Kidney transplantation in HIV-positive patients treated with a steroid-free immunosuppressive regimen.

One of the main concerns associated with renal transplantation in HIV-infected patients is the high risk of acute rejection, which makes physicians reluctant to use steroid-free immunosuppressive therapy in this subset of patients. However, steroid therapy increases cardiovascular morbidity and mortality. The aim of this study was to define the efficacy of a steroid-sparing regimen in HIV-infected renal transplant recipients. Thirteen HIV-infected patients were consecutively transplanted. The induction therapy consisted of basiliximab and methylprednisolone for 5 days followed by a calcineurin inhibitor plus mycophenolate acid. The mean follow-up was 50 ± 22 months. Eight patients (61.5%) experienced acute rejection, and 75% of the first episodes occurred within 2 months after transplantation. The probability of first acute rejection was 58% after 1 year and 69% after 4 years. Seven of eight patients recovered or maintained their kidney function after antirejection therapy and steroid resumption. At the last follow-up, seven of 13 patients (54%) had resumed steroid therapy. The 4-year patient and graft survivals were 100% and 88.9%, respectively. The benefits of this steroid-free regimen in HIV-infected renal recipients must be reconsidered because of the high rate of acute rejection. New immunosuppressive steroid-free strategies should be identi-fied in this set of patients.

Tacrolimus versus cyclosporine for early steroid withdrawal after renal transplantation.

INTRODUCTION: This study compares cyclosporine (CsA) with tacrolimus (Tac) in preventing acute rejection (AR) after steroid withdrawal (SW) 5 days after renal transplantation (Tx). METHODS: The data were collected from 2 prospective sequential studies carried out from February 2002 to May 2006. Forty-nine patients received CsA, 56 patients Tac. Rapamycin (Rapa) was added to both calcineurin inhibitors (CNIs). The studies were homogeneous regarding both clinical procedures and patient demographics. RESULTS: Three years after SW, Tac was more effective than CsA in reducing the risk both of AR (35% vs. 53%; p<0.06) and mainly of relapses (9% vs. 33%; p<0.007). In addition, Tac enabled more patients to go onto a steroid-free regime (88% vs. 65%; p<0.01). No difference arose concerning the timing of AR, graft function, CNI withdrawal, incidence of side effects or patient and graft survival rates. In both groups, rejection after SW was associated with a worse graft function. CONCLUSIONS: Tac was more effective than CsA in preventing AR after early SW, and increased significantly patient probability of maintaining a steroid-free regime. In this setting, Tac and CsA had the same safety profile. However, a follow-up longer than 3 years might be needed to estimate the consequences of the higher rate of AR encountered under CsA therapy.

Upper limb artery segmental occlusions due to chronic use of ergotamine combined with itraconazole, treated by thrombolysis.

BACKGROUND: The ergotamine tartrate associated with certain categories of drugs can lead to critical ischemia of the extremities. Discontinuation of taking ergotamine is usually sufficient for the total regression of ischemia, but in some cases it could be necessary thrombolytic and anticoagulant therapy to avoid amputation. CASE REPORT: A woman of 62 years presented with a severe pain left forearm appeared 10 days ago, with a worsening trend. The same symptoms appeared after 5 days also in the right forearm. Physical examination showed the right arm slightly hypothermic, with radial reduced pulse in presence of reduced sensitivity. The left arm was frankly hypothermic, pulse less on radial and with an ulnar humeral reduced pulse, associated to a decreased sensitivity and motility.Clinical history shows a chronic headache for which the patient took a daily basis for years Cafergot suppository (equivalent to 3.2 mg of ergotamine).From about ten days had begun therapy with itraconazole for vaginal candidiasis. The Color-Doppler ultrasound shown arterial thrombosis of the upper limbs (humeral and radial bilateral), with minimal residual flow to the right and no signal on the humeral and radial left artery. RESULTS: Angiography revealed progressive reduction in size of the axillary artery and right humeral artery stenosis with right segmental occlusions and multiple hypertrophic collateral circulations at the elbow joint. At the level of the right forearm was recognizable only the radial artery, decreased in size. Does not recognize the ulnar, interosseous artery was thin. To the left showed progressive reduction in size of the distal subclavian and humeral artery, determined by multiple segmental steno-occlusion with collateral vessels serving only a thin hypotrophic interosseous artery.Arteriographic findings were compatible with systemic drug-induced disease. The immediate implementation of thrombolysis, continued for 26 hours, with heparin in continuous intravenous infusion and subsequent anticoagulant therapy allowed the gradual disappearance of the symptoms with the reappearance of peripheral pulses. CONCLUSION: Angiography showed regression of vasospasm and the resumption of flow in distal vessels. The patient had regained sensitivity and motility in the upper limbs and bilaterally radial and ulnar were present.

Open surgery in endovascular aneurysm repair era: simplified classification in two risk groups owing to factors affecting mortality in 137 ruptured abdominal aortic aneurysms (RAAAs).

Our objective is to identify in 137 true RAAAs operated consecutively in open surgery: (1) diagnostic therapeutic aspects capable of influencing results, (2) risk classes with different prognosis, (3) any situations where the prognosis is so negative that surgery is not recommended. The relationship of 16 anamnestic, clinical and technical parameters prospectively collected with 30-day mortality was retrospectively evaluated by uni- and multivariate analyses. Thirty-day mortality was 37%. The univariate analysis identified as mortality predictors Hb ≤ 8 g/dl and circulatory shock at hospitalisation, but following the multivariate analysis only circulatory shock was a certainly significant risk-factor. The cumulative effect on mortality of the two parameters identified at univariate analysis translates into a statistically significant difference in mortality between two groups of patients: A (no or just one risk-factor) and B (two risk-factors). To reinstate euvolemia, rather than adequate haemoglobin values, improves the chances of success. A simple prognostic index into two risk classes is feasible, but abstention from surgery is not justified in any type of patient.

Early (fifth day) vs. late (sixth month) steroid withdrawal in renal transplant recipients treated with Neoral(®) plus Rapamune(®): four-yr results of a randomized monocenter study.

The most advisable timing for steroid withdrawal (CSWD) after renal transplantation (Tx) is still an open issue. This randomized study has compared early CSWD (at day 5) with late (at month 6) in patients under Neoral + Sirolimus. The primary end point was the percentage of success in CSWD at month 48. Ninety-six transplants from deceased donors were randomized to withdraw steroids either early (n = 49) or late (n = 47). At four yr, the two strategies were comparable for: success in CSWD (65% in both), graft survival (95% and 98%), patient survival (92% and 96%) creatininemia (1.7 ± 0.3 and 1.6 ± 0.4 mg/dL), side effects, being still on Sirolimus + Neoral (69% and 74%), reversibility of rejection (AR) (all cases), severity of AR (grade 1A/1B: 81% and 63%). The major differences were incidence of AR: at month twelve (48% vs. 30%, p < 0.04), at 48 (53% and 33%, p < 0.03); timing of AR (72 ± 86 d vs. 202 ± 119 d, p < 0.0001). The timing of CSWD influences neither the rate of successful CSWD nor the long-term results. However, early suspension causes a higher AR rate, mostly arising within month one, but always responsive to steroids. Yet, the early appearance of AR can make patient management easier and safer.

Steroid withdrawal five days after renal transplantation allows for the prevention of wound-healing complications associated with sirolimus therapy.

BACKGROUND: Sirolimus (SRL) can increase the risk of wound complications. In this study, we investigated the impact of steroids when added to SRL, in this side effect. METHODS: One hundred and forty-eight patients entered prospective studies comparing early (fifth day) with late (sixth month) steroid withdrawal. All patients were on SRL, added either to Tacrolimus (n = 56) or to cyclosporine (n = 97). At 15th day after transplantation, 68 patients were on steroids (On-St group) and 80 were not (Off-St group). Wound complications considered were as follows: dehiscence, lymphocele, wound leakage, hematoma and seromas. Risk factors under analysis were as follows: body mass index, diabetes, rejection, creatininemia, length of dialysis before transplantation, recipient age, being on steroids at 15th day, SRL levels. RESULTS: The overall incidence of wound complications was significantly lower in Off-St group than in On-St group: 18.8% vs. 45.6%, respectively (p < 0.0004). In detail, lymphocele: 5.0% vs. 32.3% (p < 0.0001); dehiscence 0% vs. 10.3% (p < 0.009), leakage 6.2% vs. 8.8% (p = NS), seromas 1.4% vs. 7.5% (NS). At multivariate analysis, the addition of steroids to SRL increases 4.2-fold the risk for wound complications. CONCLUSIONS: Early steroid withdrawal is effective in preventing both the incidence and the severity of wound-healing complications because of SRL regime, even when started with a loading dose.

Risk factors for immediate results and long-term survival following elective open surgery for AAA. Statistical analysis of 1111 consecutively-treated patients.

AIM OF THE STUDY: Perioperative and 10 years follow-up risk factors for 1111 consecutive open AAA repairs were statistically analyzed (X2-test and Log-rank test methods for univariate analysis, and logistic regression model and Cox proportional-hazard model for multivariate analysis). Overall operative mortality rate was 2.7%, and significant risk factors were: 1) univariate analysis: Age (>70 years 3.9% vs 1.5% <70 years); CAD (4.3% vs 1.9% without CAD); PAD (4.7% vs 2.0%); III-IV ASA classes (3.8% vs 0% in I-II ASA classes); 2) multivariate analysis: only ASA classes. RESULTS: Long-term survival (42.3 +/- 32.6 months) was 93% and 88% at 3 and 5 years respectively, with 0.2% graft-related deaths, and significant risk factors were 1) univariate analysis: Age (92% and 84% at 3 and 5 years in patients aged >70 vs 94% and 91% <70 years); ASA classes (91% and 87% at 3 and 5 years in ASA III-IV vs 98% and 92% in ASA I-II); CAD (92% and dell'85% vs 94% and 90% without CAD); COPD (90% and 80% vs 95% and 92% without COPD); CRF (90% and 82%, vs 94% and 89% without CRF); suprarenal aortic cross-clamping for pararenal aneurysms (91% and 77% in pararenal AAA, vs 94 % and 90% in infrarenal AAA; 2) multivariate analysis: Age; ASA classes; pararenal aneurysms. There was a close relation between number (0-5) of risk factors in each patient and early and late complications. These data are very satisfactory overall, and even in high risk patients who are routinely considered for EVAR.

Steroid-free immunosuppression regime reduces both long-term cardiovascular morbidity and patient mortality in renal transplant recipients.

The aim of this retrospective study was to assess the impact of steroid therapy on cardiovascular disease (CVD) and patient mortality, in 486 on-CsA renal transplant recipients, with a follow-up of 9.5 +/- 4.3 yr. Two hundred and one patients had their steroids permanently withdrawn at sixth month after transplantation (G1); 285 patients did not (G2) as they were unable (acute rejection after suspension) or unsuitable (because of clinical criteria or immunosuppressive protocols). The CVD considered were coronary artery disease diagnosed by angiography and myocardial infarction. G1 and G2 patients were well-matched regarding CVD risk factors, except for age (G1: 44 +/- 14 yr; G2: 40 +/- 12 yr; p < 0.003), incidence of male (G1: 62%; G2: 72%, p < 0.02) incidence of acute rejection (G1: 39%; G2: 83%, p < 0.0001). Both CVD and deaths occurring during the first year of transplantation were excluded from the analysis. At 20 yr, the cumulative probability of developing a CVD, was 3.8% in G1; 23.8% in G2 (p < 0.0005). Patient survival rate was 95% in G1; 62% in G2 (p < 0.003). Mortality caused by CVD was higher in G2 (4.2% vs. 0.5%; p < 0.03). The Cox analysis identified in steroid therapy the main independent risk factors for both CVD (hazard ratio 9.56 p < 0.0001) and patient mortality (hazard ratio 5.99, p < 0.0001). At 10th and 15th year after transplantation, the mean-daily dose of steroids was 4.2 mg. In the long-term, steroid therapy, even in low-doses, increases significantly both the rate of CVD and patient mortality. This retrospective study suggests that steroid-free regime should always be recommended for the prevention of post-transplant CVD. This relevant statement should be followed by a long-term prospective study.

Cholesterol crystal embolic disease in renal allografts.

Cholesterol embolic disease in the renal allograft is not recognized as an important cause of graft dysfunction. We describe here two renal transplant patients with cholesterol embolization in their allograft biopsies. The first, a 48-year-old patient, received a renal transplant from a 62-year-old donor with a history of hypertension and tobacco use. On account of initial non-function, a renal biopsy was taken, which showed acute tubular necrosis and cholesterol emboli. The second, a 55-year-old man, presented chronic allograft failure six years after transplantation; ultrasonography showed a solid renal mass. Nephrectomy specimens revealed renal carcinoma and a combination of chronic rejection and multiple cholesterol emboli. Cholesterol embolic disease is probably an under-reported cause of renal graft dysfunction. The source of the emboli may be either the donor or the recipient's vessels. Since the current tendency is to accept older donors and recipients with more advanced atherosclerotic disease, this condition is likely to become more frequent in the future. Particular care must be taken at the time of organ procurement and during the evaluation of organ donors, in order to reduce the risk of embolization.