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Background: Health information systems (HIS) are fundamental tools for the surveillance of health services, estimation of disease burden and prioritization of health resources. Several gaps in the availability of HIS for kidney disease were highlighted by the first iteration of the Global Kidney Health Atlas., Methods: As part of its second iteration, the International Society of Nephrology conducted a cross-sectional global survey between July and October 2018 to explore the coverage and scope of HIS for kidney disease, with a focus on kidney replacement therapy (KRT)., Results: Out of a total of 182 invited countries, 154 countries responded to questions on HIS (85% response rate). KRT registries were available in almost all high-income countries, but few low-income countries, while registries for non-dialysis chronic kidney disease (CKD) or acute kidney injury (AKI) were rare. Registries in high-income countries tended to be national, in contrast to registries in low-income countries, which often operated at local or regional levels. Although cause of end-stage kidney disease, modality of KRT and source of kidney transplant donors were frequently reported, few countries collected data on patient-reported outcome measures and only half of low-income countries recorded process-based measures. Almost no countries had programs to detect AKI and practices to identify CKD-targeted individuals with diabetes, hypertension and cardiovascular disease, rather than members of high-risk ethnic groups., Conclusions: These findings confirm significant heterogeneity in the global availability of HIS for kidney disease and highlight important gaps in their coverage and scope, especially in low-income countries and across the domains of AKI, non-dialysis CKD, patient-reported outcomes, process-based measures and quality indicators for KRT service delivery., (© The Author(s) 2020. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Regulatory T cells (T regs ) have been recognized as central mediators for maintaining peripheral tolerance and limiting autoimmune diseases. The loss of T regs or their function has been associated with exacerbation of autoimmune disease. However, the temporary loss of T regs in the chronic spontaneous disease model has not been investigated. In this study, we evaluated the role of T regs in a novel chronic spontaneous glomerulonephritis model of B cell lymphoma 2-interacting mediator (Bim) knock-out mice by transient depleting T regs . Bim is a pro-apoptotic member of the B cell lymphoma 2 (Bcl-2) family. Bim knock-out (Bim -/- ) mice fail to delete autoreactive T cells in thymus, leading to chronic spontaneous autoimmune kidney disease. We found that T reg depletion in Bim -/- mice exacerbated the kidney injury with increased proteinuria, impaired kidney function, weight loss and greater histological injury compared with wild-type mice. There was a significant increase in interstitial infiltrate of inflammatory cells, antibody deposition and tubular damage. Furthermore, the serum levels of cytokines interleukin (IL)-2, IL-4, IL-6, IL-10, IL-17α, interferon (IFN)-γ and tumour necrosis factor (TNF)-α were increased significantly after T reg depletion in Bim -/- mice. This study demonstrates that transient depletion of T regs leads to enhanced self-reactive T effector cell function followed by exacerbation of kidney disease in the chronic spontaneous kidney disease model of Bim-deficient mice., (© 2017 British Society for Immunology.)

Background: Non-randomized studies suggest an association between serum uric acid levels and progression of chronic kidney disease (CKD). The aim of this systematic review is to summarize evidence from randomized controlled trials (RCTs) concerning the benefits and risks of uric acid-lowering therapy on renal outcomes., Methods: Medline, Excerpta Medical Database and Cochrane Central Register of Controlled Trials were searched with English language restriction for RCTs comparing the effect of uric acid-lowering therapy with placebo/no treatment on renal outcomes. Treatment effects were summarized using random-effects meta-analysis., Results: Eight trials (476 participants) evaluating allopurinol treatment were eligible for inclusion. There was substantial heterogeneity in baseline kidney function, cause of CKD and duration of follow-up across these studies. In five trials, there was no significant difference in change in glomerular filtration rate from baseline between the allopurinol and control arms [mean difference (MD) 3.1 mL/min/1.73 m2, 95% confidence intervals (CI) -0.9, 7.1; heterogeneity χ2=1.9, I2=0%, P=0.75]. In three trials, allopurinol treatment abrogated increases in serum creatinine from baseline (MD -0.4 mg/dL, 95% CI -0.8, -0.0 mg/dL; heterogeneity χ2=3, I2=34%, P=0.22). Allopurinol had no effect on proteinuria and blood pressure. Data for effects of allopurinol therapy on progression to end-stage kidney disease and death were scant. Allopurinol had uncertain effects on the risks of adverse events., Conclusions: Uric acid-lowering therapy with allopurinol may retard the progression of CKD. However, adequately powered randomized trials are required to evaluate the benefits and risks of uric acid-lowering therapy in CKD.

Background: Blockade of CD40-CD40 ligand (CD154) interactions protects against renal injury in adriamycin nephropathy (AN) in immunocompetent mice. To investigate whether this protection relied on adaptive or cognate immunity, we tested the effect of CD40-CD154 blockade in severe combined immunodeficient (SCID) mice., Methods: SCID mice were divided into three groups: normal, AN + hamster IgG (ADR+IgG group) and AN + anti-CD154 antibody (MR1) (ADR+MR1 group). AN was induced by tail vein injection of 5.2 mg/kg of adriamycin (ADR). Hamster IgG (control Ab) or MR1 was administered intraperitoneally on days 5, 7, 9 and 11 after ADR injection. Histological and functional data were collected 4 weeks after ADR injection. In vitro experiments tested the effect of soluble and cell-bound CD154 co-cultured with CD40-expressing cells [macrophages, mesangial cells and renal tubular epithelial cells (RTEC)]., Results: All experimental animals developed nephropathy. Compared to the ADR+IgG group, ADR+MR1 animals had significantly less histological injury (glomerulosclerosis and tubular atrophy) and functional injury (creatinine clearance). Kidneys of ADR+MR1 animals had significantly less macrophage infiltration than those of ADR+IgG animals. Interestingly, expression of CD40 and CD41 (a platelet-specific marker) was significantly less in ADR+MR1 animals compared to ADR+IgG animals. In vitro, CD154 blockade significantly attenuated upregulation of CCL2 gene expression by RTEC stimulated by activated macrophage-conditioned medium. In contrast, platelet-induced upregulation of macrophage and mesangial cell proinflammatory cytokine gene expression were not CD154-dependent., Conclusion: CD40-CD154 blockade has a significant innate renoprotective effect in ADR nephrosis. This is potentially due to inhibition of macrophage-derived soluble CD154.

Background: The inclusion of consumer preferences in prioritizing research topics is widely advocated, but prioritization is driven largely by professional agendas., Methods: Patients with chronic kidney disease (CKD) were purposively sampled from four kidney dialysis and transplant centres in Australia to participate in nine focus groups (three each for pre-dialysis, dialysis and transplant patients), which were conducted from July 2006 to September 2006. Each involved 6-8 participants. Transcripts were coded and thematically analysed to identify recurrent research topics and the participants' reasons for their choices., Results: Participants suggested eight research priorities: prevention of kidney disease, better access to and improvement in kidney transplantation, reduction of symptoms of CKD and complications associated with treatment, new technological therapies, psychosocial aspects of living with CKD, whole body not organ-specialized care, and improvement in dialysis and caregiver support. Five major reasons for the selections were identified: normalization of life (developing therapies and regimens that fit into daily living), altruism (considering the welfare of others before personal needs), economic efficiency (channelling resources for maximum economic gain), personal needs (preferences based on feelings, values, personal needs) and clinical outcomes (improving health states and the physiological condition of patients with CKD)., Conclusions: A patient-focused research agenda is possible to elicit for CKD, and by inference for other healthcare issues. Unlike researchers who focus on specific interventions and questions, consumers think in terms of broad themes and quality of life outcomes. Effective methods for translating a patient-focused agenda into research priority setting and resource allocation are now needed.

Background: Carbamylation is an irreversible process of non-enzymatic modification of proteins by the breakdown products of urea. For haemoglobin (Hb), the extent of carbamylation is a marker of urea exposure and has been proposed as an indicator of the control of uraemia by dialysis, analogous to the use of Hb glycosylation in diabetic patients., Methods: We performed a cross-sectional study of haemodialysis (HD) and peritoneal dialysis (PD) patients in order to study potential determinants of carbamylated Hb (CarbHb) and to investigate the relationship between CarbHb and established measures of dialysis dose/adequacy by multivariate analysis., Results: In 80 HD patients, CarbHb was independently predicted by post-dialysis urea (r=0.40, P:<0.01), serum albumin (r=0.24, P:<0.05) and serum bicarbonate (r=-0.40, P:<0. 05). No correlation was found between CarbHb and measures of dialysis dose/adequacy (Kt/V, urea reduction ratio, weekly dialysis duration, and normalized protein catabolic rate (nPCR)). In 42 PD patients, serum urea was the only significant independent predictor of CarbHb (r=-0.51, P:=0.001). No relationship was found between CarbHb and Kt/V, corrected creatinine clearance (CrCl) or nPCR in PD patients., Conclusions: Serum urea is the most consistent independent predictor of CarbHb in dialysis patients. This association in combination with the lack of a relationship with conventional measures of dialysis dose and a positive relationship with serum albumin suggest that a single measurement of CarbHb is unlikely to be a useful indicator of the adequacy of dialysis.