Asymptomatic bacteriuria in candidates for active treatment of renal stones: results from an international multicentric study on more than 2600 patients.

The occurrence of asymptomatic bacteriuria concomitant to urolithiasis is an issue for patients undergoing renal stone treatment. Disposing of a preoperative urine culture is essential to reduce the risk of septic events. The endpoint of the study is to report which characteristics of candidates for renal stone treatment are frequently associated with positive urine culture. 2605 patients were retrospectively enrolled from 14 centers; inclusion criteria were age > 18 and presence of a single renal stone 1-2 cm in size. The variables collected included age, gender, previous renal surgery, comorbidities, skin-to-stone distance, stone size, location, density, presence of hydronephrosis. After a descriptive analysis, the association between continuous and categorical variables and the presence of positive urine culture was assessed using a logistic regression model. Overall, 240/2605 patients (9%) had preoperative bacteriuria. Positive urine culture was more frequent in females, patients with previous renal interventions, chronic kidney disease, congenital anomalies, larger stones, increased density. Multivariate analysis demonstrated that previous renal interventions (OR 2.6; 95% CI 1.9-3.4; p < 0.001), renal-related comorbidities (OR 1.31; 95% CI 1.19-1.4; p < 0.001), higher stone size (OR 1.06; 95% CI 1.02-1.1; p = 0.01) and density (OR 1.00; 95% CI 1.0-1.00; p = 0.02) were associated with bacteriuria; male gender and lower caliceal location were inversely related to it. Beyond expected risk factors, such as female gender, other parameters are seemingly favoring the presence of positive urine culture. The awareness of variables associated with bacteriuria allows to assess which individuals are at increased risk of presenting bacteriuria and reduce the rate of septic complications.

Body Composition Change, Unhealthy Lifestyles and Steroid Treatment as Predictor of Metabolic Risk in Non-Hodgkin's Lymphoma Survivors.

Unhealthy lifestyle, as sedentary, unbalanced diet, smoking, and body composition change are often observed in non-Hodgkin's lymphoma (NHL) survivors, and could be determinant for the onset of cancer treatment-induced metabolic syndrome (CTIMetS), including abdominal obesity, sarcopenia, and insulin resistance. The aim of this study was to assess whether changes in body composition, unhealthy lifestyles and types of anti-cancer treatment could increase the risk of metabolic syndrome (MetSyn) and sarcopenia in long-term NHL survivors. We enrolled 60 consecutive NHL patients in continuous remission for at least 3 years. Nutritional status was assessed by anthropometry-plicometry, and a questionnaire concerning lifestyles and eating habits was administered. More than 60% of survivors exhibited weight gain and a change in body composition, with an increased risk of MetSyn. Univariate analysis showed a significantly higher risk of metabolic disorder in patients treated with steroids, and in patients with unhealthy lifestyles. These data suggest that a nutritional intervention, associated with adequate physical activity and a healthier lifestyle, should be indicated early during the follow-up of lymphoma patients, in order to decrease the risk of MetSyn's onset and correlated diseases in the long term.

Complement Modulation of Anti-Aging Factor Klotho in Ischemia/Reperfusion Injury and Delayed Graft Function.

Klotho is an anti-aging factor mainly produced by renal tubular epithelial cells (TEC) with pleiotropic functions. Klotho is down-regulated in acute kidney injury in native kidney; however, the modulation of Klotho in kidney transplantation has not been investigated. In a swine model of ischemia/reperfusion injury (IRI), we observed a remarkable reduction of renal Klotho by 24 h from IRI. Complement inhibition by C1-inhibitor preserved Klotho expression in vivo by abrogating nuclear factor kappa B (NF-kB) signaling. In accordance, complement anaphylotoxin C5a led to a significant down-regulation of Klotho in TEC in vitro that was NF-kB mediated. Analysis of Klotho in kidneys from cadaveric donors demonstrated a significant expression of Klotho in pre-implantation biopsies; however, patients affected by delayed graft function (DGF) showed a profound down-regulation of Klotho compared with patients with early graft function. Quantification of serum Klotho after 2 years from transplantation demonstrated significant lower levels in DGF patients. Our data demonstrated that complement might be pivotal in the down-regulation of Klotho in IRI leading to a permanent deficiency after years from transplantation. Considering the anti-senescence and anti-fibrotic effects of Klotho at renal levels, we hypothesize that this acquired deficiency of Klotho might contribute to DGF-associated chronic allograft dysfunction.

"Real world" outcome of lenalidomide plus dexamethasone in the setting of recurrent and refractory multiple myeloma: extended follow-up of a retrospective multicenter study by the "rete ematologica pugliese".

This current retrospective multicenter analysis represents, to our knowledge, the first Italian study evaluating the efficacy and toxicity profile of "lenalidomide plus dexamethasone" as salvage therapy in patients with recurrent-refractory MM in the real life contest. Our study included patients who are usually excluded from clinical trials because of unfavorable baseline characteristics. Median OS was significantly longer in patients receiving "lenalidomide plus dexamethasone" for more than 12 months compared with those who had received "lenalidomide plus dexamethasone" for a shorter interval (P<0.0001). Median OS was not affected by best response achieved (P 0.4) and age (P 0.3). Quality of response did not correlate with number of previous lines of therapy (P 0.77) and age. Higher ORRs were recorded in the patients group with relapsed MM compared to those with refractory disease, but this difference was not statistically significant (P 0.38).

Complement-dependent NADPH oxidase enzyme activation in renal ischemia/reperfusion injury.

NADPH oxidase plays a central role in mediating oxidative stress during heart, liver, and lung ischemia/reperfusion injury, but limited information is available about NADPH oxidase in renal ischemia/reperfusion injury. Our aim was to investigate the activation of NADPH oxidase in a swine model of renal ischemia/reperfusion damage. We induced renal ischemia/reperfusion in 10 pigs, treating 5 of them with human recombinant C1 inhibitor, and we collected kidney biopsies before ischemia and 15, 30, and 60 min after reperfusion. Ischemia/reperfusion induced a significant increase in NADPH oxidase 4 (NOX-4) expression at the tubular level, an upregulation of NOX-2 expression in infiltrating monocytes and myeloid dendritic cells, and 8-oxo-7,8-dihydro-2'-deoxyguanosine synthesis along with a marked upregulation of NADPH-dependent superoxide generation. This burden of oxidative stress was associated with an increase in tubular and interstitial expression of the myofibroblast marker α-smooth muscle actin (α-SMA). Interestingly, NOX-4 and NOX-2 expression and the overall NADPH oxidase activity as well as α-SMA expression and 8-oxo-7,8-dihydro-2'-deoxyguanosine synthesis were strongly reduced in C1-inhibitor-treated animals. In vitro, when we incubated tubular cells with the anaphylotoxin C3a, we observed an enhanced NADPH oxidase activity and α-SMA protein expression, which were both abolished by NOX-4 silencing. In conclusion, our findings suggest that NADPH oxidase is activated during ischemia/reperfusion in a complement-dependent manner and may play a potential role in the pathogenesis of progressive renal damage in this setting.

Effects of ischemia-reperfusion injury in kidney transplantation: risk factors and early and long-term outcomes in a single center.

INTRODUCTION: Ischemia-reperfusion injury (IRI) causes a high rate of delayed graft function (DGF), the most frequent complication in the immediate postoperative period after cadaveric donor kidney transplantation. Herein we evaluated the impact of donor and recipient characteristics on DGF development in terms of the incidence of acute rejection episodes, hospital stay, renal function, and long-term graft and patient survivals. MATERIALS AND METHODS: Between February 1998 and July 2011, 761 patients underwent cadaveric donor kidney transplantations. DGF was defined as the need for dialysis in the first week. Patients were subdivided according to initial graft function as immediate graft function (IGF) or DGF. RESULTS: DGF observed in 241 patients (31.6%) was associated independently with expanded criteria donors, extended cold ischemia time, Karpinsky histological score, and prior dialysis duration both univariate and multivariate analysis. The incidence of acute rejection episodes was 18.1% among the DGF group versus 1.3% in the IGF group (P < .01). DGF significantly reduced both graft and patient survivals at 6, 12, 36, and 60 months. CONCLUSION: DGF was responsible for a longer hospital stay, worse early and long-term renal function, a higher incidence of acute rejection episodes as well as reduced graft and patient survivals.

Advanced age is not an exclusion criterion for kidney transplantation.

INTRODUCTION: Renal transplantation in patients older than 60 years has long been regarded with skepticism owing to the increased risk of complications although, as compared with dialysis treatment, a graft seems to improve not only the quality of life but also long-term patient survival. This study sought to analyze the impact of recipient age older than 60 years on patient and graft outcomes. MATERIALS AND METHODS: We retrospectively investigated the outcomes of 761 kidney transplant recipients from cadaveric donors performed between February 1998 and July 2011. While 69 subjects were at least 60 years of age (group A), 692 were younger than 60 years (group B) at the time of transplantation. RESULT: Mean follow-up was 60.1 ± 38.5 months. Delayed graft function (DGF) requiring dialysis was observed in 36 group A (52.1%) and 205 group B (29.6%) subjects (P = .001). However, there were also significant differences between group A and group B in terms of mean donor age (60.3 vs 44.6 years; P < .001) and mean donor estimated creatinine clearance (57.8 vs 83.4 mL/min; P < .001). There were no significant differences in death-censored graft survival between the two groups, but elderly patients experienced worse survival (P = .0005). The most common causes of patient death were myocardial infarction, other cardiovascular complications, and tumors. CONCLUSION: Kidney transplantation is a good option for elderly recipients with end-stage renal disease, providing long graft survival and a good quality of life, although these patients are more likely to develop cancer or cardiovascular disease. Our findings suggested that older patients should not be excluded a priori from transplantation, but meticulous screening for cancer and heart disease should be always be performed to improve outcomes.

Middle and long-term outcomes of dual kidney transplant: a multicenter experience.

INTRODUCTION: Dual kidney transplantation (DKTx) to reduce the disparity between demand and supply of organs was evaluated in two Italian centers (Bari and Novara). MATERIALS AND METHODS: Between October 2000 and October 2011, we performed 97 DKT (26 ipsilateral/71 bilateral) following routine biopsy of all kidneys obtained from expanded criteria donors by Remuzzi-Karpinsky scores. The reference group was 379 single grafts from donors older than 60 years single kidney transplantation ([SKT] × > 60). RESULTS: Good postoperative renal function was observed in 56 DKTx (57.7%); whereas acute tubular necrosis requiring dialysis was observed in 41 (42.3%) patients. After a mean follow-up of 60 months, DKTx graft survivals were 96%, 93%, and 90% and patient survivals, 96%, 91%, and 91% at 1, 3, and 5 years, respectively. Complications in expanded criteria donor kidney transplantations included a high rate of cytomegalovirus (CMV) disease especially dual kidney cases. DKTx represented the only independent risk factor for CMV disease upon multivariate analysis (odds ratio [OR] 2.33, 95% confidence interval [CI] 1.28-4.2; P = .006). We did not observe any significant difference in graft or patient survival between DKTx and SKTx > 60 years. CONCLUSIONS: We observed good outcomes up to 5 years after transplantation in terms of graft and patient survival despite the use of inferior grafts. Comparing DKTx and SKT > 60, we noted that the mean Karpinski score for SKTx was significantly better than DKTx, although patient and graft survivals were similar. This trend confirms that the use of a biopsy to allocate expanded criteria donor kidneys may be too protective; therefore, the criteria to select DKTx require further refinement.

Allograft nephrectomy: what is the best surgical technique?

BACKGROUND: The objective of this study was to evaluate differences in outcomes of allograft nephrectomies performed by extracapsular versus intracapsular techniques. METHODS: From 1993 to 2010, we performed 89 allograft nephrectomies, including 57 by extracapsular techniques and 32 by intracapsular, chosen according to feasibility at the beginning of the surgery. Fisher exact test and logistic regression were used for statistical analysis. Survival estimates after allograft nephrectomy were calculated according to the Kaplan-Meier method. RESULTS: After a mean graft survival of 49.7 months, the indications for transplant nephrectomy were chronic rejection (39.3%), acute rejection (22.5%), infection/sepsis (19.1%), gross hematuria (6.7%), renal vein thrombosis (6.7%), renal artery thrombosis (3.4%), and graft rupture (2.3%). Mean operative time, blood loss, transfusions, and complications were similar between the extracapsular and intracapsular groups. The only difference in surgical aspects between the 2 groups was the mean hospital stay, which was longer for the extracapsular group (13.8 vs 7.6 days; P = .01), a result that was confirmed by multivariate analysis (odds ratio, 1.05; 95% confidence interval, 1.0-1.1; P = .03). CONCLUSIONS: Our experience showed no significant advantages in favor of the intracapsular technique except for a shorter length of hospital stay than after the extracapsular procedure.

Four proteins governing overangiogenic endothelial cell phenotype in patients with multiple myeloma are plausible therapeutic targets.

Bone marrow (BM) angiogenesis has an important role in the initiation and progression of multiple myeloma (MM). We looked at novel mechanisms of vessel formation in patients with MM through a comparative proteomic analysis between BM endothelial cells (ECs) of patients with active MM (MMECs) and ECs of patients with monoclonal gammopathy of undetermined significance (MGECs) and of subjects with benign anemia (normal ECs). Four proteins were found overexpressed in MMECs: filamin A, vimentin, α-crystallin B and 14-3-3ζ/δ protein, not yet linked to overangiogenic phenotype. These proteins gave a typical distribution in the BM of MM patients and in MMECs versus MGECs, plausibly according to a different functional state. Their expression was enhanced by vascular endothelial growth factor, fibroblast growth factor 2, hepatocyte growth factor and MM plasma cell conditioned medium in step with enhancement of MMEC angiogenesis. Their silencing RNA knockdown affected critical MMEC angiogenesis-related functions, such as spreading, migration and tubular morphogenesis. A gradual stabilization of 14-3-3ζ/δ protein was observed, with transition from normal ECs to MGECs and MMECs that may be a critical step for the angiogenic switch in MMECs and maintenance of the cell overangiogenic phenotype. These proteins were substantially impacted by anti-MM drugs, such as bortezomib, lenalidomide and panobinostat. Results suggest that these four proteins could be new targets for the antiangiogenic management of MM patients.

IL-17 expression by tubular epithelial cells in renal transplant recipients with acute antibody-mediated rejection.

Acute rejection is still a common complication of kidney transplantation. IL-17 is known to be associated with allograft rejection but the cellular source and the role of this cytokine remains unclear. We investigated IL-17 graft expression in renal transplant recipients with acute antibody-mediated rejection (ABMR), acute T-cell-mediated rejection (TCMR), interstitial fibrosis and tubular atrophy (IFTA) and acute tubular damage due to calcineurin-inhibitor toxicity (CNI). In acute ABMR, tubular IL-17 protein expression was significantly increased compared to TCMR, where most of the IL-17⁺ cells were CD4⁺ graft infiltrating lymphocytes, IFTA and CNI control groups. The tubular expression of IL-17 in acute ABMR colocalized with JAK2 phosphorylation and peritubular capillaries C4d deposition. In addition, IL-17 tubular expression was directly and significantly correlated with the extension of C4d deposits. In cultured proximal tubular cells, C3a induced IL-17 gene and protein expression along with an increased in JAK2 phosphorylation. The inhibition of JAK2 abolished C3a-induced IL-17 expression. The use of steroids and monoclonal antibodies reduced IL-17 expression, JAK2 phosphorylation and C4d deposition in acute ABMR patients. Our data suggest that tubular cells represent a significant source of IL-17 in ABMR and this event might be mediated by the complement system activation featuring this condition.

Rapamycin-induced hypophosphatemia and insulin resistance are associated with mTORC2 activation and Klotho expression.

Rapamycin, an immunosuppressive drug used to prevent rejection after kidney transplantation, influences phosphate homeostasis, induces insulin resistance and has been shown to prolong lifespan in animal models. Because Klotho is an aging-suppressor gene controlling phosphate metabolism and insulin sensitivity, we investigated the influence of rapamycin on Klotho expression. A total of 100 kidney transplant recipients, 50 chronically treated with rapamycin and 50 with calcineurin inhibitors, were enrolled; 20 healthy subjects were employed as control. In the rapamycin group, serum phosphate was lower than in the CNI group with an increase in phosphate excretion and a reduction in its reabsorption. In addition, rapamycin increased insulin resistance as shown by HOMA index. Rapamycin treatment of an immortalized proximal tubular cell line induced the expression of Klotho, the phosphorylation of AKT in Ser473, downstream target of mTORC2 and the expression of RICTOR, mTORC2 main component. AKT inhibition reduced the rapamycin-induced expression of Klotho. In vivo rapamycin treatment induced higher degree of RICTOR and AKT Ser(473) expression directly correlating with long-term rapamycin exposure, FE(PO4) and HOMA index. In conclusion, our data would suggest that rapamycin may influence phosphate homeostasis and insulin resistance modulating Klotho expression through mTORC2 activation.

Obesity in kidney transplantation affects renal function but not graft and patient survival.

INTRODUCTION: The number of overweight and obese patients undergoing renal transplantation has increased dramatically over the past two decades. Studies on graft survival and posttransplantation complications have often yielded conflicting results. Some authors have reported similar results for graft and patient survivals between obese and normal weight patients, but with a marginally increased rate of postoperative complications. In contrast, other reports note higher percentage of graft losses as well as increased mortality. In our study, we analyzed early- and long-term outcomes among obese versus nonobese kidney transplant recipients. PATIENTS AND METHODS: Between January 2000 and December 2008, we performed 563 cadaveric kidney transplantations. Recipients were classified in 1 of 5 groups based on their body mass index (BMI) at the time of transplantation: group A (n = 68; BMI < 18.5); group B (n = 310; 18.6 < BMI < 24.9); group C (n = 143; 25 < BMI < 29.9); group D (n = 32; 30 < BMI < 34.9); and group E (n = 10; BMI ≥ 35). The comparative analysis included patient and graft survivals, postoperative complications, onset of delayed graft function (DGF), acute rejection episodes, hospital stay, and serum creatinine values in the first 3 years posttransplantation. RESULTS: At a mean follow-up of 53 months (range, 3-112 months), DGF was observed in 20 patients in group A (29.4%), 82 in group B (26.4%), 43 in group C (30%), 16 in group D (50%), and 4 in group E (40%). Nevertheless, obese patients (groups D and E) showed higher mean serum creatinine values and worse renal function at 6 months (P = .001), 1 year (P < .001), and 3 years (P = .001). Moreover, they were at increased risk of an acute rejection episode (P = .01) and more susceptible to cardiovascular and metabolic complications (P = .01). Morbidly obese patients displayed a higher incidence of postsurgical complications (P = .002). There were no differences in the incidences of chronic allograft nephropathy (CAN) or infectious complications. Despite the differences in morbidity among the 5 groups, we failed to observe significant differences in patient or graft survivals at 6, 12, 36, or 60 months. CONCLUSION: Our findings suggested that obese patients should not be discriminated against simply based on the BMI. At our center, obese (BMI >35) transplantation candidates undergo a thorough cardiac evaluation, as well as pulmonary, endocrine, and nutritional counseling seeking to minimize medical and surgical complications and improve survival and quality of life.

Extended criteria donor kidney transplantation: comparative outcome analysis between single versus double kidney transplantation at 5 years.

INTRODUCTION: Dual kidney transplantation (DKT), using extended criteria donor (ECD) grafts not suitable for single kidney transplantation (SKT), has been suggested to expand the kidney donor pool. Herein, we reviewed the long-term outcomes of DKT to assess its results versus a control group of 179 ECD SKTs. The allocation policy was based on a Remuzzi score obtained from a pretransplant biopsy. MATERIALS AND METHODS: We analyzed SKT in 179 (31.8%) and DKT in 41 (7.3%) of 563 cadaveric transplants from 2000 to 2008. Patients with DKT versus SKT showed mean recipient ages of 54 versus 51 years. We performed 17 ipsilateral and 24 bilateral DKT. The mean score was 2.78 for SKT and 4.3/4.6 for DKT. RESULTS: Delayed graft function requiring dialysis occurred in 23 (56.1%) DKT and 70 (39.1%) SKT recipients. Primary nonfunction was observed in 1 (2.4%) DKT and 7 (3.9%) SKT recipients respectively. One DKT patient underwent monolateral transplantectomy. In the DKT versus SKT group, patient survivals were 92% versus 95%, 89% versus 93%, and 89 versus 91% at 12, 36, and 60 months, respectively (P = .3). Graft survivals were 100% versus 94%, 95% versus 90%, and 89% versus 78% at 12, 36, and 60 months, respectively (P < .001). We observed a lower incidence of chronic allograft nephropathy (P = .01) and a higher incidence of surgical adverse events (P = .04) in DKT. CONCLUSIONS: ECD graft survival using DKT provided better results compared with SKT, despite the use of organs from higher-risk donors. At 5 years follow-up, DKT was a safe strategy to face the organ shortage. To optimize the use of available kidneys, the criteria for DKT require further refinement and standardization. Preimplantation evaluation must maximize transplant success and protect recipients from receiving organs at increased risk of premature failure.

Optimization of analytical and pre-analytical conditions for MALDI-TOF-MS human urine protein profiles.

Protein analysis in biological fluids, such as urine, by means of mass spectrometry (MS) still suffers for insufficient standardization in protocols for sample collection, storage and preparation. In this work, the influence of these variables on healthy donors human urine protein profiling performed by matrix assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS) was studied. A screening of various urine sample pre-treatment procedures and different sample deposition approaches on the MALDI target was performed. The influence of urine samples storage time and temperature on spectral profiles was evaluated by means of principal component analysis (PCA). The whole optimized procedure was eventually applied to the MALDI-TOF-MS analysis of human urine samples taken from prostate cancer patients. The best results in terms of detected ions number and abundance in the MS spectra were obtained by using home-made microcolumns packed with hydrophilic-lipophilic balance (HLB) resin as sample pre-treatment method; this procedure was also less expensive and suitable for high throughput analyses. Afterwards, the spin coating approach for sample deposition on the MALDI target plate was optimized, obtaining homogenous and reproducible spots. Then, PCA indicated that low storage temperatures of acidified and centrifuged samples, together with short handling time, allowed to obtain reproducible profiles without artifacts contribution due to experimental conditions. Finally, interesting differences were found by comparing the MALDI-TOF-MS protein profiles of pooled urine samples of healthy donors and prostate cancer patients. The results showed that analytical and pre-analytical variables are crucial for the success of urine analysis, to obtain meaningful and reproducible data, even if the intra-patient variability is very difficult to avoid. It has been proven how pooled urine samples can be an interesting way to make easier the comparison between healthy and pathological samples and to individuate possible differences in the protein expression between the two sets of samples.

Penile prosthesis: what should we do about complications?

Even in the era of phoshodiesterase type 5 inhibitors, penile implants are considered the definitive solution for the treatment of organic erectile disfunction. The advent of new surgical tools and new infection-resistant materials has significantly reduced the risk of intra and post-operative complications and the need for revision surgery. Various companies have also improved their mechanical systems in order to reduce the risk of failures, and their products are now so good they may last lifelong. In this article, we evaluate the intraoperative and postoperative complications recorded in our experience and in literature reports, and make some suggestions as to how to prevent or correct them.

"Deviceless" hand-assisted laparoscopic donor nephrectomy.

Hand-assisted laparoscopic nephrectomy (HLN) in living donors is a minimally invasive surgical modality that uses classic laparoscopic techniques combined with the surgeon's hand as a support tool during renal dissection. We describe our experience with 14 donors undergoing HLN with a novel "deviceless" technique (DL-HLN). We used a midline or a paramedian incision. The first 10-mm trocar (camera) was inserted near the umbilicus and another 10-mm trocar placed under laparoscopic vision at the level of the anterior axillary line above the iliac crest. DL-HLN was performed in 14 patients (11 women and 3 men) of overall mean age of 40 years (range=33-60). Left nephrectomy was performed in all cases. Mean surgical time was 105 minutes (range=60-150). Estimated blood loss was 50 to 800 mL (mean=200 mL). Mean warm ischemia time was 3.5 minutes (range=2-11). Mean hospital stay was 4 days (range=3-6). In one case, uncontrollable hemorrhage developed due to a renal vein lesion at the level of the adrenal vein outlet, requiring conversion to open surgery. As to graft function, recipient serum creatinine on day 7 ranged from 0.9 to 2.6 mg/dL (mean=1.6). We used no device in our technique. The pneumoperitoneum was maintained by the sealing effect of the muscular fascia around the surgeon's wrist. Moreover, the kidney was removed through the hand port without an Endobag. Our modified HLN technique avoids the use of costly disposables and offers the advantages of a smaller incision.

Incidentally discovered yellowish lesions in a renal graft from a deceased donor.

The opening of Gerota's fascia, soon after harvesting the kidney, is a standard kidney donor procedure in Italy to exclude a renal cell carcinoma (RCC), a frequent finding in older donors. Herein we have reported our experience with the diagnosis and management of subcapsular yellow areas suggestive of RCC on the kidney surface during back-table procedures. From 2001 to 2006, 12/445 grafts showed a single yellowish subcapsular nodule during the back-table procedure which was excised for frozen section (FS) to rule out RCC. The affected donors were 7 males and 5 females of overall mean age of 60 years (range, 25-77 years). The mean nodule diameter was 0.75 cm (range, 0.3-1.2 cm), and all lesions were located in the upper renal pole. In 5 cases, a diagnosis of RCC could not be excluded by FS, and both kidneys were discarded. The final histology confirmed RCC in only 3 cases, and adrenal heterotopia (AH) in the other 2. In the remaining 7 cases, FS showed AH in 4, 1 angiomyolipoma, and 2 areas of infarction confirmed by histology. The adrenal foci consisted of clear cells and scattered cells with eosinophilic, granular cytoplasm and small round nuclei, some with small nucleoli. Immunostains for cytokeratins, CD10, and epithelial membrane antigen were negative, confirming the adrenal origin. AH is the most common pathological yellowish lesion in the upper kidney pole found incidentally during back-table preparation. A histological differential diagnosis with RCC at FS is difficult, relying on the distinction of normal corticoadrenal spongiocytes from Fuhrman grade 1 clear cancer cells. In Italy, for any renal mass suggestive of RCC, a graft discard is mandatory, even if several reports have described cases of renal transplantation performed after back-table excision of small unifocal tumors.

Ischemia-reperfusion injury-induced abnormal dendritic cell traffic in the transplanted kidney with delayed graft function.

Delayed graft function (DGF) in kidney transplantation is associated with an increased risk of acute rejection. Myeloid dendritic cells (DCs) are involved in graft rejection, whereas plasmacytoid DCs may play a role in inducing tolerance. We evaluated the presence and phenotype of the DCs in renal graft biopsies of 15 patients with DGF collected before and 7-15 days after transplantation. Biopsies taken from normal patients and from transplant recipients with acute calcineurin inhibitors (CNIs) nephrotoxicity served as a control group. Specific markers of myeloid, plasmacytoid, and mature DCs were imaged by confocal microscopy and immunohistochemistry. In normal kidneys and pre-transplant biopsies, sparse niches of myeloid and plasmacytoid cells were found but these were significantly increased with few mature cells during DGF. This same pattern was seen in acute rejection but with overall higher cell numbers. In CNI nephrotoxicity, myeloid cells were slightly increased but plasmacytoid cells were significantly higher than in DGF. Using a pig model, we found that a short period of warm ischemia followed by reperfusion led to myeloid cell infiltration of the kidney. Our data suggest that ischemia-reperfusion injury may cause an imbalance between intragraft myeloid and plasmacytoid DCs, which might be related to DGF and acute rejection.