M Bertocchi

HLA class-I-soluble antigen serum levels in liver transplantation : a predictor marker of acute rejection

The serum levels of sHLA-I have been determined in 16 patients following liver transplantation. sHLA-I levels did not show remarkable variations in six patients without evidence of transplant-related complications. sHLA-I levels strongly increased in 10 patients undergoing acute rejection episodes. In these patients, an average 20% daily increase of sHLA-I levels was detected on the 6 days preceding and on the 2 days following the rejection episode. A fast decrease of sHLA-I levels was observed in seven patients following treatment of acute rejection with anti-CD3 mAb. The serum level of sHLA-I antigens positively correlated with ALT serum level and inversely correlated with PT. The determination of sHLA-I in serum may therefore be proposed as a useful marker in the monitoring of patients following liver transplantation. The increase of sHLA-I antigens may predict the onset of acute rejection whereas their decrease may be related to a good response of acute rejection to immunosuppressive treatment.

Vesico-ureteral reflux in pediatric kidney transplants: Clinical relevance to graft and patient outcome

Abstract: From June 1985 to December 1998, 173 pediatric renal transplants were carried out in 170 patients at our center. From this pool, 73 patients (34 males and 39 females) with a follow‐up of 48 months were examined. In all patients, ureteroneocystostomy was performed according to the Lich‐Grégoire procedure. All patients were treated with cyclosporin A (CsA)‐based immunosuppression, including prednisone and sometimes azathioprine (AZA). Six months after transplantation, voiding cystography (VCU) was performed in all patients and reflux was classified from Grade I to Grade IV. The patients were divided into two groups: those with reflux (Group A: 25 patients) and those without (Group B: 48 patients). Grade I reflux was found in four patients, Grade II in seven patients, Grade III in seven patients, and Grade IV in seven patients. All the patients with severe reflux (Grade IV) underwent a corrective surgical procedure. Both groups were examined for immunologic and non‐immunologic risk factors and no significant differences were found. Analysis of patient and graft survival rates revealed no statistical differences (NS) between Groups A and B. Mean serum creatinine (mg/dL) was 1.06 ± 0.28 and 1.12 ± 0.41 at 4 yr in Groups A and B, respectively (NS). Mean calculated creatinine clearance (cCrC; ml/min) was 76.74 ± 15.92 and 77.96 ± 15.66 in Groups A and B, respectively (NS). The analysis was further extended by considering the grade of reflux (I to IV). Again, no significant differences in the above parameters emerged between the reflux sub‐groups; only in the Grade IV sub‐group was a slight decrease in cCrC detected, although this difference was not statistically significant when compared with the other sub‐groups. In conclusion, vesico‐ureteral reflux (VUR) does not seem to negatively affect graft function. However, as all severe reflux patients (Grade IV) were surgically corrected, no conclusions can be drawn with regard to the influence of Grade IV reflux on long‐term graft function.

Late ureteral stenosis after kidney transplantation: a single-center experience.

In a retrospective study, we analyzed 1419 consecutive kidney transplantation procedures performed at a single center to identify potential predictive factors of ureteral stenosis. Only stenosis observed after the first month posttransplantation was considered. The Cox proportional hazard regression model was used to analyze donor age and serum creatinine concentration before procurement, recipient age, cold ischemia time, delayed graft function, number of renal arteries, and presence of a double-J stent. Follow-up evaluation included number and timing of acute rejection episodes, cytomegalovirus infection, acute pyelonephritis, renal function, and patient death. Ureteral stenosis developed in 45 patients (3.17%), and was correlated with donor age older than 65 years (P = .001), kidneys with more than 2 arteries (P = .009), and delayed graft function (P = .02). The data suggest a potential protective role of donor age, number of renal arteries, and delayed graft function in development of ureteral stenosis after kidney transplantation.

Kidney Intragraft Homing of De Novo Donor-Specific HLA Antibodies Is an Essential Step of Antibody-Mediated Damage but Not Per Se Predictive of Graft Loss

Donor‐specific HLA antibody (DSA)‐mediated graft injury is the major cause of kidney loss. Among DSA characteristics, graft homing has been suggested as an indicator of severe tissue damage. We analyzed the role of de novo DSA (dnDSA) graft homing on kidney transplantation outcome. Graft biopsy specimens and parallel sera from 48 nonsensitized pediatric kidney recipients were analyzed. Serum samples and eluates from graft biopsy specimens were tested for the presence of dnDSAs with flow bead technology. Intragraft dnDSAs (gDSAs) were never detected in the absence of serum dnDSAs (sDSAs), whereas in the presence of sDSAs, gDSAs were demonstrated in 72% of biopsy specimens. A significantly higher homing capability was expressed by class II sDSAs endowed with high mean fluorescence intensity and C3d‐ and/or C1q‐fixing properties. In patients with available sequential biopsy specimens, we detected gDSAs before the appearance of antibody‐mediated rejection. In sDSA‐positive patients, gDSA positivity did not allow stratification for antibody‐mediated graft lesions and graft loss. However, a consistent detection of skewed unique DSA specificities was observed over time within the graft, likely responsible for the damage. Our results indicate that gDSAs could represent an instrumental tool to identify, among sDSAs, clinically relevant antibody specificities requiring monitoring and possibly guiding patient management.

Impact of pretransplant dialysis on early graft function in pediatric kidney recipients.

Delayed graft function (DGF) is a frequent complication of kidney transplantation (KT) that may affect both short‐ and long‐term graft outcome. It has been reported that pretransplantation peritoneal dialysis was correlated with a better recovery of graft function than hemodialysis in adult kidney recipients. However, the effect of pretransplantation dialysis mode (PDM) seemed to be unclear on the early outcome of KT in pediatric recipients. In this study, the potential impact of PDM on early graft function was evaluated in 174 pediatric patients who underwent KT by using cadaveric donors. The primary outcome parameter was the time to reach a serum creatinine (SCr) level 50% of the pretransplantation value [T1/2(SCr)], while DGF was defined as a T1/2(SCr) >3 days after KT (n = 40). By stratifying kidney recipients for normal function graft or DGF, this latter group showed a significantly higher body weight (BW) on the day of KT (P = 0.014), body surface area (BSA) (P = 0.005), warm ischemia time (WIT) (P = 0.022), early SCr on the day 1 after KT (P < 0.001), and T1/2(SCr) (P < 0.001), whereas lower urine volume (UV) collected in the first 24 h after KT (P < 0.001) and fluid load (P < 0.001) occurred. Univariate exponential correlation that was carried out between T1/2(SCr) and all the other variables had shown a better value than the linear correlation for BW (R2 = 0.28 vs. R2 = 0.04), BSA (R2 = 0.29 vs. R2 = 0.03), and SCr (R2 = 0.51 vs. R2 = 0.28). In a multivariate regression analysis performed by entering T1/2(SCr) as dependent variable and following a forward stepwise method, cold ischemia time (CIT) (P = 0.027) but not PDM (P = 0.195) reached significance. In a Cox regression analysis carried out with T1/2(SCr) as dependent variable, neither CIT nor PDM gained significance. This study suggests that PDM does not affect early graft function in pediatric kidney recipients.

Single-Center Experience in Double Kidney Transplantation

Use of organs from marginal donors for transplantation is a current strategy to expand the organ donor pool. Its efficacy is universally accepted among data from multicenter studies. Herein, we have reviewed outcomes of double kidney transplantation (DKT) over an 9-year experience in our center. The aim of this study was to evaluate possible important differences between a monocenter versus multicenter studies. Between 1999 and 2008, we performed 59 DKT. Recipient mean age was 63 +/- 5 years. Mean HLA-A, -B, and -DR mismatches were 3.69 +/- 0.922. Donor mean age was 69 +/- 7 years and mean creatinine clearance was 69.8 +/- 30.8 mL/min. Proteinuria was detected in three donors (5%). Mean cold ischemia and warm ischemia times were 1130 +/- 216 and 48 +/- 11 minutes, respectively. The right and left kidney scores were 4.18 +/- 2 and 4.21 +/- 2, respectively. Thirty patients (51%) displayed good postoperative renal function; 22 (37%), acute tubular necrosis with postoperative dialysis; 3 (5%), acute rejection episodes; 4 (7%), single-graft transplantectomy due to vascular thrombosis; 1 (2%), a retransplantation; 5 (8%), a lymphocele; 3 (5%) vescicoureteral reflux or stenosis requiring surgical correction. Cytomegalovirus infection was detected in five patients (8%). In three patients (5%) displayed de novo neoplasia. Three patients showed chronic rejection (5%), whereas we observed a cyclosporine-related toxicity in 7 (12%). Nine patients (15%) developed iatrogenic diabetes. Patient and graft survivals after 3 years from DKT were 93% and 86.3%, respectively. In this study, we applied successfully a widespread score to allocate organs to single kidney transplantation or DKT. In our experience, the score is suitable for the organ allocation but it may be overprotective, excluding potentially suitable organs for a single transplantation.

Corynebacterium urealyticum Infection in a Pediatric Kidney Transplant Recipient: Case Report

The incidence of Corynebacterium urealyticum infection in kidney recipients is low. Its common clinical manifestation is encrusted cystitis or encrusted pyelitis. Herein, we report an unusual case of a 19-year-old kidney recipient with necrotizing pyelitis due to C urealyticum in the absence of mucosal encrustation or calculi. The patient was readmitted 30 days posttransplantation to remove a stent. Cystoscopy demonstrated a normal vesical wall without encrustation. The stent was removed without problems. Culture yielded negative findings. That night, the patient had fever and hematuria. Therapy included forced diuresis with high fluid intake, and diuretic and antibiotic administration. The patient was then discharged. However, 15 days later he was readmitted because of hematuria with a significant decrease in hemoglobin concentration. Echography demonstrated the presence of hyperechogenic material in the pelvis and ureter. Pyelography demonstrated the presence of numerous coagula obstructing the urinary tract. In addition, severe hematuria required transplant nephrectomy.

Nocardiosis in a kidney-pancreas transplant.

34-year-old man with chronic renal and pancreas failure in complicated diabetic disease received a kidney-pancreas transplantation. On the 32nd postoperative day, an acute kidney rejection occurred and resolved with OKT3 therapy. The patient also presented refractory urinary infection by E. Fecalis and M. Morganii, and a focal bronchopneumonia in the right-basal lobe resolved with elective chemotherapy. During the 50th post-operative day, an intense soft tissue inflammation localized in the first left metatarsal-phalangeal articulation occurred (Figure 1) followed by an abscess with a cutaneous fistula and extension to the almost totality of foot area. The radiological exam revealed a small osteo-lacunar image localized in the proximal phalanx head of the first finger foot. From the cultural examination of the purulent material, N. Asteroides was identified. An amoxicillin-based treatment was started and continued for three months, with the complete resolution of infection This case is reported for its rarity in our casuistry, and for its difficult differential diagnosis with other potentially serious infections.

Fatal Donor-Derived Carbapenem-Resistant Klebsiella pneumoniae Infection in a Combined Kidney-Pancreas Transplantation

Carbapenem-resistant Klebsiella pneumoniae (CR-KP) infections in solid organ transplant recipients are associated with high morbidity and mortality. We report a case of a fatal donor-derived CR-KP infection in a combined kidney-pancreas transplant. Given the short interval of time between donor hospitalization and organ procurement, information concerning the donor CR-KP positivity arrived only 72 hours after transplant. Based on this experience, we believe that knowledge of the donors CR-KP status should be mandatory before procurement and, if positive, pancreas donation should be contraindicated.

Nephron-sparing surgery for malignancies in kidney allografts.

Dear Editors, Nephron-sparing surgery (NSS) is a well-recognized and established surgical procedure that was, historically, first proposed for patients with tumors of native kidneys in which renal parenchyma must be preserved [1]. NSS has undergone vast development in the last decades, and current American Urologist Association guidelines identify this surgical technique as the standard of care for localized RCC tumors ≤7 cm (stages T1a and T1b) [2]. Various reports have shown successful cases of NSS in RCC tumors of kidney allografts, although the indications and limits of this procedure are not well defined. We report our single-center experience in partial nephrectomies for malignancies of kidney allografts in an attempt to discuss the main clinical and technical aspects. We retrospectively reviewed the following clinical parameters: age, date of transplantation, time interval between transplant and tumor diagnosis, adaption of immunosuppressive therapy, creatinine levels before and 1 month after surgery, localization of the tumor, number and size of the lesions, histological type, TNM staging, Fuhrman grading system, operative time, need for hilar clamping, surgical access, postoperative complications, tumor recurrence, follow-up, cause of death, 1-year graft survival and patient survival. Wilcoxon matched pairs test was used to evaluate the kidney graft function, comparing the serum creatinine levels before and 1 month after surgery. After transplantation, all patients underwent clinical follow-up, including laboratory tests at least twice a year and ultrasound (US) once a year. In cases of suspicious lesions in the allograft found at US, an abdominal contrast CT scan was performed. For all suspicious RCC confirmed at CT scan, and with a size ≤7 cm and limited to the allograft (Stage T1), we adopted a conservative approach to NSS. Depending on the location of the tumor, we adopted a different surgical approach. In the case of peripheral lesions localized on the convex edge of the allograft, we opted for an extraperitoneal access, while an intraperitoneal approach, through a midline incision with renal hilum isolation, was preferred in the case of tumors on the medial side of the kidney, close to the hilum, or attached medially to the peritoneum. Of the 1735 kidney transplants performed in our center from 1983 to 2014, eight patients (0,45%) developed a malignancy in the kidney allograft. Of these, 5 (62,5%) were stage 1 (tumor size of < 7 cm) and underwent NSS. The mean follow-up was 31.4 months (range 13–77 months). Table 1 shows the main surgical data of the patients and the characteristics of the tumors. All five surgical procedures were uneventful, and no postoperative complications were registered after surgery. Surgical margins were found to be negative in all cases. Mean creatinine levels before surgery and 1 month after surgery were 1.28 mg/dl and 1.32 mg/dl, respectively (P = NS). Graft and patient survivals were 100% after 1 year of follow-up. No cases of tumor recurrence were diagnosed during the follow-up in any of the five patients. Patient 1 was noncompliant and suspended the immunosuppressive therapy, with consequent progressive chronic renal failure, and died 31 months after surgery. Patient 2 had an intestinal occlusion caused by a strangulated incisional hernia and died 13 months after NSS. The other three patients were alive, with a normal renal function, at the end of follow-up. Traditionally, radical transplantectomy associated with the withdrawal of immunosuppression has been the treatment of choice for these tumors. Nevertheless, since the early 1990s, several studies have reported successful, isolated, cases of partial nephrectomy of the kidney allograft, with consequent graft salvage and avoidance of return to dialysis. To date, the literature on this topic is limited to around 30 case reports and only one, recent, multicenter study by a French group [3–7]. Consonant with our five successful cases, all the published studies have reported favorable results with partial nephrectomies, supporting the feasibility and the effectiveness of this surgical technique for kidney allograft tumors.