Parenthood With Kidney Failure: Answering Questions Patients Ask About Pregnancy

Achieving parenthood can be an important priority for women and men with kidney failure. In recent decades, the paradigm has shifted toward greater support of parenthood, with advances in our under- standing of risks related to pregnancy and improvements in obstetrical and perinatal care. This review, codesigned by people with personal experience of kidney disease, provides guidance for nephrologists on how to answer the questions most asked by patients when planning for parenthood. We focus on important issues that arise in preconception counseling for women receiving dialysis and postkidney transplant. We summarize recent studies reflecting pregnancy outcomes in the modern era of nephrology, obstetrical, and perinatal care in developed countries. We present visual aids to help clinicians and women navigate pregnancy planning and risk assessment. Key principles of pregnancy management are outlined. Finally, we explore outcomes of fatherhood in males with kidney failure.Shilpanjali Jesudason, Amber Williamson, Brooke Huuskes, and Erandi Hewawasa

Party politics and local government in Australia: Stability, change and implications for Australia’s polity

Local government and state-local government relations across Australia’s seven jurisdictions continue to be sites of robustly contested reforms. Both scholarly and media attention perennially focus upon several key types of reforms, most saliently [i] structural reform, or the threat of structural reforms, to whole jurisdictions or metropolitan regions; [ii] cost-shifting (in the parlance of North America, ‘unfunded mandates’); [iii] the enduring question of the financial sustainability of local government; and [iv] changes to arrangements for appointed and elected leaders. However, comparatively little attention has been paid to both the stability of, and changes to, party-politics in local government, which we define as the effect of party-political affiliation upon candidates for local government elections and their appointment, and the effect of party-political affiliation upon local government operations. While local government in Australia has infamously been labelled non-party political, recent research examining party-political affiliation in local government in New South Wales (NSW) for the elections held in 2004, 2008, 2012, 2016 and 2107 has revealed a marked increase in party-politicisation, particularly in metropolitan areas, accompanied by claims of political gerrymandering. The research presented for IPSA 2018 will examine these results. Specifically, the declared party-political affiliation of candidates and elected representatives are compared with self-described ‘independent’ candidates for recent local government elections are compared and mapped against the Australian Classification of Local Governments (ACLG) which is deployed as a measure of regionalism. The implications for, first, local government operations, second, state-local relations and third, the Australian federation are explored

Pharmacological inhibition of the NLRP3 inflammasome reduces blood pressure, renal damage, and dysfunction in salt-sensitive hypertension

Aims Renal inflammation, leading to fibrosis and impaired function is a major contributor to the development of hypertension. The NLRP3 inflammasome mediates inflammation in several chronic diseases by processing the cytokines pro-interleukin (IL)-1β and pro-IL-18. In this study, we investigated whether MCC950, a recently-identified inhibitor of NLRP3 activity, reduces blood pressure (BP), renal inflammation, fibrosis and dysfunction in mice with established hypertension. Methods and results C57BL6/J mice were made hypertensive by uninephrectomy and treatment with deoxycorticosterone acetate (2.4 mg/day, s.c.) and 0.9% NaCl in the drinking water (1K/DOCA/salt). Normotensive controls were uninephrectomized and received normal drinking water. Ten days later, mice were treated with MCC950 (10 mg/kg/day, s.c.) or vehicle (saline, s.c.) for up to 25 days. BP was monitored by tail-cuff or radiotelemetry; renal function by biochemical analysis of 24-h urine collections; and kidney inflammation/pathology was assessed by real-time PCR for inflammatory gene expression, flow cytometry for leucocyte influx, and Picrosirius red histology for collagen. Over the 10 days post-surgery, 1K/DOCA/salt-treated mice became hypertensive, developed impaired renal function, and displayed elevated renal levels of inflammatory markers, collagen and immune cells. MCC950 treatment from day 10 attenuated 1K/DOCA/salt-induced increases in renal expression of inflammasome subunits (NLRP3, ASC, pro-caspase-1) and inflammatory/injury markers (pro-IL-18, pro-IL-1β, IL-17A, TNF-α, osteopontin, ICAM-1, VCAM-1, CCL2, vimentin), each by 25-40%. MCC950 reduced interstitial collagen and accumulation of certain leucocyte subsets in kidneys of 1K/DOCA/salt-treated mice, including CD206 + (M2-like) macrophages and interferon-gamma-producing T cells. Finally, MCC950 partially reversed 1K/DOCA/salt-induced elevations in BP, urine output, osmolality, [Na + ], and albuminuria (each by 20-25%). None of the above parameters were altered by MCC950 in normotensive mice. Conclusion MCC950 was effective at reducing BP and limiting renal inflammation, fibrosis and dysfunction in mice with established hypertension. This study provides proof-of-concept that pharmacological inhibition of the NLRP3 inflammasome is a viable anti-hypertensive strategy