Design and methodology of the PRIMETIME 1 cohort study: PRecIsion MEdicine based on kidney TIssue Molecular interrogation in diabetic nEphropathy
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PROVIDER: S-EPMC10689178 | biostudies-literature | 2023 Jun
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Project description:PurposeIndividuals with diabetes and chronic kidney disease are at high risk of kidney failure, cardiovascular events and premature mortality and more research is warranted to further improve the prevention and management of complications. The PRecIsion MEdicine based on kidney TIssue Molecular interrogation in diabetic nEphropathy (PRIMETIME) 1 cohort is designed to study clinical characteristics, diagnostic accuracy and prognostic markers in a population with diabetes and kidney disease classified by biopsy.ParticipantsThis retrospective Danish nationwide cohort includes 2586 individuals with diabetes who have undergone a kidney biopsy between the 1980s and 2022.Findings to dateBy combining multiple registries and medical databases, we comprehensively describe the cohort with data on demographics, socioeconomic status, lifestyle, laboratory measurements, medication use and comorbidity at the time of diagnosis of diabetes and at the time of kidney biopsy within types of kidney disease. In individuals with type 1 diabetes, 132 cases of diabetic nephropathy were identified, with 70.5% of them being men, with a median (IQR) age of 50 (41-59) years at biopsy, and a median (IQR) estimated glomerular filtration rate (eGFR) 37 (23-5X) mL/min/1.73 m2. Among individuals with type 2 diabetes and diabetic nephropathy (n=599), 76.8% were male aged 61.9 (55-99) years at biopsy and with an eGFR 40 (24-6X) mL/min/1.73 m2.Future plansThe national population registries in Denmark provide a long follow-up period and a distinct opportunity to use superior registry data. This cohort offers a unique opportunity to study the prognostic value of findings in kidney biopsies, the impact of comorbidity and the effect of therapy at the time of kidney biopsy, with a follow-up period increasing over time with running updates.
| S-EPMC11535715 | biostudies-literature
Project description:Acute kidney injury (AKI) currently is diagnosed by a temporal trend of a single blood analyte: serum creatinine. This measurement is neither sensitive nor specific to kidney injury or its protean forms. Newer biomarkers, neutrophil gelatinase-associated lipocalin (NGAL, Lipocalin 2, Siderocalin), or kidney injury molecule-1 (KIM-1, Hepatitis A Virus Cellular Receptor 1), accelerate the diagnosis of AKI as well as prospectively distinguish rapidly reversible from prolonged causes of serum creatinine increase. Nonetheless, these biomarkers lack the capacity to subfractionate AKI further (eg, sepsis versus ischemia versus nephrotoxicity from medications, enzymes, or metals) or inform us about the primary and secondary sites of injury. It also is unknown whether all nephrons are injured in AKI, whether all cells in a nephron are affected, and whether injury responses can be stimulus-specific or cell type-specific or both. In this review, we summarize fully agnostic tissue interrogation approaches that may help to redefine AKI in cellular and molecular terms, including single-cell and single-nuclei RNA sequencing technology. These approaches will empower a shift in the current paradigm of AKI diagnosis, classification, and staging, and provide the renal community with a significant advance toward precision medicine in the analysis AKI.
| S-EPMC5753434 | biostudies-literature
Project description: Not available
| S-EPMC7812219 | biostudies-literature
Project description:IntroductionKey genes involved in tubulointerstitial injury may influence the development and progression of diabetic nephropathy (DN). We investigated whether complement-related genes are linked to the mechanism underlying tubulointerstitial injury in DN.MethodsWe analyzed the microarray data of 17 tubulointerstitial tissue samples from DN patients and 21 normal controls from the Gene Expression Omnibus. A gene co-expression network was constructed, and genes were divided into modules by weighted gene co-expression network analysis (WGCNA). We also investigated the association of C3 and C1q deposits in kidney tissues with a composite outcome of end-stage renal disease or a 50% reduction in the estimated glomerular filtration rate (eGFR) in DN patients. Finally, we performed immunohistochemical analyses of C3, C1q, C5b-9, mannose-binding lectin (MBL), and factor B in kidney tissues.ResultsNine co-expression modules were constructed using 12,075 genes from the 38 human tubulointerstitial tissue samples. Black module with more genes was positively correlated with tubulointerstitial injury in DN. C3, one of the top 10 genes in tubulointerstitial injury, was verified in an independent dataset; C3 was significantly overexpressed in tubulointerstitial tissue from patients with DN compared to the normal controls. The mRNA level of C3 in renal tubulointerstitium was negatively correlated with eGFR in DN patients (r = -0.75; p = 0.001). Analysis of the follow-up data of 54 DN patients demonstrated that codeposits of C3 and C1q in kidney tissues were independently associated with the renal outcome in DN (hazard ratio, 2.3, 95% confidence interval, 1.01-5.2, p < 0.05). Immunohistochemical analysis showed that patients with higher C1q, C3, C5b-9, MBL, or factor B expression in renal tubulointerstitium were more likely to progress to kidney failure.ConclusionLocal complement activation of the classical, lectin and alternative pathways appears linked to tubulointerstitial injury and disease progression in DN.
| S-EPMC9037626 | biostudies-literature
Project description:Some kidney donors have diabetes, and little of their natural course of diabetic nephropathy (DN) is known. The aim of this study was to analyze the changes in pathologic lesions in the diabetic donor kidney after KT by performing protocol biopsy two weeks and one year after KT. This retrospective study included 103 patients who underwent KT, with kidneys from donors with a history of diabetes mellitus (DM). Among them, data of 34 patients who underwent biopsy two weeks and one year after KT were reviewed. Biopsy specimens were reviewed using light microscopy and electron microscopy. Glomerular basement membrane (GBM) thickness at 2 weeks and 1 year was compared. Biopsy showed that DN occurred in 29 of the 34 patients. Only trivial histological changes were observed in 22 patients (64.7%), including 5 patients who did not show DN. At one year after transplantation, there was no change in the DN histologic class in 26 patients (76.5%), and there was no statistically significant difference in the change in GBM thickness. This pattern was observed regardless of the recipient's DM or glycemic control. With this understanding, clinicians can use kidneys from DM donors with more comfort, thereby reducing the kidney discard rate.
| S-EPMC9519853 | biostudies-literature
Project description:Chronic kidney disease (CKD) and acute kidney injury (AKI) are heterogeneous syndromes defined clinically by serial measures of kidney function. Each condition possesses strong histopathologic associations, including glomerular obsolescence or acute tubular necrosis, respectively. Despite such characterization, there remains wide variation in patient outcomes and treatment responses. Precision medicine efforts, as exemplified by the Kidney Precision Medicine Project (KPMP), have begun to establish evolving, spatially anchored, cellular and molecular atlases of the cell types, states, and niches of the kidney in health and disease. The KPMP atlas provides molecular context for CKD and AKI disease drivers and will help define subtypes of disease that are not readily apparent from canonical functional or histopathologic characterization but instead are appreciable through advanced clinical phenotyping, pathomic, transcriptomic, proteomic, epigenomic, and metabolomic interrogation of kidney biopsy samples. This perspective outlines the structure of the KPMP, its approach to the integration of these diverse datasets, and its major outputs relevant to future patient care.
| S-EPMC10922684 | biostudies-literature
Project description:Precision medicine is based on accurate diagnosis and tailored intervention through the use of omics and clinical data together with epidemiology and environmental exposures. Precision medicine should be achieved with minimum adverse events and maximum efficacy in patients with chronic kidney disease (CKD). In this review, the breakthroughs of omics in CKD and the application of systems biology are reviewed. The potential role of transforming growth factor-β1 in the targeted intervention of renal fibrosis is discussed as an example of how to make precision medicine work for CKD.
| S-EPMC5588375 | biostudies-literature
Project description:BackgroundRenal replacement therapy (RRT) is usually indicated for patients with chronic kidney disease (CKD) with glomerular filtration rate below 10 ml/ml/min/1.73m2. However, the need for RRT and timing of dialysis initiation are debatable for patients aged 70 years or older. We here describe the study design and methodology of the Aging Nephropathy Study (AGNES) protocol that aims at evaluating to what extent geriatric-related conditions such as frailty, cognitive dysfunction, and presence of comorbidities have an impact on survival and RRT initiation in this group of patients. In this manuscript we provide detailed information about the AGNES study design and methodology.MethodsAGNES is a prospective observational cohort that aim to investigate clinical, biochemical and demographic factors associated with RRT initiation and mortality of patients with CKD stage 4 or 5 who are aged 70 years and older. We plan to include 200 patients over 5 years. Clinically stable outpatients on conservative management for at least 6 months will be recruited from the Nephrogeriatric Clinic at the Hospital das Clinicas da Universidade de Sao Paulo, Brazil. Eligible patients are submitted to a full clinical examination, geriatric assessment, and blood test at baseline. Following the baseline visit the patients are being monitored during an observational follow up period of at least 12 months during which patients will be contacted in the clinic at their regular follow up or by phone until either RRT initiation or death occurs. This cohort includes evaluation of cognition by the education-adjusted 10-point Cognitive Screener (10-CS), frailty by Fried index score, a complete nutritional assessment (by body composition assessment, global subjective assessment and dietary intake), comorbidities by Charlson comorbidity index and biochemical markers including FGF-23 and Klotho.DiscussionThe AGNES cohort, a real-world study of current clinical practice in elderly patients with advanced CKD prior to dialysis initiation, will shed light into progression of CKD and its complications, indications of RRT and factors determining survival. This investigation will elucidate to what extent geriatric conditions, nutritional status and clinical factors are associated with survival, quality of life and RRT initiation in elderly CKD patients not yet on dialysis.Trial registrationRegistered on ClinicalTrials.gov on 18 October 2019 ( NCT04132492 ).
| S-EPMC7648411 | biostudies-literature
Project description: Not available
| S-EPMC6127413 | biostudies-literature
Project description:The effect of liraglutide on the kidney proteome in the STZ mouse model compared to healthy and STZ diabetic control groups.
2019-01-18 | PXD003007 | Pride