A very early and acute renal impairment due to polyomavirus allograft nephropathy.

Polyomavirus-associated nephropathy (PVAN) has become an important cause of graft loss in the last few years. The typical course of PVAN is characterized by an asymptomatic period of viruria followed, within weeks, by the development of viremia in the context of stable renal function. The persistence of viral replication characterized by high viremia, leads to parenchymal injuries and causes the development, within months, of PVAN that could lead to deterioration in graft function and graft loss. We reported, in a patient who received a renal transplant, an unusual presentation of PVAN characterized by the development of acute renal failurte earlier than would be expected after transplantation, where the histological presentation alone could be confused with an acute rejection. We underline the importance of the association of histological findings with the viral load in urine and blood and with ancillary techniques such as immunohistochemistry and polymerase chain reaction (PCR) in situ for virus detection. We also want to emphasize that decoy cells and PCR for BK virus DNA research could be considered among the diagnostic tools for possible acute renal failure in kidney transplant.

[Factors determining cardiovascular disease progression after kidney transplant]. / I fattori di progressione della malattia cardiovascolare dopo trapianto renale.

Cardiovascular disease is the leading cause of mortality and morbidity in renal transplant recipients as well as the leading cause of death with a functioning graft. The high cardiovascular risk is attributable to the prolonged exposure to multiple traditional and nontraditional risk factors in the pretransplant and posttransplant period. Particular attention must be paid to cardiovascular screening of candidates for kidney transplantation. After a transplant, treatment and prevention strategies should be focused on the modifiable risk factors including smoking, dietary habits, physical activity, weight control, hypertension, and dyslipidemia. Further studies on these factors are needed to better define the pharmacological approaches (hypotensive or hypolipemic drugs) and therapeutic targets. In view of the role of immunosuppressive therapy in the onset or worsening of several risk factors, it is important to tailor the treatment approach and dosage to the cardiovascular risk profile of the individual patient.

[Clinical evaluation of living donor]. / La valutazione clinica del donatore vivente.

When possible, living donor transplantation represents the best therapeutic strategy for patients suffering from chronic renal failure. Studying the donor allows a complete and thorough clinical, laboratory and instrumental assessment that guarantees good organ function whilst protecting the health of the donor. The main parameters considered within this framework are age, renal function, nephrological complications, comorbidities (diabetes, hypertension, obesity, etc.), malignancies, and infection. Moreover, particular attention is paid to the sociopsychological aspects of the donation, particularly related to the donor, the recipient, and the entire family situation.

[Preventing and reducing comorbidity in candidates for kidney transplantation for the improvement of post-operative results]. / Prevenire e ridurre le comorbilita' nei candidati al trapianto di rene per migliorare i risultati post-trapianto.

The correct and constant management of transplant waiting lists is necessary for the optimal utilization of the limited number of organs available for transplantation. The guidelines regarding placement on transplant waiting lists (absolute and relative contraindications) are well documented, even though they are in constant development. The criteria for the monitoring of patients on waiting lists, however, are not so well defined; this aspect is subject to careful evaluation on account of the widening of the criteria for transplantation suitability, the increase in the average age of patients, a rise in the number of enrolments and, as a result, prolonged waiting time (in Italy, the average time spent on a waiting list is 37 months). During the waiting period, a greater risk of clinically significant comorbidities and mortality, above all from cardiovascular events, has been noted (the annual mortality is 5-7% in the US, 1.3% in Italy). An in-depth clinical and instrumental study of patients with chronic renal failure is necessary when screening eligible candidates for transplant programs, individualizing therapeutic strategies, and identifying patients for whom the risks outweigh the potential benefits. Clinical and instrumental monitoring, as well as adequate treatment of comorbidities during the waiting period, can help improve the post-transplant outcome. This work examines the study algorithms and monitoring procedures for patients on kidney transplant waiting lists.

[Chronic allograft dysfunction: role of immunosuppressive treatment]. / Disfunzione cronica del trapianto renale (CAD): ruolo della terapia immunosoppressiva.

Renal transplantation is the treatment of choice for patients with end-stage renal disease. In recent years a major improvement has been observed in short-term graft survival, but there has been no corresponding improvement in long-term survival. Chronic allograft dysfunction (CAD) is an anatomical and clinical alteration that can lead to the loss of the transplanted organ without any specific cause. The pathogenesis of CAD, which still remains to be fully clarified, involves both immunological factors (acute rejection, subclincial rejection, HLA mismatches between donor and recipient, noncompliance, etc) and non-immunological factors (marginal donor ischemia/reperfusion injury, infection, cardiovascular risk factors, nephrotoxicity, etc). Immunosuppressive therapy represents one of the strategies for the prevention of CAD. The introduction into clinical practice of novel immunosuppressive agents with no or lower nephrotoxicity, like mycophenolate mofetile, rapamycin and everolimus, will make therapeutic strategies aimed at decreasing the incidence of CAD feasible.

Double kidney transplantation: initial experience of the Bologna Transplant Center.

AIM: Double-kidney transplantation is performed using organs from marginal donors with a histological score not suitable for single kidney transplantation. The aim of the study is to verify the results obtained with double-kidney transplantation in terms of graft and patient survival and complications. METHODS: Between September 2001 and September 2004, 16 double-kidney transplantations were performed in our center. The kidneys were all perfused with Celsior solution and the mean cold ischemia time was 17.6+/-2.7 hours. In all cases a pre-transplant kidney biopsy was performed to evaluate the damage. Immunosuppression was tacrolimus based for all patients. RESULTS: Eight patients had good renal postoperative function while the other eight had acute tubular necrosis. Two of the patients who had severe acute tubular necrosis never recovered renal function. There was only one episode of acute rejection, while the incidence of urinary complications was 31.2%; there were two surgical revisions for intestinal perforation. The graft and recipient survival was 78.1% and 100% and 78.1% and 93.7% at 3 and 36 months. CONCLUSIONS: Double-kidney transplantation is a safe way to face the organ shortage. Moreover the score used in this study is useful to determine whether a kidney should be refused or suitable for single or dual-kidney transplantation. The results of our initial experience are encouraging, but this series is too small in number to consent a conclusive statement.

Urological complications in kidney transplantation: ureterocystostomy versus uretero-ureterostomy.

In our initial experience of kidney transplantation, we performed an extravesical uretero-cystostomy (U-C), but in 1997 we shifted to a uretero-ureterostomy (U-U) with the aim of reducing early and late urological complications. A data base was constructed to compare the incidence, donor and recipient risk factors, treatments, and outcomes of urological complications with the two techniques. From 1990 to the end of July 2004, 894 kidney transplants included 43 from living donors and 851 from cadaveric donors with 804 first and 47 second transplants. We observed 48 urinary fistulas (5.4%): 45 were successfully repaired and three were treated with a ureteral stent with two good results; and one failed at a late operation. We had 26 early stenoses (2.9%), all of which were successfully treated: 16 with surgery and 10 with a stent. Donor and recipient risk factors for fistula and early stenosis did not reach statistical significance, confirming the technical etiology of these complications. There were only six cases of late ureteral stenosis in patients operated after 1990, and in eight cases of U-C we observed vesico ureteral reflux. There were 88 urological complications, with only one kidney lost. The shift from U-C to U-U did not change the incidence of urological complications, but with U-U we observed a significant decrease in the number of postoperative urinary infections, an easier possibility to resolve ureteral stenosis with endourology and no reflux. It is now our first choice with a normal ureter.

Evaluation of the resistive index (RI) for the diagnosis of acute renal rejection in renal allografts from the same donor.

PURPOSE: To investigate the importance of the resistive index (RI) in the diagnosis of acute renal rejection, compared with the RI of the twin kidney from the same donor, transplanted in two different patients. MATERIAL AND METHODS: From January to December 2000, we studied retrospectively 25 pairs (50 patients) of renal allografts from the same donor considering the RI obtained with by eco color-Doppler ultrasound, daily diuresis and renal function (serum creatinine level) in the first six days following surgery. Improvement of diuresis and renal function after corticosteroid therapy was considered the gold standard for the diagnosis of acute rejection. RESULTS: Medical complications (acute renal rejection) in the first six days were occurred in three cases, two in the first transplanted kidney as first and one in the second; all three cases showed disappearance of the diastolic waveform component. Considering a RI variation >0.15 with respect to the initial value, the sensitivity, specificity and diagnostic accuracy in the Doppler diagnosis of acute rejection were 100%, 97.1% and 97.3% respectively, with a prevalence of 7.8%. There were no statistically significant correlations between the RI variation of the renal transplant and the twin kidney from the same donor. DISCUSSION AND CONCLUSIONS: Doppler ultrasound is an important diagnostic tool in the detection of medical complications in the immediate postoperative period and during renal transplant follow-up. RI analysis, when studied serially and in the right clinical settings, allows an early diagnosis of renal rejection with high sensibility and specificity.

[Renal transplantation and malignancies: A single-centre experience (25 years)]. / Trapianto renale e neoplasie maligne: esperienza a lungo termine (25 anni) di un singolo centro.

BACKGROUND: The prevalence of post-transplant malignancies, in renal transplant recipients, is higher than that expected in age and sex-matched controls from the general population, and there is a markedly increased incidence of certain cancers. METHODS: In 1137 renal transplant recipients (1020 from cadaveric and 117 from living donors, M/F 771/366) performed at the S. Orsola Renal Transplantation Centre since 10/1976 to 9/2001, we studied the post-transplant cancer prevalence, the correlation between cancer prevalence and population characteristics, the risk factors (smoke, cancer history, positive HBsAg and antiHCV infection) and the immunosuppressive therapy. RESULTS AND CONCLUSIONS: The prevalence of malignancies was 3.86% (52 malignancies in 44 patients). The period between transplant and diagnosis of malignant disease was 59 +/- 85 months. Skin cancer was the most common (n=16; 30.7%), followed by lymphoproliferative disorders (n=8; 15.4%), Kaposi s sarcoma (n=6; 11.5%), uterine cancer (n=6; 11.5%), renal carcinoma of native kidney (n=5; 9.6%), cancer of breast/stomach/pancreas and urinary bladder (n=2; 3.8%) and other cancers (n=5; 9.6%). The mean duration of dialysis before transplantation was longer in cancer patients (41+/- 32.1 vs. 33.5 +/- 32.4 months). We found a correlation between types of malignancies and viral infection in NH-lymphoma (EBV positive 4/4) and skin cancer (HZV positive 13/16). We also detected a correlation between Aza and skin cancer (16/22) and CyA and lymphoproliferative disorders (7/8).

Application of Prastat ELISA in the determination of anti-HLA specificity for immunized patients awaiting kidney transplant: five years' experience.

Three hundred sixty-five patients who underwent cadaver donor kidney transplantation between 1993 and 1998 were divided into four groups: 40 immunized patients with at least one peak panel-reactive antibody (PRA) value more than 50%, 11 hyperimmunized patients with more than three peak PRA values over 50%, 10 retransplanted patients and 304 control patients. Before transplantation, we ascertained the antibody specificities against individual HLA antigens (Prastat Sangstat ELISA method for HLA typing of first donor, husbands of multiparous women and potential donors against whom candidates gave positive cross-matches); thus, patients underwent transplantation excluding the presence of the HLA antigens previously detected and looking for high HLA (class I and II) compatibility. Actuarial graft survival after 12 months was satisfactory in all groups: 87% immunized, 81% hyperimmunized and 80% retransplanted vs 92% controls. Renal function at the end of the first year was similar and the number of rejection episodes in the first 3 months did not significantly differ.

ELISA anti-HLA antibody screening identifies non-complement-fixing antibodies responsible for acute graft rejection. A case report.

We report on a kidney transplant recipient experiencing an unexpected early acute vascular graft rejection. Retrospective analysis of patient serum samples, utilizing a new ELISA HLA screening technique, revealed that the rejection crisis and the subsequent graft loss were due to a pretransplant donor-specific pre-sensitization caused by a non-complement-fixing antibody of IgG2 class. The case illustrates the clinical significance of non-complement-fixing anti-HLA antibodies. In addition it is shown that ELISA methods are suitable for detecting potentially harmful donor pre-sensitization in waiting-list patients not detectable by standard lymphocytotoxicity techniques. Hence ELISA could be an alternative to flow cytometry for this purpose. It is concluded that screening and cross-matching techniques which detect non-complement-fixing anti-HLA antibodies could improve graft outcome, and should form part of the immunological monitoring of kidney transplant waiting-list patients.

Treatment of uremic patients with biofiltration: efficacy, biocompatibility and medium-term results.

The present report deals with a medium-term programme using biofiltration on a group of 10 patients, who underwent a regular reduced-time schedule (3 procedures per week, 3 hours duration each) lasting up to 12 months. A polyacrylonitrile AN 69 S membrane was used together with a substitution fluid containing Na and bicarbonate. Hematochemical and nutritional parameters were regularly checked to evaluate the efficacy of treatment. Biocompatibility of materials was evaluated by humoral and cellular immunological tests.