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Introduction: The Kidney BEAM randomized controlled trial reported clinically meaningful and statistically significant improvements in mental health-related quality of life (HRQoL), physical function (sit-to-stand-60, but not the physical component of HRQoL) and patient activation after a 12-week physical activity digital health intervention (DHI). This study explores factors that contributed to the effectiveness of Kidney BEAM through mixed methods analyses., Methods: Quantitative data analysis was obtained from the recently published primary manuscript. Participants from the Kidney BEAM trial intervention group ( n  = 30) completed individualized semistructured interviews after the 12-week DHI. Interviews were analyzed using the framework method with inductive and deductive coding. Quantitative and qualitative data collection and analyses occurred concurrently, and independently, before combining using a mixed methods analysis with joint displays to triangulate datasets and further explore the primary findings., Results: The integrated mixed methods analyses facilitated explanation of the primary findings. The Kidney BEAM intervention was shown to have mental and physical wellbeing benefits and enhanced self-management in this cohort of people living with chronic kidney disease (CKD). Elements that contributed to the effectiveness of the intervention were reported, including the different functional levels and gradual progression of the program, shared lived experiences with other participants, self-monitoring, the sense of achievement, taking back control of their health, moving beyond medications, and feeling safe and confident to exercise., Conclusion: Elements of the Kidney BEAM intervention that contributed to the main quantitative trial findings were identified. This will allow researchers and practitioners to maximize the effectiveness of DHIs to enhance healthy behaviors in people living with CKD., (© 2024 International Society of Nephrology. Published by Elsevier Inc.)

Introduction: There is inequity in the provision of physical rehabilitation services for people living with chronic kidney disease (CKD). The Kidney BEAM trial evaluated the clinical value and cost effectiveness of a physical activity digital health intervention (DHI) in CKD., Methods: In a single-blind, 11 center, randomized controlled trial, 340 adult participants with CKD were randomly assigned to either the Kidney BEAM physical activity DHI or a waitlist control. This study assessed the difference in the Kidney Disease Quality of Life Short Form 1.3 Mental Component Summary (KDQoL-SF1.3 MCS) between intervention and control groups at 6-months, and cost-effectiveness of the intervention., Results: At 6-months, there was a significant difference in mean adjusted change in KDQoL MCS score between Kidney BEAM and waitlist control (intention-to-treat adjusted mean: 5.9 [95% confidence interval, CI: 4.4-7.5] arbitrary units [AU], P  < 0.0001), and a 93% and 98% chance of the intervention being cost-effective at a willingness-to-pay threshold of £20,000 and £30,000 per quality-adjusted life year gained., Conclusion: The Kidney BEAM physical activity DHI is a clinically valuable and cost-effective means to improve mental health-related quality of life (HRQoL) in people with CKD (trial registration no. NCT04872933)., (Crown Copyright © 2024 Published by Elsevier Inc. on behalf of the International Society of Nephrology.)

This trial assessed the feasibility and acceptability of Kidney BEAM, a physical activity and emotional well-being self-management digital health intervention (DHI) for people with chronic kidney disease (CKD), which offers live and on-demand physical activity sessions, educational blogs and videos, and peer support. In this mixed-methods, multicentre randomised waitlist-controlled internal pilot, adults with established CKD were recruited from five NHS hospitals and randomised 1:1 to Kidney BEAM or waitlist control. Feasibility outcomes were based upon a priori progression criteria. Acceptability was primarily explored via individual semi-structured interviews (n = 15). Of 763 individuals screened, n = 519 (68%, 95% CI 65 to 71%) were eligible. Of those eligible, n = 303 (58%, 95% CI 54-63%) did not respond to an invitation to participate by the end of the pilot period. Of the 216 responders, 50 (23%, 95% CI 18-29%) consented. Of the 42 randomised, n = 22 (10 (45%) male; 49 ± 16 years; 14 (64%) White British) were allocated to Kidney BEAM and n = 20 (12 (55%) male; 56 ± 11 years; 15 (68%) White British) to the waitlist control group. Overall, n = 15 (30%, 95% CI 18-45%) withdrew during the pilot phase. Participants completed a median of 14 (IQR 5-21) sessions. At baseline, 90-100% of outcome data (patient reported outcome measures and a remotely conducted physical function test) were completed and 62-83% completed at 12 weeks follow-up. Interview data revealed that remote trial procedures were acceptable. Participants' reported that Kidney BEAM increased their opportunity and motivation to be physically active, however, lack of time remained an ongoing barrier to engagement with the DHI. An randomised controlled trial of Kidney BEAM is feasible and acceptable, with adaptations to increase recruitment, retention and engagement.Trial registration NCT04872933. Date of first registration 05/05/2021., (© 2024. The Author(s).)

Background: Remote digital health interventions to enhance physical activity provide a potential solution to improve the sedentary behaviour, physical inactivity, and poor health-related quality of life that are typical of chronic conditions, particularly for people with chronic kidney disease. However, there is a need for high-quality evidence to support implementation in clinical practice. The Kidney BEAM trial evaluated the clinical effect of a 12-week physical activity digital health intervention on health-related quality of life., Methods: In a single-blind, randomised controlled trial conducted at 11 centres in the UK, adult participants (aged ≥18 years) with chronic kidney disease were recruited and randomly assigned (1:1) to the Kidney BEAM physical activity digital health intervention or a waiting list control group. Randomisation was performed with a web-based system, in randomly permuted blocks of six. Outcome assessors were masked to treatment allocation. The primary outcome was the difference in the Kidney Disease Quality of Life Short Form version 1.3 Mental Component Summary (KDQoL-SF1.3 MCS) between baseline and 12 weeks. The trial was powered to detect a clinically meaningful difference of 3 arbitrary units (AU) in KDQoL-SF1.3 MCS. Outcomes were analysed by an intention-to-treat approach using an analysis of covariance model, with baseline measures and age as covariates. The trial was registered with ClinicalTrials.gov, NCT04872933., Findings: Between May 6, 2021, and Oct 30, 2022, 1102 individuals were assessed for eligibility, of whom 340 participants were enrolled and randomly assigned to the Kidney BEAM intervention group (n=173) or the waiting list control group (n=167). 268 participants completed the trial (112 in the Kidney BEAM group and 156 in the waiting list control group). All 340 randomly assigned participants were included in the intention-to treat population. At 12 weeks, there was a significant improvement in KDQoL-SF.13 MCS score in the Kidney BEAM group (from mean 44·6 AU [SD 10·8] at baseline to 47·0 AU [10·6] at 12 weeks) compared with the waiting list control group (from 46·1 AU [10·5] to 45·0 AU [10·1]; between-group difference of 3·1 AU [95% CI 1·8-4·4]; p<0·0001)., Interpretation: The Kidney BEAM physical activity platform is an efficacious digital health intervention to improve mental health-related quality of life in patients with chronic kidney disease. These findings could facilitate the incorporation of remote digital health interventions into clinical practice and offer a potential intervention worthy of investigation in other chronic conditions., Funding: Kidney Research UK., Competing Interests: Declaration of interests King's College Hospital NHS Trust and SAG were involved in the conception and development of Kidney BEAM. SB is a trustee of Kidney Research UK. DCW has an ongoing consultancy contract with AstraZeneca and has received honoraria or consultancy fees from Astellas, Boehringer Ingelheim, Bayer, Eledon, Galderma, GlaxoSmithKline, Gilead, Janssen, Mundipharma, ProKidney, Tricida, Vifor, and Zydus for activities related to education and clinical trials. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Tubulointerstitial fibrosis is a major pathological feature in chronic kidney disease (CKD) and collagen type III (COL3) is a major component of the renal fibrotic scar. We hypothesized that a dysregulated turnover of COL3 is an important determinant of CKD progression. We assessed the relationship between fragments reflecting active formation (PRO-C3) and degradation (C3M) of COL3 and CKD disease progression and mortality in a prospective cohort of CKD patients., Methods: We measured PRO-C3 and C3M in urine (uPRO-C3 and uC3M) and serum (sPRO-C3 and sC3M) of 500 patients from the Renal Impairment in Secondary Care study. Disease progression was defined as a decline in estimated glomerular filtration rate >30% or the start of renal replacement therapy within 12 and 30 months., Results: Levels of uC3M/creatinine decreased, whereas levels of uPRO-C3/creatinine and sPRO-C3 increased with increasing CKD stage. uC3M/creatinine was inversely and independently associated with disease progression by 12 months {odds ratio [OR] 0.39 [95% confidence interval (CI) 0.18-0.83]; P = 0.01 per doubling of uC3M/creatinine} with development of end-stage renal disease [hazard ratio (HR) 0.70 (95% CI 0.50-0.97); P = 0.03 per doubling of uC3M/creatinine]. sPRO-C3 at baseline was independently associated with increased mortality [HR 1.93 (95% CI 1.21-3.1); P = 0.006 per doubling of sPRO-C3] and disease progression by 30 months [OR 2.16 (95% CI 1.21-3.84); P = 0.009 per doubling of sPRO-C3]., Conclusions: Dynamic products of COL3 formation and degradation were independently associated with CKD progression and mortality and may represent an opportunity to link pathological processes with targeted treatments against fibrosis., (© The Author(s) 2020. Published by Oxford University Press on behalf of ERA-EDTA.)

Since the emergency of novel coronavirus COVID-19 (SARS-CoV-2) in December 2019, infections have spread rapidly across the world. The reported incidence of acute kidney injury (AKI) in the context of COVID-19 is variable, and its mechanism is not well understood. Data are emerging about possible mechanisms of AKI including virus-induced cytopathic effect and cytokine storm-induced injury. To date, there have been few reports of kidney biopsy findings in the context of AKI in COVID-19 infection. This article describes 2 cases of collapsing glomerulopathy, 1 in a native kidney and, for the first time, 1 in a kidney transplant. Both individuals were black, and both presented without significant respiratory compromise. Indeed, the 2 patients we describe remained systemically well for the majority of their inpatient stay, which would support the hypothesis that for these patients, AKI was caused by a cytopathic viral effect, rather than that of a cytokine storm or acute tubular necrosis caused by prolonged hypovolaemia or the effect of medication known to exacerbate AKI. Here, we report 2 cases of AKI with collapsing glomerulopathy in COVID-19, one of which is in a kidney transplant recipient, not previously described elsewhere., (© 2020 S. Karger AG, Basel.)

Background: Patients with chronic kidney disease (CKD) have increased risk of development of end-stage renal disease (ESRD) and early mortality. Fibrosis is the central pathogenic process in CKD and is caused by dysregulated extracellular matrix (ECM) remodeling. The laminin γ1 chain (LAMC1) is a core structural protein present in the basement membrane of several organs, including the kidneys. We hypothesized that dysregulation of LAMC1 remodeling could be associated with a higher risk of adverse clinical outcomes in patients with CKD., Methods: A novel immunoassay targeting LG1M, a specific MMP-9-generated neo-epitope fragment of LAMC1, was developed and used to measure the levels of the fragment in urine and serum from 492 patients from the Renal Impairment in Secondary Care (RIISC) study, a prospective cohort of patients with high-risk CKD. Patients were monitored for a median follow-up time of 3.5 years. Associations between serum and urine LG1M levels and progression of CKD at 12 months were assessed by a multivariable logistic regression model. The association with ESRD or mortality was assessed by Kaplan-Meier survival curves and Cox proportional hazards regression., Results: Forty-six (11%) of the 416 patients who reached 12-month follow-up had progression of CKD; during the study follow-up, 125 patients (25.4%) developed ESRD and 71 patients (14.4%) died. Serum and urine levels of LG1M correlated with baseline eGFR (r = -0.43, p<0.0001 and r = -0.17, p = 0.0002, respectively). Serum levels of LG1M were higher in patients with one-year progression of CKD compared to those who did not progress (p<0.01). Baseline serum levels of LG1M were associated with development of ESRD (HR 3.2, 95% CI 1.99-5.2 for patients in the highest LG1M tertile compared to patient in the lowest tertile). Baseline urinary levels of LG1M (uLG1M) were significantly associated with mortality (HR 5.0, 95% CI 2.8-8.9, p<0.0001 for patients in the highest LG1M tertile compared to patients in the lowest tertile). Urine LG1M was retained in the model for prediction of mortality (HR per standard deviation of uLG1M: 1.01, 95% CI 1.00-1.02, p = 0.001)., Conclusions: LG1M, a marker of basement membrane remodeling, is increased in serum and urine of patients with CKD and levels are associated with one-year disease progression, development of ESRD, and mortality., Competing Interests: SHN, DGKR, MK and FGE are full time employees at Nordic Bioscience A/S, which is a company involved in discovery and development of biochemical biomarkers. M. A. Karsdal owns stocks at Nordic Bioscience. The Binding Site Ltd (Birmingham, UK) is acknowledged for the funding of the research fellowship of AF. There are no patents, products in development or marketed products to declare. This does not alter our adherence to all the PLOS ONE policies on sharing data and materials.

Effective diabetic kidney disease (DKD) biomarkers remain elusive, and urinary miRNAs represent a potential source of novel noninvasive disease sentinels. We profiled 754 miRNAs in pooled urine samples from DKD patients (n = 20), detecting significantly increased miR-126, miR-155, and miR-29b compared with controls (n = 20). These results were confirmed in an independent cohort of 89 DKD patients, 62 diabetic patients without DKD, and 41 controls: miR-126 (2.8-fold increase; P < 0.0001), miR-155 (1.8-fold increase; P < 0.001), and miR-29b (4.6-fold increase; P = 0.024). Combined receiver operating characteristic curve analysis resulted in an area under the curve of 0.8. A relative quantification threshold equivalent to 80% sensitivity for each miRNA gave a positive signal for 48% of DKD patients compared with 3.6% of diabetic patients without DKD. Laser-capture microdissection of renal biopsy specimens, followed by quantitative RT-PCR, detected miR-155 in glomeruli and proximal and distal tubules, whereas miR-126 and miR-29b were most abundant in glomerular extracts. Subsequent experiments showed miR-126 and miR-29b enrichment in glomerular endothelial cells (GEnCs) compared with podocytes, proximal tubular epithelial cells, and fibroblasts. Significantly increased miR-126 and miR-29b were detected in GEnC conditioned medium in response to tumor necrosis factor-α and transforming growth factor-β1, respectively. Our data reveal an altered urinary miRNA profile associated with DKD and link these variations to miRNA release from GEnCs., (Copyright © 2018 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Introduction: Marked arterial adaptation is critical in permitting and sustaining the increased blood flow within an arteriovenous fistula (AVF). The aim of this investigation was to evaluate markers of arterial disease and their association with the early post-operative AVF outcomes., Methods: We included all patients in whom an AVF had been performed after enrolment to the Renal Impairment In Secondary Care (RIISC) study. Primary AVF failure (PFL) was defined as thrombosis at six-week review. All patients underwent BP Tru and Vicorder pulse wave analysis assessments and also had assays of advanced glycation end-products prior to AVF formation. These were correlated with the short-term AVF outcomes., Results: One hundred and eight AVFs were created in 86 patients. The primary patency (PPT) group were found to have significantly higher body mass index (BMI) (p = 0.01). Intraluminal vein diameter was significantly greater in the PPT group than the PFL group (p≤0.01). Mean augmentation index and augmentation index 75 was significantly higher in the PPT group than the PFL group (p = 0.03 and 0.03, respectively). Aortic pulse wave velocity was slower in the PPT group at 10.2 m/s than the PFL group at 10.8 m/s (p = 0.32). Advanced glycation end-product measurements did not vary significantly between the PPT and PFL groups (p = 0.4). Logistic regression analysis provided a predictive model, which demonstrated a predictive value of 78.1% for AVF patency at 6 weeks., Conclusions: All patients in this end-stage renal disease cohort have significant aortic stiffness. The results for pulse wave velocity were slower in the PPT group suggesting a tendency towards stiffer vessels and PFL.

Renal fibrosis is the central pathogenic process in progression of chronic kidney disease (CKD). Collagen type VI (COL VI) is upregulated in renal fibrosis. Endotrophin is released from COL VI and promotes pleiotropic pro-fibrotic effects. Kidney disease severity varies considerably and accurate information regarding CKD progression may improve clinical decisions. We tested the hypothesis that urinary endotrophin derived during COL VI deposition in fibrotic human kidneys is a marker for progression of CKD in the Renal Impairment in Secondary Care (RIISC) cohort, a prospective observational study of 499 CKD patients. Endotrophin localised to areas of increased COL VI deposition in fibrotic kidneys but was not present in histologically normal kidneys. The third and fourth quartiles of urinary endotrophin:creatinine ratio (ECR) were independently associated with one-year disease progression after adjustment for traditional risk factors (OR (95%CI) 3.68 (1.06-12.83) and 8.65 (2.46-30.49), respectively). Addition of ECR quartiles to the model for disease progression increased prediction as seen by an increase in category-free net reclassification improvement (0.45, 95% CI 0.16-0.74, p = 0.002) and integrated discrimination improvement (0.04, 95% CI 0.02-0.06, p < 0.001). ECR was associated with development of end-stage renal disease (ESRD). It is concluded that ECR predicts disease progression of CKD patients.

Background: Arteriosclerosis is an independent predictor of increased cardiovascular mortality in chronic kidney disease (CKD). Histologically it is characterized by hypertrophy and fibrosis of the arterial media wall leading to increased arterial stiffness and end-organ damage. Caveolin-1 acts as an intracellular signalling pathway chaperone in human fibrotic and vascular diseases. The purpose of this study was to assess the association between caveolin-1 (CAV1) single-nucleotide polymorphism (SNP) rs4730751 and arterial stiffness as measured by arterial pulse wave velocity (PWV) in an early-stage CKD cohort and in a cohort with more severe CKD., Methods: Two prospectively maintained patient cohorts with non-dialysis CKD were studied: 144 patients in the Chronic Renal Impairment in Birmingham (CRIB) cohort and 147 patients in the Renal Impairment in Secondary Care (RIISC) cohort, with matched exclusion criteria and DNA sampling availability. At entry to each cohort database, each patient's initial arterial PWV was measured, as well as their anthropomorphic and biochemical data. CAV1 rs4730751 SNP genotyping was performed using Taqman technology., Results: The CAV1 rs4730751 SNP CC genotype was associated with lower arterial PWV in both CRIB early stage CKD patients [8.1 versus 8.6 m/s; coefficient -0.780 (-1.412, -0.149); P = 0.016] and RIISC more advanced stage CKD patients [8.7 versus 9.4 m/s; coefficient -0.695 (-1.288, -0.102); P = 0.022]; these relationships held following adjustment for other important confounders., Conclusions: This replicated study suggests potential utility of the studied CAV1 SNP as a genetic biomarker in CKD and a role for CAV1 in the development of arteriosclerosis in this setting. Further studies are warranted to further explore the basic science driving these clinical observations., (© The Author 2015. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Objectives: The aim of this study was to report the long-term outcomes in patients with multiple myeloma (MM) who receive dialysis treatment for acute kidney injury (AKI) due to myeloma cast nephropathy and subsequently recover renal function., Methods: Patients presenting with dialysis-dependent AKI secondary to myeloma cast nephropathy and subsequently recovering independent renal function between January 2005 and December 2012 were included in this study. Both renal and haematological parameters were collected at multiple time points as part of routine clinic practice. Factors associated with renal function and overall survival (OS) were determined., Results: Twenty-four patients fulfilled the criteria for inclusion. Mean age was 62.1 years; 75% were male and 75% were of White ethnicity. The median OS was 64.1 months (95% confidence interval [CI] 34.8-93.3). Twenty-three (95.8%) patients remained dialysis-independent until death or end of follow-up; one patient required further haemodialysis treatment during the follow-up period. The independent determinant of worse OS was a known history of chronic kidney disease (CKD) at presentation. Shorter length of time on haemodialysis and higher percentage reduction in clonal serum FLC at day 21 from baseline predicted better excretory renal function (estimated glomerular filtration rate) at 6 months., Conclusion: In this series, the large majority of patients with MM and dialysis-dependent AKI secondary to myeloma cast nephropathy who recovered independent renal function had no requirement for further dialysis. Survival following recovery of renal function is good, and early variables are independently associated with survival and future renal function., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Introduction: Chronic kidney disease (CKD) is associated with significant morbidity and mortality. There is a need to identify novel and modifiable risk factors in such patients. The periodontal component of the Renal Impairment In Secondary Care (RIISC) study aims to evaluate the association between chronic periodontitis and CKD progression., Methods: The RIISC study is a prospective, observational cohort study of patients with CKD from a renal clinic at a hospital in the West Midlands region of the UK. Patients undergo a periodontal examination and plaque and saliva sampling. To benchmark the oral health status of the RIISC cohort, we compared it to the Adult Dental Health Survey 2009 (ADHS), a representative survey of the oral health of community dwelling adults in the UK., Results: Of the first 500 patients recruited into the RIISC study, 469 patients underwent a dental examination and 80 (17%) were edentulous. Among dentate subjects, patients within RIISC were significantly more likely to have any (OR 4.0 95% CI 2.7-5.9) or severe (OR 3.8 95% CI 2.5-5.6) periodontitis compared to the ADHS sample., Conclusion: The prevalence and severity of chronic periodontitis in this cohort of CKD patients is markedly higher than a geographically matched control population., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: To assess the impact of chronic kidney disease (CKD) and cardiovascular comorbidity on mortality in a multiethnic primary care population., Design: Retrospective cohort study., Setting: Inner-city primary care trust in West Midlands, UK., Participants: Individuals aged 40 years and older, of South Asian, black or white ethnicity, registered with a general practice and with their kidney function checked within the last 12 months (n=31 254)., Outcome Measure: All-cause mortality., Results: Reduced estimated glomerular filtration rate, higher albuminuria, older age, white ethnicity (vs South Asian or black ethnicity) and increasing cardiovascular comorbidities were independent determinants of a higher mortality risk. In the multivariate model including comorbidities and kidney function, the HR for mortality for South Asians was 0.697 (95% CI 0.56 to 0.868, p=0.001) and for blacks it was 0.533 (95% CI 0.403 to 0.704, p<0.001) compared to whites., Conclusions: The HR for death is lower for South Asian and black individuals compared to white individuals. This is, in part, independent of age, gender, socioeconomic status, kidney function and comorbidities. Risk of death is higher in individuals with CKD and with a higher cumulative cardiovascular comorbidity.

Background: Chronic kidney disease (CKD) affects up to 16% of the adult population and is associated with significant morbidity and mortality. People at highest risk from progressive CKD are defined by a sustained decline in estimated glomerular filtration rate (eGFR) and/or the presence of significant albuminuria/proteinuria and/or more advanced CKD. Accurate mapping of the bio-clinical determinants of this group will enable improved risk stratification and direct the development of better targeted management for people with CKD., Methods/design: The Renal Impairment In Secondary Care study is a prospective, observational cohort study, patients with CKD 4 and 5 or CKD 3 and either accelerated progression and/or proteinuria who are managed in secondary care are eligible to participate. Participants undergo a detailed bio-clinical assessment that includes measures of vascular health, periodontal health, quality of life and socio-economic status, clinical assessment and collection of samples for biomarker analysis. The assessments take place at baseline, and at six, 18, 36, 60 and 120 months; the outcomes of interest include cardiovascular events, progression to end stage kidney disease and death., Discussion: The determinants of progression of chronic kidney disease are not fully understood though there are a number of proposed risk factors for progression (both traditional and novel). This study will provide a detailed bio-clinical phenotype of patients with high-risk chronic kidney disease (high risk of both progression and cardiovascular events) and will repeatedly assess them over a prolonged follow up period. Recruitment commenced in Autumn 2010 and will provide many outputs that will add to the evidence base for progressive chronic kidney disease.

Background: It is proposed that chronic calcineurin inhibitor (CNI) nephrotoxicity has a central role in chronic kidney disease after nonrenal solid organ transplantation (NRSOT), although there are little data on renal histology in this setting. The aim of this study was to assess the histological features and renal outcomes of a cohort of patients with chronic kidney disease after NRSOT., Methods: Renal biopsies of 62 NRSOT recipients were evaluated for histological diagnoses. Biopsies were graded for chronic allograft damage index parameters and for arteriolar hyalinosis. The sum of all chronic allograft damage index parameters and arteriolar hyalinosis scores was called chronic damage index., Results: The biopsies were performed at a median of 4 (range: 0.3-15.9) years after NRSOT and at serum creatinine of 318±17.7 μmol/L (mean±standard deviation). Twenty-two (35.5%) biopsies showed predominant features of chronic CNI nephrotoxicity, 27 (43.5%) predominant features of hypertensive nephropathy, and 12 (19.3%) an alternative primary renal pathology. Twenty-four (38.7%) patients had progression to end-stage renal disease, at a median of 1.5 (0-10.1) years after biopsy and 6.9 (0.3-19.2) years after NRSOT. The risk of renal progression was associated with in situ damage measured by chronic damage index., Conclusions: Although CNI nephrotoxicity is an important cause of renal failure after NRSOT, many patients do not have overt histological evidence of CNI toxicity. Quantitative parameters of chronic damage can stratify renal prognosis.

Fibroblasts, which originate from embryonic mesenchymal cells, are the predominant cell type seen in loose connective tissue. As the main components of the internal environment that cells depend on for survival, fibroblasts play an essential role in tissue development, wound healing, and the maintenance of tissue homeostasis. Furthermore, fibroblasts are also involved in several pathological processes, such as fibrosis, cancers, and some inflammatory diseases. In this review, we analyze the latest research progress on fibroblasts, summarize the biological characteristics and physiological functions of fibroblasts, and delve into the role of fibroblasts in disease pathogenesis and explore treatment approaches for fibroblast-related diseases. [ABSTRACT FROM AUTHOR]

Background: National guidance recognises the key role of rehabilitation in improving outcomes for people living with chronic kidney disease. Implementation of this guidance is reliant upon an adequate and skilled rehabilitation workforce. Data relating to this is currently lacking within the UK. This survey aimed to identify variations and good practices in kidney physiotherapy (PT), occupational therapy (OT) and clinical exercise physiologist (CEP) provision; and to understand barriers to implementation. Methods: An online survey was sent to all 87 UK kidney units between June 2022 and January 2023. Data was collected on the provision of therapy services, barriers to service provision and responses to the COVID-19 pandemic. The quantitative survey was analysed using descriptive statistics. Free-text responses were explored using reflexive thematic analysis. Results: Forty-five units (52%) responded. Seventeen (38%) units reported having a PT and 15 (33%) an OT with a specialist kidney role; one unit (7%) had access to a CEP. Thirty units (67%) offered inpatient therapy services, ten (22%) outpatient therapy clinics, six (13%) intradialytic exercise, six (13%) symptom management and three (7%) outpatient rehabilitation. Qualitative data revealed lack of money/funding and time (both n = 35, 85% and n = 34, 83% respectively) were the main barriers to delivering kidney-specific therapy. Responders saw an increase in the complexity of their caseload, a reduction in staffing levels and consequently, service provision during the COVID-19 pandemic. Exemplars of innovative service delivery, including hybrid digital and remote services, were viewed as positive responses to the COVID-19 pandemic. Conclusion: Despite clear evidence of the benefits of rehabilitation, across the UK, there remains limited and variable access to kidney-specific therapy services. Equitable access to kidney-specific rehabilitation services is urgently required to support people to 'live well' with kidney disease. [ABSTRACT FROM AUTHOR]

Simple Summary: Chronic kidney disease remains a global health priority, only detected at relatively advanced stages by current markers. Identifying alternative markers for early detection is imperative. In this study, we profiled the urinary proteome in patients with albuminuria and well-preserved eGFR. We identified 80 proteins that were differentially abundant between the cases (albuminuria) and controls (normoalbuminuria). Among these, 12 proteins (SERPINA1, ALB, SERPINC1, AFM, PIGR, A1BG, COL6A1, MYG, LV39, MUC1, ICOSLG, and UMOD) had the highest discriminating abilities (area under curve > 0.8) between the cases and controls. When differentially abundant proteins were combined into an 80-protein model, the model was able to predict cases from controls with a predictive accuracy of 91.3%. The top five enriched biological pathways associated with the differentially abundant proteins included insulin growth factor functions, innate immunity, platelet degranulation, and extracellular matrix organization. Albuminuria may precede decreases in the glomerular filtration rate (GFR) and both tests are insensitive predictors of early stages of kidney disease. Our aim was to characterise the urinary proteome in black African individuals with albuminuria and well-preserved GFR from South Africa. This case-controlled study compared the urinary proteomes of 52 normoalbuminuric (urine albumin: creatinine ratio (uACR) < 3 mg/mmol) and 56 albuminuric (uACR ≥ 3 mg/mmol) adults of black African ethnicity. Urine proteins were precipitated, reduced, alkylated, digested, and analysed using an Evosep One LC (Evosep Biosystems, Odense, Denmark) coupled to a Sciex 5600 Triple-TOF (Sciex, Framingham, MA, USA) in data-independent acquisition mode. The data were searched on SpectronautTM 15. Differentially abundant proteins (DAPs) were filtered to include those with a ≥2.25-fold change and a false discovery rate ≤ 1%. Receiver–operating characteristic curves were used to assess the discriminating abilities of proteins of interest. Pathway analysis was performed using Enrichr software. As expected, the albuminuric group had higher uACR (7.9 vs. 0.55 mg/mmol, p < 0.001). The median eGFR (mL/min/1.73 m2) showed no difference between the groups (111 vs. 114, p = 0.707). We identified 80 DAPs in the albuminuria group compared to the normoalbuminuria group, of which 59 proteins were increased while 21 proteins were decreased in abundance. We found 12 urinary proteins with an AUC > 0.8 and a p < 0.001 in the multivariate analysis. Furthermore, an 80-protein model was developed that showed a high AUC ˃ 0.907 and a predictive accuracy of 91.3% between the two groups. Pathway analysis found that the DAPs were involved in insulin growth factor (IGF) functions, innate immunity, platelet degranulation, and extracellular matrix organization. In albuminuric individuals with a well-preserved eGFR, pathways involved in preventing the release and uptake of IGF by insulin growth factor binding protein were significantly enriched. These proteins are indicative of a homeostatic imbalance in a variety of cellular processes underlying renal dysfunction and are implicated in chronic kidney disease. [ABSTRACT FROM AUTHOR]

Acute kidney injury (AKI) is a public health concern associated with high rates of mortality, even in milder cases. One of the reasons for the difficulty in managing AKI in patients is due to its association with pre-existing comorbidities, such as diabetes. In fact, diabetes increases the susceptibility to develop more severe AKI after renal ischemia. However, the long-term effects of this association are not known. Thus, an experimental model was designed to evaluate the chronic effects of renal ischemia/reperfusion (IR) in streptozotocin (STZ)-treated mice. We focused on the glomerular and tubulointerstitial damage, as well as kidney function and metabolic profile. It was found that pre-existing diabetes may potentiate progressive kidney disease after AKI, mainly by exacerbating proinflammatory and sustaining fibrotic responses and altering renal glucose metabolism. To our knowledge, this is the first report that highlights the long-term effects of renal IR on diabetes. The findings of this study can support the management of AKI in clinical practice. NEW & NOTEWORTHY: This study demonstrated that early diabetes potentiates progressive kidney disease after ischemia/reperfusion (IR)-induced acute kidney injury, mainly by exacerbating pro-inflammatory and sustaining fibrotic responses and altering renal glucose metabolism. Thus, these findings will contribute to the therapeutic support of patients with type 1 diabetes with eventual renal IR intervention in clinical practice. [ABSTRACT FROM AUTHOR]

Periodontal diseases, ranging from gingivitis to periodontitis, are prevalent oral diseases affecting over 50% of the global population. These diseases arise from infections and inflammation of the gums and supporting bones, significantly impacting oral health. The established link between periodontal diseases and systemic diseases, such as cardiovascular diseases, underscores their importance as a public health concern. Consequently, the early detection and prevention of periodontal diseases have become critical objectives in healthcare, particularly through the integration of advanced artificial intelligence (AI) technologies. This paper aims to bridge the gap between clinical practices and cutting-edge technologies by providing a comprehensive review of current research. We examine the identification of causative factors, disease progression, and the role of AI in enhancing early detection and treatment. Our goal is to underscore the importance of early intervention in improving patient outcomes and to stimulate further interest among researchers, bioengineers, and AI specialists in the ongoing exploration of AI applications in periodontal disease diagnosis. [ABSTRACT FROM AUTHOR]

Long-acting dual amylin and calcitonin receptor agonists (DACRAs) are novel candidates for the treatment of type 2 diabetes and obesity due to their beneficial effects on body weight, glucose control, and insulin action. However, how the metabolic benefits are maintained after long-lasting treatment is unknown. This study investigates the long-term anti-obesity and anti-diabetic treatment efficacy of the DACRA KBP-336 alone and combined with the GLP-1 analog semaglutide. Zucker diabetic Sprague Dawley (ZDSD) rats with obesity and diabetes received KBP-336 (4.5 nmol/kg Q3D), semaglutide (50 nmol/kg Q3D), or the combination for 7 mo, and the treatment impact on body weight, food intake, glucose control, and insulin action was evaluated. Furthermore, serum levels of the cardiac fibrosis biomarker endotrophin were evaluated. KBP-336, semaglutide, and the combination lowered body weight significantly compared with the vehicle, with the combination inducing a larger and more sustained weight loss than either monotherapy. All treatments resulted in reduced fasting blood glucose levels and HbA1c levels and improved glucose tolerance compared with vehicle-treated rats. Furthermore, all treatments protected against lost insulin secretory capacity and improved insulin action. Serum levels of endotrophin were significantly lowered by KBP-336 compared with vehicle. This study shows the benefit of combining KBP-336 and semaglutide to obtain significant and sustained weight loss, as well as improved glucose control. Furthermore, KBP-336-driven reductions in circulating endotrophin indicate a clear reduction in the risk of complications. Altogether, KBP-336 is a promising candidate for the treatment of obesity and type 2 diabetes both alone and in combination with GLP-1 analogs. NEW & NOTEWORTHY: These studies describe the benefit of combining dual amylin and calcitonin receptor agonists (DACRA) with semaglutide for long-term treatment of obesity and type 2 diabetes. Combination treatment induced sustained weight loss and improved glucose control. A DACRA-driven reduction in a serological biomarker of cardiac fibrosis indicated a reduced risk of complications. These results highlight DACRAs as a promising candidate for combination treatment of obesity and type 2 diabetes and related long-term complications. [ABSTRACT FROM AUTHOR]

Chronic kidney disease (CKD) is defined by persistent abnormalities of kidney function or structure that have consequences for the health. A progressive decline of excretory kidney function has effects on body homeostasis. CKD is tightly associated with accelerated cardiovascular disease and severe infections, and with premature death. Kidney failure without access to kidney replacement therapy is fatal - a reality in many regions of the world. CKD can be the consequence of a single cause, but CKD in adults frequently relates rather to sequential injuries accumulating over the life course or to the presence of concomitant risk factors. The shared pathomechanism of CKD progression is the irreversible loss of kidney cells or nephrons together with haemodynamic and metabolic overload of the remaining nephrons, leading to further loss of kidney cells or nephrons. The management of patients with CKD focuses on early detection and on controlling all modifiable risk factors. This approach includes reducing the overload of the remaining nephrons with inhibitors of the renin-angiotensin system and the sodium-glucose transporter 2, as well as disease-specific drug interventions, if available. Hypertension, anaemia, metabolic acidosis and secondary hyperparathyroidism contribute to cardiovascular morbidity and reduced quality of life, and require diagnosis and treatment., Competing Interests: Competing interests: Related to the content of this paper, H.-J.A. received funding from Boehringer Ingelheim and consultancy fees from Novartis, AstraZeneca, Bayer, Boehringer Ingelheim, Vifor, Otsuka, Roche and Eli Lilly. H.-J.A. received payments from the European Renal Association for his role as Editor-in-Chief of Nephrology Dialysis Transplantation. H.-J.A. is a member of the Western-European Regional board of the International Society of Nephrology (ISN). Related to the content of this paper, M.N. received research funding from Kyowa-Kirin, Daiichi-Sankyo, Astellas, Ono, Mitsubishi-Tanabe, Japan Tobacco, Chugai, Bayer, Torii and Takeda. M.N. received honoraria and advisory fees from Kyowa-Kirin, Astellas, AstraZeneca, GlaxoSmithKline, Daiichi-Sankyo, Mitsubishi-Tanabe, Chugai, Torii, Japan Tobacco, Novo Nordisk and Boehringer Ingelheim. M.N. is President of the ISN, President of the Japanese Society of Nephrology, Immediate President of the Asian Pacific Society of Nephrology, President of the Japanese Society of Internal Medicine and Vice President of the Japanese Medical Science Federation. A.L. has no conflicts of interest regarding her contribution to this article, although she was the co-chair of the KDIGO Update on Chronic Kidney Disease Evaluation and Management 2024. B.R.-I. and P.R. declare no competing interests. R.A. reports personal fees from Akebia Therapeutics, Inc., Bayer Healthcare Pharmaceuticals Inc., Boehringer Ingelheim, Chinook, Vertex, Alynlam, Intercept, Eloxx and Novartis. R.A. is an associate editor at Nephrology Dialysis Transplantation and American Journal of Nephrology, and acting Editor in Chief of American Journal of Nephrology. He is a section editor of nephrology at UpToDate. J.C.N.C. reports receiving grants (through institutions) and/or honoraria for consultancy or giving lectures from Applied Therapeutics, AstraZeneca, Bayer, Boehringer Ingelheim, Celltrion, Eli Lilly, Hua Medicine, Powder Pharmaceuticals, Roche, Merck, MSD, Pfizer, Sanofi, Servier, Viatris and Zuellig Therapeutics. She is a co-inventor of patents assigned to the Chinese University of Hong Kong with claims of using genetic and multiomic markers to identify patients at high risk for diabetes and its complications for personalized treatment. She is the co-founder of GemVCare, a technology company, with partial support from the Hong Kong Government, which uses biogenetic markers and information technology to implement precision diabetes care and prevention through partnerships. J.C.N.C. is the Chief Executive Officer (pro bono) of the Asia Diabetes Foundation that developed the web-based JADE platform for implementation of data-driven diabetes care. She is a member of the Global Council of the European Association for Study of Diabetes and a member of the International Diabetes Federation Global Guidelines for type 2 diabetes and member of working groups of KDIGO. R.K. is a member of the African board of the ISN. S.K. is a member of the North American board of the ISN, an adviser to the Middle-East board of the ISN, a member of the education workgroup and the social media team of the ISN, a member of the core program committee of the ISN, and the chair of the young nephrologists committee of the ISN. S.K. is also a member of the clinical nephrology commission of the Société Francophone de Néphrologie Dialyse et Transplantation (SFNDT) and of the webinars committee of the SFNDT. She is also the co-chair of the education committee of the American Society of Onco-nephrology., (© 2025. Springer Nature Limited.)

Chronic kidney disease (CKD) represents an increasing health burden. Evidence suggests the importance of miRNA in diagnosing CKD, yet the reports are inconsistent. This study aimed to determine novel miRNA biomarkers and potential therapeutic targets from hypothesis-free miRNA profiling studies in human and murine CKDs. Comprehensive literature searches were conducted on five databases. Subgroup analyses of kidney diseases, sample types, disease stages, and species were conducted. A total of 38 human and 12 murine eligible studies were analyzed using Robust Rank Aggregation (RRA) and vote-counting analyses. Gene set enrichment analyses of miRNA signatures in each kidney disease were conducted using DIANA-miRPath v4.0 and MIENTURNET. As a result, top target genes, Gene Ontology terms, the interaction network between miRNA and target genes, and molecular pathways in each kidney disease were identified. According to vote-counting analysis, 145 miRNAs were dysregulated in human kidney diseases, and 32 were dysregulated in murine CKD models. By RRA, miR-26a-5p was significantly reduced in the kidney tissue of Lupus nephritis (LN), while miR-107 was decreased in LN patients' blood samples. In both species, epithelial-mesenchymal transition, Notch, mTOR signaling, apoptosis, G2/M checkpoint, and hypoxia were the most enriched pathways. These miRNA signatures and their target genes must be validated in large patient cohort studies. [ABSTRACT FROM AUTHOR]

This article discusses the terminology and classification of non-alcoholic fatty liver disease (NAFLD) in pediatrics. It proposes the term "metabolic dysfunction-associated steatotic liver disease" (MASLD) to replace NAFLD, linking fatty liver with metabolic dysfunction and insulin resistance. The article explores the pathogenesis of MASLD, including factors such as lipogenesis, oxidative stress, gut microbiota, and genetics. Diagnostic criteria for MASLD are discussed, as well as non-invasive assessments for early detection and prevention of disease progression. The article also discusses diagnostic and therapeutic approaches for pediatric NAFLD, including the use of algorithms, biomarkers, imaging tests, and various interventions such as omega-3 fatty acids, vitamin E supplementation, and pharmaceutical interventions. Additionally, the document provides a list of completed clinical trials related to the treatment of NAFLD in children, conducted in different countries. However, no results are available for these trials. The document also includes information about the authors' contributions, institutional review board statement, informed consent statement, data availability statement, and conflicts of interest. [Extracted from the article]

Background and aims: Serum polyclonal free light chains (FLCs) levels are associated with overall survival in the general population, reflecting their utility as a biomarker of underlying immune activation and inflammation. Regular exercise is known to ameliorate low-grade inflammation in chronic diseases such as type 2 diabetes; however, the effects of different exercise training modalities on FLCs in adults with type 2 diabetes is unknown. This study investigated the effects of 9-month of aerobic, resistance or combined supervised exercise on serum FLCs in 164 patients with type 2 diabetes (age 58 ± 8 years; 63% female). Methods: 164 participants from the Health Benefits of Aerobic and Resistance Training in individuals with type 2 diabetes trial (HART-D) were randomly assigned to no exercise (n = 27), aerobic exercise alone (n = 41), resistance exercise alone (n = 49), or a combination of aerobic and resistance exercise (n = 47). Fasting serum samples were collected before and after completion of the intervention to quantify changes in kappa and lambda FLCs, and serum creatinine, using commercially-available ELISAs. Results: At baseline, combined kappa and lambda FLCs (FLC sum; calculated as kappa + lambda FLCs) were positively correlated with high-sensitive C-reactive protein (hs-CRP) (r = 0.237, p < 0.05) and fat mass (r = 0.162, p < 0.05), and negatively associated with aerobic fitness (r = -0.238, p < 0.05). While nonexercise controls exhibited an increase in FLCs over the 9-month study, exercise training blunted this increase (FLC sum control arm: 3.25 ± 5.07 mg·L-1 vs. all exercise arms: -0.252 ± 6.60 mg·L-1, p < 0.05), regardless of exercise modality. Conclusion: Serum FLCs were associated with physical fitness and body composition in patients with type 2 diabetes. 9-month of exercise training prevented the accumulation of FLCs, regardless of exercise modality. Unlike hs-CRP--which did not change during the trial--serum FLCs may serve as a more sensitive biomarker of chronic low-grade inflammation in this population. [ABSTRACT FROM AUTHOR]

This article provides information on the diagnosis and management of smouldering myeloma, a precursor condition to multiple myeloma. It discusses various diagnostic tests and imaging techniques used to identify smouldering myeloma and emphasizes the importance of restaging if there is evidence of progression. The article also provides recommendations for screening and initial investigations for suspected myeloma. Additionally, it discusses risk stratification models and treatment options for smouldering myeloma, including the use of lenalidomide. The article concludes by highlighting ongoing clinical trials and the need for further research in the treatment of smouldering myeloma. [Extracted from the article]

Background: Acute kidney injury (AKI) in patients with multisystem inflammatory syndrome (MIS), COVID-19 related infection has been increasingly recognized with a paucity of data on AKI incidence, related mortality, and the requirement of renal replacement therapy in children with MIS (MIS-C). Methods: This is a retrospective study evaluating the prevalence, severity, management and outcomes of AKI in a cohort of Egyptian children with MIS-children (MIS-C) post-COVID infection. Patients were included if they met the criteria for MIS-C based on CDC guidelines. All patients were evaluated for AKI diagnosis and staging according to the Kidney Disease Improving Global Outcomes (KDIGO) criteria. Results: Between March 2021 and June 2023, a total of 655 confirmed COVID-19 cases were admitted and then followed up in our hospital, of whom 138 (21%) were diagnosed with MIS-C. Fifty-one patients developed AKI associated with MIS-C post-COVID infection, 42 of whom were included in the analysis. Thirty-one patients had AKI in a formerly healthy kidney, of whom 51% (16 patients) were classified as KDIGO stage 3, 5 patients needed hemodialysis and 13 needed mechanical ventilation. Higher WBCs count, and serum ferritin on admission were associated with more severe AKI (KDIGO stage 3) (p = 0.04), while multivariate analysis showed high serum ferritin to be independent predictor of more severe AKI (p = 0.02). Two patients (2/31) died during hospital admission, while no residual renal impairment was reported at the time of discharge of patients with previously normal kidney functions. Conclusion: More than one-third of patients with MIS-C develop AKI. Avoidance of nephrotoxic drugs, early recognition, and prompt management of AKI, including well-timed commencement of dialysis in MIS-C cases, is associated with favorable outcomes. [ABSTRACT FROM AUTHOR]

Aims: Extracellular matrix remodelling is one of the key pathways involved in heart failure (HF) progression. Sodium–glucose cotransporter 2 inhibitors (SGLT2i) may have a role in attenuating myocardial fibrosis. The impact of SGLT2i on blood markers of collagen turnover in humans is not fully elucidated. This study aimed to investigate the effect of empagliflozin on serum markers of collagen turnover in patients enrolled in the EMPEROR‐Preserved and EMPEROR‐Reduced trials. Methods and results: Overall, 1084 patients (545 in empagliflozin and 539 in placebo) were included in the analysis. Procollagen type I carboxy‐terminal propeptide (PICP), a fragment of N‐terminal type III collagen (PRO‐C3), procollagen type I amino‐terminal peptide (PINP), a fragment of C‐terminal type VIa3 collagen (PRO‐C6), a fragment of type I collagen (C1M), and a fragment of type III collagen (C3M) were measured in serum at baseline, 12 and 52 weeks. A mixed model repeated measurements model was used to evaluate the effect of empagliflozin versus placebo on the analysed biomarkers. Higher baseline PICP, PRO‐C6 and PINP levels were associated with older age, a more severe HF presentation, higher levels of natriuretic peptides and high‐sensitivity troponin T, and the presence of comorbid conditions such as chronic kidney disease and atrial fibrillation. Higher PICP levels were associated with the occurrence of the study primary endpoint (a composite of HF hospitalization or cardiovascular death), and PRO‐C6 and PINP were associated with the occurrence of sustained worsening of kidney function. On the other hand, PRO‐C3, C1M, and C3M were not associated with worse HF severity or study outcomes. Compared to placebo, empagliflozin reduced PICP at week 12 by 5% and at week 52 by 8% (week 12: geometric mean ratio = 0.95, 95% confidence interval [CI] 0.91–0.99, p = 0.012; week 52: geometric mean ratio = 0.92, 95% CI 0.88–0.97, p = 0.003). Additionally, empagliflozin reduced PRO‐C3 at week 52 by 7% (week 12: geometric mean ratio = 0.98, 95% CI 0.95–1.02, p = 0.42; week 52: geometric mean ratio = 0.93, 95% CI 0.89–0.98, p = 0.003), without impact on other collagen markers. Conclusion: Our observations are consistent with experimental observations that empagliflozin down‐regulates profibrotic signalling. The importance of such an effect for the clinical benefits of SGLT2i in HF remains to be elucidated. [ABSTRACT FROM AUTHOR]

Dual amylin and calcitonin receptor agonists (DACRAs) are effective treatments for obesity and type 2 diabetes (T2D). They provide beneficial effects on body weight, glucose control, and insulin action. However, whether DACRAs protect against diabetesrelated kidney damage remains unknown. We characterize the potential of long-acting DACRAs (KBP-A, Key Bioscience Peptide- A) as a treatment for T2D-related pathological alterations of the kidney extracellular matrix (ECM) in Zucker diabetic fatty rats (ZDF). We examined levels of endotrophin (profibrotic signaling molecule reflecting collagen type VI formation) and tumstatin (matrikine derived from collagen type IVα3) in serum and evaluated kidney morphology and collagen deposition in the kidneys. We included a study in obese Sprague--Dawley rats to further investigate the impact of KBP-A on ECM biomarkers. In ZDF vehicles, levels of endotrophin and tumstatin increased, suggesting disease progression along with an increase in blood glucose levels. These rats also displayed damage to their kidneys, which was evident from the presence of collagen formation in the medullary region of the kidney. Interestingly, KBP-A treatment attenuated these increases, resulting in significantly lower levels of endotrophin and tumstatin than the vehicle. Levels of endotrophin and tumstatin were unchanged in obese Sprague--Dawley rats, supporting the relation to diabetes-related kidney complications. Furthermore, KBP-A treatment normalized collagen deposition in the kidney while improving glucose control. These studies confirm the beneficial effects of DACRAs on biomarkers associated with kidney fibrosis. Moreover, these antifibrotic effects are likely associated with improved glucose control, highlighting KBP-A as a promising treatment of T2D and its related late complications. [ABSTRACT FROM AUTHOR]