Focal segmental glomerulosclerosis(FSGS) represents one of the most severe glomerular diseases, with frequent progression to end-stage renal disease and a high rate of recurrence in renal allografts(30%-50%). Recurren...Focal segmental glomerulosclerosis(FSGS) represents one of the most severe glomerular diseases, with frequent progression to end-stage renal disease and a high rate of recurrence in renal allografts(30%-50%). Recurrent FSGS portends a negative outcome, with the hazard ratio of graft failure being two-fold higher then that of other glomerulonephritis. Two patterns of clinical presentations are observed: Early recurrence, which is characterized by massive proteinuria within hours to days after implantation of the renal graft, and late recurrence, which occurs several months or years after the transplantation. Many clinical conditions have been recognized as risk factors for recurrence, including younger age, rapid progression of the disease to end-stage renal disease on native kidneys, and loss of previous renal allografts due to recurrence. However, much less is known about the incidence and risk factors of the so-called "de novo " type of FSGS, for which sufferers are transplanted patients without disease on native kidneys; but, rapid development of allograft failure is frequently observed. Management of both forms is challenging, and none of the approaches proposed to date have been demonstrated as consistently beneficial or effective. In the present review we report an update on the available therapeutic strategies for FSGS in renal transplantation within the context of a critical overview of the current literature.展开更多
Background:Increasing demand for high-value fish species and pressure on forage fish is challenging aquaculture to ensure sustainable growth by replacing protein sources in aquafeeds with plant and terrestrial animal ...Background:Increasing demand for high-value fish species and pressure on forage fish is challenging aquaculture to ensure sustainable growth by replacing protein sources in aquafeeds with plant and terrestrial animal proteins,without compromising the economic value and quality of the final fish product.In the present study,the effects of a plant protein-based diet(CV),two plant-based diets in which graded amounts of plan protein mixtures were replaced with Hermetia illucens meal alone(VH10)or in combination with poultry by-product meal(PBM)(VH10P30),a fishmeal(FM)diet(CF)and an FM diet supplemented with H.illucens(FH10)on growth performance,gut health and homeostasis of farmed subadult European seabass were tested and compared.Results:Fish fed the VH10 and VH10P30 diets showed the highest specific growth rates and lowest feed conversion ratios among the tested groups.Expectedly,the best preservation of PI morphology was observed in fish fed the CF or FH10 diets,while fish fed the CV diet exhibited significant degenerative changes in the proximal and distal intestines.However,PBM supplementation mitigated these effects and significantly improved all gut morphometric parameters in the VH10P30 group.Partial substitution of the plant mixture with insect meal alone or PBM also induced most BBM genes and activated BBM enzymes,suggesting a beneficial effect on intestinal digestive/absorption functions.Regarding intestinal microbiota,fish fed diets containing H.illucens meal(FH10,VH10,VH10P30)had the highest richness of bacterial communities and abundance of beneficial genera such as Lactobacillus and Bacillus.On the other hand,fish fed CV had the highest microbial diversity but lost a significant component of fish intestinal microbiota,the phylum Bacteroidetes.Finally,skin pigmentation most similar to that of farmed or even wild seabass was also observed in the fish groups fed CF,FH10 or VH10P30.Conclusion:Plant-based diets supplemented with PBM and H.illucens pupae meal have great potential as alternative diets for European seabass,without affecting growth performance,gut homeostasis,or overall fitness.This also highlights the importance of animal proteins in diets of European seabass,as the addition of a small amount of these alternative animal protein sources significantly improved all measured parameters.展开更多
AIM To evaluate the role of a therapeutic regimen with plasma exchange, intravenous immunoglobulins and rituximab in chronic-active antibody-mediated rejection(c AMR) settings.METHODS We compared 21 kidney transplant ...AIM To evaluate the role of a therapeutic regimen with plasma exchange, intravenous immunoglobulins and rituximab in chronic-active antibody-mediated rejection(c AMR) settings.METHODS We compared 21 kidney transplant recipients(KTRs) with a diagnosis of c AMR in a retrospective casecontrol analysis: nine KTRs treated with plasmapheresis, intravenous immunoglobulins and rituximab(PE-IVIGRTX group) vs 12 patients(control group) not treated with antibody-targeted therapies. We examined kidney survival and functional outcomes 24 mo after diagnosis. Histological features and donor-specific antibody(DSA) characteristics(MFI and C1 q-fixing ability) were also investigated.RESULTS No difference in graft survival between the two groups was noted: three out of nine patients in the PE-IVIG-RTX group(33.3%) and 4/12 in the control group(33.3%) experienced loss of allograft function at a median time after diagnosis of 14 mo(min 12-max 18) and 15 mo(min 7-max 22), respectively. Kidney functional tests and proteinuria 24 mo after cA MR diagnosis were also similar in both groups. Only microvascular inflammation(glomerulitis + peritubular capillaritis score) was significantly reduced after PE-IVIG-RTX in seven out of eight patients(87.5%) in the PE-IVIG-RTX group(median score 3 in pre-treatment biopsy vs 1.5 in post-treatment biopsy; P = 0.047), without any impact on kidney survival and/or DSA characteristics. No functional or histological parameter at diagnosis was predictive of clinical outcome.CONCLUSION Our data showed no difference in the two year posttreatment outcome of kidney grafts treated with PE-IVIGRTX for c AMR diagnosis, however there were notable improvements in microvascular inflammation in posttherapy protocol biopsies. Further studies, especially involving innovative therapeutic approaches, are required to improve the management and long-term results of this severe condition.展开更多
The identification of complement activity in serum and immunohistochemical samples represents a core element of nephropathology. On the basis of this observation, different experimental models and molecular studies ha...The identification of complement activity in serum and immunohistochemical samples represents a core element of nephropathology. On the basis of this observation, different experimental models and molecular studies have shown the role of this cascade in glomerular disease etiology, but the absence of inhibiting drugs have limited its importance. Since 2006, the availability of target-therapies re-defined this ancient pathway, and its blockage, as the new challenging frontier in renal disease treatment. In the graft, the complement cascade is able to initiate and propagate the damage in ischemia-reperfusion injury, C3 glomerulopathy, acute and chronic rejection, atypical hemolytic uremic syndrome and, probably, in many other conditions. The importance of complement-focused research is revealed by the evidence that eculizumab, the first complementtargeting drug, is now considered a valid option in atypical hemolytic uremic syndrome treatment but it is also under investigation in all the aforementioned con-ditions. In this review we evaluate the importance of complement cascade in renal transplantation diseases, focusing on available treatments, and we propose a speculative identification of areas where complement inhibition may be a promising strategy.展开更多
文摘Focal segmental glomerulosclerosis(FSGS) represents one of the most severe glomerular diseases, with frequent progression to end-stage renal disease and a high rate of recurrence in renal allografts(30%-50%). Recurrent FSGS portends a negative outcome, with the hazard ratio of graft failure being two-fold higher then that of other glomerulonephritis. Two patterns of clinical presentations are observed: Early recurrence, which is characterized by massive proteinuria within hours to days after implantation of the renal graft, and late recurrence, which occurs several months or years after the transplantation. Many clinical conditions have been recognized as risk factors for recurrence, including younger age, rapid progression of the disease to end-stage renal disease on native kidneys, and loss of previous renal allografts due to recurrence. However, much less is known about the incidence and risk factors of the so-called "de novo " type of FSGS, for which sufferers are transplanted patients without disease on native kidneys; but, rapid development of allograft failure is frequently observed. Management of both forms is challenging, and none of the approaches proposed to date have been demonstrated as consistently beneficial or effective. In the present review we report an update on the available therapeutic strategies for FSGS in renal transplantation within the context of a critical overview of the current literature.
基金funded by the Interreg project AdriAquaNet (Project ID10045161)
文摘Background:Increasing demand for high-value fish species and pressure on forage fish is challenging aquaculture to ensure sustainable growth by replacing protein sources in aquafeeds with plant and terrestrial animal proteins,without compromising the economic value and quality of the final fish product.In the present study,the effects of a plant protein-based diet(CV),two plant-based diets in which graded amounts of plan protein mixtures were replaced with Hermetia illucens meal alone(VH10)or in combination with poultry by-product meal(PBM)(VH10P30),a fishmeal(FM)diet(CF)and an FM diet supplemented with H.illucens(FH10)on growth performance,gut health and homeostasis of farmed subadult European seabass were tested and compared.Results:Fish fed the VH10 and VH10P30 diets showed the highest specific growth rates and lowest feed conversion ratios among the tested groups.Expectedly,the best preservation of PI morphology was observed in fish fed the CF or FH10 diets,while fish fed the CV diet exhibited significant degenerative changes in the proximal and distal intestines.However,PBM supplementation mitigated these effects and significantly improved all gut morphometric parameters in the VH10P30 group.Partial substitution of the plant mixture with insect meal alone or PBM also induced most BBM genes and activated BBM enzymes,suggesting a beneficial effect on intestinal digestive/absorption functions.Regarding intestinal microbiota,fish fed diets containing H.illucens meal(FH10,VH10,VH10P30)had the highest richness of bacterial communities and abundance of beneficial genera such as Lactobacillus and Bacillus.On the other hand,fish fed CV had the highest microbial diversity but lost a significant component of fish intestinal microbiota,the phylum Bacteroidetes.Finally,skin pigmentation most similar to that of farmed or even wild seabass was also observed in the fish groups fed CF,FH10 or VH10P30.Conclusion:Plant-based diets supplemented with PBM and H.illucens pupae meal have great potential as alternative diets for European seabass,without affecting growth performance,gut homeostasis,or overall fitness.This also highlights the importance of animal proteins in diets of European seabass,as the addition of a small amount of these alternative animal protein sources significantly improved all measured parameters.
文摘AIM To evaluate the role of a therapeutic regimen with plasma exchange, intravenous immunoglobulins and rituximab in chronic-active antibody-mediated rejection(c AMR) settings.METHODS We compared 21 kidney transplant recipients(KTRs) with a diagnosis of c AMR in a retrospective casecontrol analysis: nine KTRs treated with plasmapheresis, intravenous immunoglobulins and rituximab(PE-IVIGRTX group) vs 12 patients(control group) not treated with antibody-targeted therapies. We examined kidney survival and functional outcomes 24 mo after diagnosis. Histological features and donor-specific antibody(DSA) characteristics(MFI and C1 q-fixing ability) were also investigated.RESULTS No difference in graft survival between the two groups was noted: three out of nine patients in the PE-IVIG-RTX group(33.3%) and 4/12 in the control group(33.3%) experienced loss of allograft function at a median time after diagnosis of 14 mo(min 12-max 18) and 15 mo(min 7-max 22), respectively. Kidney functional tests and proteinuria 24 mo after cA MR diagnosis were also similar in both groups. Only microvascular inflammation(glomerulitis + peritubular capillaritis score) was significantly reduced after PE-IVIG-RTX in seven out of eight patients(87.5%) in the PE-IVIG-RTX group(median score 3 in pre-treatment biopsy vs 1.5 in post-treatment biopsy; P = 0.047), without any impact on kidney survival and/or DSA characteristics. No functional or histological parameter at diagnosis was predictive of clinical outcome.CONCLUSION Our data showed no difference in the two year posttreatment outcome of kidney grafts treated with PE-IVIGRTX for c AMR diagnosis, however there were notable improvements in microvascular inflammation in posttherapy protocol biopsies. Further studies, especially involving innovative therapeutic approaches, are required to improve the management and long-term results of this severe condition.
文摘The identification of complement activity in serum and immunohistochemical samples represents a core element of nephropathology. On the basis of this observation, different experimental models and molecular studies have shown the role of this cascade in glomerular disease etiology, but the absence of inhibiting drugs have limited its importance. Since 2006, the availability of target-therapies re-defined this ancient pathway, and its blockage, as the new challenging frontier in renal disease treatment. In the graft, the complement cascade is able to initiate and propagate the damage in ischemia-reperfusion injury, C3 glomerulopathy, acute and chronic rejection, atypical hemolytic uremic syndrome and, probably, in many other conditions. The importance of complement-focused research is revealed by the evidence that eculizumab, the first complementtargeting drug, is now considered a valid option in atypical hemolytic uremic syndrome treatment but it is also under investigation in all the aforementioned con-ditions. In this review we evaluate the importance of complement cascade in renal transplantation diseases, focusing on available treatments, and we propose a speculative identification of areas where complement inhibition may be a promising strategy.
