Low-molecular-weight iron dextran in the management of renal anaemia in patients on haemodialysis--the IDIRA Study.

BACKGROUND: Intravenous iron supplementation is a basic principle in the therapy of haemodialysis (HD) patients with renal anaemia. In the Iron Dextran in Renal Anaemia (IDIRA) study, we analysed the efficacy of a therapy with low-molecular-weight iron dextran (LMW-ID) in stable HD patients with adequate iron stores previously treated with ferric gluconate. METHODS: IDIRA was an open-label, prospective, non-randomized, observational multicenter trial over 12 months in iron-repleted HD patients. All patients were treated with intravenous LMW-ID. Measures of efficacy were changes of haemoglobin (Hb), serum ferritin, erythropoietin dose and the response to iron therapy calculated as ferritin efficacy and Hb efficacy. Statistical analysis was done by the Wilcoxon test. RESULTS: A total of 221 HD patients with a mean age 63.7 +/- 13.8 years were included. A total of 208 out of 221 patients were on erythropoietin therapy. Median time on dialysis was 2 (1-4) years. Mean Kt/V was 1.3. Of the 221 patients, 208 completed the 12-month study period. Mean Hb and serum ferritin increased without the need for higher erythropoietin doses. The mean amount of iron per week administered remained stable. Ferritin efficacy and Hb efficacy improved using LMW-ID (p < 0.01). CONCLUSIONS: We conclude that LMW-ID improves anaemia management even in iron-pretreated HD patients.

Endovascular therapy of chronic mesenteric ischaemia.

BACKGROUND: Chronic mesenteric ischaemia (CMI) is associated with a high morbidity and mortality. Most likely causes of CMI are atherosclerosis, external compression (Dunbar Syndrome) and vasculitis. We report on our experience with endovascular stent therapy. PATIENTS AND METHODS: Between Sept. 1998 and Dec. 2005 we treated 21 consecutive patients (52% male; mean age 64+/-15 years, range 18-81 years) due to symptomatic CMI. A total of 34 interventions with 41 treated lesions were performed. Aetiology of vessel obstruction was atherosclerosis in 14 patients (67%), Dunbar syndrome in 3 patients (14%), chronic type B aortic dissection in 2 patients (9%), Takayasu's arteritis in 1 patient (4.5%), external compression following abdominal surgery in 1 patient (4.5%). Target lesions were celiac trunk (n=16), superior mesenteric artery (n=24), and inferior mesenteric artery (n=1). Twenty-two percent (n=9) of the lesions were total occlusions. The patients underwent serial follow-up duplex examinations before discharge and every 6 months thereafter or in case of symptom recurrence. RESULTS: Thirty-one of the 34 (91%) interventions were technically successful (37/41 lesions; 90%). Two of these 4 lesions were treated successfully using another approach in a second intervention. Brachial access was used in 16/34 cases (47%). One or more stents were placed in 29/34 interventions (85%) and 35/41 lesions. In 3 cases, in-stent restenosis was treated with balloon angioplasty alone, and in two cases, 3 occlusions could not be reopened. During 6 interventions, drug eluting stents were placed. All patients treated successfully were free of symptoms immediately after the intervention with recurrence of symptoms in case of restenosis. After a mean follow-up of 31+/-26 (range 0-87) months restenosis was detected in 6 patients (29%). Two major complications occurred which were treated without permanent sequelae. CONCLUSION: Stenoses of mesenteric arteries resulting in symptomatic CMI can be treated successfully with stent-angioplasty; for anatomical reasons, the brachial approach should be considered. Recanalisation of total obstructions is feasible if a stump of the occluded artery is detectable. Restenosis is frequent and can easily be treated with balloon angioplasty or stent-in-stent placement.

Long-term results after directional atherectomy of femoro-popliteal lesions.

OBJECTIVES: Our objective in this research was the evaluation of the long-term results after directional atherectomy using the Silverhawk device (FoxHollow Technologies, Redwood City, California) of femoro-popliteal lesions. BACKGROUND: Considering reports on stent fractures in femoro-popliteal arteries, atherectomy may be a valuable alternative to stenting. METHODS: Eighty-four patients with 100 legs and 131 lesions with peripheral occlusive disease Rutherford categories 2 to 5 were included in a prospective registry. Forty-five lesions were de novo lesions (group 1; 34%), 43 lesions native vessel restenoses (group 2; 33%), and 43 lesions in-stent restenoses (group 3; 33%). Additional low pressure balloon angioplasty was used in 78 of 131 lesions (59%) and stenting in 8 lesions (6%). RESULTS: Technical success rate was 86% for atherectomy only and 100% after additional therapy. Mean lesion length was 43 +/- 54 mm, 105 +/- 122 mm, and 131 +/- 111 mm for group 1, group 2, and group 3, respectively (p < 0.001). Primary patency, defined as freedom of a >50% restenosis detected by duplex, was 84%, 54%, and 54% at 12 months (p = 0.002) and 73%, 42%, and 49%, at 18 months (p = 0.008); secondary patency rates were 100%, 93%, and 91% at 12 months (p = NS) and 89%, 67%, and 79% at 18 months (p = 0.001), respectively; and target lesion revascularization rate was 16%, 44%, and 47% at 12 months and 22%, 56%, and 49% at 18 months (p = 0.003 each) for group 1, group 2, and group 3, respectively. The only independent predictor for restenosis was treatment of restenotic lesions. Ankle-brachial index was significantly improved after 12 months and 18 months in all groups. CONCLUSIONS: Long-term technical and clinical results after directional atherectomy of femoro-popliteal lesions are in favor of de novo lesions compared with restenotic lesions.

Restenosis after stenting of atherosclerotic renal artery stenosis: is there a rationale for the use of drug-eluting stents?

Percutaneous stent-angioplasty has become an accepted therapy for the treatment of atherosclerotic renal artery stenosis (RAS) because of higher acute and long-term success rates compared with balloon angioplasty alone. Restenosis rates after successful renal stent placement vary from 6 to 20% and depend mainly on the definition of restenosis and the vessel diameter of the renal artery or stent. We recommend that restenosis should be defined as >70%. The safety and efficacy of drug-eluting stents for the treatment of RAS is poorly defined. The currently partially published GREAT study (Palmaz Genesis peripheral stainless steel balloon expandable stent: comparing a sirolimus-coated vs. a bare stent in REnal Artery Treatment) examined the effect of a sirolimus-coated stent on restenosis rate in 102 patients and found a relative risk reduction of angiographic binary in-stent restenosis by 50% (7% versus 14%, P = ns). Given the lack of outcome data, the considerable expenses associated with drug-eluting stents, morbidity, and cost associated with prolonged dual antithrombotic therapy, the use of drug-eluting stents in RAS should be restricted to clinical trials. This is a review on restenosis rate following renal stenting, its definition, and the potential use for implantation of a drug-eluting stent in RAS, which so far for this indication is not yet commercially available.

Association of the P-glycoprotein transporter MDR1(C3435T) polymorphism with the susceptibility to renal epithelial tumors.

Except for hereditary disease, genetic factors that contribute to the development of renal epithelial tumors are unknown. There is a possibility that the MDR1 encoded plasma membrane transporter P-glycoprotein (PGP) influences the risk of development of renal neoplasms. PGP is known to be involved in uptake, binding, transport, and distribution of xenobiotics. There is evidence that the MDR1(C3435T) polymorphism drives expression and modulates disease risk. In an explorational case-control study, constitutional genotype frequencies were established at MDR1(C3435T) of 537 healthy control subjects and compared with those of 212 patients with renal epithelial tumors. There were 179 clear cell renal cell carcinoma (CCRCC) and 33 tumors collectively assigned as non-CCRCC. In a second study, genotypes of another 150 healthy control subjects and 50 patients with three non-CCRCC types (26 papillary RCC, 11 chromophobe RCC, and 13 renal oncocytic adenoma) were compared. PCR-restriction fragment length polymorphism-based analysis of constitutional DNA, and statistical analysis were applied. PGP expression was analyzed by quantitative immunohistochemistry. The explorational study showed a significant association between T allele frequency and the occurrence of tumors (P = 0.007). When tumors were histopathologically distinguished into frequent CCRCC and less frequent non-CCRCC, both patient groups contributed to this effect with a seemingly strong influence by the latter (P = 0.0419). The second study established the T allele as a risk factor especially for non-CCRCC (P = 0.0005) with the highest risk for homozygote TT allele carriers (P < 0.0001). Independently, MDR1(C3435T) genotype associated variations in PGP expression were shown in normal renal parenchyma with a 1.5-fold difference of median values (TT, 1.9; CC, 2.8; P = 0.0065). The data provide evidence for PGP to influence the susceptibility to develop renal epithelial tumors by virtue of its MDR1(C3435T) polymorphism and changes in expression. Especially T and TT carriers are at risk for developing non-CCRCC, i.e., papillary and chromophobe RCC as well as oncocytic adenomas.