scholarly journals A Novel Multi-Biomarker Assay for Non-Invasive Quantitative Monitoring of Kidney Injury

2019 ◽  
Vol 8 (4) ◽  
pp. 499 ◽  
Author(s):  
Drew Watson ◽  
Joshua Y. C. Yang ◽  
Reuben D. Sarwal ◽  
Tara K. Sigdel ◽  
Juliane M. Liberto ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Renal Function ◽  
Kidney Disease ◽  
Early Stage ◽  
Kidney Injury ◽  
Adverse Outcomes ◽  
Urine Samples ◽  
Potential Contribution ◽  
Test Kit ◽  
Injury Status

The current standard of care measures for kidney function, proteinuria, and serum creatinine (SCr) are poor predictors of early-stage kidney disease. Measures that can detect chronic kidney disease in its earlier stages are needed to enable therapeutic intervention and reduce adverse outcomes of chronic kidney disease. We have developed the Kidney Injury Test (KIT) and a novel KIT Score based on the composite measurement and validation of multiple biomarkers across a unique set of 397 urine samples. The test is performed on urine samples that require no processing at the site of collection and without target sequencing or amplification. We sought to verify that the pre-defined KIT test, KIT Score, and clinical thresholds correlate with established chronic kidney disease (CKD) and may provide predictive information on early kidney injury status above and beyond proteinuria and renal function measurements alone. Statistical analyses across six DNA, protein, and metabolite markers were performed on a subset of residual spot urine samples with CKD that met assay performance quality controls from patients attending the clinical labs at the University of California, San Francisco (UCSF) as part of an ongoing IRB-approved prospective study. Inclusion criteria included selection of patients with confirmed CKD and normal healthy controls; exclusion criteria included incomplete or missing information for sample classification, logistical delays in transport/processing of urine samples or low sample volume, and acute kidney injury. Multivariate logistic regression of kidney injury status and likelihood ratio statistics were used to assess the contribution of the KIT Score for prediction of kidney injury status and stage of CKD as well as assess the potential contribution of the KIT Score for detection of early-stage CKD above and beyond traditional measures of renal function. Urine samples were processed by a proprietary immunoprobe for measuring cell-free DNA (cfDNA), methylated cfDNA, clusterin, CXCL10, total protein, and creatinine. The KIT Score and stratified KIT Score Risk Group (high versus low) had a sensitivity and specificity for detection of kidney injury status (healthy or CKD) of 97.3% (95% CI: 94.6–99.3%) and 94.1% (95% CI: 82.3–100%). In addition, in patients with normal renal function (estimated glomerular filtration rate (eGFR) ≥ 90), the KIT Score clearly identifies those with predisposing risk factors for CKD, which could not be detected by eGFR or proteinuria (p < 0.001). The KIT Score uncovers a burden of kidney injury that may yet be incompletely recognized, opening the door for earlier detection, intervention and preservation of renal function.

scholarly journals Postoperative acute kidney injury in adult non-cardiac surgery: joint consensus report of the Acute Disease Quality Initiative and PeriOperative Quality Initiative

2021 ◽  
Author(s):  
John R. Prowle ◽  
Lui G. Forni ◽  
Max Bell ◽  
Michelle S. Chew ◽  
Mark Edwards ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Acute Kidney Injury ◽  
Cardiac Surgery ◽  
Kidney Disease ◽  
Kidney Injury ◽  
Adverse Outcomes ◽  
Baseline Risk ◽  
Major Surgery ◽  
Increased Risk

AbstractPostoperative acute kidney injury (PO-AKI) is a common complication of major surgery that is strongly associated with short-term surgical complications and long-term adverse outcomes, including increased risk of chronic kidney disease, cardiovascular events and death. Risk factors for PO-AKI include older age and comorbid diseases such as chronic kidney disease and diabetes mellitus. PO-AKI is best defined as AKI occurring within 7 days of an operative intervention using the Kidney Disease Improving Global Outcomes (KDIGO) definition of AKI; however, additional prognostic information may be gained from detailed clinical assessment and other diagnostic investigations in the form of a focused kidney health assessment (KHA). Prevention of PO-AKI is largely based on identification of high baseline risk, monitoring and reduction of nephrotoxic insults, whereas treatment involves the application of a bundle of interventions to avoid secondary kidney injury and mitigate the severity of AKI. As PO-AKI is strongly associated with long-term adverse outcomes, some form of follow-up KHA is essential; however, the form and location of this will be dictated by the nature and severity of the AKI. In this Consensus Statement, we provide graded recommendations for AKI after non-cardiac surgery and highlight priorities for future research.

scholarly journals Clinical Effectiveness and Safety of Gliclazide MR and Linagliptin Combination in the Management of Patients With T2DM and Chronic Kidney Disease (CKD) Switched From Glimepiride - a Real-World, Retrospective, Observational Study

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A407-A408
Author(s):  
Supratik Bhattacharyya ◽  
Maneesha Khalse
Keyword(s):  
Chronic Kidney Disease ◽  
Renal Function ◽  
Kidney Disease ◽  
Clinical Effectiveness ◽  
Adverse Outcomes ◽  
Average Dose ◽  
Urine Albumin ◽  
Medical Study ◽  
Background Therapy ◽  
Stage 1

Abstract Background: Type 2 diabetes (T2DM) patients are at high risk of developing to CKD and progressing to adverse outcomes vs Nondiabetics. The aim was to evaluate the effectiveness and safety of gliclazide MR switched from glimepiride in combination with linagliptin considering their associated potential benefits in albuminuria reduction and delaying progression of adverse renal outcomes in T2DM patients with kidney disease as shown in previous data. Methodology: The medical study database of the author’s hospital identified T2DM patients with stage 1–3 CKD with mean eGFR of 50.4 ± 8.56 ml/min/1.73 m2 and were inadequately controlled with glimepiride (mean dose 3.24mg) for the last 3 months. These patients were switched to gliclazide MR with appropriate equivalent dose while DPP-4 inhibitors like linagliptin (5 mg OD) (79%), sitagliptin (14%), vildagliptin (7%), were continued as background therapy. About 59.35% of subjects were on glimepiride 2 mg, 21.93% subjects on glimepiride 3 mg and 18.7% on glimepiride 4 mg. The gliclazide dose was up titrated by 30 mg every 15 days to achieve a target post-prandial glucose (PPG) ≤180 mg/dL. The average dose of gliclazide MR during the study was 44 mg; approximately two-thirds of patients 61% were on 60 mg, 22% on 90mg, and 7% on 30 mg. Patients were counselled to recognize the symptoms and record the hypoglycemic episodes. The statistical analysis included the analysis of changes in glycemic control, risk of hypoglycemia & renal function parameters. The patients were followed up for 24 weeks duration. Results: A total 218 eligible patients (110 female & 108 male) with CKD (stages 1–3) were included. The mean age, body weight, baseline HbA1c, FPG, PPG levels, mean eGFR, and UACR (urine albumin creatinine ratio) were 62.94 ± 8.72 years, 67.9 ± 9.33 kg, 8.51 ±0.81%, 148.53 ± 16.72, 202 ± 18.45 mg/dL, 50.49 ± 8.56 ml/min/1.73 m2 and 154.34 mg/g respectively. Gliclazide MR was initiated substituting glimepiride with appropriate dosing determined by the physician. Two subjects discontinued the therapy due to intolerability. At 24 weeks follow up, HbA1c, FPG, PPG level was reduced by -0.63, -10.33, -30.04%, respectively (p&lt; 0.001). There was a significant reduction in events of overall hypoglycemia (22.25%). Improvement in renal function with respect to eGFR level (+1.77 ml/min/1.73 m2) and albuminuria reduction (-45.56 mg/g) were also observed in patients. Conclusion: This study demonstrates the clinical effectiveness and safety of gliclazide MR with the combination of DPP-4is like linagliptin as an alternate option to glimepiride in diabetes patients with chronic kidney disease.

scholarly journals A Novel Creatinine-Based Equation to Estimate Glomerular Filtration Rate in Chinese Population With Chronic Kidney Disease: Implications for DOACs Dosing in Atrial Fibrillation Patients

2021 ◽  
Vol 12 ◽  
Author(s):  
Ling-Yun Zhou ◽  
Wen-Jun Yin ◽  
Jun Zhao ◽  
Bi-Kui Zhang ◽  
Can Hu ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Chronic Kidney Disease ◽  
Renal Function ◽  
Glomerular Filtration Rate ◽  
Kidney Disease ◽  
Glomerular Filtration ◽  
Filtration Rate ◽  
Linear Regression Analysis ◽  
Dynamic Imaging ◽  
Adverse Outcomes

Background: Over/under-estimating renal function may increase inappropriate dosing strategy associated adverse outcomes; however, previously reported equations to estimate renal function have limited accuracy in chronic kidney disease (CKD) patients. Consequently, we intended to develop a novel equation to precisely estimate renal function and subsequently guide clinical treatment for CKD patients.Methods: A novel approach, Xiangya-s equation, to estimate renal function for CKD patients was derived by linear regression analysis and validated in 1885 patients with measured glomerular filtration rate (mGFR) &lt; 60 ml/min/1.73 m2 by renal dynamic imaging at three representative hospitals in China, with the performance evaluated by accuracy, bias and precision. In the meanwhile, 2,165 atrial fibrillation (AF) patients who initiated direct oral anticoagulants (DOACs) between December 2015 and December 2018 were identified and renal function was assessed by estimated creatinine clearance (eCrCl). Events per 100 patient-years was calculated. Cox proportional hazards regression was applied to compare the incidence of outcomes of each group.Results: Xiangya-s equation demonstrated higher accuracy, lower bias and improved precision when compared with 12 creatinine-based and 2 CysC-based reported equations to estimate GFR in multi-ethnic Chinese CKD patients. When we applied Xiangya-s equation to patients with AF and CKD prescribed DOACs, wide variability was discovered in eCrCl calculated by the Cockcroft-Gault (CG), Modification of Diet in Renal Disease Study (MDRD), Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), Xiangya equation which we had developed for generally patients and Xiangya-s equations, which persisted after grouping by different renal function stages. Equation choice affected drug-dosing adjustments, with the formulas agreeing for only 1.19%, 5.52%, 33.22%, 26.32%, and 36.61% of potentially impacted patients for eCrCl cutoffs of &lt;15, &lt;30, 15–49, 30–49, ≥50 ml/min, respectively. Relative to CG equation, accordance in DOACs dosage was 81.08%, 88.54%, 62.25%, and 47.68% for MDRD, CKD-EPI, Xiangya and Xiangya-s equations for patients with CrCl &lt; 50 ml/min (eCrCl cutoffs of &lt;30, 30–49, ≥50 ml/min), respectively. Reclassification of renal function stages by Xiangya-s equation was significantly associated with stroke or systemic embolism, non-major clinically relevant bleeding and any bleeding events.Conclusion: Xiangya-s equation provides more accurate GFR estimates in Chinese CKD patients who need consecutive monitoring of renal function, which may assist clinicians in choosing appropriate drug dosages.

scholarly journals The dirty little secret of urate-lowering therapy: useless to stop chronic kidney disease progression and may increase mortality

2020 ◽  
Vol 13 (6) ◽  
pp. 936-947
Author(s):  
Guillermo Gonzalez-Martin ◽  
Jaime Cano ◽  
Sol Carriazo ◽  
Mehmet Kanbay ◽  
Maria Vanessa Perez-Gomez ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Kidney Injury ◽  
Serum Urate ◽  
Adverse Outcomes ◽  
P Value ◽  
Ckd Progression ◽  
Mortality Trends ◽  
Open Label ◽  
Lowering Therapy

Abstract Hyperuricaemia is frequent in chronic kidney disease (CKD). Observational studies have shown an association with adverse outcomes and acquired hyperuricaemia (meaning serum urate levels as low as 1.0 mg/dL) in animal models induces kidney injury. This evidence does not justify the widespread use of urate-lowering drugs for asymptomatic hyperuricaemia in CKD. However, promising results from small, open-label studies led some physicians to prescribe urate-lowering drugs to slow CKD progression. Two recent, large, placebo-controlled trials (CKD-FIX and PERL) showed no benefit from urate lowering with allopurinol on the primary endpoint of CKD progression, confirming prior negative results. Despite these negative findings, it was still argued that the study population could be optimized by enrolling younger non-proteinuric CKD patients with better preserved glomerular filtration rate (GFR). However, in these low-risk patients, GFR may be stable under placebo conditions. Additionally, the increased mortality trends already identified in gout trials of urate-lowering therapy were also observed in CKD-FIX and PERL, sending a strong safety signal: 21/449 (4.7%) and 10/444 (2.2%) patients died in the combined allopurinol and placebo groups, respectively [chi-squared P-value 0.048; relative risk 2.07 (95% CI 0.98–4.34); P = 0.06]. Given the absent evidence of benefit in multiple clinical trials and the potentially serious safety issues, the clear message should be that urate-lowering therapy should not be prescribed for the indication of slowing CKD progression. Additionally, regulatory agencies should urgently reassess the safety of chronic prescription of urate-lowering drugs for any indication.

scholarly journals Acute kidney injury pathology and pathophysiology: a retrospective review

2020 ◽  
Author(s):  
Joseph P Gaut ◽  
Helen Liapis
Keyword(s):  
Chronic Kidney Disease ◽  
Acute Kidney Injury ◽  
Renal Function ◽  
Kidney Disease ◽  
Renal Biopsy ◽  
Retrospective Review ◽  
Patient Management ◽  
Kidney Injury ◽  
High Morbidity ◽  
Underlying Pathology

Abstract Acute kidney injury (AKI) is the clinical term used for decline or loss of renal function. It is associated with chronic kidney disease (CKD) and high morbidity and mortality. However, not all causes of AKI lead to severe consequences and some are reversible. The underlying pathology can be a guide for treatment and assessment of prognosis. The Kidney Disease: Improving Global Outcomes guidelines recommend that the cause of AKI should be identified if possible. Renal biopsy can distinguish specific AKI entities and assist in patient management. This review aims to show the pathology of AKI, including glomerular and tubular diseases.

scholarly journals Chronic Kidney Disease, Obesity, and Hypertension: The Role of Leptin and Adiponectin

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
M. Tesauro ◽  
A. Mascali ◽  
O. Franzese ◽  
S. Cipriani ◽  
C. Cardillo ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Renal Function ◽  
Kidney Disease ◽  
Kidney Injury ◽  
Public Health Problem ◽  
Major Public Health Problem ◽  
Renal Progression ◽  
Obesity Hypertension ◽  
Progression Factor

Chronic kidney disease is a major public health problem and characterized by a progressive loss in renal function over a period of months or years as defined by structural or functional abnormalities of the kidney. Several elements contribute to determine a progression of the kidney injury, inducing a worsening of renal damage and accelerating the decline of renal function: obesity and hypertension are two known factors of kidney progression. Remarkable improvements have been recently achieved in the study of the endocrine features of the adipose tissue and have been able to produce hormone-like peptides named adipokines or adipocytokines. Among these adipocytokines, which represent a link between obesity, hypertension, and chronic nephropathy, leptins and adiponectin appear to play an important role. Leptin not only is a prohypertension element (renal progression factor) through the activation sympathetic nervous, but also is able to induce prosclerotic effects directly on the kidney. In contrast, a decline of adiponectin levels has been shown to be related to a picture of hypertension: an endothelial dysfunction has been described as the main pathogenic mechanism responsible for this phenomenon.

scholarly journals Prognostic ability of mid-term worsening renal function after percutaneous coronary intervention: findings from the SHINANO registry

2021 ◽  
Author(s):  
Yoshiteru Okina ◽  
Takashi Miura ◽  
Keisuke Senda ◽  
Minami Taki ◽  
Masanori Kobayashi ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Renal Function ◽  
Kidney Disease ◽  
Cardiovascular Events ◽  
Kidney Injury ◽  
Coronary Intervention ◽  
First Year ◽  
Percutaneous Coronary ◽  
Onset Atrial Fibrillation ◽  
New Onset

AbstractChronic kidney disease is a prognostic factor for cardiovascular disease. Worsening renal function (WRF), specifically, is an important predictor of mortality in patients with acute myocardial infarction undergoing primary percutaneous coronary intervention (PCI). We evaluate the prognostic impact of mid-term WRF after PCI on future cardiovascular events. We examined the renal function data of 1086 patients in the first year after PCI using the SHINANO 5-year registry. Patients were divided into two groups, mid-term WRF and non-mid-term WRF, and primary outcomes were major adverse cardiovascular events (MACE) and death. Mid-term WRF was defined as an increase in creatinine (≥ 0.3 mg/dL) in the first year after PCI. Mid-term WRF was found in 101 patients (9.3%), and compared to non-mid-term WRF, it significantly increased the incidence of MACE (p < 0.001), and all-cause death (p < 0.001), myocardial infarction (p = 0.001). Furthermore, mid-term WRF patients had higher incidence of future heart failure (p < 0.001) and new-onset atrial fibrillation (p = 0.01). Patients with both mid-term WRF and chronic kidney disease had increased MACE compared to patients with either condition alone (p < 0.001). Similarly, patients with mid-term WRF and acute kidney injury had increased MACE compared to patients with either condition alone (p < 0.001). Multivariate Cox regression analysis revealed mid-term WRF as a strong predictor of MACE (hazard ratio: 2.50, 95% confidence interval 1.57–3.98, p < 0.001). Mid-term WRF after PCI negatively affects MACE, as well as future admission due to heart failure and new-onset atrial fibrillation, chronic kidney disease, and acute kidney injury.

scholarly journals Estimated 24 h Urinary Sodium-to-Potassium Ratio Is Related to Renal Function Decline: A 6-Year Cohort Study of Japanese Urban Residents

2020 ◽  
Vol 17 (16) ◽  
pp. 5811
Author(s):  
Hiroko Hattori ◽  
Aya Hirata ◽  
Sachimi Kubo ◽  
Yoko Nishida ◽  
Miki Nozawa ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Renal Function ◽  
Kidney Disease ◽  
Early Stage ◽  
Urban Residents ◽  
Normal Range ◽  
Multivariable Logistic Regression Model ◽  
Renal Function Decline ◽  
Increased Risk ◽  
Egfr Decline

The effect of the sodium-to-potassium ratio (Na/K) on renal function within the clinically normal range of renal function are limited. We investigated the effects of an estimated 24 h urinary Na/K (e24hUNa/K) on a 6-year renal function decline among 927 urban Japanese community dwellers with no history of cardiovascular diseases and medication for hypertension, diabetes, or dyslipidemia. We partitioned the subjects into quartiles according to the e24hUNa/K. The estimated glomerular filtration rate (eGFR) was calculated using the chronic kidney disease epidemiology collaboration (CKD/EPI) formula and renal function decline was defined as an absolute value at or above the third quartile of the eGFR decline rate. A multivariable logistic regression model was used for estimation. Compared with the first quartile of the e24hUNa/K, multivariable-adjusted odds ratios (ORs) for eGFR decline in the second, third, and fourth quartiles were 0.96 (95% confidence interval: 0.61–1.51), 1.06 (0.67–1.66), and 1.65 (1.06–2.57), respectively. These results were similar when the simple spot urine Na/K ratio was used in place of the e24hUNa/K. Apparently healthy urban residents with an almost within normal range mean baseline eGFR and high e24hUNa/K ratios had an increased risk for a future decline in renal function. Reducing the Na/K ratio may be important in the prevention of chronic kidney disease in its early stage.

scholarly journals The Urinary Phosphate to Serum Fibroblast Growth Factor 23 Ratio, Deemed the Nephron Index, Is a Useful Clinical Index for Early Stage Chronic Kidney Disease in Patients with Type 2 Diabetes: An Observational Pilot Study

2018 ◽  
Vol 2018 ◽  
pp. 1-4 ◽  
Author(s):  
Hodaka Yamada ◽  
Makoto Kuro-o ◽  
Shunsuke Funazaki ◽  
San-e Ishikawa ◽  
Masafumi Kakei ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Chronic Kidney Disease ◽  
Renal Function ◽  
Growth Factor ◽  
Kidney Disease ◽  
Early Stage ◽  
Fibroblast Growth Factor 23 ◽  
Fibroblast Growth

Renal function decline is associated with progressive type 2 diabetes mellitus, which causes mineral and bone disorders. In the present study, we defined the ratio of urinary phosphate excretion (mg/day) to serum fibroblast growth factor 23 as the nephron index. We examined changes in the nephron index in type 2 diabetes patients with early stage chronic kidney disease (stages 1–3), enrolling 15 patients and retrospectively analysing the follow-up data. After follow-up at 5.4 years, we observed no significant changes in the estimated glomerular filtration rate; the nephron index, however, was significantly reduced between the baseline and the follow-up. We propose that the nephron index may be potentially useful as a biomarker for monitoring the decline of renal function in the early stages of diabetic chronic kidney disease patients.

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