in CLI patients compared to CI patients. QST showed elevated thermal and mechanical detection pain thresholds as well as dynamic mechanical allodynia, particularly in patients with advanced disease. IENFD was reduced in PAD compared to controls (P<0.05), more pronounced in the CLI subgroup (CLI: 1.3 ± 0.5 fibers/mm, CI: 2.9 ± 0.5 fibers/mm, controls: 5.3 ± 0.6 fibers/mm). In particular, increased mechanical and heat pain thresholds negatively correlated with lower IENFD. Mean S100 beta levels were in the normal range but were higher in advanced disease. Patients with chronic ischemic pain had a reduced IENFD associated with impaired sensory functions. These findings support the concept of a neuropathic component in ischemic pain.

Listen to the axillary artery: diagnosis of occult giant cell arteritis.

Large-vessel involvement is increasingly recognized in giant cell arteritis (GCA) and frequently occurs with an unspecific systemic inflammatory syndrome or fever of unknown origin. We describe the case of a 68-year-old woman with a history of polymyalgia rheumatica who presented with progressive weight loss, unexplained anemia, and a marked humoral inflammatory response. Diagnosis of large-vessel GCA was facilitated by axillary artery auscultation, revealing a bilateral axillary artery bruit. The diagnosis was confirmed by color duplex sonography and temporal artery biopsy. In elderly patients with an unspecific systemic inflammatory condition, axillary artery auscultation is a simple but valuable tool for detection of underlying occult large-vessel GCA.

Upper extremity deep venous thrombosis.

Upper extremity deep venous thrombosis is a serious disease entity which, based on the pathogenesis and in view of the individual patient's prognosis, must be divided into a primary and a secondary form. Primary upper extremity deep venous thrombosis is, when related to effort, a rather benign disease with excellent prognosis quoad vitam, carrying only a minor potential of developing disabling post-thrombotic syndrome. If primary upper extremity deep venous thrombosis occurs without any obvious cause, screening for underlying malignancy is recommended. Secondary upper extremity deep venous thrombosis typically occurs in older patients with severe comorbidities, mainly related to indwelling central venous catheters and cancer. As a consequence of the underlying diseases, prognosis of secondary upper extremity deep venous thrombosis is poor. Despite a lack of high-quality validation data, ultrasonography is regarded the first-line imaging technique, since it is a non-invasive method without exposure to radiation. In case of a non-diagnostic result of ultrasonography, other imaging modalities such as magnetic resonance imaging and computed tomography may be applied. Regardless of the etiology, the cornerstone of therapy is anticoagulant treatment with low molecular weight heparin or unfractionated heparin and vitamin K antagonists in order to prevent thrombus progression and pulmonary embolism. Owing to a lack of evidence, the optimal duration of anticoagulant treatment remains unclear. The additional benefit of compression therapy as well as of more aggressive therapeutic approaches such as thrombolysis, angioplasty and surgical decompression of the thoracic outlet needs to be investigated in randomized trials.

Successful antibiotic treatment of severe staphylococcal infection of a long stent graft in the superficial femoral artery with graft preservation in the long term.

INTRODUCTION: Bacterial infection of endovascular stent grafts is a serious condition, regularly leading to graft replacement by open bypass surgery. CASE REPORT: We describe the case of a staphylococcal infection of a 150-mm covered stent graft (Gore Viabahn), placed in the superficial femoral artery. Stent graft infection was successfully treated by oral administration of penicillinase-resistant flucloxacillin and the lipopeptide daptomycin with complete graft preservation, not requiring surgical treatment. During 1-year follow-up, the graft infection did not reappear. However, the patient developed restenosis at the proximal margin of the stent with recurrence of mild claudication, so far treated conservatively. CONCLUSION: With the increased use of covered stent grafts in the peripheral vasculature, the frequency of graft infection will increase. We demonstrate that with newly developed antibiotics, it is possible to treat this severe complication conservatively, with complete graft preservation and without the need for bypass surgery in selected cases.

Giant cell arteritis: a systemic vascular disease.

Giant cell arteritis (GCA) is increasingly being recognized as a systemic vascular disease, not confined to the cranial arteries. Epidemiological studies have shown that almost one-third of the patients with GCA develop serious peripheral vascular complications during long-term follow up, and there is growing evidence that unrecognized extracranial involvement may be even more common. GCA of large- and medium-sized peripheral arteries typically leads to long tapering and occlusion of the arterial lumen due to concentric intimal thickening, sometimes accompanied by spontaneous dissection. Depending on the extent of the arterial obliteration and on the anatomy of the involved arterial segment, this may result in severe ischemia of the limbs during the acute phase of the disease. GCA of the aorta usually remains asymptomatic for many years, and leads to a markedly increased risk of aneurysms and dissections, particularly of the thoracic aorta. Evolving vascular imaging techniques such as duplex ultrasound, computer tomography (CT), magnetic resonance imaging (MRI), and fluorine-18-desoxyglucose positron emission tomography (18F-FDG-PET) have greatly improved our ability to detect and study arterial changes in large-artery vasculitis. Boosted by these advances in vascular imaging, vascular specialists are increasingly involved in the early diagnosis, follow-up and treatment of patients with large-vessel vasculitis.

Large external iliac vein aneurysm in a patient with a post-traumatic femoral arteriovenous fistula.

We report about a young patient with a large aneurysm of the left external iliac vein associated with a traumatic arteriovenous fistula between the left superficial femoral artery and the femoral vein after a stab wound 20 years ago. The patient presented with swelling of the left leg, which developed during the past years and worsened after saphenectomy 12 months before hospital admission. The chronically hyperperfused common iliac artery proximal to the arteriovenous fistula was compressing the common iliac vein. The venous outflow obstruction and subsequent venous hypertension render a possible explanation for the formation of the iliac vein aneurysm. Surgical repair of the venous aneurysm by interposition grafting and closure of the arteriovenous fistula was successful. A postoperative computed tomography scan showed a 50% size reduction of the feeding artery, underlining the ability of the arterial system to normalize arterial diameter in response to flow reduction, even after a high flow situation had existed for probably >20 years.

Structure and function of the MRP2 (ABCC2) protein and its role in drug disposition.

The multi-drug resistance protein 2 (MRP2; ABCC2) is an ATP-binding cassette transporter playing an important role in detoxification and chemoprotection by transporting a wide range of compounds, especially conjugates of lipophilic substances with glutathione, glucuronate and sulfate, which are collectively known as phase II products of biotransformation. In addition, MRP2 can also transport uncharged compounds in cotransport with glutathione, and thus can modulate the pharmacokinetics of many drugs. The other way around, its expression and activity are also altered by certain drugs and disease states. Unlike other members of the MRP/ABCC family, MRP2 is specifically expressed on the apical membrane domain of polarised cells as hepatocytes, renal proximal tubular cells, enterocytes and syncytiotrophoblasts of the placenta. Several naturally occurring mutations leading to the absence of functional MRP2 protein from the apical membrane have been described causing the human Dubin-Johnson syndrome associated with conjugated hyperbilirubinaemia. Experimental mutation studies have revealed critical amino acids for substrate binding in the MRP2 molecule. This review is, therefore, focused on the structure and function of MRP2, the substrates transported and the clinical relevance of MRP2.