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The International Society of Nephrology (ISN) region of Oceania and South East Asia (OSEA) is a mix of high- and low-income countries, with diversity in population demographics and densities. Three iterations of the ISN-Global Kidney Health Atlas (GKHA) have been conducted, aiming to deliver in-depth assessments of global kidney care across the spectrum from early detection of CKD to treatment of kidney failure. This paper reports the findings of the latest ISN-GKHA in relation to kidney-care capacity in the OSEA region. Among the 30 countries and territories in OSEA, 19 (63%) participated in the ISN-GKHA, representing over 97% of the region’s population. The overall prevalence of treated kidney failure in the OSEA region was 1203 per million population (pmp), 45% higher than the global median of 823 pmp. In contrast, kidney replacement therapy (KRT) in the OSEA region was less available than the global median (chronic hemodialysis, 89% OSEA region vs. 98% globally; peritoneal dialysis, 72% vs. 79%; kidney transplantation, 61% vs. 70%). Only 56% of countries could provide access to dialysis to at least half of people with incident kidney failure, lower than the global median of 74% of countries with available dialysis services. Inequalities in access to KRT were present across the OSEA region, with widespread availability and low out-of-pocket costs in high-income countries and limited availability, often coupled with large out-of-pocket costs, in middle- and low-income countries. Workforce limitations were observed across the OSEA region, especially in lower-middle–income countries. Extensive collaborative work within the OSEA region and globally will help close the noted gaps in kidney-care provision.

Fibrosis is characterized by progressively excessive deposition of matrix components and may lead to organ failure. Transforming growth factor-β (TGF-β) is a key cytokine involved in tissue repair and fibrosis. TGF-β′s profibrotic signaling pathways converge at activation of β-catenin. β-Catenin is an important transcription cofactor whose function depends on its binding partner. Promoting β-catenin binding to forkhead box protein O (Foxo) via inhibition of its binding to T-cell factor (TCF) reduces kidney fibrosis in experimental murine models. Herein, we investigated whether β-catenin/Foxo diverts TGF-β signaling from profibrotic to physiological epithelial healing. In an in vitromodel of wound healing (scratch assay), and in an in vivomodel of kidney injury, unilateral renal ischemia reperfusion, TGF-β treatment in combination with either ICG-001 or iCRT3 (β-catenin/TCF inhibitors) increased β-catenin/Foxo interaction, increased scratch closure by increased cell proliferation and migration, reduced the TGF-β–induced mesenchymal differentiation, and healed the ischemia reperfusion injury with less fibrosis. In addition, administration of ICG-001 or iCRT3 reduced the contractile activity induced by TGF-β in C1.1 cells. Together, our results indicate that redirection of β-catenin binding from TCF to Foxo promotes β-catenin/Foxo–mediated epithelial repair. Targeting β-catenin/Foxo may rebuild normal structure of injured kidney.

β‐Catenin is an important co‐factor which binds multiple transcriptional molecules and mediates fibrogenic signaling pathways. Its role in kidney transplantation is unknown. We quantified binding of β‐catenin within renal tubular epithelial cells to transcription factors, TCF1 and FoxO1, using a proximity ligation assay in 240 transplanted kidneys, and evaluated their pathological and clinical outcomes. β‐Catenin/FoxO1 binding in 1‐month protocol biopsies inversely correlated with contemporaneous chronic fibrosis, subsequent inflammation. and inflammatory fibrosis (P< .001). The relative binding of β‐catenin/TCF1 versus β‐catenin/FoxO1 (TF ratio) was the optimal biomarker, and abnormal in diverse fibrotic transplant diseases. A high 1‐month TF ratio was followed by greater tubular atrophy and interstitial fibrosis scores, cortical inflammation, renal impairment, and proteinuria at 1 year (n = 131, all P< .001). The TF ratio was associated with reduced eGFR (AUC 0.817), mild fibrosis (AUC 0.717), and moderate fibrosis (AUC 0.769) using receiver operating characteristic analysis. An independent validation cohort (n = 76) confirmed 1‐month TF was associated with 12‐month moderate fibrosis (15.8% vs. 2.6%, P= .047), however, not with other outcomes or 10‐year graft survival, which limits generalizabilty of these findings. In summary, differential binding of β‐catenin to TCF1 rather than FoxO1 in renal tubular cells was associated with the fibrogenic response in transplanted kidneys. The binding of β‐catenin to TCF1 and FoxO1 within renal tubular epithelial cells in 1‐month protocol biopsies is associated with tubular atrophy, interstitial fibrosis, inflammation, renal impairment, and proteinuria at 1 year.

Innate lymphoid cells are a recently recognized group of immune cells with critical roles in tissue homeostasis and inflammation. Regulatory innate lymphoid cells are a newly identified subset of innate lymphoid cells, which play a suppressive role in the innate immune response, favoring the resolution of intestinal inflammation. However, the expression and role of regulatory innate lymphoid cells in kidney has not been reported. Here, we show that regulatory innate lymphoid cells are present in both human and mouse kidney, express similar surface markers and form a similar proportion of total kidney innate lymphoid cells. Regulatory innate lymphoid cells from kidney were expanded in vitrowith a combination of IL-2, IL-7 and transforming growth factor-β. These cells exhibited immunosuppressive effects on innate immune cells via secretion of IL-10 and transforming growth factor-β. Moreover, treatment with IL-2/IL-2 antibody complexes (IL-2C) promoted expansion of regulatory innate lymphoid cells in vivo, and prevent renal ischemia/reperfusion injury in Rag–/– mice that lack adaptive immune cells including Tregs. Depletion of regulatory innate lymphoid cells with anti-CD25 antibody abolished the beneficial effects of IL-2C in the Rag–/– mice. Adoptive transfer of ex vivoexpanded regulatory innate lymphoid cells improved renal function and attenuated histologic damage when given before or after induction of ischemia/reperfusion injury in association with reduction of neutrophil infiltration and induction of reparative M2 macrophages in kidney. Thus, our study shows that regulatory innate lymphoid cells suppress innate renal inflammation and ischemia/reperfusion injury.

Transforming growth factor β (TGF-β) is the key cytokine involved in causing fibrosis through cross-talk with major profibrotic pathways. However, inhibition of TGF-β to prevent fibrosis would also abrogate its anti-inflammatory and wound-healing effects. β-catenin is a common co-factor in most TGF-β signaling pathways. β-catenin binds to T-cell factor (TCF) to activate profibrotic genes and binds to Forkhead box O (Foxo) to promote cell survival under oxidative stress. Using a proximity ligation assay in human kidney biopsies, we found that β-catenin/Foxo interactions were higher in kidney with little fibrosis, whereas β-catenin/TCF interactions were upregulated in the kidney of patients with fibrosis. We hypothesised that β-catenin/Foxo is protective against kidney fibrosis. We found that Foxo1 protected against rhTGF-β1-induced profibrotic protein expression using a CRISPR/cas9 knockout of Foxo1 or TCF1 in murine kidney tubular epithelial C1.1 cells. Co-administration of TGF-β with a small molecule inhibitor of β-catenin/TCF (ICG-001), protected against kidney fibrosis in unilateral ureteral obstruction. Collectively, our human, animal and in vitro findings suggest β-catenin/Foxo as a therapeutic target in kidney fibrosis.

Transforming growth factor β (TGF-β) is the key cytokine involved in causing fibrosis through cross-talk with major profibrotic pathways. However, inhibition of TGF-β to prevent fibrosis would also abrogate its anti-inflammatory and wound-healing effects. β-catenin is a common co-factor in most TGF-β signaling pathways. β-catenin binds to T-cell factor (TCF) to activate profibrotic genes and binds to Forkhead box O (Foxo) to promote cell survival under oxidative stress. Using a proximity ligation assay in human kidney biopsies, we found that β-catenin/Foxo interactions were higher in kidney with little fibrosis, whereas β-catenin/TCF interactions were upregulated in the kidney of patients with fibrosis. We hypothesised that β-catenin/Foxo is protective against kidney fibrosis. We found that Foxo1 protected against rhTGF-β1-induced profibrotic protein expression using a CRISPR/cas9 knockout of Foxo1 or TCF1 in murine kidney tubular epithelial C1.1 cells. Co-administration of TGF-β with a small molecule inhibitor of β-catenin/TCF (ICG-001), protected against kidney fibrosis in unilateral ureteral obstruction. Collectively, our human, animal and in vitro findings suggest β-catenin/Foxo as a therapeutic target in kidney fibrosis.

Tissue macrophages are crucial players in homeostasis, inflammation, and immunity. They are characterized by heterogeneity and plasticity, due to which they display a continuum of phenotypes with M1/M2 presenting 2 extremes of this continuum. M2 macrophages are usually termed in the literature as anti-inflammatory and wound healing. Substantial progress has been made in elucidating the biology of M2 macrophages and their potential for clinical translation. In this review we discuss the current state of knowledge in M2 macrophage research with an emphasis on kidney disease. We explore their therapeutic potential and the challenges in using them as cellular therapies. Some new regulators that shape macrophage polarization and potential areas for future research are also examined.

The decision about when to start dialysis for end-stage kidney disease (ESKD) is complex and is influenced by many factors. ESKD-related symptoms and signs are the most common indications for dialysis initiation. Creatinine-based formulae to estimate glomerular filtration rate (GFR) are inaccurate in patients with ESKD and, thus, the decision to start dialysis should not be based solely on estimated GFR (eGFR).Early dialysis initiation (ie, at an eGFR > 10 mL/min/1.73 m2) is not associated with a morbidity and mortality benefit, as shown in the Initiating Dialysis Early and Late (IDEAL) study. This observation has been incorporated into the latest guidelines, which place greater emphasis on the assessment of patients’ symptoms and signs rather than eGFR. It is suggested that in asymptomatic patients with stage 5 chronic kidney disease, dialysis may be safely delayed until the eGFR is at least as low as 5–7 mL/min/1.73 m2if there is careful clinical follow-up and adequate patient education.The decision on when to start dialysis is even more challenging in older patients. Due to their comorbidities and frailty, dialysis initiation may be associated with worse outcomes and quality of life. Therefore, the decision to start dialysis in these patients should be carefully weighed against its risks, and conservative care should be considered in appropriate cases.To optimise the decision-making process for dialysis initiation, patients need to be referred to a nephrologist in a timely fashion to allow adequate pre-dialysis care and planning. Dialysis initiation and its timing should be a shared decision between physician, patients and family members, and should be tailored to the individual patient's needs.

Many studies have assessed rates of histological bone marrow (BM) involvement in non-Hodgkin’s lymphoma (NHL) but there are currently no data on the reproducibility of these results. This study was conducted to determine the rates of inter- and intra-observer variability in detection of BM involvement in NHL.