Kidney injury molecule-1 correlates with kidney function in renal allograft recipients

IntroductionKIM-1 (kidney injury molecule-1) is responsible for the clearance of debris from damaged renal tubules. KIM-1 can be expressed and excreted in urine within 12 hours after the initial ischemic insult and before regeneration of the epithelium, persisting over time thereafter. Urinary KIM-1 has been reported to be a noninvasive, rapid, sensitive, and reproducible biomarker of experimental nephrotoxic and ischemic acute kidney injury. Renal KIM-1 expression is significantly increased in human kidney tissue among patients with a wide range of kidney diseases, including various types of glomerulonephritis, chronic allograft nephropathy, acute rejection, hypertension, and Wegener's granulomatosis. Both renal and urinary KIM-1 correlate with kidney damage and negatively with renal function, but not with proteinuria. The aim of this study was to assess whether urinary KIM-1 correlated with kidney function in kidney allograft recipients.MethodsSerum NGAL, creatinine and estimated glomerular filtration rate (eGFR) were evaluated in 170 kidney allograft recipients on therapy with a calcineurin inhibitor plus mycophenolate mofetil or azathioprine and prednisone as well as in healthy volunteers. KIM-1 was estimated in urine using a commercially available kit.ResultsKidney transplant recipients showed significantly higher KIM-1 values than the control group. Normotensive kidney allograft recipients displayed significantly lower NGAL results than hypertensive subjects. Urinary KIM-1 was significantly higher among diabetic than nondiabetic subjects, whereas creatinine did not differ significantly between them. Upon univariate analysis urinary KIM-1 strongly correlated with serum creatinine (r = .64) and eGFR (r = ?.71), and only weakly with other parameters. Upon multiple regression analysis, the best predictor of urinary KIM-1 was eGFR (beta ?0.61), which explained 61% of KIM-1 concentrations.ConclusionEven a successful kidney transplantation is associated with kidney injury as reflected by elevated urinary KIM-1 and lower eGFR. Therefore, KIM-1 needs to be investigated as a potential early marker for impaired renal function/kidney injury, especially in patients with other risk factors for damage such as hypertension or diabetes.     

Value of urine IL-8, NGAL and KIM-1 for the early diagnosis of acute kidney injury in patients with ureteroscopic lithotripsy related urosepsis

PurposeTo investigate the clinical value of urine interleukin-18 (IL-8), neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) for the early diagnosis of acute kidney injury (AKI) in patients with ureteroscopic lithotripsy (URL) related urosepsis.MethodsA retrospective study was carried out in 157 patients with urosepsis after URL. The patients were divided into AKI group and non-AKI group according to the Kidigo guideline and urine IL-8, NGAL and KIM-1 levels were detected by enzyme-linked immunosorbent assay at 0, 4, 12, 24 and 48 h after the surgery. Receiver operating characteristic curve (ROC) was used to evaluate the diagnostic value of these three biomarkers for postoperative AKI.ResultsThe level of urine IL-8, NGAL and KIM-1 in AKI group was significantly higher than that in non-AKI group at 4, 12, 24 and 48 h (p < 0.01). The ROC analysis showed the combined detection of urine IL-8, NGAL and KIM-1 at 12 h had a larger area under curve (AUC) than a single marker (0.997, 95% CI: 0.991–0.998), and the sensitivity and specificity were 98.2% and 96.7%, respectively. Pearson correlation analysis showed that the levels of urine NGAL at 4, 12, 24 and 48 h in AKI patients were positively correlated with the levels of urine KIM-1 and IL-18 (p < 0.01).ConclusionAKI could be quickly recognized by the elevated level of urine IL-8, NGAL and KIM-1 in patients with URL-related urosepsis. Combined detection of the three urine biomarkers at 12 h after surgery had a better diagnostic performance, which may be an important reference for the early diagnosis of AKI.     

Efficacy of statins on renal function in patients with chronic kidney disease: a systematic review and meta-analysis

BackgroundStudies have shown that the use of statins could significantly improve lipid profiles; however, it remains controversial whether the use of statins could improve renal function in patients with chronic kidney disease (CKD). Therefore, we conducted a meta-analysis of randomized controlled trials (RCTs) to evaluate the effects of statins on renal function in patients with CKD.MethodsWe systematically searched PubMed, EMBASE, and the Cochrane Library databases for eligible RCTs from inception to October 2020. Pooled effect estimates were assigned as weighted mean differences (WMDs) with 95% confidence intervals (CIs) using the random-effects model.ResultsWe selected 33 RCTs that recruited 37,391 patients with CKD patients. The summary results suggested that statin use significantly reduced urinary albumin (WMD: −2.04; 95%CI: −3.53 to −0.56; p = .007) and protein (WMD: −0.58; 95%CI: −0.95 to −0.21; p = .002) excretions and increased creatinine clearance (WMD: 0.86; 95%CI: 0.32–1.41; p = .002). However, there were no significant differences between statin and control groups in terms of changes in estimated glomerular filtration rate (WMD: 0.38; 95%CI: −0.04 to 0.79; p = .075), and serum creatinine levels (WMD: −0.07; 95%CI: −0.25, 0.12; p = .475).ConclusionsWe found that statin use in patients with CKD may slow CKD progression by lowering urinary albumin and protein excretions or increasing creatinine clearance. Further large-scale RCTs should be conducted to evaluate the long-term effects of statins on renal outcomes. Abbreviations: CKD: chronic kidney disease; RCT: randomized controlled trials; WMD: weighted mean differences; CI: confidence intervals; ACEI: angiotensin-converting enzyme inhibitors; eGFR: estimated glomerular filtration rate     

Acute kidney injury in idiopathic membranous nephropathy with nephrotic syndrome

Background and objectivesThe impact of acute kidney injury (AKI) on the progression of renal function in idiopathic membranous nephropathy (iMN) with nephrotic syndrome (NS) patients have not yet been reported, we sought to investigate the incidence, clinical features and prognosis of AKI in iMN with NS patients and determine clinical predictors for progression from AKI to advanced chronic kidney disease (CKD) stage.MethodsWe analyzed clinical and pathological data of iMN with NS patients retrospectively collected from Jan 2012 to Dec 2018. The primary renal endpoint was defined as persistent eGFR <45ml/min per 1.73 m² more than 3 months. Comparisons of survival without primary renal endpoint were performed by Kaplan-Meier curves and log-rank test. Univariate and multivariate Cox proportional hazard models were constructed to determine independent variables associated with primary renal endpoint .Results434 iMN with NS patients were enrolled. The incidence of AKI 1 stage, AKI 2 stage and AKI 3 stage was 23.1, 4.8 and 0.7% respectively. 66 (53.2%) patients with AKI had complete renal function recovery and 42 (33.9%) patients with AKI reached primary renal endpoint. Survival without primary renal endpoint was worse in AKI patients than No AKI patients (67.1 ± 5.3 and 43.7 ± 7.3% vs 99.5 ± 0.5 and 92.5 ± 4.2% at 2 and 4 years,p < 0.001). AKI was independently associated with primary renal endpoint, with an adjusted hazard ratio(HR) of 25.1 (95%CI 7.7–82.1, p < 0.001).ConclusionsAKI was usually mild and overlooked in iMN patients with NS, but it had a strong association with poor clinical outcomes and was an independent risk factor for CKD progression.     

Calcium-sensing receptor promotes calcium oxalate crystal adhesion and renal injury in Wistar rats by promoting ROS production and subsequent regulation of PS ectropion,OPN, KIM-1, and ERK expression

ObjectivesTo explore the mechanism of calcium-sensing receptors (CaSRs) during the development of nephrolithiasis.Materials and methodsWistar rats were treated with ethylene glycol to induce calcium oxalate crystallization, and gadolinium chloride (GdCl₃, an agonist of CaSR) and NPS 2390 (an antagonist of CaSR) were added. Oxidative stress (OS) and calcium oxalate crystals in the kidney were observed. CaSR expression and the expression of extracellular signal-regulated protein kinase (ERK), OPN, and KIM-1 were determined by western blotting. In addition, renal tubular epithelial cells were isolated from the kidney to observe phosphatidylserine (PS) ectropion using flow cytometric analysis. Various biochemical parameters were assessed in serum and urine at the end of the experiment.ResultsCalcium oxalate increased OS, crystal adhesion, PS ectropion, and the expression of CaSR and ERK, OPN, and KIM-1 in vivo. In addition, lower levels of urine citrate as well as increased serum creatinine and urea levels were observed after treatment with calcium oxalate (p < .05). Compared with calcium oxalate treatment alone, the above deleterious changes were further significantly confirmed by GdCl₃ but were reversed by NPS-2390. However, urine calcium excretion was decreased after ethylene glycol treatment but was significantly reduced by NPS 2390 and increased by GdCl₃ (p < .05).ConclusionsThe results suggest that CaSR might play significant roles in the induction of nephrolithiasis in rats by regulating reactive oxygen species (ROS) and PS ectropion and the composition of urine, OPN, KIM-1, and ERK expression.     

Optimal timing of coronary angiograms for patients with chronic kidney disease: association between the duration of kidney dysfunction and SYNTAX scores

BackgroundChronic kidney disease (CKD) is associated with an increased risk of the progression of coronary artery disease (CAD). However, there are few data on the relationship between CAD severity and the duration of CKD. This study assessed the predictive value of the duration of kidney dysfunction in CKD patients with CAD severity.MethodsIn 145 patients (63.4% male, n = 92; mean age, 68.8 ± 12.8 years) with CKD, severity of CAD was assessed by coronary angiography and quantified by SYNTAX scores, and duration of kidney dysfunction was either assessed by checking historical biochemical parameters of individuals or was based on enquiries.ResultsPatients with high SYNTAX scores (≥ 22) had a greater prevalence of cardiovascular risk factors including age, gender, history of heart failure and smoking. In CKD patients, SYNTAX scores were positively correlated to duration of CKD and serum uric acid (UA), and negatively correlated to high-density lipoprotein-cholesterol (HDL-C) and ApoA1 levels. Univariate binary logistic regression and multivariate logistic analyses showed that SYNTAX scores correlated significantly with CKD duration, UA, and HDL-C. Receiver-operating characteristic analysis was used to explore a time point when coronary angiography application was economical and effective and yielded a Youden index of 6.5 years.ConclusionsTogether, our results demonstrated that the duration of kidney dysfunction was an independent correlate of the severity of CAD in patients with CKD. Our findings suggest that coronary angiography should be considered for CKD patients with renal insufficiency having lasted for more than 6.5 years.     

Chronic kidney disease stage stratifies short- and long-term outcomes after aortic root replacement

OBJECTIVESChronic kidney disease (CKD) is prevalent in patients undergoing cardiovascular surgery, and it negatively impacts procedural outcomes; however, its influence on the outcomes of aortic surgery has not been well studied. This study aims to elucidate the importance of CKD on the outcomes of aortic root replacement (ARR).Open in a separate windowMETHODSPatients who underwent ARR between 2005 and 2019 were retrospectively reviewed (n = 882). Patients were divided into 3 groups based on the Kidney Disease: Improving Global Outcomes criteria: Group 1 [estimated glomerular filtration rate (eGFR) ≥ 60 ml/min/1.73 m², n = 421); Group 2 (eGFR = 30–59 ml/min/1.73 m², n = 424); and Group 3 (eGFR < 30 ml/min/1.73 m², n = 37). To reduce potential confounding, a propensity score matching was also performed between Group 1 and the combined group of Group 2 and Group 3. The primary end point was 10-year survival. Secondary end points were in-hospital mortality and perioperative morbidity.RESULTSSevere CKD patients presented with more advanced overall chronic and acute illnesses. Kaplan–Meier analysis showed a significant correlation between CKD stage and 10-year survival (log-rank P < 0.001). The number of events for Group 1 was 15, Group 2 was 49 and Group 3 was 11 in 10 years. Group 3 had significantly higher in-hospital mortality (13.5% vs 3.5% in Group 2 vs 0.7% in Group 1, P < 0.001) and stroke (8.1% vs 7.1% vs 1.2%, P < 0.001) as well as introduction to new dialysis (27.0% vs 5.4% vs 1.7%, P < 0.001). eGFR was shown to be an independent predictor of mortality (hazard ratio, 0.98; 95% confidence interval, 0.96–0.99). Comparison between propensity matched groups showed similar postoperative outcomes, and eGFR was still identified as a predictor of mortality (hazard ratio, 0.97; 95% confidence interval, 0.95–0.99).CONCLUSIONSHigher stage in CKD negatively impacts the long-term survival in patients who are undergoing ARR.     

Improved performance of urinary biomarkers of acute kidney injury in the critically ill by stratification for injury duration and baseline renal function

To better understand the diagnostic and predictive performance of urinary biomarkers of kidney injury, we evaluated γ-glutamyltranspeptidase (GGT), alkaline phosphatase (AP), neutrophil-gelatinase-associated lipocalin (NGAL), cystatin C (CysC), kidney injury molecule-1 (KIM-1), and interleukin-18 (IL-18) in a prospective observational study of 529 patients in 2 general intensive care units (ICUs). Comparisons were made using the area under the receiver operator characteristic curve (AUC) for diagnosis or prediction of acute kidney injury (AKI), dialysis, or death, and reassessed after patient stratification by baseline renal function (estimated glomerular filtration rate, eGFR) and time after renal insult. On ICU entry, no biomarker had an AUC above 0.7 in the diagnosis or prediction of AKI. Several biomarkers (NGAL, CysC, and IL-18) predicted dialysis (AUC over 0.7), and all except KIM-1 predicted death at 7 days (AUC between 0.61 and 0.69). Performance was improved by stratification for eGFR or time or both. With eGFR <60?ml/min, CysC and KIM-1 had AUCs of 0.69 and 0.73, respectively, within 6?h of injury, and between 12 and 36?h, CysC (0.88), NGAL (0.85), and IL-18 (0.94) had utility. With eGFR >60?ml/min, GGT (0.73), CysC (0.68), and NGAL (0.68) had the highest AUCs within 6?h of injury, and between 6 and 12?h, all AUCs except AP were between 0.68 and 0.78. Beyond 12?h, NGAL (0.71) and KIM-1 (0.66) performed best. Thus, the duration of injury and baseline renal function should be considered in evaluating biomarker performance to diagnose AKI.     

Prognosis of severe drug-induced acute interstitial nephritis requiring renal replacement therapy

ObjectiveDrug-induced acute interstitial nephritis (DAIN) is often associated with improved outcomes, whereas some patients may still progress to chronic kidney disease (CKD). The aim of this study was to evaluate the prognosis of patients with severe DAIN requiring renal replacement therapy (RRT) at baseline, and to explore the risk factors of progression to CKD.MethodsWe performed a retrospective study of patients with severe DAIN confirmed by renal biopsies in our center over a 10 years period, all the patients received RRT at presentation. The clinical and pathological characteristics at baseline were recorded, and the outcomes (renal function recovered or progressed to CKD) during follow-ups were also evaluated. Univariate and multivariate logistic regression analysis were performed to identify the independent risk factors of progression to CKD.ResultsSeventy-two patients who met the inclusion criteria were enrolled, 13 patients (18.0%) progressed to CKD (GFR < 60 ml/min/1.73 m²) after at least 6 months of follow-up, the remaining 59 patients achieved a favorable renal function recovery. Compared with patients who achieved renal function recovery (recovery group), the patients progressed to CKD (progression group) were older and had longer interval from symptom onset to treatment with steroids. The peak serum cystatin C concentration was higher in progression group than recovery group. Higher score of interstitial fibrosis/tubular atrophy (IFTA) and more interstitial inflammatory cells infiltration were detected in renal tissue in progression group. According to multivariable analysis, higher peak cystatin C concentration (OR = 2.443, 95% CI 1.257, 4.746, p = 0.008), longer interval to treatment with corticosteroids (OR = 1.183, 95% CI 1.035, 1.352, p = 0.014) were independent risk factors of progression to CKD. The cutoff value of cystatin C concentration was 4.34 mg/L, at which the sensitivity and specificity were 76.9% and 89.3%, respectively; the cutoff value of interval to treatment with corticosteroids was 22.5 days, at which the sensitivity and specificity were 81.8% and 79.5%, respectively.ConclusionRenal function was reversible in majority of patients with severe DAIN requiring RRT when early identification and treatment. Higher peak cystatin C concentration and longer interval to treatment with corticosteroids associated with worse renal prognosis.     

Effects of intensive blood pressure control on mortality and cardiorenal function in chronic kidney disease patients

BackgroundBlood pressure (BP) variability is highly correlated with cardiovascular and kidney outcomes in patients with chronic kidney disease (CKD). However, appropriate BP targets in patients with CKD remain uncertain.MethodsWe searched PubMed, Embase, and the Cochrane Library for randomized controlled trials (RCTs) of CKD patients who underwent intensive BP management. Kappa score was used to assess inter-rater agreement. A good agreement between the authors was observed to inter-rater reliability of RCTs selection (kappa = 0.77; P = 0.005).ResultsTen relevant studies involving 20 059 patients were included in the meta-analysis. Overall, intensive BP management may reduce the incidence of cardiovascular disease mortality (RR: 0.69, 95% CI: 0.53 to 0.90, P: 0.01), all-cause mortality (RR: 0.77, 95% CI: 0.67 to 0.88, P < 0.01) and composite cardiovascular events (RR: 0.84 95% CI: 0.75 to 0.95, P < 0.01) in patients with CKD. However, reducing BP has no significant effect on the incidence of doubling of serum creatinine level or 50% reduction in GFR (RR: 1.26, 95% CI: 0.66 to 2.40, P = 0.48), composite renal events (RR 1.07, 95% CI: 0.81 to 1.41, P = 0.64) or SAEs (RR: 0.97, 95% CI: 0.90 to 1.05, P = 0.48).ConclusionIn patients with CKD, enhanced BP management is associated with reduced all-cause mortality, cardiovascular mortality, and incidence of composite cardiovascular events.     

The protective effects of exogenous spermine on renal ischemia-reperfusion injury in rats

BackgroundTo investigate the protective effects of exogenous spermine on renal ischemia-reperfusion injury in rats.Methods(I) Different doses of spermine were injected into rats to determine the safe dose on the kidneys. Kidney toxicity was assessed by hematoxylin and eosin (HE) staining of kidney tissue and enzyme-linked immunosorbent assay (ELISA) detection of neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule 1 (KIM-1) in the venous blood. (II) A rat model of renal ischemia-reperfusion injury was established. Different doses of spermine were injected into the rats through the tail vein 30 minutes before and 3 days after the establishment of the model. Blood samples and kidney tissues were collected and renal injury was assessed via HE staining of the renal tissue, detection of apoptosis using the TUNEL assay, and detection of NGAL and KIM-1 in blood samples using ELISA. (III) Human HK-2 renal tubular epithelial cells were cultured under hypoxia/reoxygenation conditions. To evaluate the protective effects of spermine, apoptosis was assessed by flow cytometry and TUNEL assay. The mechanisms underlying the effects of spermine were studied using Western blot analyses.ResultsAt spermine concentrations below 200 µM (2 mL/kg body weight), no significant damage to the kidney was observed by HE staining, and there was no significant difference in NGAL and KIM-1 levels between rats treated with spermine and control rats (P<0.05). At spermine doses below 200 µM, HE staining showed that the degree of renal ischemia-reperfusion injury was gradually alleviated with increasing doses of spermine. TUNEL assays demonstrated that spermine reduced the apoptosis of renal tissue, and increasing doses of spermine gradually decreased the levels of NGAL and KIM-1 in the blood compared with the control group (P<0.05). Western blot analysis revealed that spermine increased the expression of pro-caspase9, phosphorylated protein kinase B (p-Akt), hypoxia-inducible factor 1 alpha (HIF-1α), B cell lymphoma 2 (Bcl-2), and Bcl2 interacting protein 3 (BNIP3), and decreased the expression of cleaved caspase-3, Bax and cytochrome C compared to control cells.ConclusionsExogenous spermine exerted a protective effect on renal ischemia-reperfusion injury in rats by inhibiting the apoptosis of renal tubular epithelial cells.     

Coronavirus-associated kidney outcomes in COVID-19, SARS,and MERS: a meta-analysis and systematic review

ObjectivesA meta-analysis and systematic review was conducted on kidney-related outcomes of three recent pandemics: SARS, MERS, and COVID-19, which were associated with potentially fatal acute respiratory distress syndrome (ARDS).MethodsA search of all published studies until 16 June 2020 was performed. The incidence/prevalence and mortality risk of acute and chronic renal events were evaluated, virus prevalence, and mortality in preexisting hemodialysis patients was investigated.ResultsA total of 58 eligible studies involving 13452 hospitalized patients with three types of coronavirus infection were included. The reported incidence of new-onset acute kidney injury (AKI) was 12.5% (95% CI: 7.6%–18.3%). AKI significantly increased the mortality risk (OR = 5.75, 95% CI 3.75–8.77, p < 0.00001) in patients with coronavirus infection. The overall rate of urgent-start kidney replacement therapy (urgent-start KRT) use was 8.9% (95% CI: 5.0%–13.8%) and those who received urgent-start KRT had a higher risk of mortality (OR = 3.43, 95% CI 2.02–5.85, p < 0.00001). Patients with known chronic kidney disease (CKD) had a higher mortality than those without CKD (OR = 1.97, 95% CI 1.56–2.49, p < 0.00001). The incidence of coronavirus infection was 7.7% (95% CI: 4.9%–11.1%) in prevalent hemodialysis patients with an overall mortality rate of 26.2% (95% CI: 20.6%–32.6%).ConclusionsPrimary kidney involvement is common with coronavirus infection and is associated with significantly increased mortality. The recognition of AKI, CKD, and urgent-start KRT as major risk factors for mortality in coronavirus-infected patients are important steps in reducing future mortality and long-term morbidity in hospitalized patients with coronavirus infection.     

Association between atherosclerotic cardiovascular diseases risk and renal outcome in patients with type 2 diabetes mellitus

AimsChronic kidney disease (CKD) and diabetes mellitus increase atherosclerotic cardiovascular diseases (ASCVD) risk. However, the association between renal outcome of diabetic kidney disease (DKD) and ASCVD risk is unclear.MethodsThis retrospective study enrolled 218 type 2 diabetic patients with biopsy-proven DKD, and without known cardiovascular diseases. Baseline characteristics were obtained and the 10-year ASCVD risk score was calculated using the Pooled Cohort Equation (PCE). Renal outcome was defined as progression to end-stage renal disease (ESRD). The association between ASCVD risk and renal function and outcome was analyzed with logistic regression and Cox analysis.ResultsAmong all patients, the median 10-year ASCVD risk score was 14.1%. The median of ASCVD risk score in CKD stage 1, 2, 3, and 4 was 10.9%, 12.3%, 16.5%, and 14.8%, respectively (p = 0.268). Compared with patients with lower ASCVD risk (＜14.1%), those with higher ASCVD risk had lower eGFR, higher systolic blood pressure, and more severe renal interstitial inflammation. High ASCVD risk (>14.1%) was an independent indicator of renal dysfunction in multivariable-adjusted logistic analysis (OR, 3.997; 95%CI, 1.385–11.530; p = 0.010), though failed to be an independent risk factor for ESRD in patients with DKD in univariate and multivariate Cox analysis.ConclusionsDKD patients even in CKD stage 1 had comparable ASCVD risk score to patients in CKD stage 2, 3, and 4. Higher ASCVD risk indicated severe renal insufficiency, while no prognostic value of ASVCD risk for renal outcome was observed, which implied macroangiopathy and microangiopathy in patients with DKD were related, but relatively independent.     

Urinary biomarkers in the early detection and follow-up of tubular injury in childhood urolithiasis

Background

To investigate relationships among urinary biomarkers [kidney injury molecule-1 (KIM-1), N-acetyl-β-glucosaminidase (NAG)], neutrophil gelatinase-associated lipocalin (NGAL) levels and renal tubular injury in childhood urolithiasis.

Methods

Seventy children [36 girls, mean age: 7.3 ± 5.0 years (0.5–18.2)] with urolithiasis/microlithiasis and 42 controls [18 girls, mean age: 8.5 ± 3.8 years (0.9–16.2)] were included in this multicenter, controlled, prospective cohort study. Patients were evaluated three times in 6-month intervals (0, 6 and 12th months). Anthropometric data, urinary symptoms, family history and diagnostic studies were recorded. Urine samples were analyzed for metabolic risk factors (urinary calcium, uric acid, oxalate, citrate, cystine, magnesium, and creatinine excretion), and the urinary KIM-1, NAG, and NGAL levels were measured.

Results

Stones were mostly located in the upper urinary system (82.9%), and six patients (8.6%) had hydronephrosis. Thirty patients (42.9%) had several metabolic risk factors, and the most common metabolic risk factor was hypocitraturia (22.9%). Urinary KIM-1/Cr, NAG/Cr and NGAL/Cr ratios were not significantly different between patients and controls. Furthermore, no significant changes in their excretion were shown during follow-up. Notably, the urinary KIM-1/Cr, NAG/Cr, and NGAL/Cr levels were significantly higher in children under 2 years of age (p = 0.011, p = 0.006, and 0.015, respectively). NAG/Cr and NGAL/Cr ratios were significantly increased in patients with hydronephrosis (n = 6, p = 0.031 and 0.023, respectively).

Conclusions

The results of this study suggest that none of the aforementioned urinary biomarkers (KIM-1, NAG and NGAL levels) may be useful for the early detection and/or follow-up of renal tubular injury and/or dysfunction in childhood urolithiasis.

     

Urinary Exosomes as a Source of Kidney Dysfunction Biomarker in Renal Transplantation

End-stage renal disease (ESRD) requires for its treatment permanent dialysis or kidney transplantation (KT). KT is the best clinical treatment, however, the early function of the allograft varies depending on multiple factors associated with cold ischemia time (CIT) and the allograft rejection process. It is known that serum creatinine is an insensitive and late marker for predicting graft recovery after KT, mainly in patients with delayed graft function (DGF). Neutrophil gelatinase-associated lipocalin (NGAL) is produced in the distal nephron and it is one of the most promising novel biomarkers for acute kidney injury (AKI) and chronic kidney disease (CKD). NGAL has been proposed to be a predictor of organ recovery from DGF after KT from donors after cardiac death. Because nonrenal diseases can also induce NGAL, more information is necessary to validate the sensitivity and specificity of urine and plasma NGAL in clinical samples. The exosomes are vesicles released into the urine from the kidney epithelium and they have been proposed as better source to explore as biomarker of renal dysfunction. The molecular composition of the urinary exosomes could be representative of the physiological or physiopathologic condition of the urinary system. We propose that determination of NGAL in urinary exosomes is a better predictor of kidney dysfunction after KT than other urinary fractions. We analyzed 15 kidney allograft recipients, with a mean age of 36 years (range, 16–60 years) and 75% were male: 11 living donors (LD) and 4 deceased donors (DD). The average length of CIT was 14 hours in DD and less than 1 hour in LD. Three patient developed DGF. Using Western blot analysis, NGAL was detectable in the cellular and exosomal fraction of the urine. The exosomes expressed higher levels of NGAL than the cellular fraction. The expression of NGAL was observed from the first day after transplantation. In the cellular fraction of the urine, no significant differences of NGAL were observed between the patients. However, the median of NGAL expression in the exosomes fraction was significantly higher in DD patient, from the first day after KT (P < .05). Moreover, we noticed that NGAL expression in exosomes remained elevated in the patients with DGF compared with non-DGF patients (P < .05). Considering the highest abundance of NGAL in the urinary exosomes and its correlation with DGF patients, we suggest the exosomal fraction as a more sensitive substrate to evaluate early biomarkers of DGF after KT.     

Chronic kidney disease recognition amongst physicians and advanced practice providers

ObjectiveChronic kidney disease is a worldwide public health issue, with increasing prevalence resulting in high morbidity and mortality. As a result, recognizing and treating it early can lead to improved outcomes. We hypothesized that some providers might be more comfortable making this diagnosis than others.MethodsRetrospective study of 380 patients with chronic kidney disease seen between 2012 and 2016 in an outpatient setting.ResultsThree hundred and sixteen patients were treated by physicians and sixty-four by advanced practice providers. Chronic kidney disease was identified by the primary care providers in 318 patients (83.6%). Patients recognized with chronic kidney disease were older, 76 ± 8.8 vs 72 ± 7.45 years, p = 0.001; had lower GFR, 37 [29, 46] vs 57 [37, 76] ml/min/1.73 m², p < 0.0001 and were more likely to be seen by a physician compared to an advanced practice provider: 272/316 (86%) vs 46/64 (71.8%), p = 0.008. In multivariate analyses, care by a physician, OR = 2.27 (1.13–4.58), p = 0.02 was associated with increased recognition of chronic kidney disease. On the other hand, higher GFR was associated with decreased diagnosis of chronic kidney disease, OR = 0.95 (0.93–0.96), p < 0.0001.ConclusionThe odds of chronic kidney disease recognition were higher amongst physicians in comparison to non-physician providers.     

Urinary and Serum Biomarkers after Cardiac Catheterization in Diabetic Patients with Stable Angina and without Severe Chronic Kidney Disease

Background/Aims. Different serum and urinary biomarkers have been recently proposed to serve as markers of acute kidney injury. We tested the hypothesis whether NGAL and other biomarkers could represent an early biomarker of contrast nephropathy (CIN) in diabetic patients with normal serum creatinine undergoing cardiac catheterization in comparison with non-diabetic patients. Methods. Serum, urinary NGAL, cystatin C, urinary kidney injury molecule-1 (KIM-1), interleukin-18 (IL-18), and liver-type fatty acid binding protein (L-FABP) were evaluated before and 2, 4, 8, 24, and 48 hours after cardiac catheterization using commercially available kits. Results. In both groups we found a significant rise in serum NGAL after 2, 4, and 8 hours, and in urinary NGAL and IL-18 after 4, 8, and 24 hours after cardiac catheterization. Serum cystatin C increased significantly 8 hours, reaching peak 24 hours after cardiac catheterization in both groups, and then decreased after 48 hours. L-FABP and KIM-1 increase significantly after 24 and 48 hours after cardiac catheterization. Conclusions. CIN was similarly prevalent in both diabetic and non-diabetic patients undergoing cardiac catheterization. NGAL seems to be a potential early marker for nephrotoxicity and predictor of contrast nephropathy. It is particularly important in the upcoming setting of short-time hospitalizations for cardiac catheterization.     

Critically ill,tubular injury,delayed early recovery: characteristics of acute kidney disease with renal oxalosis

ObjectsThis study aimed to analyze the clinicopathological features of acute kidney disease (AKD) with renal oxalosis.MethodsData for biopsy-proven AKD with oxalosis diagnosed from Jan 2011 to Oct 2018 was collected. The underlying diseases, dietary habits, clinical and pathological characteristics of newly emerging kidney disease were analyzed. The long-term renal prognosis was observed.ResultsA total of 23 patients were included, comprised of 18 men and 5 women with a mean age of 51.6 ± 15.9 years. The peak Scr was 669.9 ± 299.8 μmol/L, and 95.7% of patients had stage 3 acute kidney injury (AKI). Drug-induced tubulointerstitial nephritis (TIN) was the most common cause (65.2%) of AKD, followed by severe nephrotic syndrome (17.4%). All patients had pathological changes indicating TIN, and 11 patients were complicated with the newly emerging glomerular disease (GD). The risk of oxalosis caused by increased enterogenous oxalate absorption accounted for only 26.1%, and others came from new kidney diseases. The majority (75%) of abundant (medium to severe) oxalosis occurred in patients without GD. There were no significant differences in the score for tubular injury (T-IS) and interstitial inflammation with different severities of oxalosis. Rate of Scr decrease (ΔScr%) at 2 weeks was negatively correlated with the severity of oxalosis (R = −0.542, p = 0.037), score for T-IS (R = −0.553, p = 0.033), and age (R = −0.736, p = 0.002). The decrease in Scr at 4 weeks was correlated with T-IS (R = −0.433), but had no correlation with oxalosis.ConclusionsThe present findings revealed that 95.7% of AKD with secondary renal oxalosis occurred in critically ill patients. AKD from tubular injury was the prominent cause. Severe oxalosis contributed to delayed early recovery of AKD.     

Analysis of a Urinary Biomarker Panel for Incident Kidney Disease and Clinical Outcomes

Whether novel biomarkers improve the assessment of incident kidney disease and related adverse outcomes remains to be tested in longitudinal observational studies. We tested 14 urinary biomarkers for association with incident kidney, cardiovascular, and mortality outcomes in 2948 Framingham Heart Study participants. Baseline examinations were performed between 1995 and 1998; mean follow-up was 10.1 years for renal outcomes and 11.2 years for survival analyses. Primary outcomes were incident CKD, incident albuminuria, incident cardiovascular disease, and all-cause mortality. Secondary analyses assessed incident congestive heart failure (CHF) and mortality with coexistent kidney disease. Biomarkers were tested for association with renal end points using logistic regression and incident cardiovascular and mortality outcomes in proportional hazards models; α1-microglobulin, Kim-1, and TFF-3 predicted all-cause mortality (hazard ratio per SD increase in log-transformed biomarker [HR] range, 1.15 to 1.21; 95% confidence interval [CI] range, 1.04 to 1.34; P values=0.007 to <0.001), whereas α1-microglobulin, β2-microglobulin, KIM-1, and TFF-3 associated with death with coexistent kidney disease (HR range, 1.72–2.25; 95% CI, 1.17 to 3.24; P values<0.01). KIM-1 also associated with the risk of incident CHF (HR, 1.32; 95% CI, 1.07 to 1.63; P=0.008). CTGF associated nominally with CKD (HR, 0.83; 95% CI, 0.71 to 0.98; P=0.03), but no other biomarkers associated with incident CKD or albuminuria. Addition of α1-microglobulin and TFF-3 resulted in a nonsignificant net reclassification index (NRI) of 3% for all-cause mortality beyond clinical risk factors. In conclusion, components of a panel of 14 subclinical biomarkers of kidney injury were associated with important clinical outcomes and merit additional investigation.During the past 50 years, cardiac injury biomarkers, such as creatine-kinase MB isoenzyme and troponin, have transformed the assessment and management of patients with heart disease.¹ During this time, clinically validated biomarkers available for the assessment of kidney disease have remained unchanged. The current benchmarks, serum creatinine and albuminuria, lack sensitivity in early disease and provide limited insight into the nature of the underlying renal injury.^2,3There is a need for novel biomarkers that identify at-risk individuals before the development of overt kidney disease. Kidney injury biomarkers can provide mechanistic insights by precisely localizing the affected kidney compartment and permit monitoring and assessment of distinct renal pathophysiological pathways, which may have prognostic implications for patients. Furthermore, they can provide insight into disease biology and help to better classify at-risk individuals in the absence of overt clinical disease.Several novel renal biomarkers, detectable as proteins in urine, have been proposed for these purposes in experimental and clinical settings, but they require validation in prospective human cohorts.^2,4,5 We used a panel of 14 biomarkers identified in animal studies of AKI as well as cross-sectional human studies.^2,4,5 The panel includes all five biomarkers recently proposed by the Food and Drug Administration and the European Medicines Evaluation Agency for use as indicators of drug-induced AKI through the Critical Path Initiative: kidney injury molecule 1 (KIM-1), β2-microglobulin, cystatin C, clusterin, and trefoil factor-3 (TFF-3).⁶ We hypothesized that these biomarkers would be associated with an increased risk of kidney disease and related adverse outcomes. Our specific aim was to determine if the urinary biomarker panel is associated with incident CKD (estimated GFR<60 ml/min per 1.73 m²), incident albuminuria, cardiovascular disease (CVD), and mortality. To address this question, we performed prospective analyses in unselected participants from the Framingham Heart Study (FHS).     

A combination of SOFA score and biomarkers gives a better prediction of septic AKI and in-hospital mortality in critically ill surgical patients: a pilot study

Background

Sepsis is a syndrome characterized by a constellation of clinical manifestations and a significantly high mortality rate in the surgical intensive care unit (ICU). It is frequently complicated by acute kidney injury (AKI), which, in turn, increases the risk of mortality. Therefore, it is of paramount importance to identify those septic patients at risk for the development of AKI and mortality. The objective of this pilot study was to evaluate several different biomarkers, including NGAL, calprotectin, KIM-1, cystatin C, and GDF-15, along with SOFA scores, in predicting the development of septic AKI and associated in-hospital mortality in critically ill surgical patients.

Methods

Patients admitted to the surgical ICU were prospectively enrolled, having given signed informed consent. Their blood and urine samples were obtained and subjected to enzyme-linked immunosorbent assay (ELISA) to determine the levels of various novel biomarkers. The clinical data and survival outcome were recorded and analyzed.

Results

A total of 33 patients were enrolled in the study. Most patients received surgery prior to ICU admission, with abdominal surgery being the most common type of procedure (27 patients (81.8%)). In the study, 22 patients had a diagnosis of sepsis with varying degrees of AKI, while the remaining 11 were free of sepsis. Statistical analysis demonstrated that in patients with septic AKI versus those without, the following were significantly higher: serum NGAL (447.5?±?35.7 ng/mL vs. 256.5?±?31.8 ng/mL, P value 0.001), calprotectin (1030.3?±?298.6 pg/mL vs. 248.1?±?210.7 pg/mL, P value 0.049), urinary NGAL (434.2?±?31.5 ng/mL vs. 208.3?±?39.5 ng/mL, P value <?0.001), and SOFA score (11.5?±?1.2 vs. 4.4?±?0.5, P value <?0.001). On the other hand, serum NGAL (428.2?±?32.3 ng/mL vs. 300.4?±?44.3 ng/mL, P value 0.029) and urinary NGAL (422.3?±?33.7 ng/mL vs. 230.8?±?42.2 ng/mL, P value 0.001), together with SOFA scores (10.6?±?1.4 vs. 5.6?±?0.8, P value 0.003), were statistically higher in cases of in-hospital mortality. A combination of serum NGAL, urinary NGAL, and SOFA scores could predict in-hospital mortality with an AUROC of 0.911.

Conclusions

This pilot study demonstrated a promising panel that allows an early diagnosis, high sensitivity, and specificity and a prognostic value for septic AKI and in-hospital mortality in surgical ICU. Further study is warranted to validate our findings.