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IntroductionChronic kidney disease (CKD) affects 1 in 10 people worldwide and can progress towards kidney failure, which is best predicted by the severity of kidney fibrosis. Currently, kidney fibrosis can only be detected by invasive kidney biopsy which carries procedural risks with limitations on repeat testing. MRI techniques have emerged as potential surrogate markers for kidney fibrosis, though data remain limited. To date, no studies have examined postgadolinium contrast T1 mapping in kidney fibrosis despite its proven utility in assessing myocardial fibrosis. This study aims to develop a multiparametric MRI biomarker including postcontrast imaging to quantify kidney fibrosis in individuals with CKD.Methods and analysisIn this observational cohort study, a control group of 20 healthy adult volunteers will establish healthy kidney MRI parameters. Two adult non-dialysis CKD cohorts (each n=24) who have undergone kidney biopsy within the last month will derive and validate the MRI models, respectively. Tubulointerstitial fibrosis on kidney biopsy will be assessed by Masson trichrome staining and quantified based on the percentage of cortex affected by blinded pathologists. All participants will undergo a single multiparametric kidney MRI including kidney volumetry, T1 mapping (pre-low-dose and post-low-dose contrast), T2 mapping, T2* mapping, diffusion weighted imaging and phase-contrast MRI of renal artery flow. The primary outcome will be the association between a composite multiparametric MRI marker and tubulointerstitial fibrosis with a minimum variance of 50%. The association between the multiparametric MRI marker and individual MRI variables, and tubulointerstitial fibrosis, estimated glomerular filtration rate and albuminuria will also be studied.Ethics and disseminationEthics approval has been obtained by the Northern Sydney Local Health District Human Research Ethics Committee (2022/ETH00972). Results will be disseminated in relevant peer-reviewed journals and presented at academic conferences.Trial registration numberACTRN12622000855729p (Pre-results).

Optimally preserved urinary exfoliated renal proximal tubule cells were assessed by multispectral imaging of cell autofluorescence. We demonstrated different multispectral autofluorescence signals in such cells extracted from the urine of patients with healthy or diseased kidneys. Using up to 10 features, we were able to differentiate cells from individuals with heathy kidneys and impaired renal function (indicated by estimated glomerular filtration rate (eGFR) values) with the receiver operating characteristic area under the curve (AUC) of 0.99. Using the same method, we were also able to discriminate such urine cells from patients with and without renal fibrosis on biopsy, where significant differences in multispectral autofluorescence signals (AUC = 0.90) were demonstrated between healthy and diseased patients ( p  < 0.05). These findings show that multispectral assessment of the cell autofluorescence in urine exfoliated proximal tubule kidney cells has the potential to be developed as a sensitive, non-invasive diagnostic method for CKD.

A Mediterranean dietary pattern is widely recommended for the prevention of chronic disease. We sought to define the most likely effects of the Mediterranean diet on vascular disease and mortality. We searched MEDLINE, EMBASE and the Cochrane Central Register without language restriction for randomized controlled trials comparing Mediterranean to control diets. Data on study design, patient characteristics, interventions, follow-up duration, outcomes and adverse events were sought. Individual study relative risks (RR) were pooled to create summary estimates. Six studies with a total of 10950 participants were included. Effects on major vascular events (n = 477), death (n = 693) and vascular deaths (n = 315) were reported for 3, 5 and 4 studies respectively. For one large study (n = 1000) there were serious concerns about the integrity of the data. When data for all studies were combined there was evidence of protection against major vascular events (RR 0.63, 95% confidence interval 0.53-0.75), coronary events (0.65, 0.50-0.85), stroke (0.65, 0.48-0.88) and heart failure (0.30, 0.17-0.56) but not for all-cause mortality (1.00, 0.86-1.15) or cardiovascular mortality (0.90, 0.72-1.11). After the study of concern was excluded the benefit for vascular events (0.69, 0.55-0.86) and stroke (0.66, 0.48-0.92) persisted but apparently positive findings for coronary events (0.73, 0.51-1.05) and heart failure (0.25, 0.05-1.17) disappeared. The Mediterranean diet may protect against vascular disease. However, both the quantity and quality of the available evidence is limited and highly variable. Results must be interpreted with caution.

Background: The administration of corticosteroids in addition to supportive care to delay progressive Immunoglobulin A nephropathy (IgAN), the most common primary glomerulonephritis worldwide, remains controversial. This is partly due to the paucity of well-designed randomized controlled trials and well-known corticosteroid-related side effects. As a result, clinical equipoise in corticosteroid therapy exists depending on geographical regions and the clinician’s preference. Summary: Better understanding around the pathogenesis of IgAN has prompted several clinical trials exploring the effects of immunosuppressive agents including corticosteroids. Earlier studies of corticosteroids were limited by suboptimal study designs, inadequate implementation of standard of care and inconsistent adverse events data collection. Two well designed, adequately powered, multi-centre randomized controlled trials, the STOP-IgAN and TESTING studies, have reported contrasting kidney outcomes that have further fuelled the clinical conundrum regarding the efficacy of corticosteroids. Both studies independently reported greater adverse events with corticosteroids. A novel targeted release formulation of budesonide, which has been hypothesised to reduce the adverse events associated with systemic corticosteroids, has shown promising results in the Phase 3 NefigaRD trial. Studies of treatments targeting B-cells and the complement cascade are currently underway and early data appear encouraging. This review provides an overview of the current literature around the understanding of the pathomechanisms, and benefits and harm of corticosteroid use in IgAN. Key Messages: Recent evidence suggests the use of corticosteroids in a selected cohort of people with IgAN at high risk of disease progression can improve kidney outcomes but comes with an associated risk of treatment-related adverse events particularly with higher doses. Management decisions should therefore follow an informed patient-clinician discussion.

This study introduces advanced Joint Models (JM) to enhance mortality prediction in dialysis patients, addressing the inadequacies of existing models which lack clinical precision. We analyzed the relationship between albumin trajectories and mortality in 314 peritoneal dialysis patients over eight years, using training and validation datasets. We developed 12 JM, incorporating seven baseline risk factors; 10 models addressed individual and within-patient trajectory outliers, and six models included the competing events of hemodialysis transfer and kidney transplantation. These were also applied to a hemodialysis cohort of 315 patients. Findings showed a consistent albumin hazard ratio for death across all JM, ranging from 1.22 to 1.28, confirmed by two simulation studies. JM software optimizations achieved 3- to sixfold faster processing and 4.1- to 12.9-fold higher efficiency than conventional software. Longer follow-up improved all JM accuracies, and models with competing risks outperformed those considering only outliers. Across forecasting periods up to five years, all JM consistently surpassed benchmark Cox models, demonstrating significantly higher Area Under Curve (AUC) scores in both peritoneal and hemodialysis groups. In conclusion, our JM combine established risk factors with dynamic individual albumin profiles, integrating outliers and competing risks, substantially enhancing mortality predictions for dialysis patients.

[This corrects the article DOI: 10.1371/journal.pone.0116888.].

Semicarbazide-sensitive amine oxidase (SSAO) is an enzyme with a unique dual function in controlling inflammation as well as reactive oxygen species (ROS) generation. We have demonstrated benefit of SSAO inhibition in acute kidney fibrosis. However the function of SSAO in chronic kidney disease (CKD) and diabetic kidney disease (DKD) is yet to be determined. We aimed to assess the effectiveness of a SSAO inhibitor (SSAOi; PXS-4728A) as an antifibrotic agent using a diabetic model of CKD. Diabetic mice were treated with SSAOi for 24 weeks and outcomes compared with untreated diabetic mice and telmisartan treated animals as a standard of care comparator. Extracellular matrix markers, fibronectin and oxidative stress, were downregulated in diabetic mice treated with SSAOi compared with untreated diabetic mice. Expression of the pan-leukocyte marker CD45 was also supressed by SSAOi. SSAO inhibition in diabetic mice resulted in a significant reduction in glomerulosclerosis and associated albuminuria compared to untreated diabetic mice. However, the effect of SSAO inhibition was less obvious in the tubulointerstitial compartment than in the glomeruli. Therefore, SSAO may be a potential target for diabetic glomerulosclerosis.

Developmental programming induced by maternal obesity influences the development of chronic disease in offspring. In the present study, we aimed to determine whether maternal obesity exaggerates obesity-related kidney disease. Female C57BL/6 mice were fed high-fat diet (HFD) for six weeks prior to mating, during gestation and lactation. Male offspring were weaned to normal chow or HFD. At postnatal Week 8, HFD-fed offspring were administered one dose streptozotocin (STZ, 100 mg/kg i.p.) or vehicle control. Metabolic parameters and renal functional and structural changes were observed at postnatal Week 32. HFD-fed offspring had increased adiposity, glucose intolerance and hyperlipidaemia, associated with increased albuminuria and serum creatinine levels. Their kidneys displayed structural changes with increased levels of fibrotic, inflammatory and oxidative stress markers. STZ administration did not potentiate the renal effects of HFD. Though maternal obesity had a sustained effect on serum creatinine and oxidative stress markers in lean offspring, the renal consequences of maternal obesity were overwhelmed by the powerful effect of diet-induced obesity. Maternal obesity portends significant risks for metabolic and renal health in adult offspring. However, diet-induced obesity is an overwhelming and potent stimulus for the development of CKD that is not potentiated by maternal obesity.

Residual kidney function (RKF) is associated with improved survival and quality of life in dialysis patients. Previous studies have suggested that initiation of peritoneal dialysis (PD) may slow RKF decline compared to the pre-dialysis period. We sought to evaluate the association between PD initiation and RKF decline in the Initiating Dialysis Early And Late (IDEAL) trial. In this post hoc analysis of the IDEAL randomized controlled trial, PD participants were included if results from 24-hour urine collections had been recorded within 30 days of dialysis initiation, and at least one value pre- and one value post-dialysis commencement were available. The primary outcome was slope of RKF decline, calculated as mean of urinary creatinine and urea clearances. Secondary outcomes included slope of urine volume decline and time from PD initiation to anuria. The study included 151 participants (79 early start, 72 late start). The slope of RKF decline was slower after PD initiation (-2.69±0.18mL/min/1.73m2/yr) compared to before PD (-4.09±0.33mL/min/1.73m2/yr; change in slope +1.19 mL/min/1.73m2/yr, 95%CI 0.48-1.90, p<0.001). In contrast, urine volume decline was faster after PD commencement (-0.74±0.05 L/yr) compared to beforehand (-0.57±0.06L/yr; change in slope -0.18L/yr, 95%CI -0.34--0.01, p = 0.04). No differences were observed between the early- and late-start groups with respect to RKF decline, urine volume decline or time to anuria. Initiation of PD was associated with a slower decline of RKF compared to the pre-dialysis period.