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Background: cDC1 is a subset of conventional DCs, whose most recognized function is cross-presentation to CD8+ T cells. We conducted this study to investigate the number and location of cDC1s in various human kidney diseases as well as their correlation with clinico-pathological features and CD8+ T cells. Methods: We analyzed 135 kidney biopsies samples. Kidney diseases included: acute tubular necrosis (ATN), acute interstitial nephritis (AIN), proliferative glomerulonephritis (GN) (IgA nephropathy, lupus nephritis, pauci-immune GN, anti-GBM disease), non-proliferative GN (minimal change disease, membranous nephropathy) and diabetic nephropathy. Indirect immunofluorescence staining was used to quantify cDC1s, CD1c+ DCs, and CD8+ T cells. Results: cDC1s were rarely present in normal kidneys. Their number increased significantly in ATN and proliferative GN, proportionally much more than CD1c+ DCs. cDC1s were mainly found in the interstitium, except in lupus nephritis, pauci-immune GN and anti-GBM disease, where they were prominent in glomeruli and peri-glomerular regions. The number of cDC1s correlated with disease severity in ATN, number of crescents in pauci-immune GN, interstitial fibrosis in IgA nephropathy and lupus nephritis, as well as prognosis in IgA nephropathy. The number of CD8+ T cells also increased significantly in these conditions and cDC1 number correlated with CD8+ T cell number in lupus nephritis and pauci-immune GN, with many of them closely co-localized. Conclusions: cDC1 number correlated with various clinic-pathological features and prognosis reflecting a possible role in these conditions. Their association with CD8+ T cells suggests a combined mechanism in keeping with the results in animal models. [ABSTRACT FROM AUTHOR]

Background Chronic kidney disease (CKD) is a global public health problem, which lacks effective treatment. Previously, we have shown that CD103+ dendritic cells (DCs) are pathogenic in adriamycin nephropathy (AN), a model of human focal segmental glomerulosclerosis (FSGS). Fms-like tyrosine kinase 3 (Flt3) is a receptor that is expressed with high specificity on tissue resident CD103+ DCs. Methods To test the effect on CD103+ DCs and kidney injury of inhibition of Flt3, we used a selective Flt3 inhibitor (AC220) to treat mice with AN. Results Human CD141+ DCs, homologous to murine CD103+ DCs, were significantly increased in patients with FSGS. The number of kidney CD103+ DCs, but not CD103− DCs or plasmacytoid DCs, was significantly decreased in AN mice after AC220 administration. Treatment with AC220 significantly improved kidney function and reduced kidney injury and fibrosis in AN mice. AC220-treated AN mice had decreased levels of inflammatory cytokines and chemokines, tumor necrosis factor-α, interleukin (IL)-1β, IL-6, CCL2 and CCL5 and reduced kidney infiltration of CD4 T cells and CD8 T cells. The protective effect of AC220 was associated with its suppression of CD103+ DCs-mediated CD8 T cell proliferation and activation in AN mice. Conclusion Flt3 inhibitor AC220 effectively reduced kidney injury in AN mice, suggesting that this inhibitor might be a useful pharmaceutical agent to treat CKD. [ABSTRACT FROM AUTHOR]

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 m2 if 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. [ABSTRACT FROM AUTHOR]

Introduction: Lanthanum carbonate (LC) and sevelamer hydrochloride (SH) are non-calcium-based phosphate binders (NCPB), used to manage hyperphosphatemia in patients with chronic kidney disease. We compared the efficacy of LC and SH in lowering serum phosphate level in patients on haemodialysis or continuous ambulatory peritoneal dialysis. Methods: Treatment profiles of a group of dialysis patients on NCPB were retrospectively analyzed between 2010 and 2014 for a mean duration of one year. The treatment group included patients (n = 28) who were initially on SH and switched to LC because of uncontrolled hyperphosphataemia. Patients receiving ≥12 months SH treatment were included in the control group (n = 10). Results: There was a significant within patient fall in serum phosphate from a mean of 2.4 ± 0.5 mmol/L after 3-6 months on SH to 1.7 ± 0.4 mmol/L following 3-6 months on LC (p < 0.001). These within patient changes differed significantly from those observed in the control group (interaction p = 0.003). Mean phosphate binder pill burden also fell significantly from 5.6 ± 2.3 tablets to 2.6 ± 0.8 tablets daily (p < 0.001). A significant within patient increase in serum bicarbonate level from 23.2 ± 3.5 to 24.7 ± 2.7 mmol/L (p = 0.020) was observed in the treated patients, reflecting a resolution of mild acidosis associated with the hydrochloride salt of sevelamer which was not evident in the control group (interaction p = 0.022). Conclusion: This study demonstrates the efficacy of LC in reducing the serum phosphate level, pill burden, and improving bicarbonate level in dialysis patients. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 55-year old man who presented with abdominal pain and a history of end-stage kidney disease (ESKD) secondary to IgA nephropathy. He was diagnosed with acquired cystic disease-associated with renal cell carcinoma and had been on haemodialysis for 8 years, since a failed deceased donor kidney transplant in 2007. His computed tomography of his abdomen showed a right kidney lesion, suspicious of RCC.

The article presents a case study of a 65-year-old Croatian Man suggested with a medical history of hypertension treated with an angiotensin II receptor blocker. Topics discussed includes capillary basement membranes, immunofluorence for immune mediated processes, transverse band structure and Electron Microscopy.

The authors discuss the challenges of preventing chronic kidney disease (CKD). Among the challenges of CKD prevention are low awareness of CKD in the general public and among primary health care professionals, imperfections of the existing CKD screening methods, and high prevalence of CKD among Indigenous Australians.

Introduction: In Non-Hodgkin Lymphoma (NHL), bone marrow histology is the gold standard against which ancillary investigations such as immunophenotyping and gene rearrangement studies are interpreted. There is currently no data on the reproducibility of histological findings. This study was conducted to determine the rates of inter- and intra-observer agreement in histological detection of bone marrow involvement in the two major subtypes of NHL, Diffuse Large B-cell Lymphoma (DLBCL), and Follicular Lymphoma (FL).Methods: The bone marrow slides of randomly selected DLBCL and FL cases were independently examined by two hematologists using standardized reporting criteria on two occasions at least two weeks apart. Samples included both aspirate and trephine biopsy slides. Weighted kappa statistics were used to examine agreement for the discrete measures.Results: Weighted kappa analyses showed variable inter-observer agreement in 38 DLBCL cases [aspirate=0.52; trephine= 0.77] and 38 FL cases [aspirate=0.48; trephine=0.77].Conclusion: Overall, higher agreement rates were noted with trephine biopsies than with aspirates. Except for the high intra-observer agreement on trephine biopsy assessment in FL, there is poor agreement in histological staging of both FL and DLBCL which demonstrates the limitations of histological diagnosis and the futility of interpreting ancillary tests against histology. [ABSTRACT FROM AUTHOR]

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., (© 2024 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

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 vitro with 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 vivo expanded 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., (Copyright © 2019 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Background: Chronic kidney disease (CKD) is a global public health problem, which lacks effective treatment. Previously, we have shown that CD103+ dendritic cells (DCs) are pathogenic in adriamycin nephropathy (AN), a model of human focal segmental glomerulosclerosis (FSGS). Fms-like tyrosine kinase 3 (Flt3) is a receptor that is expressed with high specificity on tissue resident CD103+ DCs., Methods: To test the effect on CD103+ DCs and kidney injury of inhibition of Flt3, we used a selective Flt3 inhibitor (AC220) to treat mice with AN., Results: Human CD141+ DCs, homologous to murine CD103+ DCs, were significantly increased in patients with FSGS. The number of kidney CD103+ DCs, but not CD103- DCs or plasmacytoid DCs, was significantly decreased in AN mice after AC220 administration. Treatment with AC220 significantly improved kidney function and reduced kidney injury and fibrosis in AN mice. AC220-treated AN mice had decreased levels of inflammatory cytokines and chemokines, tumor necrosis factor-α, interleukin (IL)-1β, IL-6, CCL2 and CCL5 and reduced kidney infiltration of CD4 T cells and CD8 T cells. The protective effect of AC220 was associated with its suppression of CD103+ DCs-mediated CD8 T cell proliferation and activation in AN mice., Conclusion: Flt3 inhibitor AC220 effectively reduced kidney injury in AN mice, suggesting that this inhibitor might be a useful pharmaceutical agent to treat CKD., (© The Author(s) 2018. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

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., (Copyright © 2019 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Background: Dialysis patients have an exceedingly high mortality rate. Biomarkers may be useful tools in risk stratification of this population. We evaluated the prognostic value of high-sensitivity cardiac troponin T (hs-cTnT) and CRP (C-reactive protein) in predicting adverse outcomes in stable hemodialysis and peritoneal dialysis (PD) patients. Variability in hs-cTnT was also examined., Methods and Results: A retrospective cohort study included 574 dialysis patients (hemodialysis 347, PD 227). Outcomes examined included mortality and major adverse cardiovascular events, with median follow-up of 3.5 years. hs-cTnT was an independent predictor of both outcomes in hemodialysis and PD patients. Increased risk only became significant when hs-cTnT reached quintile 3 (>49 ng/L). Area under the receiver operating curve analysis showed that the addition of hs-cTnT to clinical parameters significantly improved its prognostic performance for mortality in PD patients ( P =0.002). CRP was an independent predictor of both outcomes in PD patients only. Only CRP in the highest quintile (>16.8 mg/L) was associated with increased risk. hs-cTnT remained relatively stable for the whole follow-up period for hemodialysis patients, whereas for PD patients, hs-cTnT increased by 23.63% in year 2 and 29.13% in year 3 compared with baseline ( P <0.001)., Conclusions: hs-cTnT and CRP are useful tools in predicting mortality and major adverse cardiovascular events in hemodialysis and PD patients. Given that hs-cTnT levels increase over time in PD patients, interval monitoring may be valuable for risk assessment. In contrast, hs-cTnT in hemodialysis patients has little interval change and progress monitoring is not indicated., (© 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)