Long-term outcome of renal transplantation in adults with focal segmental glomerulosclerosis

P>Little information is available about the long-term results of kidney transplantation in adults with focal segmental glomerulosclerosis (FSGS). The outcomes of 52 renal transplants performed between 1988 and 2008 in 47 adults with FSGS were compared with those of 104 matched controls (median follow-up 93.4 vs. 109.4 months respectively). At 15 years, patient survival was 100% and graft survival 56% in FSGS patients vs. 88.3% and 64% respectively in controls (P = NS). FSGS recurred in 12 out of 52 grafts (23%) and led to graft failure in seven within 10 months (median). In the other five cases, proteinuria remitted and grafts are functioning 106 months (median) after transplantation. A second recurrence developed in five out of eight re-transplanted patients (62.5%) who lost their first graft because of recurrence; only one graft was lost. Patients with recurrence were more frequently male subjects (83% vs. 40%, P = 0.02), younger at diagnosis of FSGS (16.3 +/- 6.8 vs. 24.1 +/- 11.5 years, P = 0.03) and of younger age at transplantation (28.4 +/- 7.8 vs. 35.8 +/- 12.2 years, P = 0.05). Treatment with plasmapheresis plus ACE inhibitors achieved either complete or partial remission in 80% of the cases. Long-term patient and renal allograft survivals of adults with FSGS were comparable to those of controls. Recurrence was more frequent in young patients and in patients who lost a previous graft from recurrence. Graft loss resulting from a second recurrence is lower than expected

The long-term outcome of 93 patients with proliferative lupus nephritis

Background. Few data are available about the very long-term outcome of patients with proliferative lupus nephritis. Methods. Ninety-three Italian patients with biopsy-proven proliferative lupus nephritis (15 with class III, 9 with class III + V, 64 with class IV and 5 with class IV + V) followed for a median follow-up of 15 years in a single renal unit were considered for this observational study. Patients were treated with an induction treatment consisting of high doses of corticosteroids plus immunosuppressive agents in the more severe cases. This treatment was repeated in the event of a renal flare. Then corticosteroids and immunosuppressive agents were reduced to the minimal effective dose for maintenance. Results. Renal survival including death was 97% at 10 years and 82% at 20 years. At the last follow-up visit, 59 patients were in complete renal remission, 18 were in partial renal remission, four patients had chronic renal insufficiency, six had entered end-stage renal disease and six patients had died. At multivariate analysis the lack of achievement of complete renal remission and the occurrence of nephritic flares were significantly correlated both with the risk of doubling plasma creatinine and death or dialysis. Those patients who entered complete renal remission had significantly less probability of developing nephritic flares. Conclusion. The long-term prognosis of Caucasian patients with proliferative lupus nephritis may be better than usually thought. Favorable factors for good long-term outcome are the achievement of complete renal remission, the absence of nephritic flares and their complete reversibility after therapy

Long-term outcome of renal transplantation in patients with idiopathic membranous glomerulonephritis (MN)

Methods. The outcomes of 35 first renal transplants performed between 1975 and 2008 in patients with MN were compared with those of 70 controls transplanted in the same period and matched for sex, age and source of donors. Results. The mean post-transplant follow-up was 117 +/- 86 months for MN patients and 123 +/- 83 months for controls. At 15 years, patient survival was 96% in patients with MN and 88% in the controls (P = ns), while graft survival rates were respectively 40% and 69% (P = 0.06). MN recurred in 12 patients (34%), namely in 4/8 (50%) patients who received the kidney from related living donors and in 8/27 (29.6%) who received the kidney from a deceased donor. Recurrence led to graft failure in six patients, all deceased donor kidney recipients, within 54 +/- 33 months. The other six grafts are functioning 134 +/- 73 months after transplantation. Patients with recurrence were more frequently females (42% vs 4.3%, P = 0.02). The recurrence occurred earlier (4.8 +/- 3.0 vs 45.6 +/- 46.9 months, P = 0.05), and there was a trend to develop a higher proteinuria (7.1 +/- 5.5 vs 3.67 +/- 2.6 g/24 h, P = 0.1) in grafts eventually lost because of recurrence. Conclusions. The long-term patient survival was similar in renal transplant recipients with MN and in controls. The graft survival was lower in MN patients than in controls, although the difference was at borderline significance. Recurrence occurred in one-third of the patients and caused graft loss in half of them

Artificial Intelligence Can Guide Antibiotic Choice in Recurrent UTIs and Become an Important Aid to Improve Antimicrobial Stewardship

Background: A correct approach to recurrent urinary tract infections (rUTIs) is an important pillar of antimicrobial stewardship. We aim to define an Artificial Neural Network (ANN) for predicting the clinical efficacy of the empiric antimicrobial treatment in women with rUTIs. Methods: We extracted clinical and microbiological data from 1043 women. We trained an ANN on 725 patients and validated it on 318. Results: The ANN showed a sensitivity of 87.8% and specificity of 97.3% in predicting the clinical efficacy of empirical therapy. The previous use of fluoroquinolones (HR = 4.23; p = 0.008) and cephalosporins (HR = 2.81; p = 0.003) as well as the presence of Escherichia coli with resistance against cotrimoxazole (HR = 3.54; p = 0.001) have been identified as the most important variables affecting the ANN output decision predicting the fluoroquinolones-based therapy failure. A previous isolation of Escherichia coli with resistance against fosfomycin (HR = 2.67; p = 0.001) and amoxicillin-clavulanic acid (HR = 1.94; p = 0.001) seems to be the most influential variable affecting the output decision predicting the cephalosporins- and cotrimoxazole-based therapy failure. The previously mentioned Escherichia coli with resistance against cotrimoxazole (HR = 2.35; p < 0.001) and amoxicillin-clavulanic acid (HR = 3.41; p = 0.007) seems to be the most influential variable affecting the output decision predicting the fosfomycin-based therapy failure. Conclusions: ANNs seem to be an interesting tool to guide the antimicrobial choice in the management of rUTIs at the point of care

Renal transplantation in adults with Henoch-Schonlein purpura: long-term outcome

Background. Little information is available about the long-term outcome of renal transplantation in adults with Henoch-Schonlein purpura (HSP). Methods. We compared the outcomes of 17 patients with HSP who received 19 renal transplants with those of 38 controls matched for time of transplantation, age, gender and source of donor. The mean post-transplant follow-up was 109 +/- 99 months for HSP patients and 110 +/- 78 months for controls. Results. The actuarial 15-year patient Survival was 80% in HSP patients and 82% in controls, and the death-censored graft survival was 64% in FISP patients and in controls. The risks of acute rejection, chronic graft dysfunction, arterial hypertension and infection were not different between the two groups. In eight grafts (42%) recurrence of HSP nephritis was found (0.05/patient/year). In spite of therapy, one patient died and four eventually restarted dialysis respectively 10, 32, 35 and 143 months after renal transplant. Seventy-one percent of grafts transplanted in patients with necrotizing/crescentic glomerulonephritis of the native kidney had HSP recurrence in comparison to 12% of recurrences in patients with mesangial nephritis (P = 0.05) Conclusions. Long-term patient and allograft survival of HSP patients was good. However, 42% of HSP patients, particularly those with necrotizing/crescentic glomerulonephritis of the native kidneys, developed a recurrence of HSP nephritis that eventually caused the loss of the graft function in half of them

Renal transplantation in adults with Henoch-Schonlein purpura: long-term outcome

Background. Little information is available about the long-term outcome of renal transplantation in adults with Henoch-Schonlein purpura (HSP). Methods. We compared the outcomes of 17 patients with HSP who received 19 renal transplants with those of 38 controls matched for time of transplantation, age, gender and source of donor. The mean post-transplant follow-up was 109 +/- 99 months for HSP patients and 110 +/- 78 months for controls. Results. The actuarial 15-year patient Survival was 80% in HSP patients and 82% in controls, and the death-censored graft survival was 64% in FISP patients and in controls. The risks of acute rejection, chronic graft dysfunction, arterial hypertension and infection were not different between the two groups. In eight grafts (42%) recurrence of HSP nephritis was found (0.05/patient/year). In spite of therapy, one patient died and four eventually restarted dialysis respectively 10, 32, 35 and 143 months after renal transplant. Seventy-one percent of grafts transplanted in patients with necrotizing/crescentic glomerulonephritis of the native kidney had HSP recurrence in comparison to 12% of recurrences in patients with mesangial nephritis (P = 0.05) Conclusions. Long-term patient and allograft survival of HSP patients was good. However, 42% of HSP patients, particularly those with necrotizing/crescentic glomerulonephritis of the native kidneys, developed a recurrence of HSP nephritis that eventually caused the loss of the graft function in half of them

The long-term prognosis of renal transplant in patients with systemic vasculitis

Little information is available about the long-term outcome of renal transplantation in patients with systemic vasculitis (SV). We compared the outcomes of 19 renal transplant recipients with SV with those of 38 controls matched for time of transplantation, age, gender and source of donor. The mean post-transplant follow-up was 58 +/- 57 months for vasculitic patients and 61 +/- 49 months for controls. The actuarial 10-year patient survival was 87% in vasculitic patients and 90% in controls, death-censored graft survival were 84% and 100%, respectively. The risks of acute and chronic rejection, and arterial hypertension were not significantly different between the two groups. Infection was significantly more frequent in vasculitic patients (74% vs. 34%; p = 0.01). Seven patients (36.8%) had a recurrence of vasculitis in mean 45 months after renal transplant (0.076/patients/year). After recurrence, one patient had an irreversible humoral rejection, another died from hemophagocytosis and another restarted dialysis 1 year later. Long-term patient and renal allograft survival in vasculitic patients was good. Although graft function recovered in most relapsers after reinforcement of immunosuppression, one patient died and two lost graft function

Oleoylethanolamide decreases frustration stress-induced binge-like eating in female rats: a novel potential treatment for binge-eating disorder

Binge-eating disorder (BED) is the most frequent eating disorder, for which current pharmacotherapies show poor response rates and safety concerns, thus highlighting the need for novel treatment options. The lipid-derived messenger oleoylethanolamide (OEA) acts as a satiety signal inhibiting food intake through the involvement of central noradrenergic and oxytocinergic neurons. We investigated the anti-binge effects of OEA in a rat model of binge-like eating, in which, after cycles of intermittent food restrictions/refeeding and palatable food consumptions, female rats show a binge-like intake of palatable food, following a 15-min exposure to their sight and smell (“frustration stress”). Systemically administered OEA dose-dependently (2.5, 5, and 10 mg kg–1) prevented binge-like eating. This behavioral effect was associated with a decreased activation (measured by mapping the expression of c-fos, an early gene widely used as a marker of cellular activation) of brain areas responding to stress (such as the nucleus accumbens and amygdala) and to a stimulation of areas involved in the control of food intake, such as the VTA and the PVN. These effects were paralleled, also, to the modulation of monoamine transmission in key brain areas involved in both homeostatic and hedonic control of eating. In particular, a decreased dopaminergic response to stress was observed by measuring dopamine extracellular concentrations in microdialysates from the nucleus accumbens shell, whereas an increased serotonergic and noradrenergic tone was detected in tissue homogenates of selected brain areas. Finally, a decrease in corticotropin-releasing factor (CRF) mRNA levels was induced by OEA in the central amygdala, while an increase in oxytocin mRNA levels was induced in the PVN. The restoration of a normal oxytocin receptor density in the striatum paralleled the oxytocinergic stimulation produced by OEA. In conclusion, we provide evidence suggesting that OEA might represent a novel potential pharmacological target for the treatment of binge-like eating behavior

A Novel Role of Peripheral Corticotropin-Releasing Hormone (CRH) on Dermal Fibroblasts

Corticotropin-releasing hormone, or factor, (CRH or CRF) exerts important biological effects in multiple peripheral tissues via paracrine/autocrine actions. The aim of our study was to assess the effects of endogenous CRH in the biology of mouse and human skin fibroblasts, the primary cell type involved in wound healing. We show expression of CRH and its receptors in primary fibroblasts, and we demonstrate the functionality of fibroblast CRH receptors by induction of cAMP. Fibroblasts genetically deficient in Crh (Crh−/−) had higher proliferation and migration rates and compromised production of IL-6 and TGF-β1 compared to the wildtype (Crh+/+) cells. Human primary cultures of foreskin fibroblasts exposed to the CRF1 antagonist antalarmin recapitulated the findings in the Crh−/− cells, exhibiting altered proliferative and migratory behavior and suppressed production of IL-6. In conclusion, our findings show an important role of fibroblast-expressed CRH in the proliferation, migration, and cytokine production of these cells, processes associated with the skin response to injury. Our data suggest that the immunomodulatory effects of CRH may include an important, albeit not explored yet, role in epidermal tissue remodeling and regeneration and maintenance of tissue homeostasis