Arteriovenous fistula as stable venous access in children with severe haemophilia.

Treatment for children with severe haemophilia is based on prophylaxis and, if inhibitors occur, on immune tolerance induction (ITI). Both regimens require frequent infusions at early ages and therefore an adequate venous access is essential. Peripheral veins represent the best option; however, central venous catheters (CVCs) have been used to facilitate regular treatment. Unfortunately, survival of CVCs is affected by infectious and/or thrombotic complications that often lead to premature removal and consequent treatment discontinuation. This aspect may have an impact on treatment outcome, especially in the case of ITI. In light of this, internal arteriovenous fistula (AVF) has been proposed as an alternative option because of a lower rate of infectious complications. Moreover, AVF is easy to use in the home setting and is well accepted by children and parents. The possible complications are postoperative haematoma and transient symptoms of distal ischaemia; one case of symptomatic thrombosis has been reported to date. Other complications include loss of patency, aneurysmatic dilatation and limb dysmetria. A regular follow-up is mandatory to allow early remedial interventions. Surgical AVF dismantlement is recommended as soon as transition to peripheral vein access is possible.

Pediatric kidney transplantation: a snapshot 10 years later.

Herein we report the outcomes of pediatric kidney recipients who underwent transplantation at least 10 years prior. A cohort of 36 patients (mean age, 26.4+/-6 years) with a mean follow-up time of 14.2+/-4 years was selected for the study. Immunosuppression consisted of cyclosporine and steroids. Actuarial patient and graft survivals 15 years after the transplantation were 97% and 86%, respectively. Only 1 patient died due to a complicated sclerosant peritonitis. Graft function was good with a mean serum creatinine of this selected cohort of 1.5+/-0.6 mg/dL. Eighteen percent were class 1, 33% class 2, and 49% chronic kidney disease. Hypertension was treated in almost 80% of the patients. The majority of patients were smaller than the average population with a final height (between 0 and -2) standard deviation score (HSDS) but only 27% had a severe growth impairment (HSDS>-2). Regarding nutritional status, fewer than 30% were overweight and only 1 patient was obese with a body mass index (BMI) >30. The majority of patients, except 2 mentally retarded individuals, are or have been attending normal school and achieved full-time employment. In conclusion, long-term survivors of a kidney transplant received during childhood reached a high degree of rehabilitation despite a long period of immunosuppression.

Best results in living donor transplantation using an aggressive policy in microsurgical bench reconstruction of nonoptimal arterial supply.

The increasing of number of patients awaiting kidney transplantation have forced surgeons to use nonoptimal organs, such as kidneys with multiple/diseased arteries as well as those coming from living donors (LDs). Two hundred and sixty six LD transplants performed in cyclosporine era included 44 coming from a LD over 60 years of age. They were categorized into three groups according to the number of renal arteries and the surgical techniques employed for the arterial anastomosis: group I (n = 213) had a single "normal" renal artery. Group II (n = 11) were grafts with two (n = 10) or three (n = 1) arteries, which were directly reconstructed by intracorporeal conventional separate anastomoses. Group III of 42 recipients had grafts with either one artery affected by intrinsic renovascular disease (n = 18) or multiple arteries (n = 24) that were reconstructed at the bench. Recipient survival at 1 year was comparable, namely, 98%, 100%, and 100% rates in groups I, II, and III, respectively. Graft survivals not censored for death were 87%, 85%, 100% at 3 years for groups I, II, and III, respectively. The use of microvascular reconstructions ex vivo can widen the criteria for acceptance of LDs who display multiple or diseased renal arteries.

Immediate graft function positively affects long-term outcome of renal allografts from older but not from younger donors.

There is disagreement about the impact of delayed graft function (DGF) on renal allograft outcome. This may depend on several variables including the age of the donor. We evaluated whether DGF could have different effects in recipients of kidneys from donors aged more than 60 years versus well-matched recipients of younger kidney donors. Patients were retrospectively subdivided into 3 groups. Immediate graft function (IGF), DGF without dialysis (DGF-ND), DGF requiring dialysis (DGF-D). DGF-ND and DGF-D occurred more frequently among 198 older than 198 younger donors (P = .016 and P = .044, respectively). The 5-year patient (96% vs 93%) and pure graft (96% vs 89%) survivals were significantly better in younger recipients, while the incidence of acute rejection was similar. After a mean follow-up of 66 +/- 44 months in older donor recipients, the graft survival was significantly better among IGF than patients in the DGF-ND (P = .046) or DGF-D (P = .003) groups. Instead, in younger recipients there was no difference in graft survival between IGD and DGF-ND. Only patients with DGF-D showed a significantly worse outcome. Upon multivariate analysis of older donors, their recipients, showed the pattern of graft function recovery to be the only variable associated with allograft outcome. Instead in younger donor recipients, acute rejection and time on dialysis were the main variables associated with a poor outcome. In older donor recipients, DGF was an independent variable associated with a poor graft outcome. In younger donor recipients, duration of dialysis and rejection were the most important predictors of poor graft outcomes.

The endless history of vascular access: a surgeon's perspective.

Gaining access to blood circulation has been a major breakthrough of modern medical care and, despite the evolution of dialysis technology, vascular access (VA) remains the main impediment in providing quantity as well as quality of life to the end-stage renal disease (ESRD) patient. The external Scribner shunt and the internal Brescia/Cimino arteriovenous fistula (AVF) opened the way for further advancements such as graft angioaccess and other sophisticated devices. Forty years later, the radio-cephalic fistula remains the VA with the longest patency and the lowest complications. Although various technical solutions can be adopted for constructing access to the patient's vessels, the nephrologist must bear in mind that every VA in the upper limb, lower limb or body wall needs a run-in and a run-off: currently, thrombosis of the central vessels due to the excessive widespread use of central venous catheters (CVCs) emerge as a substantial cause of hemodialysis (HD) morbidity and mortality. Moreover, as there is a risk of central vein stenosis, even 2 weeks after catheter placement, and an impaired venous outflow precludes the creation of any VA and sometimes the placement of a kidney transplant in the iliac fossa for many years, we agree with McGill et al, who in 2005 said that ''expansion of catheter access may contribute to the reduced survival of hemodialysis patients in the United States''.

Technical problems in living donor transplantation.

Inferior outcomes are generally described with grafts having multiple arteries or renovascular disease. A consecutive series of 261 living donor (LD) transplants performed in the CsA era was classified in three groups with regard to the graft arterial abnormalities and the techniques employed for revascularization. Two hundred eleven recipients had a kidney with one "healthy" renal artery (Group I); 11 patients, multiple arteries, which were reconstructed by various intracorporeal techniques (Group II); 39 patients, one diseased renal artery or multiple arteries, which were reconstructed on the bench (Group III). One- and 3-year graft survivals not censored for death, were 91%, 82%, 100% and 87%, 82%, 100%, respectively, for Group I, Group II, and Group III. An aggressive policy in performing microsurgical bench reconstruction, also for kidneys with one artery that are affected by intrinsic disease, allowed us to obtain a 3-year graft survival of 100% in our more recent consecutive series of 53 LD transplants.

Nosocomial infection in kidney transplant recipients: a retrospective analysis of a single-center experience.

Posttransplant bacterial infections are important because of their influence on patient and graft outcomes. Therefore, prevention of infection as well as prompt diagnosis and appropriate treatment are crucial. In this retrospective analysis, we reviewed all posttransplant bacterial infections occurring during the admission of kidney transplant patients from January 2000 to May 2004. Of our patients, 25% had at least one episode of infection. Patients with immunosuppression based on an mTOR inhibitor showed the highest rate of wound infections compared to those receiving a calcineurin inhibitor (odds ratio 5.6, P < .001). Patients with renal failure caused by a urologic disease revealed a increased risk of a urinary tract infections (odds ratio 5.9, P < .001). Although infection complications are an important cause of morbidity in renal transplantation, the extensive use of antibiotics should be avoided in favor of a strict policy for infection prevention and control.

Value of intraoperative resistive index in kidney transplant.

The value of the resistive index (RI) obtained by echo color doppler evaluation of the transplanted kidney is still not well established. Many authors consider the RI to be nonspecific sign of rejection, acute tubular necrosis, or urinary tract obstruction, but its specificity remains low. In this paper, we report our experience with RI determinations in 34 consecutive kidney transplants at different times namely: perioperatively, at 24 hours, at 3 days, at 6 and at 9 days posttransplant. In all patients intraoperative RI was normal. RI increased significantly after transplantation in 10 patients who eventually developed a complication: delayed function, acute rejection, and spontaneous kidney ruptures. This increment from the baseline value was already significant at 24 hours after the kidney transplant, indicating a possible posttransplant complication (0.62 +/- 0.07 vs 0.76 +/- 0.04; P = .0004). We conclude that the value of RI in the early posttransplant phase should be considered an important aid for the early diagnosis of posttransplant complications.

[Renal transplantation in the North Italy Transplant program (NITp): Organ allocation and results]. / Il trapianto renale nel Nord Italia Transplant program (NITp): assegnazione degli organi e risultati.

Renal transplantation is an effective therapeutic tool for patients with end-stage renal diseases (ESRDs). Data reported in this article summarize the results obtained from 30 years' activity in the North Italy Transplant program (NITp), the first transplant organization in Italy that implemented a donor procurement and organ transplantation network. In the NITp kidney allocation is governed by a computerized algorithm, NITK3, put in place in 1997, aimed at ensuring equity, transparency and traceability during the stages of the allocation decision-making process. The NITp working group has recognized the NITK3 criteria and they are periodically reviewed following the results of the analysis of patients' transplantation odds. The results obtained with the use of the NITK3 algorithm have been very satisfactory: after 6 yrs, a significantly higher percentage of patients at immunological risk (sensitized or waiting for re-transplant), of patients waiting for >3 yrs and of patients with 0-1 HLA A,B,DR mismatches have been transplanted. Moreover, a higher percentage of kidneys were used locally (in a hospital within the procurement area), and this is known to stimulate donor procurement. Finally, we performed a preliminary statistical analysis of transplants carried out from 1998-2002 in 5/16 centers of the NITp area, demonstrating the quality of the NITp program in terms of patient and graft survival, and that donor and recipient age are the variables significantly impacting on transplant results.

De novo cancers in paediatric renal transplant recipients: a multicentre analysis within the North Italy Transplant programme (NITp), Italy.

The purpose of this study was to determine the frequency and the outcome of de novo malignancies in a cohort of renal transplant paediatric patients. The records of 493 kidney transplants, carried out in 454 paediatric recipients at the three paediatric transplant centres of the North Italy Transplant programme (NITp, Italy) were reviewed. 10 cases of malignancies (2.2%) comprising both PTLD (post-transplant lymphoproliferative disorders) (6 cases, 1.3%) and non-PTLD malignancies (4 cases, 0.88%) were reported. Non-PTLD included one urothelial carcinoma and one Wilms' tumour of the recipient's left native kidney, one abdominal dysgerminoma and one optic nerve glioma of the left eye. The PTLD consisted of localised or disseminated Epstein-Barr virus (EBV)--associated B-lymphocyte monoclonal (5 cases) and polyclonal (1 case) proliferations. All patients suffering from PTLD had been EBV-negative at the time of transplantation, but developed EBV primary infection after transplantation. All PTLD patient donors were EBV-positive. In addition, all but 1 patient received, before and/or after transplantation, a range of immunosuppressive drugs in addition to the baseline prophylactic immunosuppressive regimen. Moreover, 3 patients suffered from syndromes associated with a genetic predisposition to cancer. Finally, the malignancies reported here were associated with 20% graft failure and 20% mortality rates.

Advantages of cyclosporine as sole immunosuppressive agent in children with transplanted kidneys.

A prospective study of intentional stopping of steroids 6 months after transplantation was done with 29 pediatric renal transplant recipients with a mean age of 10.4 +/- 3.4 years. Immunosuppression consisted of cyclosporine and methylprednisolone. We stopped giving MP to 24 children: to twenty after six months, four after 11-20 months. "Crude graft survival" was 97% during a mean follow-up of 36.7 +/- 15 months. The rejection rate was 48% during the first 6 months and 29% in the period after stopping MP. At present, 20/24 children (83%) have remained on CsA alone (18 patients) or CsA and azathioprine (2 patients) during a mean follow-up of 30 +/- 17 months. CsA nephrotoxicity occurred in 20.6% of patients, gum hypertrophy in 45%, hypertrichosis in 24%, and neurological symptoms in two patients (6.8%). Linear growth significantly improved after stopping MP: mean catch-up growth for prepuberal children 1.38 height standard deviation score (HSDS) and for pubertal children 1.6 HSDS. Bone age did not increase more rapidly than chronologic age. Weight/height index (W/HI) also improved. There was also a significant reduction in the use of antihypertensive drugs. Calculated glomerular filtration rate was decreased, though not significantly, after stopping MP. Thus, when graft survival is good, stopping corticosteroids corrects the major handicap of children with irreversible uremia--the poor linear growth--and improves the W/HI and control of arterial pressure. Longer follow-up periods are necessary to exclude significant worsening of renal function and an increased incidence of chronic rejection after stopping the steroid.

A randomized trial comparing triple-drug and double-drug therapy in renal transplantation.

A controlled trial was carried out in 86 cadaveric and 14 living haploidentical renal transplant recipients to compare the effects of low doses of cyclosporine (CsA), azathioprine (Aza) and steroids with those of higher doses of CsA plus steroids. Patients were followed for 12-26 months after transplantation. The actuarial 2-year patient and graft survival rate was 100% for living-donor transplants. In cadaver renal transplants the 2-year patient survival rate was 100% for patients assigned to the triple regimen and 93% for those allocated to the double regimen. The actuarial 2-year cadaver graft survival rates were 86% and 90.6%, respectively. There were significantly more patients who had severe infections (P less than 0.05), particularly interstitial pneumonia (P less than 0.005), in the double-therapy group. On the other hand, there were more patients who rejected and more patients with severe rejections; more pulses of steroids were also required for patients on the triple regimen, although these differences were not significant. The mean trough blood levels of cyclosporine at the various times were about half as high in patients on triple therapy. There were no differences between the two groups in creatinine clearance at any time. A control renal biopsy, taken from patients with stable renal function after 6-12 months, showed only mild abnormalities. The lesions were semiquantitatively assessed. There was a higher score for interstitial infiltrate in patients on triple therapy (P less than 0.05). On the other hand, the incidence and the mean score of interstitial fibrosis were greater in patients on double therapy, although these differences were not significant. Thus, although similar results were obtained with both regimens, at the doses we used double therapy seems to have more powerful immunosuppressive effects and may prevent rejection, either acute or chronic, better. However, it might expose the patient to a greater risk of infection and of cyclosporine-related nephrotoxicity than triple therapy.

Safe utilization and long-term follow-up of 368 marginal kidneys.

Three-hundred sixty-eight grafts of 1701 KTs performed during a 25-year period showed major anatomical anomalies: 358 kidneys presented an abnormal vascular supply, 8 organs had a double ureters, 2 were indivisible horseshoe kidneys. The outcome of these MKs is virtually identical (84%) to those obtained with transplant of normal grafts (85%). The advantages of ex vivo arterioplasty have been advocated.

Cyclosporine monitoring in stable, long-term, pediatric kidney transplant recipients: the value of C2 determination.

Although a generalized consensus has been reached for therapeutic drug monitoring of cyclosporine microemulsion in adult transplant patients, clear guidelines are recently not available for the pediatric population. In this retrospective analysis of pharmacokinetic data obtained from stable, long-term, pediatric kidney transplant recipients, we sought to define a possible approach to manage cyclosporine therapy in a pediatric setting. The 2-hour postdose cyclosporine blood concentration, C(2), rather than trough levels, was the best single time point predictor of the area under the concentration curve. We concluded that therapeutic drug monitoring of cyclosporine-based immunosuppressive regimens should be tailored based on C(2) determinations for pediatric kidney transplant recipients.

C2 is an age-independent parameter for optimal cyclosporine exposure in long-term kidney transplant recipients.

The argument for therapeutic drug monitoring (TDM) of cyclosporine (Cya) has been discussed for the last two decades. So far, a generalized consensus has been reached for TDM of Cya microemulsion in adult transplant recipients, being Cya blood levels obtained 2 hours after the administration (C2), the most reliable in reflecting the overall Cya exposure. However, clear guidelines are not available for the pediatric population because of the distinct metabolism of the drug in this patient population. Therefore, adult data do not necessarily apply to children. In this retrospective analysis, the authors sought to define a universal parameter for pharmacokinetic clinical monitoring of Cya in long-term kidney transplant recipients, regardless of their age. Lower C2 levels were observed in all patients, adult and pediatric, who eventually developed chronic allograft dysfunction (CRAD) compared with patients who maintained stable kidney function throughout the entire follow-up (pediatric CRAD, 933 +/- 455 ng/mL; vs Stable, 1236 +/- 347 ng/mL, P = .0001; and adult CRAD, 781 +/- 518 ng/mL; vs Stable, 1088 +/- 452 ng/mL, P = .009). On the other hand, the risk of Cya underexposure was not highlighted by trough level monitoring (C0) because all patients have been maintained steadily on therapeutical C0 levels for the entire follow-up. In conclusion, for Cya maintenance therapy, C2 appears to be a superior strategy to C0 monitoring in both adult and pediatric kidney transplant recipients.

Use of homologous vein grafts for chronic hemodialysis.

The Authors propose using of homologous saphenous vein grafts, coming from a normal saphenectomy by stripping in patients affected by primary varicose veins. The graft is preserved in a particular solution at 4 degrees C in a normal refrigerator and transplanted in uremic patients, which have no more vessels suitable for creating a conventional arteriovenous fistula.

Cirrhosis and hyperdynamic circulatory state due to a dysplasic giantism of the hepatic artery.

The authors here refer about the clinical case of a patient suffering from cirrhosis and hyperdynamic circulatory state due to a giantism of the hepatic artery. The surgical ligature of the main hepatic artery determined the complete regression of the abdominal pain and melena: the high output cardiac failure also disappeared with surgical correction.

Morphological aspects of the human intimal surface at scanning electron microscope. A preliminary approach in surgical material (iliac arteries).

Human iliac arteries, obtained at surgery, were examined at SEM. The ultrastructural aspects has evidenced pathological pictures, quite unexpected. The material observed resulted very adapt for scanning electron microscope.

Color Doppler imaging study in patients with primary open-angle glaucoma treated with timolol 0.5% and carteolol 2%.

PURPOSE: To evaluate with color Doppler imaging (CDI), in patients with primary open-angle glaucoma (PDAG), the possible influence on ocular hemodynamics of a beta-blocking agent with intrinsic sympathomimetic acitivity (carteolol 2%) compared to a beta-blocker agent without this activity. METHODS: A study was carried out on 20 patients, with bilateral POaG, intraocular pressure (IOP) < or = 20 mmHg, all treated twice a day with timolol maleate 0.5% ophthalmic solution. The visual field was evaluated (Octopus 2000 perimeter, G1 program) examining the mean sensitivity (MS) and the mean defect (MD). CDI was carried out to evaluate the resistance index of the internal carotid artery (ICA), the ophthalmic artery (OA), the central retinal artery (CRA), and the short posterior ciliary arteries (SPCA). After these examinations, the therapy was changed to carteolol 2% twice a day. After six months of treatment the examinations were repeated. The data were analysed statistically using Student's t test. RESULTS: The mean intraocular pressure during treatment with timolol 0.5% was 16.7 +/- 1.67 mmHg and 16.33 +/- 1.72 mmHg after treatment with carteolol 2%, the difference not being significant (p=0.494). After six months of treatment with carteolol 2% the MS increased significantly from 22.4 +/- 2.5 dB to 24.1 +/- 1.8 dB (p=0.018), and the mean defect (MD) fell from 5.3 +/- 0.8 dB to 4.7 +/- 0.6 dB (p=0.011). There was no significant difference in the resistance index of the CA, the OA and the CRA with the two treatments, whereas the resistance index of the SPCA dropped significantly, from 0.80 +/- 0.05 to 0.77 +/- 0.02 (p = 0.017). CONCLUSIONS: CDI did not show significant differences in the resistance indexes of the internal CA, the OA, and the CRA after treatment with carteolol 2% but the resistance index of the SPCA was significantly reduced. Carteolol 2% induced significant changes in the perimetric indexes examined, with an increase in MS and a decrease in MD. These findings suggest that the intrinsic sympathomimetic activity of carteolol may reduce peripheral vascular resistance of the SCA, thus improving perfusion of the optic nerve head, with a protective effect on visual function.

[Surgical treatment of renvascular hypertension. Personal cases]. / Il trattamento chirurgico dell'ipertensione nefro-vascolare. Casistica personale.

Authors analyze a personal series of patients surgically treated for renal artery diseases (177 cases). Criteria of screening and diagnosis of stenosis are discussed and also are referred the clinical data. Authors describe their own personal reconstructive technique on renal arteries. Early and late results are widely analyzed.