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Tubulointerstitial fibrosis is a common consequence of a diverse range of kidney diseases that lead to end-stage renal failure. The degree of fibrosis is related to leukocyte infiltration. Here, we determined the role of different T cell populations on renal fibrosis in the well-characterized mouse model of unilateral ureteric obstruction. Depletion of CD4(+) T cells in wild-type mice with a monoclonal antibody significantly reduced the amount of interstitial expansion and collagen deposition after 2 weeks of obstruction. Reconstitution of lymphopenic RAG knockout mice with purified CD4(+) but not CD8(+) T cells, prior to ureteric obstruction, resulted in a significant increase in interstitial expansion and collagen deposition. Wild-type mice had significantly greater interstitial expansion and collagen deposition compared with lymphopenic RAG(-/-) mice, following ureteric obstruction; however, macrophage infiltration was equivalent in all groups. Thus, our results suggest that renal injury with subsequent fibrosis is likely to be a multifactorial process, with different arms of the immune system involved at different stages. In this ureteric obstruction model, we found a critical role for CD4(+) T cells in kidney fibrosis. These cells could be a potential target of therapeutic intervention to prevent excessive fibrosis and loss of function due to renal injury.

Complement activation during ischemia and reperfusion contributes to the development of tissue injury with severe negative impact on outcomes in transplantation. To counter the effect of complement, we present a strategy to deliver a novel complement regulator stabilized on cell surfaces within donor organs. The membrane-bound complement regulator is able to inhibit complement activation when the donor organ is revascularized and exposed to host-circulating complement. Application of this construct to donor kidneys protected transplanted tissues from ischemia/reperfusion injury and reduced the deposition of activated complement and histological signs of damage under conditions in which a nontargeted control construct was ineffective. Treatment of donor organs in this way improved graft performance in the short and long term. An analysis of the immune response in allograft recipients showed that reducing graft damage at the time of transplantation through complement regulation also modulated the alloresponse. Additionally, the results of perfusion studies with human kidneys demonstrated the feasibility of targeting endothelial and epithelial surfaces with this construct, to allow investigation in clinical transplantation.

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BackgroundWomen with chronic kidney disease have an increased risk of maternal and fetal complications in pregnancy. Pre-pregnancy counselling is recommended but the format of the counselling process and the experience of the patient have never been assessed. This study examines the experience of women with chronic kidney disease attending pre-pregnancy counselling and evaluates their pregnancy outcomes.MethodsThis is a cross-sectional assessment of 179 women with chronic kidney disease attending a pre-pregnancy counselling clinic (2003–2011) with retrospective evaluation of aetiology, comorbidity, treatment and adverse pregnancy outcome compared with 277 hospital controls. It includes an analysis of descriptive data and free text content from 72 questionnaire responders.Results65/72 (90%) of women found the clinic informative. 66 women (92%) felt that the consultation had helped them decide about pursuing pregnancy. 12 women (17%) found the multidisciplinary process intimidating. Free text comments supported the positive nature of the counselling experience, but also highlighted issues of access and emotional impact. Adverse pregnancy outcome rates were significantly higher in women with chronic kidney disease: 7/35 (20%) had pre-eclampsia (p < 0.001), 8/35 (23%) infants were small for gestational age (p < 0.001), 11/35 (31%) had preterm deliveries (<37 weeks) (p < 0.001) and 5/35 (14%) had a pregnancy loss compared with 4%, 10%, 8% and 3% of controls respectively.ConclusionsWomen with a diverse range of renal disease severity and complexity attend pre-pregnancy counselling. Factors affecting pregnancy include hypertension, proteinuria and teratogenic medication. It is important to be able to inform women of the risks to them and their babies before pregnancy in order to facilitate informed-decision making. Most women with chronic kidney disease attending a pre-pregnancy counselling clinic report a positive experience.Electronic supplementary materialThe online version of this article (doi:10.1186/s12882-015-0024-6) contains supplementary material, which is available to authorized users.

Infection of the urinary tract remains one of the most common infections affecting mankind. Renal epithelial cells, being one of the first cells to come into contact with invading organisms, are in a key position to coordinate host defense. The epithelium not only provides a physical barrier to infection, but can also augment the immune response via the production of a number of inflammatory mediators and antimicrobial proteins. Recent work has demonstrated that cells of the innate immune system, including epithelial cells, express toll-like receptors (TLRs), with the capacity to recognize bacterial components. Although the exact mechanisms remain unclear, engagement of TLRs can lead to epithelial cell activation and the production of inflammatory mediators. These include complement proteins, other bactericidal peptides, and chemotactic cytokines. The resulting inflammatory infiltrate serves to aid bacterial clearance, but can also lead to renal damage. In this review, we describe how renal epithelial cells contribute to the innate immune response to ascending urinary tract infection. We specifically relate previous work to more recent developments in this field. An improved understanding of the mechanisms involved may highlight potential therapeutic avenues to aid bacterial clearance and prevent the renal scarring associated with infection.

The complement system plays a vital role in mediating disease processes within renal allografts. Eculizumab is a humanized monoclonal antibody that targets complement protein C5, inhibiting cleavage into C5a and C5b, and therefore preventing formation of the membrane attack complex (MAC). It has been used primarily within renal transplantation to treat atypical hemolytic-uremic syndrome (aHUS) and antibody-mediated rejection (AMR) post-transplant, and also as prophylaxis in transplants at high risk for these conditions. Eculizumab appears to be effective in protecting renal allografts when post-transplant aHUS or AMR occur, although the published cases report relatively short follow-up. It is unclear how long treatment should continue (a particularly important issue given the expense of the drug), or whether eculizumab contributes to the development of accommodation in humans. When used for prophylaxis, eculizumab also appears to be effective. Some highly sensitized patients have developed either acute AMR or features of chronic AMR despite administration of the drugthis suggests that complement activation is not the only mechanism responsible for AMR. All patients should receive vaccination against Neisseria meningitidis prior to receiving eculizumab. Clinical trials, predominantly in antibody-incompatible renal transplantation, are ongoing to determine the optimal use of C5 inhibition.