Moderate and severe fetal pyelectasis: Correlation between prenatal aspects and postnatal outcome.

BACKGROUND: Renal pelvic dilatation (RPD) is a frequent finding in fetal ultrasound. The aim of the study is to correlate the prenatally detected moderate and severe pyelectasis with the postnatal outcome. METHODS: A retrospective analysis involving 90 cases of prenatally detected moderate and severe RPD referred to our prenatal diagnosis centre with 18 months of urological follow-up. Prenatal ultrasound was correlated with postnatal renal function, assessed by plasmatic creatinine and/or renal scintigraphy performed before surgery. RESULTS: Cases were divided between two groups according to postnatal management: group A including 35 newborns (38.9%) that needed surgical treatment and group B with 55 patients (61.1%) who were managed conservatively. The group A presented higher median RPD (18 mm, IQR 12-25 mm) compared to the group B (11 mm, IQR 10-14 mm). The most common anomaly detected within group A was pelvi-ureteric junction (PUI) obstruction (43%). Within group B 32 cases (58%) showed spontaneous resolution of hydronephrosis during postnatal follow up. In case of moderate pyelectasis the risk of postnatal surgery was 25% and raised to 60% for severe RPD. In our study, 29 newborns showed pathologic scintigraphies: 25 required surgery while 4 did not find indication for surgery due to ipsilateral renal function irreversible damage. 6 patients had high creatinine level (>0.6 mg/dl). 35 cases out of 90 (39%) developed monolateral irreversible renal function impairment. CONCLUSION: Moderate and severe RPD are often correlated with postnatal renal damage, therefore a close multidisciplinary follow-up is required. Prenatal scanning is highly predictive of postnatal outcome and can address properly the prenatal counseling.

The prognostic value of antenatal ultrasound in cases complicated by fetal ovarian cysts.

OBJECTIVE: Ovarian cysts are relatively common prenatal findings in female fetuses. The aim of this study is to evaluate the ability of antenatal ultrasound in predicting spontaneous regression or a need for surgery. DESIGN: All cases of fetal ovarian cysts treated in our Department between 2007 and 2016 were included. Patients underwent a sonographic monitoring in utero and after birth until spontaneous or surgical resolution. Subjects were divided into two groups according to their postnatal management. Receiver-operating characteristics (ROC) curves were used to test the predictive ability for postnatal surgery of the cyst's mean and maximum diameters; their optimal cut off points were also determined. RESULTS: 38 cases of antenatally-detected fetal ovarian cysts were included. 12/38 cases underwent surgery (Group A). 26/38 cases were resolved spontaneously (Group B). Cyst size of those which were surgically excised significantly differed from those that regressed spontaneously. ROC curve pointed to 45 mm and 47 mm as optimal cut off points for the mean and the maximum cystic diameters, respectively. CONCLUSIONS: Cyst size and echo-structure seemed good predictors for prognosis after birth. The optimal cut off points of the cysts mean and maximum diameters in predicting postnatal surgery have been identified as 45 mm and 47 mm, respectively.

Psychological Aspects and Psychopharmacologic Treatment in the Very Early Period After Kidney Transplantation: Role of a Multidisciplinary Approach.

BACKGROUND: In the context of kidney transplantation (KT), multidisciplinary interventions, including assessment and management of psychosocial aspects, are important to improve transplant's outcome. The aim of this study was to describe a multidisciplinary team approach to KT, with a specific focus on early detection and treatment of psychological distress and psychopathologic conditions in the early phase postsurgery. METHODS: The multidisciplinary team in kidney transplantation was implemented in January 2016. In this team approach, all transplant recipients are invited to 3 scheduled appointments for a multidisciplinary evaluation at 1, 3, and 6 months posttransplant, including a psychiatric interview, with the aim to assess the patient's adjustment after transplantation and provide support when necessary. RESULTS: This pilot study involved all 41 KT recipients consecutively referred for the first multidisciplinary appointment after transplantation. Five subjects (12% of the study sample) presented with a current psychiatric diagnosis. Psychopharmacologic treatment was confirmed or introduced for all these patients. Further psychological support was suggested to 4 other patients (10%). CONCLUSION: KT significantly improves patients' quality of life. However, the percentage of subjects receiving psychopharmacologic treatment and referred for further psychological and psychiatric support (22%) suggests the need for careful monitoring of psychosocial aspects over the long term.

Living Kidney Donation Is Recipient Age Sensitive and Has a High Rate of Donor Organ Disqualifications.

BACKGROUND: Living donor kidney transplantation (LDKT) is the best therapy for patients with chronic renal failure. Its advantages, compared with cadaveric transplantation, include the possibility of avoiding dialysis, the likelihood of best outcome, and donor pool expansion. Careful assessment of potential donors is important to minimize the risks and ensure success. However, the proportion of donors disqualified has been poorly investigated. The aim of this work is to describe our experience and present the main reasons for missed donation. METHODS: This was a single-center, retrospective study of all potential donors and recipients evaluated for LDKT between January 2008 and December 2017. RESULTS: During the period of study, 81 donor-recipient pairs were evaluated. Of these, 45.7% were disqualified and 37 LDKTs were carried out. LDKT was the first choice in 68% of cases and preemptive in 20%; 60% of transplants were among family members. Sex distribution revealed a prevalence of females in the donor group (69%) and males in the recipient group (70%). The mean living donor age was 53 ± 9.5 years; the mean recipient age was lower in recipients listed in the living transplant program than those listed for cadaver transplantation (45.8 ± 13.4 vs 54.2 ± 11.08; P < .0001). Reasons for denial included hypertension (18.9%), deceased donor transplant performed during the study period (16.2%), urologic pathology (13.5%), incompatibility (13.5%), withdrawal of consent by donor or recipient (13.5%), psychological unsuitability (8.1%), donor cancer (5.4%), and reduced renal clearance (2.7%). CONCLUSION: LDKT is considered an option especially for younger recipients. Of the potential kidney living donors, 45.7% were disqualified during the evaluation, with medical reasons being the primary cause.

Global Performance Status Score: A New Tool to Assess Physical Performance in Kidney Transplant Patients.

BACKGROUND: Information on physical performance in renal transplantation is limited because of the shortage of specifically designed evaluation instruments. Therefore, we elaborated and validated the Global Performance Status (GloPerSta) score to provide a new and comprehensive tool, exploring the different components of physical performance in kidney transplant patients. METHODS: We elaborated the GloPerSta score on the basis of the data obtained from a cross-sectional study, in which we evaluated the physical performance of a cohort of kidney transplant patients. The results of these analyses were weighted to describe the different contribution of any single test, via the generation of a structural equation model, resulting in the definition of the GloPerSta. Then, to internally validate this score, we studied its correlation with clinical parameters and quality of life (evaluated as KDQOL-SF, Kidney Disease Quality of Life-Short Form) in the same patient population. RESULTS: We enrolled 132 patients in whom the functional tests revealed a great heterogeneity. GloPerSta allowed the stratification of the patients in 3 different physical performance categories (low: score 0-11; medium: 12-22; high: 23-33). Internal validation showed that GloPerSta was directly and significantly correlated with the quality of life and allograft function, independent of the time from transplantation. CONCLUSIONS: The GloPerSta is a reliable tool to assess physical performance in a kidney transplant population. Its application might be of help in identifying patients needing intensive and personalized rehabilitation programs.

Robot-Assisted Harvesting of Kidneys for Transplantation and Global Complications for the Donor.

INTRODUCTION: Robot-assisted kidney harvesting from living donors is feasible and safe. We report the results of a mono-centric experience relative to 98 consecutive robotic nephrectomies with emphasis on global donor complications. MATERIALS AND METHODS: This is a retrospective cohort study. Donors underwent robot-assisted kidney harvesting. The preferred kidney was the left one even in the presence of vascular anomalies. In the first cases we used a robotic hand-assisted technique, then the totally robotic technique, and finally the modified totally robot-assisted technique. Postoperative complications were ranked according to the five-grade Clavien-Dindo classification. RESULTS: Between November 2009 and November 2016, 98 living donors underwent nephrectomy. We experienced 14 complications. The 3 intraoperative ones (3.06%) were 1 pneumothorax and 2 acute bleedings, 1 of them requiring transfusion. The 11 postoperative complications (11.22%) were as follows: 5 wound seromas, 1 rhabdomyolisis (Clavien I), 1 paretic ileum, 1 anemia requiring transfusion, 1 hypertensive crisis (Clavien II), and 2 chylus collections drained by interventional radiologists (Clavien III). Transfusion rate was 2.1%; conversions, reoperations, and mortality were nil. No statistically significant difference was observed between the patients with complications and without in terms of gender, age, anatomical anomalies, body mass index (BMI), and learning curve. We observed a longer global operation length of time in patients with complications. CONCLUSION: Robotic assistance results in shorter and simpler learning curves for the harvesting of kidneys from living donors. It enables an easier and more efficient management of possible intraoperative complications. The rate of postoperative complications is comparable with the rate of complications encountered in traditional laparoscopic series with high numbers of harvestings.

Understanding Bone Damage After Kidney Transplantation: A Retrospective Monocentric Cross Sectional Analysis.

BACKGROUND: Kidney transplantation (KT) immunosuppression may induce bone tissue damage with bone mineral density (BMD) loss increasing bone fractures risk. Steroid therapy is considered the major player, but others factors are still under review. PATIENTS AND METHODS: We designed an observational retrospective cohort study to evaluate bone damage after KT. The prevalence of osteopenia, osteoporosis, bone fractures, and the associated risk factors were investigated. The following parameters were recorded before transplantation and at the last follow-up: demographic indexes, cumulative steroid dose (CSD), dialytic and transplantologic age, previous nephropathy, femoral and lumbar BMD, fractures, immunosuppressors, calcemia, phosphoremia, rejection episodes, estimated glomerular filtration rate, and parathyroid hormone and vitamin D levels. Stata software (Stata Corporation, College Station, Texas, United States) was used for the statistical analysis, to perform the Fisher's exact test, Kruskal-Wallis test, Student t test, as well as univariate and multivariate analyses. RESULTS: The analyzed cohort was composed of 297 patients (65.3% males and 34.7% females). Sixty percent of KT patients had normal BMD, 24% had osteopenia, and 15% had osteoporosis. Twelve percent were victims of bone fractures (8.4% minor, 2% femoral, and 1.7% vertebral). A significant correlation (P <.05) was observed for both osteopenia and osteoporosis with menopause, transplantologic age, CSD, previous glomerulonephritis, and mammalian target of rapamycin (mTOR) inhibitors treatment (imTOR). CONCLUSION: This study confirms the correlation between CSD (both before and after transplantation) and post-transplantation bone damage. It also shows that a large fraction of these patients had normal BMD related with a low steroid dose in our protocols. This correlation between imTOR assumption and osteoporosis deserves attention and warrants further in vitro analyses to be performed.

Erythema nodosum in kidney transplant recipient: a rare complication of pneumonia treatment.

Erythema nodosum (EN) is a cutaneous inflammatory reaction, usually reported in young women, but it is rarely observed among transplant patients. Localization in the lower extremities is typical, mostly involving the anterior surfaces of the legs. Several viral, bacterial, mycotic, and non-infectious etiologies, such as autommune disorders, drugs, inflammatory bowel diseases, sarcoidosis, pregnancy, and malignancies, have been found. We describe the case of a young woman kidney transplant recipient developing bilateral, erythematous, warm nodules localized on the anterior surface of her legs after antibiotic treatment for pneumonia with levofloxacin. Her immunosuppression was sirolimus and mycophenolate mofetil. EN was diagnosed by skin biopsy; microscopic examination showed septal panniculitis with granulomas. As a complete remission of the lesions was obtained in our patient after interruption of levofloxacin therapy, we suspect that levofloxacin was involved in the pathogenesis of EN. In fact, the management of EN is based on the treatment of underlying or associated conditions.

PP057. The role of uterine artery pulsatility index for prediction of pregnancy outcome, in women affected by pre-eclampsia.

INTRODUCTION: Uterine artery (UtA) Pulsatility index assessed in the second trimester is known to be the best predictor of Pre-eclampsia (PE) in women with risk factors. The role of this index when PE occurs seems to be related with clinical outcome. OBJECTIVES: To detect if there does exist a correlation between mean UtA PI, assessed at diagnosis of PE, and: (A) Gestational Age (GA) at delivery; (B) birth weight (BW) percentile. To detect the predictive value of mean UtA PI and the development of adverse pregnancy outcome (APO). METHODS: Cohort study on 100 consecutive singleton pregnancies complicated with pre-eclampsia referred to our Department from January 2010 and December 2011. Doppler evaluations were performed from diagnosis to delivery. Mean UtA PI obtained at time of diagnosis of PE were analysed. PE was defined according to ISSHP criteria. Clinical and perinatal outcomes were reviewed. APO was defined as Apgar score less than 7 at five minutes, pH <7.20; birth weight <5th percentile (SGA), stillbirth or neonatal death. Receiver-operating characteristics (ROC) curve was used to determine the predictive ability for subsequent development of APO. RESULTS: Maternal characteristics and main pregnancy outcomes are shown in Table 1. Fifty-six pregnancies developed APO. One case of stillbirth and four cases of neonatal death were observed. SGA occurred in 56/100 neonates; 52/95 (55%) live births were admitted to Neonatal Intensive Care Unit. Table 1. Mean UtA PI at diagnosis of PE was 1.40 (SD±0.28) in women that developed APO and 1.10 (SD±0.41) in women that did not develop APO (p=0.02). Pearson's Correlation coefficient for mean UtA PI and GA at Delivery was -0.533 (p=0.002); while for mean UtA PI and BW percentile was -0.466 (p=0.007). The prediction of subsequent development of APO, expressed as the area under ROC curve, was 61.6 (95% CI 0.44-0.79) for UtA PI at Diagnosis of PE. CONCLUSION: Our data confirm that mean UtA PI, assessed at diagnosis of PE, represent a good independent predictor for GA at delivery end BW percentile. However the predictive value for development of APO seems to be poor.

PP110. The role of doppler to predict adverse pregnancy outcome in patients with pre-eclampsia.

INTRODUCTION: Recently Middle Cerebral Artery (MCA) to uterine artery (UtA) Pulsatility Index (PI) ratio and MCA to Umblical Artery (UA) PI ratio have been described to be good predictors of neonatal outcome in pre-eclamptic patients in the third trimester and have been proposed to identify fetuses at risk of morbidity and mortality. OBJECTIVES: To investigate the value of doppler indexes such as MCA PI, UA PI; MCA to UtA PI ratio and MCA to UA PI ratio to predict adverse pregnancy outcome (APO) in patients affected by Pre-eclampsia (PE). METHODS: Cohort study on 100 consecutive singleton pregnancies complicated with pre-eclampsia referred to our Department from January 2010 and December 2011.Doppler evaluations were performed from diagnosis to delivery.UtA, UA and ACM PI were assessed at each scan, Measurements obtained within one week from delivery were analysed, and MCA/UA PI ratio and MCA/UtA PI ratio calculated.PE was defined according to ISSHP criteria.Clinical and perinatal outcomes were reviewed.APO was defined as Apgar score less than 7 at five minutes, pH<7.20; birth weight <5th percentile (SGA), stillbirth or neonatal death. Receiver-operating characteristics (ROC) curves were used to determine the predictive ability for subsequent development of APO. Logistic regression was run to assess the additional value to the routine indexes for both ratios. RESULTS: One case of stillbirth and four cases of neonatal death were observed.SGA was present in 56/100 neonates; 52/95 (55%) live births were admitted to Neonatal Intensive Care Unit.Maternal Age was 33years (mean, SD±5yy), mean maternal BMI was 23.6Kg/mq (SD±4.9Kg/mq), gestational age (GA at diagnosis of PE was 32+5w (mean, SD±3+6w), GA at delivery was 33+4w (mean, SD±3+4w), birth weight percentile was 13.33 (mean, SD±18.23), pH was 7.26 (mean, SD±0.11)Fifty-six pregnancies developed APO. Doppler findings assessed within one week from delivery are shown in Table 1, values are expressed as mean (±SD). The prediction of subsequent development of APO, expressed as the area under ROC curve, was 0.695 (95% CI 0.59-0.80) for UtA PI; 0.730 (95% CI 0.62-0.81) for UAPI; 0.677 (95% CI 0.55-0.78) for MCA PI; 0.785 (95% CI 0.66-0.87) for MCA/UA PI; 0.774 (95% CI 0.66-0.86) for MCA/UtA PI. Moreover, a MCA/UA PI=1.28 showed a sensitivity of 74.4% and a specificity of 76.0% in predicting APO. Logistic regression analysis showed that the better index combination is represented by MCA/UA PI and MCA/UtA PI. CONCLUSION: In addition to UtA and UAPI, MCA/UA PI ratio and MCA/UtA PI ratio are useful predictors of neonatal outcome in pregnancies complicated with PE.

PP149. Hypertensive risk factors: Do they influence pregnancy outcome in women affected by new onset pre-eclampsia?

INTRODUCTION: Pre-eclampsia (PE) is a leading cause of maternal and foetal mortality and morbidity. Chronic Hypertension (CH) and a previous PE are well known risk factors for PE. If the prevalence of PE in nulliparous is about 2%, it raise up to 7-10% in women with CH or a previous PE. However, the role of these risk factors when PE occurs is still under discussion OBJECTIVES: To detect if maternal history of previous PE and/or Chronic Hypertension (CH) is associated with a worse clinical outcome in women affected by PE. METHODS: Cohort study on 100 consecutive singleton pregnancies complicated by PE referred to our Department from January 2010 to December 2011. PE and CH were defined according to ISSHP criteria. Small for Gestational Age (SGA) was defined as Birth Weight under the 5th percentile per Gestational Age. Patients were divided into two groups depending on positive (Group A, n=25) or negative (Group B, n=75) history for PE and/or Chronic Hypertension (CH). Patients assessed to group A were under prophylactic therapy with ASA 100mg oid. Clinical and perinatal outcomes were reviewed. Adverse Pregnancy Outcome (APO) was defined as Apgar score less than seven at five minutes, pH<7.20; birth weight<5th percentile (SGA), stillbirth or neonatal death. RESULTS: Groups were comparable for Maternal Age (Group A: 34years median, IQR 30-36yy; Group B: 34years, IQD 28-36yy ) and BMI (Group A: 23.7Kg/mq median, IQR 20.8-27.1Kg/mq; Group B: 22.4Kg/mq median IQR 20.3-26.0Kg/mq). One case of stillbirth (Group A) and four cases of neonatal death were observed, 1/25 in Group A (4%) and 3/75 (4%) in Group B. No differences were found in Gestational Age (GA) at diagnosis of PE (Group A: 32+2w median, IQR 28+0-35+4w; Group B: 33+2w median, IQR 30+0-36+1w); GA at delivery (Group A: 34+1w median, IQR 31+5-36+5w; Group B: 34+2w median, IQR 32+0-36+3w) Birth Weight percentile (Group A: 6th percentile median, IQR 2-21th percentile; Group B: 5th percentile median, IQR 1-15th percentile), prevalence of Small for Gestational Age (14/25 and 42/75, for Group A and B respectively), prevalence of APO (13/25 and 44/75, for Group A and B respectively). CONCLUSION: Our data suggest that a positive history for PE and/or CH does not influence clinical outcome in women affected by PE. This result could be explained by the administration of prophylactic ASA 100mg oid in this group of patients.

PP173. The role of mean artery blood pressure in the prediction of pre-eclampsia in pregnancies complicated with chronic hypertension.

INTRODUCTION: Chronic hypertension (CH) is a common disorder occurring in approximately 1-5% of pregnant women. Many studies emphasize that the development of superimposed preeclampsia (PE) is associated with high rates of adverse pregnancy outcome. Accurate prediction of women at risk for PE is crucial to judicious allocation of monitoring resources and use of preventive treatment, in order to improve maternal and neonatal outcome. Recent systematic review and meta-analysis showed that mean arterial pressure (MAP) is a better predictor for pre-eclampsia than systolic blood pressure and diastolic blood pressure OBJECTIVES: To detect the value of MAP in the first and second trimesters to predict PE in women with CH. To determine if MAP, assessed in the second trimester, can increase the predictive value for PE of II trimester UtA PI. METHODS: Cohort study on 100 consecutive singleton pregnancies complicated with CH referred to our Department from January 2008 to June 2011. Blood pressure was measured by a mercury sphygmomanometer at 11-14+6w and 23+0-25+6w, MAP was calculated. Doppler-velocimetry was performed at 23+0-25+6w, mean UtA PI was calculated. PE and CH were defined according to ISSHP criteria. Clinical and perinatal outcomes were reviewed. Receiver-operating characteristic (ROC) curves were used to determine the predictive ability of I and II trimesters MAP and II trimester mean UtA PI for subsequent development of PE. Logistic regression analysis was run to assess the additional value of II trimester MAP to II trimester UtA PI. RESULTS: Mean maternal age was 36 years (SD ±5yy); mean Body mass Index was 24Kg/mq (SD ±5Kg/mq); GA at I Trimester evaluation was 11+4w (SD ±1+5w); I trimester MAP was 100.46mmHg (mean, SD ±9.94mmHg); GA at Doppler and II trimester MAP was 24+4w (SD ±4dd); II trimester MAP 97.53mmHg (mean, SD ±10.27mmHg). Nineteen cases of PE were observed. Seventy patients were under prophylactic ASA 100mg oid. Fifty-two patients were under anti-hypertensive therapy from the first trimester. No differences in prevalence of PE were observed between patients in and out prophylactic treatment, as well as no differences in prevalence of PE were observed between patients under anti-hypertensive treatment or not. The prediction of subsequent development of PE, expressed as the area under ROC curve, was 0.469 (95% CI 0.34-0.59) for I trimester MAP; 0.659 (95% CI 0.55-0.76) for II trimester MAP; 0.748 (95% CI 0.65-0.83) for II trimester mean UtA PI; GA at delivery was 37+4w(mean, SD ±3+2w); mean BW was 2958g (SD ±735g); BW percentile was 38 (mean SD ±29 percentiles); mean BW z-Score was -0.63 (SD ±1.6). Logistic regression analysis showed that MAP does not increase the predictive ability of II trimester UtA PI in women with CH. CONCLUSION: In our findings, MAP seems not to be a good predictor for subsequent development of PE in women with CH, moreover, it seems to be not useful to increase the predictive value for PE of II trimester UtA PI. II trimester UtA PI has been confirmed to be the best predictor for subsequent development of PE.

Mesenchymal stem cells infusion prevents acute cellular rejection in rat kidney transplantation.

Mesenchymal stem cells (MSC) are multipotent cells that differentiate into various mature cell lineages. MSC show immunomodulatory effects by inhibiting T-cell proliferation. We evaluated the effect of the infusion of MSC in rats experimental kidney transplantation. Sprague-Dawley transgenic rats (SD) able to express the green fluorescent protein (EGFP) were used as MSC donors. Syngeneic (Lewis to Lewis, n = 10) and allogeneic (Fischer to Lewis, n = 10) kidney transplantations were performed after bilateral nephrectomy. Five transplanted rats who received syngeneic grafts, were treated with 3 x 10(6) MSC (Gr B), while the other 5 did not received MSC (Gr A). Five rats with allogenic grafts received 3 x 10(6) MSC (Gr C) and another 5 did not receive MSC (Gr D). The MSC were infused directly into the renal artery of the graft. No immunosuppressive therapy was provided. The animals were killed after 7 days. Biochemical analysis for renal function, histological (Banff criteria) and immunohistological analysis (ED1+ and CD8+) were performed on treated animals. MSC improved kidney function in Gr B and D vs Gr A and C. The tubular damage appeared to be less severe among Gr B and Gr D with respect to Gr A and C (P < .01). Vasculitis was more accentuated in Gr A and C (P < .01). MSCs reduced the inflammatory infiltrate; in Gr B and D, the number of ED1+ cells was lower than in Gr A and C (P < .005), which was also observed for CD8+ cells (P < .05). Our study demonstrated that the infusion of MSC attenuated histological damage from acute rejection by reducing the cellular infiltration.

Which is the most suitable and effective route of administration for mesenchymal stem cell-based immunomodulation therapy in experimental kidney transplantation: endovenous or arterial?

Immunomodulating cell therapy represents a new perspective for the control of cellular immune responses that determine the occurrence of acute rejection (ACR) in allo-transplantation. Mesenchymal stem cells (MSC) demonstrate immunoregulatory effects by inactivating T-cell components that regulate tissue damage in transplantation models. The presumed mechanism of action is recruitment of cells by a cytokine network. The purpose of this study was to test which route of administration (intra-arterial vs intravenous) was the most effective route to achieve immunomodulating effects in experimental rat kidney transplantation. Transgenic Sprague-Dawley rats (SD) expressing the enhanced green fluorescent protein (EGFP) at the somatic level were used as MSC donors: Allogeneic Fischer to Lewis grafts (n = 4 per group) were performed in rats after bilateral nephrectomy. In Gr B, 3 x 10(6) MSCs were infused into the renal graft artery, whereas in Gr C, they were infused into the tail vein. The untreated Gr A were a control group. No immunosuppressive therapy was administered. The animals were sacrificed at day 7 postoperatively. Biochemical analysis for renal function, histological (Banff criteria) and immunohistological (anti-EGFP-Immunoglobulin) analysis were performed on the transplanted animals. In Gr B, functional recovery was more rapid (creatinine: Gr B vs Gr C, P < .05). The inflammatory infiltrate in the graft was less in Gr B vs Gr C, with preservation of tubules, arteries, and glomeruli (P < .01). Intra-arterial infusion of MSCs was more effective to control ACR.

Oligomeric structure of the Bacillus subtilis cell division protein DivIVA determined by transmission electron microscopy.

DivIVA from Bacillus subtilis is a bifunctional protein with distinct roles in cell division and sporulation. During vegetative growth, DivIVA regulates the activity of the MinCD complex, thus helping to direct cell division to the correct mid-cell position. DivIVA fulfils a quite different role during sporulation in B. subtilis when it directs the oriC region of the chromosome to the cell pole before asymmetric cell division. DivIVA is a 19.5 kDa protein with a large part of its structure predicted to form a tropomyosin-like alpha-helical coiled-coil. Here, we present a model for the quaternary structure of DivIVA, based on cryonegative stain transmission electron microscopy images. The purified protein appears as an elongated particle with lateral expansions at both ends producing a form that resembles a 'doggy-bone'. The particle mass estimated from these images agrees with the value of 145 kDa measured by analytical ultracentrifugation suggesting 6- to 8-mers. These DivIVA oligomers serve as building blocks in the formation of higher order assemblies giving rise to strings, wires and, finally, two-dimensional lattices in a time-dependent manner.

Hepatocyte growth factor/scatter factor released during peritonitis is active on mesothelial cells.

Peritonitis causes mesothelial detachment that may result in persistent peritoneal denudation and fibrosis. We investigated whether hepatocyte growth factor (HGF), a scatter factor that induces detachment from substrate and fibroblastic transformation of several cell types, is produced during peritonitis and is active on mesothelial cells. We studied 18 patients on peritoneal dialysis, 9 uncomplicated, 9 with peritonitis. HGF was measured in serum, peritoneal fluid, and supernatant of peripheral blood mononuclear cells and peritoneal mononuclear cells. Primary culture of human peritoneal mesothelial cells and the human mesothelial cell line MeT-5A were conditioned with recombinant HGF, serum, and peritoneal fluid. HGF levels were significantly higher in serum and peritoneal fluid of peritonitic than uncomplicated patients. Mononuclear cells of peritonitic patients produced more HGF than cells of uncomplicated patients. Recombinant HGF, serum, and peritoneal fluid of peritonitic patients caused mesothelial cell growth, detachment, transformation from epithelial to fibroblast-like shape, overexpression of vimentin, and synthesis of type I and III collagen. In conclusion, HGF released during peritonitis causes a change in mesothelial cell phenotype and function. HGF may affect the healing process facilitating repair through mesothelial cell growth, but may contribute to peritoneal fibrosis inducing cell detachment with mesothelial denudation and collagen synthesis.