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Discusses the role of tubular cells in the progression of renal damage. Progressive development of sclerosis in remnant globeruli after initial renal damage caused by hyperfiltration; Renal tubular epithelial cells; Conclusion that renal injury is characterized by a decreased neural mass, glomerular hyperfiltration and proteinuria which permanently stimulates tubular cells in the production of cytokines, growth factors and chemokines.

Objective/Background. To describe an uncommon, life-threatening condition such as angiosarcoma of a fistula for hemodialysis occurring in a transplant recipient affected by Lowe's syndrome. Summary. We present the case of a 56-year-old male kidney transplant recipient affected by Lowe's syndrome, also known as oculocerebrorenal syndrome, a rare X-linked disorder characterized by congenital cataracts, hypotonia, intellectual disability, and Fanconi-like renal tubular dysfunction, who was diagnosed with angiosarcoma of a functioning arteriovenous fistula for hemodialysis. Conclusion. Angiosarcoma is a rare soft tissue tumor, and only 22 cases of angiosarcoma of arteriovenous fistulae were described so far; although a correlation between Lowe's syndrome and a higher risk of tumor compared to the general population has not been described so far, the mechanisms of disease causation could be an interesting starting point for future studies on a possible connection between the two events. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background The single-nucleotide polymorphisms (SNPs) of the Multidrug resistance 1 (MDR1) gene have been associated with changes in the pharmacokinetics of cyclosporine (CsA) and tacrolimus (FK506). Our aim was investigate the influence of MDR1 SNPs on long-term graft survival in a population of kidney transplant recipients. Methods We retrospectively analyzed 154 patients; they were genotyped for the SNPs C1236T, G2677T/A, and C3435T and evaluated for the influence of those 3 SNPs on CsA or FK506 pharmacokinetics and on long-term graft survival. Results Thirty-one patients were wild-type for C1236T, G2677T/A, and C3435T polymorphisms (group A), 76 patients had ≥1 heterozygous mutations (group B), and 47 patients had ≥1 homozygous mutations (group C). CsA-receiving patients in group C needed a significantly higher oral dose than patients in groups B and A ( P = .02). No differences in FK506 trough level nor in oral dose taken were observed in FK506-receiving patients. Kaplan-Meier analysis did not show survival differences in the 3 groups, and Cox proportional hazards model confirmed that the MDR1 SNPs did not represent a risk for graft loss. Conclusions Pretransplantation determination of MDR1 SNPs may be helpful to optimize the starting dose of CsA but can not predict long-term graft survival. [ABSTRACT FROM AUTHOR]

Abstract: 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. [Copyright &y& Elsevier]

Abstract: 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. [Copyright &y& Elsevier]

Abstract: 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. [Copyright &y& Elsevier]

Abstract: 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. [Copyright &y& Elsevier]

Abstract: 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. [Copyright &y& Elsevier]

Abstract: Oxidative stress and vascular calcifications are emergent risk factors for the accelerated atherosclerosis process featuring chronic kidney disease (CKD). Vascular calcification is an active process similar to bone modelling, where BMP-2 may play a pathogenic role. Aim of our study was to investigate the link between oxidative stress, BMP-2 protein expression and vascular disease in CKD. We enrolled 85 CKD patients (K-DOQI stage II or higher) and 41 healthy individuals. 8-Oxo-7,8-dihydro-2′-deoxyguanosine (8-OHdG) was used as a marker of oxidative stress. Brachial-ankle pulse wave velocity (baPWV) was used as a measure of arterial stiffness. BMP-2 serum levels were significantly higher in CKD patients than in controls (p <0.0001). Serum 8-OHdG levels were significantly higher in CKD patients compared to controls (p <0.05). BMP-2 serum levels were inversely associated with eGFR (r =−0.3; p =0.01) and directly correlated with 8-OHdG serum concentrations (r =−0.3; p =0.03). Arterial stiffness was inversely correlated with eGFR (r =−0.4; p =0.001) and directly correlated with BMP-2 (r =0.3; p =0.03), 8-OHdG (r =0.4, p =0.02) and phosphorus serum levels (r =0.3; p =0.007). In a multiple regression model, phosphorus and BMP-2 were independently correlated with baPWV. In vitro exposure to H2O2 induced a time and dose-dependent increase in BMP-2 expression in an immortalized endothelial cell line. Moreover, H2O2 pre-incubation of cultured vascular smooth muscle cell enhanced the BMP-2-induced up-regulation of ALPL, an osteoblastic phenotype marker. Our data suggest that in CKD BMP-2 may represent the molecular link between oxidative stress and arterial stiffness due to vascular calcification. [ABSTRACT FROM AUTHOR]

Abstract: 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. [Copyright &y& Elsevier]

Although notable progress has been made in the therapeutic management of patients with chronic kidney disease in both conservative and renal replacement treatments (dialysis and transplantation), the occurrence of medication-related problems (lack of efficacy, adverse drug reactions) still represents a key clinical issue. Recent evidence suggests that adverse drug reactions are major causes of death and hospital admission in Europe and the United States. The reasons for these conditions are represented by environmental/non-genetic and genetic factors responsible for the great inter-patient variability in drugs metabolism, disposition and therapeutic targets. Over the years several genetic settings have been linked, using pharmacogenetic approaches, to the effects and toxicity of many agents used in clinical nephrology. However, these strategies, analysing single gene or candidate pathways, do not represent the gold standard, being the overall pharmacological effects of medications and not typically monogenic traits. Therefore, to identify multi-genetic influence on drug response, researchers and clinicians from different fields of medicine and pharmacology have started to perform pharmacogenomic studies employing innovative whole genomic high-throughput technologies. However, to date, only few pharmacogenomics reports have been published in nephrology underlying the need to enhance the number of projects and to increase the research budget for this important research field. In the future we would expect that, applying the knowledge about an individual's inherited response to drugs, nephrologists will be able to prescribe medications based on each person's genetic make-up, to monitor carefully the efficacy/toxicity of a given drug and to modify the dosage or number of medications to obtain predefined clinical outcomes. [ABSTRACT FROM AUTHOR]

The production of cytokines by resident and non-resident renal cells during immunoglobulin A nephropathy (IgAN) plays a key role in the progression of renal damage. The aim of this study was to determine if measurements of urinary epidermal growth factor (EGF) and monocyte chemotactic peptide-1 (MCP-1), at the time of renal biopsy, were a predictor of end-stage renal disease (ESRD) in a cohort of 132 patients with biopsy-proven IgAN. Outcome measures were a doubling of the baseline serum creatinine (sCr) and/or ESRD. Patients with ratios of EGF/MCP-1 in the lowest tertile had a significant decline in renal survival, while patients in the highest tertile maintained 100% renal survival at 48 and 84 months of follow-up. Multivariate Cox's regression analysis showed that the urine EGF/MCP-1 ratio was an independent prognostic factor and indirectly correlated with the combined outcome. The predictive value was also measured by the area under the receiver operating characteristic curve (ROC). The area of the EGF/MCP-1 ratio was significantly higher than that of EGF or MCP-1 alone, histologic grade, creatinine clearance, or proteinuria. Our study suggests that the urinary EGF/MCP-1 ratio may be used as a prognostic marker of ESRD for patients with IgAN.Kidney International (2008) 73, 327–333; doi:10.1038/sj.ki.5002621; published online 17 October 2007 [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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.Kidney International (2007) 72, 994–1003; doi:10.1038/sj.ki.5002468; published online 8 August 2007 [ABSTRACT FROM AUTHOR]

The role of hepatits C virus (HCV) in the production of renal injury has been extensively investigated, though with conflicting results. Laser capture microdissection (LCM) was performed to isolate and collect glomeruli and tubules from 20 consecutive chronically HCV-infected patients, namely 6 with membranoproliferative glomerulonephritis, 4 with membranous glomerulonephritis, 7 with focal segmental glomerulosclerosis and 3 with IgA-nephropathy. RNA for amplification of specific viral sequences was provided by terminal continuation methodology and compared with the expression profile of HCV core protein. For each case two glomeruli and two tubular structures were microdissected and processed. HCV RNA sequences were demonstrated in 26 (65%) of 40 glomeruli, but in only 4 (10%) of the tubules (P < 0·05). HCV core protein was concomitant with viral sequences in the glomeruli and present in 31 of the 40 tubules. HCV RNA and/or HCV core protein was found in all four disease types. The immunohistochemical picture of HCV core protein was compared with the LCM-based immunoassays of the adjacent tissue sections. Immune deposits were detected in 7 (44%) of 16 biopsy samples shown to be positive by extraction methods. The present study indicates that LCM is a reliable method for measuring both HCV RNA genomic sequences and HCV core protein in kidney functional structures from chronically HCV-infected patients with different glomerulopathies and provides a useful baseline estimate to define the role of HCV in the production of renal injury. The different distribution of HCV RNA and HCV-related proteins may reflect a peculiar‘affinity’ of kidney microenvironments for HCV and point to distinct pathways of HCV-related damage in glomeruli and tubules. [ABSTRACT FROM AUTHOR]

Background: Obstructive nephropathy is characterized at the histologic level by tubular atrophy and interstitial monocyte infiltration. The molecular mechanisms underlying these histologic changes are still poorly defined. Epidermal growth factor (EGF) produced by tubular cells seems to play a pivotal role in the modulation of tubular cell growth, while monocyte chemotactic peptide-1 (MCP-1) is a powerful and specific chemotactic and activating factor for monocytes. Methods: Twenty-four patients with congenital ureteropelvic junction obstruction [UPJO; 10 with recurrent urinary tract infection (UTI) and 10 with no UTI] and 15 healthy children were studied. Diagnosis was made by renal ultrasound, intravenous pielography, and MAG3 scan. Urinary samples were collected before and after surgery. In 10 patients, urine was also collected directly from the affected pelvis at the time of surgery. Urinary EGF and MCP-1 levels were measured by enzyme-linked immunosorbent assay. MCP-1 and EGF gene expression were evaluated by in situ hybridization in 15 biopsies from congenital UPJO and in 10 normal kidneys. Results: In normal kidneys, there was a high expression of EGF mRNA, whereas MCP-1 mRNA was undetectable. MCP-1 gene expression was strikingly increased at the tubulointerstitial level in UPJO biopsies compared with controls and was directly correlated with the extent of monocyte infiltration. In addition, UPJO kidney sections showed a marked reduction in EGF gene expression that was directly correlated with the degree of tubular damage. EGF urine concentration was significantly reduced in UPJO when compared with control and directly correlated with its renal gene expression. On the other hand, the MCP-1 urine concentration was strikingly increased in UPJO patients. It is noteworthy that a significant and inverse correlation was observed between the MCP-1 concentration in the urine collected from the obstructed pelvis and the MAG3 clearance of the obstructed kidney (r = -0.76). The presence of recurrent UTI was associated with a significantly higher MCP-1 excretion and a slight reduction in EGF urine concentration. The surgical correction of UPJO was followed by an improvement of renal function together with a significant reduction in MCP-1 excretion and a marked increase in EGF urine concentrations. Interestingly, EGF urine concentration measured before surgery was significantly correlated with the difference between the MAG3 clearance of the obstructed kidney before and after surgery. Conclusions: MCP-1 and EGF seem to be involved in the pathogenesis of tubulointerstitial damage in congenital obstructive nephropathy, and their urine excretion may represent a powerful prognostic marker in this form of renal disease. [ABSTRACT FROM AUTHOR]

Abstract: The placement of a double J stent to protect a uretero-vesical anastomosis in a kidney transplant is a widespread procedure performed to reduce the incidence of fistula and stenosis at the anastomosis. However, the presence of a double J stent may cause vesicoureteral reflux (VUR), predisposing one to urinary tract infections (UTIs), which may be a significant source of morbidity for the graft. We evaluated whether a ureteral stent incorporating an antireflux device can reduce the incidence of ureteral reflux and UTIs. From January to December 2003, 44 kidney transplant recipients were randomized to receive a 14-cm 4.8-F double J stent with (group A) or without an anti-reflux device (group B). Primary end points were the reduction of the incidence of VUR and of UTIs. The secondary end point was the graft function, on the basis of mean serum creatinine level at 3, 6, and 12 months. We failed to observe statistically significant differences in terms of either the incidence of VUR and UTIs, or the short-term outcomes of the grafts. We concluded that the anti-reflux device does not have an impact on the incidence of stent-related side effects. [Copyright &y& Elsevier]

This study was aimed to evaluate the clinical benefit of C2 monitoring in 191 stable renal transplant patients previously monitored by C0. All patients had been transplanted for at least 1 year and received cyclosporine (CsA)-based immunosuppression since the start. At the inceptions C0 levels were significantly correlated with C2 values (P < .0001). Patients with starting C2 levels >1000 ng/mL showed significantly higher levels of serum creatinine (sCr) both at inception (1.66 ± 0.50 vs 1.44 ± 0.41 mg/dL; P = .0021) and at the end of a 2-year follow-up (1.84 ± 0.80 vs 1.46 ± 0.51 mg/dL; P = .005). C2 monitoring revealed that a high percentage of patients were overexposed to CsA, mainly in the subgroup with most recent renal engraftments (12 to 24 months). The switch to C2 monitoring was associated with a slower deterioration of graft function (P = .02). Further, the mean values of C2 over a 2-year follow-up were inversely correlated with sCr at the end of follow-up (P = .0005). Finally, patients with mean threshold C2 levels above 720 ng/mL, roughly corresponding to the median value of C2, showed significantly lower levels of sCr at the end of follow-up (P = .0004). In conclusion, C2 monitoring of maintenance renal transplant patients allows one to identify a significant percentage of overexposed subjects, possibly limiting the rate of progression of chronic graft dysfunction. Target range values between 700 and 900 ng/mL appear to be associated with better long-term kidney graft function. [Copyright &y& Elsevier]