Advances in apheresis therapy for glomerular diseases

This article is an overview of the immunomodulatory effects of apheresis in renal diseases, especially primary and secondary glomerulonephritis, and the clinical evidence for the efficacy of apheresis therapy. Permeability factor(s) derived from circulating T cells are speculated to have a crucial role in the proteinuria of nephrotic syndrome (NS). Plasma exchange (PE); immunoadsorption plasmapheresis (IAPP), using protein A sepharose cartridges; low-density lipoprotein apheresis; and lymphocytapheresis (LCAP) have been used to remove such factors or pathogenic T cells. Other glomerular diseases induced by specific antibodies such as anti-glomerular basement membrane antibodies, anti-neutrophil cytoplasmic antibodies, and immune-complexes have also been treated with PE, double-filtration plasmapheresis, IAPP, and LCAP. Recommendations, based on the evidence from recent randomized controlled studies, have been established in apheresis therapy for various glomerular diseases. © 2007 Japanese Society of Nephrology

Enterokinase and IAV Infection

Cleavage and activation of hemagglutinin (HA) by trypsin-like proteases in influenza A virus (IAV) are essential prerequisites for its successful infection and spread. In host cells, some transmembrane serine proteases such as TMPRSS2, TMPRSS4 and HAT, along with plasmin in the bloodstream, have been reported to cleave the HA precursor (HA0) molecule into its active forms, HA1 and HA2. Some trypsinogens can also enhance IAV proliferation in some cell types (e.g., rat cardiomyoblasts). However, the precise activation mechanism for this process is unclear, because the expression level of the physiological activator of the trypsinogens, the TMPRSS15 enterokinase, is expected to be very low in such cells, with the exception of duodenal cells. Here, we show that at least two variant enterokinases are expressed in various human cell lines, including A549 lung-derived cells. The exogenous expression of these enterokinases was able to enhance the proliferation of IAV in 293T human kidney cells, but the proliferation was reduced by knocking down the endogenous enterokinase in A549 cells. The enterokinase was able to enhance HA processing in the cells, which activated trypsinogen in vitro and in the IAV-infected cells also. Therefore, we conclude that enterokinase plays a role in IAV infection and proliferation by activating trypsinogen to process viral HA in human cell lines

Clinical practice guideline for drug-induced kidney injury in Japan 2016: digest version

Approximately one in eight adults has chronic kidney disease (CKD) in Japan, and the prevalence rate is expected to rise steeply due to the aging of the population in this country. In patients with CKD, quite a few medications require the dosage reduction or discontinuation because of their reduced urinary excretion and the increased risk of further renal impairment. Therefore, CKD patients are often treated by insufficient amounts of the medications, even though they may suffer from various complications. Moreover, it is empirically known that drug-induced kidney injury (DKI) accelerates the progression of renal failure, while it is not superficially ranked as a primary cause of kidney disease.In this context, the early detection, prevention, and treatment of DKI are very important issue in preventing the progression of CKD and the development of renal failure. However, there are no comprehensive and practical guideline on the diagnosis and treatment of DKI for CKD patients and on dosage adjustments for these patients.In response to this need, a clinical practice guideline for DKI was developed with the support of a Health and Labour Science Research Grant from the Ministry of Health, Labour, and Welfare (MHLW) and the Japan Agency for Medical Research and Development (AMED) for Practical Research Project for Renal Diseases, “Early detection and treatment of drug-induced kidney injury that aggravate chronic kidney disease.” This guideline was established by doing a clinical survey on DKIs, evaluating clinicopathological factors, investigating the methods of the early detection of the disease, and analyzing animal models. The present article represents a Committee of Clinical Practice Guideline for DKI. We collected supportive evidence and analyzed data, focusing on several clinical questions that have practical importance

Root-to-Shoot Transport of Sulfate in Arabidopsis. Evidence for the Role of SULTR3;5 as a Component of Low-Affinity Sulfate Transport System in the Root Vasculature

Xylem transport of sulfate regulates distribution of sulfur in vascular plants. Here, we describe SULTR3;5 as an essential component of the sulfate transport system that facilitates the root-to-shoot transport of sulfate in the vasculature. In Arabidopsis (Arabidopsis thaliana), SULTR3;5 was colocalized with the SULTR2;1 low-affinity sulfate transporter in xylem parenchyma and pericycle cells in roots. In a yeast (Saccharomyces cerevisiae) expression system, sulfate uptake was hardly detectable with SULTR3;5 expression alone; however, cells coexpressing both SULTR3;5 and SULTR2;1 showed substantial uptake activity that was considerably higher than with SULTR2;1 expression alone. The V(max) value of sulfate uptake activity with SULTR3;5-SULTR2;1 coexpression was approximately 3 times higher than with SULTR2;1 alone. In Arabidopsis, the root-to-shoot transport of sulfate was restricted in the sultr3;5 mutants, under conditions of high SULTR2;1 expression in the roots after sulfur limitation. These results suggested that SULTR3;5 is constitutively expressed in the root vasculature, but its function to reinforce the capacity of the SULTR2;1 low-affinity transporter is only essential when SULTR2;1 mRNA is induced by sulfur limitation. Consequently, coexpression of SULTR3;5 and SULTR2;1 provides maximum capacity of sulfate transport activity, which facilitates retrieval of apoplastic sulfate to the xylem parenchyma cells in the vasculature of Arabidopsis roots and may contribute to the root-to-shoot transport of sulfate

Phloem-Localizing Sulfate Transporter, Sultr1;3, Mediates Re-Distribution of Sulfur from Source to Sink Organs in Arabidopsis

For the effective recycling of nutrients, vascular plants transport pooled inorganic ions and metabolites through the sieve tube. A novel sulfate transporter gene, Sultr1;3, was identified as an essential member contributing to this process for redistribution of sulfur source in Arabidopsis. Sultr1;3 belonged to the family of high-affinity sulfate transporters, and was able to complement the yeast sulfate transporter mutant. The fusion protein of Sultr1;3 and green fluorescent protein was expressed by the Sultr1;3 promoter in transgenic plants, which revealed phloem-specific expression of Sultr1;3 in Arabidopsis. Sultr1;3-green fluorescent protein was found in the sieve element-companion cell complexes of the phloem in cotyledons and roots. Limitation of external sulfate caused accumulation of Sultr1;3 mRNA both in leaves and roots. Movement of (35)S-labeled sulfate from cotyledons to the sink organs was restricted in the T-DNA insertion mutant of Sultr1;3. These results provide evidence that Sultr1;3 transporter plays an important role in loading of sulfate to the sieve tube, initiating the source-to-sink translocation of sulfur nutrient in Arabidopsis

Advances in apheresis therapy for glomerular diseases

This article overviewed the immunomodulation effects and clinical evidence of apheresis in renal diseases, especially primary and secondary glomerulonephritis. A considerable permeability factor(s) derived from circulating T cells is speculated to have a crucial role in proteinuria of nephrotic syndrome (NS). Plasma exchange (PE), immunoadsorption (IAPP) using Protein A sepharose cartridges, low density lipoprotein apheresis and lymphocyte apheresis (LCAP) were tried to remove such factors or pathogenic T cells. Other glomerular diseases induced by specific antibodies such as anti-glomerular basement membrane antibodies, anti-neutrophil cytoplasmic antibodies and immune-complexes were also treated with PE, double filtration plasma apheresis, IAPP and LCAP. The recommendations based on the evidence from recent randomized controlled studies have been established in apheresis therapy for the treatment of various glomerular diseases