1,721,036 research outputs found
[The usefulness of protocol biopsies after kidney transplant: pros and cons].
No full textTransplant centers carrying out protocol biopsies in kidney transplant recipients do so to make an early diagnosis of subclinical rejection or chronic transplant glomerulopathy. However, proof is still lacking to document that an early diagnosis of subclinical rejection is useful to improve long-term outcome. Protocol biopsies represent a classical controversy in renal transplantation and it is still not clear whether the benefits outweigh the risks. In this paper the authors will elucidate the pros and cons of protocol biopsies and identify issues where consensus is mandatory. Protocol biopsies need to be performed in the following clinical conditions: at the time of transplantation to obtain information about the transplanted kidney; in the case of prolonged delayed graft function; in patients at increased immunological risk; and in the case of clinical trials performed to assess the safety and efficacy of new immunosuppressive drugs
The innate immune system in human kidney inflammaging
Full text linkElderly individuals with chronic disorders tend to develop inflammaging, a condition associated with elevated levels of blood inflammatory markers, and increased susceptibility to chronic disease progression. Native and adaptive immunity are both involved in immune system senescence, kidney fibrosis and aging. The innate immune system is characterized by a limited number of receptors, constantly challenged by self and non-self stimuli. Circulating and kidney resident myeloid and lymphoid cells are all equipped with pattern recognition receptors (PRRs). Recent reports on PRRs show kidney overexpression of toll-like receptors (TLRs) in inflammaging autoimmune renal diseases, vasculitis, acute kidney injury and kidney transplant rejection. TLR upregulation leads to proinflammatory cytokine induction, fibrosis, and chronic kidney disease progression. TLR2 blockade in a murine model of renal ischemia reperfusion injury prevented the escape of natural killer cells and neutrophils by inflammaging kidney injury. Tumor necrosis factor-alpha blockade in endothelial cells with senescence-associated secretory phenotype significantly reduced interleukin-6 release. These findings should encourage experimental and translational clinical trials aimed at modulating renal inflammaging by native immunity blockade
Scatter Factors in renal disease: Dr.Jeckyll and Mr. Hyde?
No full textThe Scatter Factors are two homologous proteins, named Scatter Factor/Hepatocyte Growth Factor and Macrophage Stimulating Protein. Their receptors are the products of two oncogenes, Met and Ron, respectively. The Scatter Factors induce movement, stimulate proliferation, regulate apoptosis and are morphogenic, i.e. operate an integrated program that seems tailored to drive organ development and to regenerate injured tissues. On the other hand, Scatter Factors may be responsible for pathologic tissue remodeling, infiltration of inflammatory cells, and tumor growth and diffusion. The review describes the involvement of Scatter Factors in renal disease, including acute renal failure, glomerulonephritis, chronic fibrosing nephropathies, dialysis, renal transplantation and renal tumors, and discusses the double-faced role of Scatter Factors, that play either a protective or a pathogenic role
Macrophage-stimulating protein is produced by tubular cells and activates mesangial cells.
No full textUntil now, hepatocytes have been the only known cell source of macrophage-stimulating protein (MSP), and tissue macrophages have been the cells on which the biologic effects of MSP have been proved. To extend the understanding of the biologic meaning of MSP, it was investigated whether MSP operates in the kidney. MSP protein was evaluated by Western blot in supernatant of cultured human tubular cells (HK2) and human mesangial cells (HMC). MSP mRNA was investigated in HK2 by reverse transcription-polymerase chain reaction (RT-PCR). The expression of the MSP receptor, RON, was evaluated in HMC and HK2 by Western blot. RON mRNA was investigated in HMC by RT-PCR. The expression of MSP and RON in normal human renal tissue was studied by immunohistochemistry. HMC were stimulated with recombinant MSP (rMSP) and HK2 supernatant to study cell growth, migration, and the capacity to invade an artificial collagen matrix and synthesize interleukin-6 (IL-6). HK2 produced MSP and expressed RON in a form that was phosphorylated by rMSP. HMC expressed RON but did not produce MSP. MSP in HK2 supernatant and rMSP induced in HMC phosphorylation of RON, growth, migration, invasion, and IL-6 synthesis. In normal human kidney, tubules expressed MSP and RON. These results indicate a novel field of operation for MSP and suggest a pathogenic role of the MSP/RON system in renal disease. In fact, MSP released by tubular cells may recruit monocytes/macrophages in inflammatory tubulointerstitial disorders. In addition, MSP either circulating or as paracrine product may sustain glomerular mesangioproliferative disease
· Macrophage Stimulating Protein and its receptor RON are effectors of monocyte invasion
No full textHepatocyte growth factor (HGF) and hemodialysis: physiopathology and clinical implications
No full textHepatocyte growth factor (HGF) is a pleiotropic cytokine which exerts a variety of effects on several cells, being involved in the regulation of many biological processes, such as inflammation, tissue repair, morphogenesis, angiogenesis, tumour propagation, immunomodulation of viral infections and cardio-metabolic activities. Patients undergoing regular hemodialysis (HD) present elevated levels of HGF, mainly due to the leukocyte activation associated with HD treatment. High HGF levels might account for specific clinical features of HD patients, i.e. mild liver damage in course of HCV-infection and high cardiovascular risk profile. Moreover, in patients with acute kidney injury, the induction of HGF may represent a crucial step to promote renal recovery, which can have important prognostic consequences in the short and long-term. In this review we discuss the mechanisms underlying HGF production in HD patients, the role of HGF in this particular patient population and the potential clinical implications derived from the study of HGF in HD patients
Pre-transplant IE1-specific T-cell response and CD8+ T-cell count as predictive markers of treated HCMV reactivation in kidney transplant recipients
No full textBackground: Human cytomegalovirus (HCMV) infection represents a significant
complication for kidney transplant recipients (KTRs). The goal of this study was to
evaluate potential immunological markers at pre-transplant in HCMVseropositive
KTRs for predicting HCMV severe reactivation (e.g treated HCMV
reactivation) during the first year after transplant.
Methods: Before transplant, lymphocyte count was measured in whole blood
and HCMV-specific T-cell response was determined using ELISpot assay after
stimulation with pp65, IE-1 and IE-2 peptides pool. HCMV DNA was monitored
during the first year after transplant. Among the 65 KTRs enrolled, 44 (68%)
patients had HCMV self-resolving reactivation (Controllers) while 21 (32%)
required antiviral treatment for HCMV reactivation (Non-Controllers).
Results: No significant difference in CD4 T-cell count was observed, but
Controllers had higher CD8+ T-cell counts compared to Non-Controllers.
Based on ROC analysis, a CD8+ T-cell count ≥215 cells/ml was associated with
a lower incidence of HCMV reactivation after transplant. Additionally, a higher IE-
1-specific T-cell response was observed in Controllers and patients with IE1-
specific T-cell response ≥60 spots showed a reduced incidence of HCMV
reactivation and lower DNAemia peak.
Discussion: Lymphocyte counts and HCMV-specific T-cell response can be
measured at pre-transplant in KTRs in order to efficiently predict the risk of
treated HCMV reactivation during the first year after transplant. Potential cut-off
and diagnostics algorithm should be better investigated in a large patients setting
- …
