Approaches For Chronic Kidney Disease Research Articles

Omics Studies in CKD: Diagnostic Opportunities and Therapeutic Potential

ABSTRACTOmics technologies have significantly advanced the prediction and therapeutic approaches for chronic kidney disease (CKD) by providing comprehensive molecular insights. This is a review of the current state and future prospects of integrating biomarkers into the clinical practice for CKD, aiming to improve patient outcomes by targeted therapeutic interventions. In fact, the integration of genomic, transcriptomic, proteomic, and metabolomic data has enhanced our understanding of CKD pathogenesis and identified novel biomarkers for an early diagnosis and targeted treatment. Advanced computational methods and artificial intelligence (AI) have further refined multi‐omics data analysis, leading to more accurate prediction models for disease progression and therapeutic responses. These developments highlight the potential to improve CKD patient care with a precise and individualized treatment plan .

#2114 TIE2 activation promotes vascular protection of tubules to reduce PDGFB driven tubulointerstitial fibrosis in experimental chronic kidney disease

Abstract Background and Aims The relevance of endothelial dysfunction for tubulointerstitial fibrosis in chronic kidney disease (CKD) is poorly understood. Here, we utilize gain- and loss-of-function experiments to investigate the role of endothelial tyrosine kinase TIE2 for vascular-mediated protection in experimental CKD. Method TIE2 activation was achieved using a human TIE2-activating antibody (ABX), or conditional endothelial knockout of vascular endothelial protein tyrosine phosphatase (Veptp). Conditional endothelial knockout of Tie2 served as a TIE2-incompetent signalling model. CKD was induced by unilateral ureter obstruction (UUO). Results ABX treated and Veptp knockout mice were significantly protected from UUO-induced endothelial dysfunction, tubular injury, and tubulointerstitial fibrosis. Capillary density was preserved as well as fenestrations of peritubular capillaries. In contrast, Tie2 knockout mice had aggravated disease. Mechanistically, the link between endothelial dysfunction and tubulointerstitial fibrosis was tubular expression of PDGFB, which was reduced by ABX treatment and Veptp knockout. A role for endothelial-to-mesenchymal transition was ruled out by careful lineage tracing of endothelial cells and reporter for mesenchymal cells. UUO-induced tubulointerstitial fibrosis was reduced in Pdgfb knockout mice, supporting causality of PDGFB in mesenchymal activation and fibrosis. ABX treated and Veptp knockout mice had significantly lower UUO-induced PDGFB levels. Conclusion Our data supports a key role of the endothelium and TIE2 signalling in CKD. We introduce ABX as a new therapeutic approach in CKD and demonstrate the sequence of events from endothelial dysfunction to tubulointerstitial fibrosis.

Dietary inflammatory index and lower glomerular filtration rate in Mexican adults

We hypothesized that higher scores on the dietary inflammatory index (DII) would be associated with a lower glomerular filtration rate (GFR). This cross-sectional study included 2098 participants from Mexican Teachers Cohort Study, the Health Workers Cohort Study, and the Comitán Study belonging to the RenMex consortium. Energy-adjusted DII scores were estimated using a semi-quantitative food frequency questionnaire (FFQ). eGFR was estimated by the CKD Epidemiology Collaboration equation. Quantile regression models and ordered regression models were estimated to assess the associations of interest. Median age of study participants was 47 years, median eGFR was 102.9 mL/min/1.73m2, and the median energy-adjusted DII was 0.89 (range, -2.25, +4.86). The median eGFR was lower in participants in the highest percentile of DII compared to those in the lowest percentile (103.8 vs 101.4). We found that continuous and categorical energy-adjusted DII scores were associated with lower eGFR, especially at the lower percentiles. In adjusted ordered logistic regression, we found that the highest DII category was associated with 1.80 times the odds of belonging to the mildly decreased eGFR category or moderately decreased eGFR category compared lowest DII category (OR: 1.80, 95%CI 1.35, 2.40). A high DII score was associated with a lower eGFR among the Mexican population. Additional studies are crucial to validate these findings and explore potential strategies to reduce the consumption of pro-inflammatory foods as a preventive approach for chronic kidney disease (CKD).

Multiprofessional Approach for Chronic Kidney Disease (CKD) Risk Reduction and Prophylaxis in the Kushiro Medical Area

Chronic kidney disease (CKD) is closely related to disorders of various organs of the body and is also a factor in increasing social security costs such as medical costs for dialysis. Multiprofessional public health associations in Kushiro City jointly manage CKD-targeted action as "Kushiro CKD network" composed of medical/dental physicians, nurses, nutritionists and pharmacists. Pharmacists have played a central role in affixing a CKD sticker to a patient's medicine notebook when the patient's estimated glomerular filtration rate (eGFR) <45 mL/min/1.73 m2, in order to highlight the risk of CKD for those patients and related medical staff. There are many drugs that require dose reduction considering for renal function, but we had found cases where renal function was not monitored and pharmaceutical dispensation adjusted before the CKD network started. Therefore, we took this opportunity to investigate the impact of CKD stickers on pharmacists' work. During the period from August 2018 to August 2021, about 3200 CKD stickers were affixed by pharmacists, and about 4500 cases of decreased renal function were detected at pharmacies. In addition, there were 334 cases in which renal function deterioration was identified by the CKD stickers and led to further inquiries, of which 265 cases, or about 80%, resulted in prescription changes. Based on these results, it is considered that CKD stickers are effective method for pharmacies understand renal function deterioration and conduct appropriate prescription reviews. Finally, and perhaps most importantly, the use of CKD stickers can help assure that patients with renal impairment care treated with appropriate medication doses.

Exploring the clinical efficacy and mechanism of high-position colon dialysis combined with Traditional Chinese Medicine retention enema in real-world patients with stage 3-5 chronic kidney disease (non-dialysis) based on the theory of the Gut-Kidney axis.

Background: With societal and economic development, the annual incidence of chronic kidney disease (CKD) is increasing. Current treatments for CKD are limited, and once patients progress to the uraemic stage, it places a significant economic burden on families and society. Based on the "gut-kidney axis" theory and real-world research, this study aims to evaluate the clinical efficacy, safety, and potential mechanism of high-position colon dialysis combined with traditional Chinese medicine (TCM) retention enema in treating stage 3-5 chronic kidney disease (non-dialysis). Additionally, it seeks to identify new therapeutic targets and approaches for CKD treatment. Methods: The TCM decoction was analyzed using Ultra-Performance Liquid Chromatography-Quadrupole-Orbitrap-High Resolution Mass Spectrometry (UPLC-Q-Orbitrap-HRMS). Participants meeting the inclusion criteria were divided into a control group (n = 153) and a treatment group (n = 159) based on their preferences and physicians' recommendations. Both groups adhered to a high-quality low-protein, low-salt, low-phosphorus, and low-fat diet supplemented with essential amino acids, and were monitored for blood pressure, blood glucose, and blood lipids. The treatment group received high-position colon dialysis combined with TCM retention enemas (administered at least 12 times every other day). Results: Thirteen compounds were identified from the herbs by UPLC-Q-Orbitrap-HRMS. The CKD3-5 treatment group exhibited improvements in blood biochemistry and other laboratory indices, with significant enhancements in renal function-related indices for CKD4 and CKD5 stages (p < 0.05). Following treatment, indoxyl sulfate (IS), endotoxin, and D-lactic acid levels decreased to a certain extent in both groups, with a statistically significant difference observed within the treatment group (p < 0.05). The treatment group displayed a significant reduction in aerobic bacterial colonies, an increase in anaerobic bacterial colonies, a decrease in Escherichia coli colonies, and an increase in Bifidobacterium and Lactobacillus colonies (p < 0.05). No significant changes in colony numbers were observed in the control group. Conclusion: High-position colon dialysis combined with TCM retention enema may serve as an adjuvant treatment for CKD4-5 (non-dialysis), and its mechanism may be related to the reduction of uraemic toxins, improvement of intestinal mucosal barrier function, and regulation of intestinal microecology. Clinical Trial Registration: https://www.chictr.org.cn/, identifier ChiCTR2200062852.

Beneficiary Effects of Colchicine on Inflammation and Fibrosis in a Mouse Model of Kidney Injury

Introduction: Low-grade inflammation is seen in many chronic illnesses, including chronic kidney disease (CKD). We have recently reported on beneficiary effects of anti-inflammatory treatment in the interleukin (IL-) 1 pathway on anemia as well as CKD extent in a mouse model. Colchicine has been shown to have beneficiary effects in several inflammatory conditions through various mechanisms, including inhibition of tubulin polymerization as well as caspase-1-mediated IL-1 activation. Methods: Kidney injury (KI) was induced by administering an adenine diet to 8-week-old C57BL/6J mice treated with colchicine (Col) (30 µg/kg) or saline injections for 3 weeks, generating 4 groups: C, Ccol, KI, and KIcol. Results: KI animals had an increase in inflammation indices in the blood (neutrophils), liver, and kidneys (uromodulin, IL-6, pSTAT3). Increased kidney tubulin polymerization and caspase-1 in KI, as well as kidney Mid88 and IRAK4 (downstream of IL-1), were inhibited in KIcol. Kidney macrophage and polymorphonuclear infiltration (positive for F4/80 and MPO, respectively), the percentage of fibrotic area, and TGFβ mRNA levels were lower in KIcol versus KI. Conclusions: Colchicine inhibited tubulin polymerization and caspase-1 activation and attenuated kidney inflammation and fibrosis in a mouse model of adenine-induced KI. Given its reported safety profile for long-term anti-inflammatory therapy without increasing infection tendency, it may serve as novel therapeutic approach in CKD.

An easy-to-use phosphate triggered zinc-azophenine complex assisted metal extrusion assay: A diagnostic approach for chronic kidney disease and in silico docking studies

Regular monitoring of H2PO4- is inevitable owing to its physiological, chemical as well as environmental significance. Herein, a new and promising azophenine-functionalized Zn2+ complex, CN-1·Zn2+ is rationally designed for the selective and sensitive colorimetric detection (LOD = 67.9 ppb) of monophosphorylated species, H2PO4- based on H2PO4--specific metal-extrusion assay through hypsochromic shift in the UV–vis spectra. The sensing phenomenon has been authenticated via UV–vis, ESI-MS, CV, LSV, 1H NMR studies with theoretical (DFT) substantiation. CN-1·Zn2+ has been exploited towards two-input-two-output logic circuitry fabrication, advantageous for molecular-level information storage. Moreover, TLC strip-based contact mode analysis is beneficial for its on-spot applicability. Smartphone-assisted chromogenic recognition efficiency of CN-1·Zn2+via RGB analysis has been well-correlated with spectrophotometric outcomes, demonstrating reliability of the present method. Phosphate detection efficacy of CN-1·Zn2+ in serum specimens with qualified recovery (90.9–98.9 %) makes it a potential diagnostic tool for monitoring chronic kidney disease (CKD). Additionally, CN-1·Zn2+ exhibited DNA binding activity through non-intercalation mode, examined via UV–vis, fluorescence spectroscopic studies with in silico docking. This is the first Zn2+-complex in azophenine family, effectively employed for smartphone-assisted phosphate detection having promising DNA-binding activity, thereby leaving a sustainable footprint in the domain of supramolecular and bio-medical functional world of applications.

MHC class II in renal tubules plays an essential role in renal fibrosis.

Immunomodulation is considered a potential therapeutic approach for chronic kidney disease (CKD). Although it has been previously reported that CD4+ T cells contribute to the development of renal fibrosis, the role of MHC class II (MHCII) in the development of renal fibrosis remains largely unknown. The present study reports that the expression of MHCII molecules in renal cortical tubules is upregulated in mouse renal fibrosis models generated by unilateral ureter obstruction (UUO) and folic acid (FA). Proximal tubule epithelial cells (PTECs) are functional antigen-presenting cells that promote the proliferation of CD4+ T cells in an MHCII-dependent manner. PTECs from mice with renal fibrosis had a stronger ability to induce T cell proliferation and cytokine production than control cells. Global or renal tubule-specific ablation of H2-Ab1 significantly alleviated renal fibrosis following UUO or FA treatment. Renal expression of profibrotic genes showed a consistent reduction in H2-Ab1 gene-deficient mouse lines. Moreover, there was a marked increase in renal tissue CD4+ T cells after UUO or FA treatment and a significant decrease following renal tubule-specific ablation of H2-Ab1. Furthermore, renal tubule-specific H2-Ab1 gene knockout mice exhibited higher proportions of regulatory T cells (Tregs) and lower proportions of Th2 cells in the UUO- or FA-treated kidneys. Finally, Immunohistochemistry (IHC) studies showed increased renal expression of MHCII and the profibrotic gene α smooth muscle actin (α-SMA) in CKD patients. Together, our human and mouse data demonstrate that renal tubular MHCII plays an important role in the pathogenesis of renal fibrosis.

Pharmacological Inhibition of STAT6 Ameliorates Myeloid Fibroblast Activation and Alternative Macrophage Polarization in Renal Fibrosis.

A hallmark of chronic kidney disease is renal fibrosis, which can result in progressive loss of kidney function. Currently, there is no effective therapy for renal fibrosis. Therefore, there is an urgent need to identify potential drug targets for renal fibrosis. In this study, we examined the effect of a selective STAT6 inhibitor, AS1517499, on myeloid fibroblast activation, macrophage polarization, and development of renal fibrosis in two experimental murine models. To investigate the effect of STAT6 inhibition on myeloid fibroblast activation, macrophage polarization, and kidney fibrosis, wild-type mice were subjected to unilateral ureteral obstruction or folic acid administration and treated with AS1517499. Mice treated with vehicle were used as control. At the end of experiments, kidneys were harvested for analysis of myeloid fibroblast activation, macrophage polarization, and renal fibrosis and function. Unilateral ureteral obstruction or folic acid administration induced STAT6 activation in interstitial cells of the kidney, which was significantly abolished by AS1517499 treatment. Mice treated with AS1517499 accumulated fewer myeloid fibroblasts and myofibroblasts in the kidney with ureteral obstruction or folic acid nephropathy compared with vehicle-treated mice. Moreover, AS1517499 significantly suppressed M2 macrophage polarization in the injured kidney. Furthermore, AS1517499 markedly reduced the expression levels of extracellular matrix proteins, and development of kidney fibrosis and dysfunction. These findings suggest that AS1517499 inhibits STAT6 activation, suppresses myeloid fibroblast activation, reduces M2 macrophage polarization, attenuates extracellular matrix protein production, and preserves kidney function. Therefore, targeting STAT6 with AS1517499 is a novel therapeutic approach for chronic kidney disease.

POS-330 RISK PERCEPTIONS ABOUT COVID-19 AMONG A COHORT OF CHRONIC KIDNEY DISEASE PATIENTS IN RURAL INDIA

COVID-19 pandemic has resulted in disruption to routine health services delivery as strict lockdowns were implemented in India. The nation-wide lockdown lasting 2 months was imposed with an aim to reduce the spread of infection and prepare the health systems capacity for the pandemic. The Government of India issued advisory for those with chronic conditions to avoid visits to healthcare facilities for non-emergency consultations.The ‘Study to Test and Operationalize Preventive approaches for chronic kidney disease of undetermined aetiology (STOP CKDu)’ is following up a community-based cohort of 2419 participants over the age of 18 years in 40 clusters (75 villages) of Srikakulam District in Andhra Pradesh, India since Feb 2018.

Microbiome modulation as a novel therapeutic approach in chronic kidney disease.

Gut dysbiosis has been implicated in the pathogenesis of chronic kidney disease (CKD). Interventions aimed at restoring gut microbiota have emerged as a potential therapeutic option in CKD. This review summarizes the current evidence on gut microbiota-targeted strategies in patients with CKD. A growing number of studies have shown that plant-based diets, low-protein diets, prebiotic, probiotic, and synbiotic supplementation, and constipation treatment may lead to favorable alterations in the gut microbiota. Current evidence suggests that the implementation of both plant-based and low-protein diets has potential benefits for the primary prevention of CKD, and for slowing CKD progression, with minimal risk of hyperkalemia and/or cachexia. The use of prebiotics, probiotics, and synbiotics and laxatives may have beneficial effects on uremic toxin generation, but their evidence is limited for the prevention and treatment of CKD. Recent advances in diagnostic technologies (e.g., high-throughput sequencing and nanotechnology) could enhance rapid diagnosis, monitoring, and design of effective therapeutic strategies for mitigating gut dysbiosis in CKD. Plant-based and low-protein diets, prebiotic, probiotic, and synbiotic supplementation, and constipation treatment represent novel gut microbiota-targeted strategies in the conservative management of CKD, which could improve clinical outcomes in CKD.

Genetics-first approach improves diagnostics of ESKD patients

Often only chronic kidney disease (CKD) patients with high likelihood of genetic disease are offered genetic testing. Early genetic testing could obviate the need for kidney biopsies, allowing for adequate prognostication and treatment. To test the viability of a 'genetics-first' approach for CKD, we performed genetic testing in a group of kidney transplant recipients aged <50 years, irrespective of cause of transplant. From a cohort of 273 transplant patients, we selected 110 that were in care in the University Medical Center Utrecht, had DNA available and were without clear-cut non-genetic disease. Forty patients had been diagnosed with a genetic disease prior to enrollment; in 70 patients, we performed a whole-exome sequencing-based 379 gene panel analysis. Genetic analysis yielded a diagnosis in 51%. Extrapolated to the 273 patient cohort, who did not all fit the inclusion criteria, the diagnostic yield was still 21%. Retrospectively, in 43% of biopsied patients, the kidney biopsy would not have had added diagnostic value if genetic testing had been performed as a first-tier diagnostic. The burden of monogenic disease in transplant patients with end-stage kidney disease (ESKD) of any cause prior to the age of 50 years is between 21% and 51%. Early genetic testing can provide a non-invasive diagnostic, impacting prognostication and treatment, and obviating the need for an invasive biopsy. We conclude that in patients who expect to develop ESKD prior to the age of 50 years, genetic testing should be considered as first mode of diagnostics.

Anti-Inflammatory and Anti-Oxidative Therapeutic Approach in Chronic Kidney Disease with Statin Consumption

Inflammation and oxidative stress are 2 factors that play an important role in Chronic Kidney Disease (CKD). Controlling these 2 factors is expected to give better kidney functions outcomes. Statins have anti-inflammatory and antioxidative stress effects apart from their lipid-lowering effect. In this study, we want to analyze that statin might be one of a renoprotective agent through their pleiotropic effect as an anti-inflammation and anti-oxidative in CKD patients. This is a cross-sectional study that enrolled of 40 patients with CKD: 20 patients consumed statin and 20 patients did not consume statin. We compared HDL; inflammatory markers: high sensitive – C reactive protein (hsCRP), absolute neutrophil count, absolute leukocyte count, absolute eosinophil count, and neutrophil-lymphocyte ratio (NLR); and oxidative stress marker malondialdehyde (MDA) with kidney functions (GFR, cystatin c, BUN, albumin urine, and creatinine serum) between groups. Then we analyze the correlation between HDL, inflammatory markers, and oxidative marker with kidney functions. The results are HDL and MDA had a correlation with all the kidney function, hs-CRP correlated with GFR, cystatin c, and BUN, and NLR correlated with GFR, cystatin c, BUN, and creatinine serum. Statin group significantly have lower hs-CRP, NLR, and MDA. HDL, absolute neutrophil, leukocyte, and eosinophil count are lower in the statin group but not significantly. All the kidney function markers significantly have a better outcome in the statin group. This study concludes that lowering inflammation and oxidative stress levels using statin could be one of the strategy therapies in CKD to achieve better kidney function outcomes.

Study to Test and Operationalize Preventive Approaches for CKD of Undetermined Etiology in Andhra Pradesh, India

IntroductionHigh prevalence of chronic kidney disease (CKD) not associated with known risk factors has been reported from coastal districts of Andhra Pradesh. The Study to Test and Operationalize Preventive Approaches for Chronic Kidney Disease of Undetermined Etiology in Andhra Pradesh (STOP CKDu AP) aims to ascertain the burden (prevalence and incidence) of CKD, the risk factor profile, and the community perceptions about the disease in the Uddanam area of Andhra Pradesh.MethodsStudy participants will be sampled from the Uddanam area using multistage cluster random sampling. Information will be collected on the demographic profile, occupational history, and presence of conventional as well as nonconventional risk factors. Glomerular filtration rate (GFR) will be estimated using the Chronic Kidney Disease Epidemiology Collaboration equation, and proteinuria will be measured. All abnormal values will be confirmed by repeat testing after 3 months. Cases of CKD not associated with identified etiologies will be identified. Biospecimens will be stored to explore future hypotheses. The entire cohort will be followed up every 6 months to determine the incidence of CKD and to identify risk factors for decline in kidney function. Qualitative studies will be performed to understand the community perceptions and expectations with respect to the interventions.ImplicationsCKD is an important public health challenge in low- and middle-income countries. This study will establish the prevalence and determine the incidence of CKD not associated with known risk factors in a reported high-burden region, and will provide insights to help design targeted health systems responses. The findings will contribute to the policy development to tackle CKD in the region and will permit international comparisons with other regions with similar high prevalence.

Inhibition of 5-lipoxygenase decreases renal fibrosis and progression of chronic kidney disease.

In inflammatory diseases, the 5-lipoxygenase (5-LO) pathway contributes to epithelial damage and fibrosis by catalyzing the production of leukotrienes (LTs). Antagonists of the 5-LO pathway are currently approved for use in patients and are well tolerated. We found that expression of 5-LO is strongly induced in three models of chronic kidney disease: unilateral ureteral obstruction (UUO), folate nephropathy, and an orthologous mouse model of polycystic kidney disease. Immunohistochemistry showed that macrophages are the dominant source of 5-LO. Zileuton, a US Food and Drug Administration-approved antagonist of 5-LO, significantly reduced fibrosis at 7 and 14 days after UUO; these findings were confirmed using a genetically modified [5-LO-associated protein-knockout ( Alox5ap-/-)] mouse strain. Inhibition of 5-LO did not appear to change infiltration of leukocytes after UUO as measured by flow cytometry. However, fluorescence-lifetime imaging microscopy showed that 5-LO inhibitors reversed the glycolytic switch in renal tubular epithelial cells after UUO. Two downstream enzymes of 5-LO, LTA4 hydrolase (LTA4H) and LTC4 synthase (LTC4S), are responsible for the synthesis of LTB4 and cysteinyl LTs, respectively. Fibrosis was reduced after UUO in Ltc4s-/-, but not Lta4h-/-, mice. In contrast, using the folate nephropathy model, we found reduced fibrosis and improved renal function in both Ltc4s-/- and Lta4h-/- mice. In summary, our studies suggest that manipulation of the 5-LO pathway may represent a novel treatment approach for chronic kidney disease.

Failure to sense energy depletion may be a novel therapeutic target in chronic kidney disease

The kidneys consume a large amount of energy to regulate volume status and blood pressure and to excrete uremic toxins. The identification of factors that cause energy mismatch in the setting of chronic kidney disease (CKD) and the development of interventions aimed at improving this mismatch are key research imperatives. Although the critical cellular energy sensor 5'-adenosine monophosphate (AMP)-activated protein kinase (AMPK) is known to be inactivated in CKD, the mechanism of AMPK dysregulation is unknown. In a mouse model of CKD, metabolome analysis confirmed a decrease in AMPK activation in the kidneys despite a high AMP: ATP ratio, suggesting that AMPK did not sense energy depletion. Similar AMPK inactivation was found in heart and skeletal muscle in CKD mice. Several uremic factors were shown to inactivate AMPK invitro and in exvivo preparations of kidney tissue. The specific AMPK activator A-769662, which bypasses the AMP sensing mechanism, ameliorated fibrosis and improved energy status in the kidneys of CKD mice, whereas an AMP analog did not. We further demonstrated that a low-protein diet activated AMPK independent of the AMP sensing mechanism, leading to improvement in energy metabolism and kidney fibrosis. These results suggest that a failure to sense AMP is the key mechanism underlying the vicious cycle of energy depletion and CKD progression and direct AMPK activation may be a novel therapeutic approach in CKD.

Impact of an Early Invasive Strategy versus Conservative Strategy for Unstable Angina and Non-ST Elevation Acute Coronary Syndrome in Patients with Chronic Kidney Disease: A Systematic Review.

BackgroundClinical practice guidelines support an early invasive approach after NSTE-ACS in patients with chronic kidney disease (CKD). There is no direct randomised controlled trial evidence in the CKD population, and whether the benefit of an early invasive approach is maintained across the spectrum of severity of CKD remains controversial.MethodsWe conducted a systematic review to evaluate the association between an early invasive approach and all-cause mortality in patients with CKD. We searched MEDLINE and EMBASE (1990-May 2015) and article reference lists. Data describing study design, participants, invasive management strategies, renal function, all-cause mortality and risk of bias were extracted.Results3,861 potentially relevant studies were identified. Ten studies, representing data on 147,908 individuals with NSTE-ACS met the inclusion criteria. Qualitative heterogeneity in the definitions of early invasive approach, comparison groups and renal dysfunction existed. Meta-analysis of the RCT derived and observational data were generally supportive of an early invasive approach in CKD (RR0.76 (95% CI 0.49–1.17) and RR0.50 (95%CI 0.42–0.59) respectively). Meta-analysis of the observational studies demonstrated a large degree of heterogeneity (I2 79%) driven in part by study size and heterogeneity across various kidney function levels.ConclusionsThe observational data support that an early invasive approach after NSTE-ACS confers a survival benefit in those with early-moderate CKD. Local opportunities for quality improvement should be sought. Those with severe CKD and the dialysis population are high risk and under-studied. Novel and inclusive approaches for CKD and dialysis patients in cardiovascular clinical trials are needed.

Novel therapeutic approaches for chronic kidney disease due to glomerular disorders.

Improved understanding of glomerular disease mechanisms over the past decade has led to the emergence of new and targeted therapeutic strategies for chronic kidney disease (CKD). Most promising among these are the administration of recombinant mutated human angiopoietin-like 4, sialic acid-related sugars that induce sialylation in vivo, compounds related to Bis-T-23, and immune depletion of the soluble urokinase receptor from the circulation. Taking these therapeutic strategies into clinical trials will be the first step away from repurposed and relatively toxic drugs currently used for treating kidney disease.

Building Chronic Kidney Disease Clinical Practice Guidelines Using the openEHR Guideline Definition Language.

As a result of the disease's high prevalence, chronic kidney disease (CKD) has become a global public health problem. A clinical decision support system that integrates with computer-interpretable guidelines (CIGs) should improve clinical outcomes and help to ensure patient safety. The openEHR guideline definition language (GDL) is a formal language used to represent CIGs. This study explores the feasibility of using a GDL approach for CKD; it also attempts to identify any potential gaps between the ideal concept and reality. Using the Kidney Disease Improving Global Outcomes (KDIGO) anemia guideline as material, we designed a development workflow in order to establish a series of GDL guidelines. Focus group discussions were conducted in order to identify important issues related to GDL implementation. Ten GDL guidelines and 37 archetypes were established using the KDIGO guideline document. For the focus group discussions, 16 clinicians and 22 IT experts were recruited and their perceptions, opinions and attitudes towards the GDL approach were explored. Both groups provided positive feedback regarding the GDL approach, but raised various concerns about GDL implementation. Based on the findings of this study, we identified some potential gaps that might exist during implementation between the GDL concept and reality. Three directions remain to be investigated in the future. Two of them are related to the openEHR GDL approach. Firstly, there is a need for the editing tool to be made more sophisticated. Secondly, there needs to be integration of the present approach into non openEHR-based hospital information systems. The last direction focuses on the applicability of guidelines and involves developing a method to resolve any conflicts that occur with insurance payment regulations.

Urinary proteomics in the assessment of chronic kidney disease

Urinary proteomics has emerged as an approach that could deliver relevant clinical information. In this review, we aim at highlighting the recent developments, especially with respect to clinical implementation. We review several of the recent publications reporting on larger cohorts, focusing on those that aim at qualification and/or validation of urinary proteomics biomarkers. Several components of the urinary proteome, especially its low molecular weight fraction (sometimes referred to as the 'peptidome'), have been significantly associated with chronic kidney disease (CKD). Independent studies, encompassing sometimes close to 1000 independent samples, indicate that specific peptides from extracellular matrix (ECM) proteins encompass a major component of the urinary proteome. Highly significant changes in the abundance of some of these peptides are associated with CKD indicating that alterations in ECM, reflected via the urinary proteome, may represent an early stage in CKD pathology. These peptides may serve as specific early biomarkers, and interference with pathological ECM accumulation may be a valuable new therapeutic approach in CKD. Urinary proteomic biomarkers have emerged as clinically relevant variables. First studies involving several hundred individuals indicate a potential added benefit of urinary proteomic biomarkers. First large clinical trials are being initiated to employ urinary proteomics in clinical decision making.