Early Renal Injury Research Articles

Aminopeptidases in Cardiovascular and Renal Function. Role as Predictive Renal Injury Biomarkers.

Aminopeptidases (APs) are metalloenzymes that hydrolyze peptides and polypeptides by scission of the N-terminus amino acid and that also participate in the intracellular final digestion of proteins. APs play an important role in protein maturation, signal transduction, and cell-cycle control, among other processes. These enzymes are especially relevant in the control of cardiovascular and renal functions. APs participate in the regulation of the systemic and local renin–angiotensin system and also modulate the activity of neuropeptides, kinins, immunomodulatory peptides, and cytokines, even contributing to cholesterol uptake and angiogenesis. This review focuses on the role of four key APs, aspartyl-, alanyl-, glutamyl-, and leucyl-cystinyl-aminopeptidases, in the control of blood pressure (BP) and renal function and on their association with different cardiovascular and renal diseases. In this context, the effects of AP inhibitors are analyzed as therapeutic tools for BP control and renal diseases. Their role as urinary biomarkers of renal injury is also explored. The enzymatic activities of urinary APs, which act as hydrolyzing peptides on the luminal surface of the renal tubule, have emerged as early predictive renal injury biomarkers in both acute and chronic renal nephropathies, including those induced by nephrotoxic agents, obesity, hypertension, or diabetes. Hence, the analysis of urinary AP appears to be a promising diagnostic and prognostic approach to renal disease in both research and clinical settings.

Evaluation of renal ischemia-reperfusion injury by magnetic resonance imaging texture analysis: An experimental study.

To explore the value of MRI texture analysis in evaluating the presence and severity of early renal ischemia-reperfusion injury (IRI). Healthy New Zealand rabbits were used (IRI group, N=54; control group, N=8). Rabbits in the IRI group underwent left renal artery clamping for 60minutes. Magnetic resonance imaging was performed before and at 1, 12, 24, and 48hours after IRI. The relationship between MRI texture features and histopathology parameters was assessed using Pearson's correlation coefficients. The diagnostic performance of texture features in kidney differentiation at different time points was assessed by receiver operating characteristic curve analysis. T2 WI_S(3,-3)Inverse_Difference_Moment had the strongest correlation with brush border destruction, tubular epithelial edema, necrosis, and cast (r=0.56, -0.58, 0.62, and 0.69, respectively; all P<.001). BOLD_S(4,-4)Correlation had the strongest correlation with interstitial inflammatory cell infiltration (r=0.63, P<.001). SWI_S(4,4)Difference_Entropy had the strongest correlation with microvessel density (r=0.61, P<.001). The areas under the curve for T2 WI_S(3,-3)Inverse_Difference_Moment, SWI_S(4,4)Difference_Entropy, and BOLD_S(4,-4)Correlation in kidney differentiation before IRI and that at 1 and 12hours after reperfusion were 0.76, 0.72, and 0.70, respectively; the values before IRI and at 24 and 48hours after reperfusion were 0.84, 0.81, and 0.69, respectively. The area under the curve for T2 WI_S(3,-3)Inverse_Difference_Moment in kidney differentiation at 1 and 12hours after reperfusion and that at 24 and 48hours after reperfusion was 0.66. Magnetic resonance imaging texture analysis can be used for evaluating the presence and severity of early renal IRI.

2151-PUB: Association of Homocysteine with Early Nephropathy in Patients with Type 2 Diabetes

Early predication and intervention of diabetic nephropathy is increasingly imperative. Hyperhomocysteinemia is common and chronically induces arteriolar thickening, and tubulointerstitial and podocyte injury, therefore, could play a causative role in early renal injury in the kidney in type 2 diabetes. In this study, we for the first time investigated the relation of plasma total homocysteine concentration to early nephropathy in type 2 diabetes. We enrolled 183 type 2 diabetic patients in a cross-sectional study. Early diabetic nephropathy status was diagnosed by presence of microalbuminuria. Plasma total homocysteine levels were measured using fluorescence polarization immunoassay. Variables for diabetic nephropathy were obtained from fasting blood samples and interviewer- questionnaire. We found that plasma total homocysteine concentrations were elevated in subjects with early diabetic nephropathy than without (13.3±2.9)µmol/l vs. (8.5 ± 1.4)μmol/l, p &amp;lt; 0.01). The association of homocysteine with the diabetic nephropathy was independent of major traditional risk factors for diabetic nephropathy (duration of diabetes, HbA1c, and blood pressure) and determinants of higher homocysteine concentration (age, sex, serum folate and vitamin B12, Biguanide use, and serum cystatin or creatinine levels,) (OR: 1.36 (1.08-1.74), p &amp;lt; 0.05). Furthermore, per increase of 5.0 μmol/l plasma homocysteine was related to early nephropathy (OR: 1.15 (1.04-1.29), p &amp;lt; 0.05), after controlling for per unit increase of other factors: per 5 year increase of duration of diabetes, per 1% increase of HbA1c, per 10 nmol/l increase of serum folate, per 100 pmol/l increase of serum B12, per 0.1 mg/L increase of serum cystatin or per 10 μmol/l increase of creatinine, and per 10 or 5 mmHg increase of systolic or diastolic blood pressure. We concluded that plasma total homocysteine concentration was independently associated with occurrence of early diabetic nephropathy. Future prospective studies are warranted. Disclosure J. Li: None. Q. Lv: None. H. Lu: None. H. Zhang: None. J. Zhou: None. Funding National Natural Science Foundation of China (81070655); Jiangsu Provincial Natural Science Foundation of China (BK2009441)

A probabilistic approach for benchmark dose of melamine exposure for a marker of early renal dysfunction in patients with calcium urolithiasis.

Environmental exposure to melamine has been associated with early renal injury in urolithiasis patients even when urinary concentrations of melamine are low. The aim of this study was to derive a benchmark dose (BMD) for melamine for urolithiasis patients. To do this, one-spot urine sample from 309 participants was obtained to measure urinary melamine and N-acetyl β-D-glucosaminidase (NAG), an early renal damage biomarker. The participants were then classified into four exposure groups based on the outcomes of melamine tableware usage questionnaire. A beta distribution of urinary excretion fraction for each group was assumed to estimate their average daily intakes (AvDIs) of melamine. The BMD and the corresponding one-sided 95% lower bound (BMDL) was then derived based on Bayesian model averaging of alternative regression models between the participants' NAG levels and their estimated AvDIs, adjusting for age, gender, and other covariates. Bayesian Markov chain Monte Carlo simulations were used for all the estimates. With a benchmark response of 0.10, the simulated BMDL of 4.89 μg/kg-bw/day for melamine exposure threshold was much lower than the WHO's current recommended tolerable daily intake of 200μg/kg_bw/day and the US FDA's 63μg/kg_bw/day. The current regulation level of melamine might not safeguard urolithiasis patients from further deterioration of renal function.

Ligliptin for treatment of type 2 diabetes mellitus with early renal injury: Efficacy and impact on endogenous hydrogen sulfide and endothelial function.

BACKGROUNDDiabetes is a clinically common chronic disease, and its incidence has been increasing in recent years. Diabetes is believed to accelerate the process of atherosclerosis in patients, and abnormal endothelial function is an important factor leading to diabetic kidney damage.AIMTo investigate the efficacy of ligliptin in the treatment of type 2 diabetes mellitus (T2DM) with early renal injury and its effect on serum endogenous hydrogen sulfide (H2S), endothelial cell particles, and endothelial function.METHODSFrom January 2018 to April 2019, 110 patients with T2DM and early kidney injury treated at our hospital were divided into an observation group (receiving ligliptin treatment, n = 54) and a control group (receiving gliquidone therapy, n = 56). Blood glucose and renal function before and after treatment were compared between the two groups.RESULTSThe differences in fasting blood glucose, 2 h blood glucose, and glycated hemoglobin were not statistically significant between the two groups after treatment. The urinary albumin excretion rate after treatment in the ligliptin group was 70.32 ± 11.21 µg/min, which was significantly lower than that of the gliquidone group (P = 0.000). Serum endogenous H2S and endothelial cell microparticles of the ligliptin treatment group were 40.04 ± 8.82 mol/L and 133.40 ± 34.39, respectively, which were significantly lower than those of the gliquidone treatment group (P = 0.000 for both); endothelin-dependent diastolic function and nitric oxide after treatment in the ligliptin group were 7.98% ± 1.22% and 190.78 ± 30.32 mol/L, significantly higher than those of the gliquidone treatment group (P = 0.000 for both).CONCLUSIONLigliptin treatment of T2DM with early renal injury has the same glucose-lowering effect as gliquidone treatment. Ligliptin treatment has a better effect and it can significantly improve the renal function and vascular endothelial function of patients, and reduce serum endogenous H2S and endothelial cell particle levels.

Fenestrated/Branched Endovascular Repair for Postdissection Thoracoabdominal Aneurysms: A Systematic Review with Pooled Data Analysis.

Patients who have survived an acute aortic dissection remain at risk for postdissection thoracoabdominal aortic aneurysms (PD-TAAAs). Fenestrated/branched endovascular repair for PD-TAAA is increasingly used in some high-volume centers, but outcomes are still limited because of the additional challenges compared to atherosclerotic thoracoabdominal aneurysms. This study was performed to evaluate the literature on fenestrated/branched endovascular repair for PD-TAAAs. PubMed, Embase, and the Cochrane Database were searched for relevant studies published until September 2019. Outcome data were extracted to evaluate the technical success, 30-day mortality, later survival, major complications, endoleaks, target vessel patency, and reintervention. Studies were analyzed in a pooled proportion meta-analysis. In total, 143 patients from 4 studies were identified for the pooled data analysis. The pooled technical success rate was 98% (95% CI: 86%-100%). After the treatment, the overall estimated 30-day mortality rate was 3% (95% CI: 1%-8%), early spinal cord ischemia rate was 10% (95% CI: 4%-21%), early renal injury rate was 5% (95% CI: 1%-19%), endoleak rate was 33% (95% CI: 22%-47%), reintervention rate at a median follow-up of 22.5 months was 34% (95% CI: 27%-42%), and all-cause mortality rate was 12% (95% CI: 6%-24%). The use of fenestrated/branched stent grafts for the treatment of PD-TAAA appears generally feasible based on the limited literature, but endoleaks and reinterventions are frequent.

Early Postoperative Renal Dysfunction Predicts Long-Term Renal Function Degradation after Type IV Thoracoabdominal Aortic Aneurysm Surgical Repair

Type IV thoracoabdominal aortic aneurysm surgical repair is often complicated by postoperative acute kidney injury. The aim was to evaluate early renal injury influence on long-term renal function. All type IV thoracoabdominal surgical repair performed between January 2000 and January 2014 in our tertiary hospital were included in this retrospective observational study. All procedures were performed through a retroperitoneal approach with at least suprarenal aortic cross-clamping. Cold Ringer Lactate was used to perfuse the kidneys. Serum creatinine (Scr.) and glomerular filtration rate (GFR) were recorded preoperatively, daily until discharge and at least annually during follow-up. Postoperative renal dysfunction was classified using the RIFLE score. Predictors of long-term renal decline were identified by logistic regression and a Cox model. Of total, 80 patients were included. Aortic clamping level was suprarenal (10%), supramesenteric (37%) or supracoeliac (53%). Ischemic durations were 29±9min for the gastrointestinal tract and the right kidney, 54±28min for the left kidney. Three patients died postoperatively. At discharge, 31 (38.8%) patients did not have a postoperative renal impairment (RIFLE-), compared with 49 (61.2%) who had a renal dysfunction (RIFLE+). GFR was 89±29ml/min vs 68±37ml/min, respectively (P<0.01). In the RIFLE+group, Scr. was increased by x1.5 (Risk) for 22 patients, x2 (Injury) for 19 patients, and ×3 (Failure) for 8 patients. Mean follow-up was 59months. Eighteen patients died, and 2 patients started permanent dialysis at 46 and 118months during follow-up. The only predictive factor of long-term GFR degradation was a postoperative GFR below 45ml/min (OR: 16.5; 95%; P<0.001). Postoperative renal dysfunction was a frequent complication, associated with long-term renal function degradation.

Clinical significance of serum cystatin C in early evaluation of renal impairment caused by chemotherapy in elderly patients.

BackgroundThis study aims to discuss the application value of serum cystatin C (Cys C) in detecting early renal function injury in elderly patients with malignant tumors after chemotherapy.MethodsThe data at different chemotherapy time points (before chemotherapy, after two cycles of chemotherapy, and after four cycles of chemotherapy) were analyzed.ResultsSerum Cys C was significantly higher after chemotherapy than before chemotherapy in elderly patients with malignant tumors, and the endogenous creatinine clearance rate (CCr) significantly decreased. These were significantly correlated. However, there was no significant change in serum creatinine (SCr) and blood urea nitrogen (BUN). Cys C continued to increase with the prolonged time of chemotherapy. In addition, Cys C was sensitive for detecting renal impairment caused by platinum-based chemotherapy drugs.ConclusionsThe diagnostic effect of Cys C on early renal function injury after chemotherapy in elderly patients with malignant tumors is better, when compared to traditional renal function test items, such as SCr, BUN and CCr.

Early Hyperglycemic Renal Injury in a Novel One‐Kidney Rat Model

Diabetes remains one of the main culprits of end‐stage kidney disease in the US. Investigation into the role of nephron number in chronic kidney disease (CKD) alone or with hypertension has revealed a strong inverse relationship (i.e., lower nephron number ‐‐&gt; increased susceptibility to hypertension and CKD); however, not much is known about the connection between nephron number and diabetic kidney disease. To address this gap in knowledge we utilize the HSRA rat, a novel inbred genetic model of nephron deficiency and chronic kidney disease. HSRA rats exhibit failure of one kidney to develop (HSRA‐S, ~20,400 nephrons) in 50–75% of offspring, while remaining offspring are born with two kidneys (HSRA‐C, ~50,000 nephrons). HSRA‐S rats can be directly compared to nephrectomized HSRA‐C rats (HSRA‐UNX, ~25,100 nephrons), which provides insight into the impact of nephron number differences across the three groups. HSRA‐S rats develop significant renal injury with age when compared with HSRA‐C and HSRA‐UNX; the difference in injury is significantly exacerbated in the presence of DOCA+salt hypertension. The current study sought to address the hypothesis that nephron deficiency in the HSRA rat is a risk factor for renal injury, secondary to hyperglycemia (similar to what is seen with hypertension). Streptozotocin (STZ) was used to induce a diabetic phenotype in HSRA‐S, HSRA‐C, and HSRA‐UNX at nine weeks of age, and animals were followed for 15 weeks. All animals exposed to STZ developed robust hyperglycemia (random glucose averages: 415mg/dL – 456 mg/dL), but in contrast to the response to hypertension, neither HSRA‐S nor HSRA‐UNX developed overt proteinuria, nor were there significant differences between groups at the conclusion of the experiment. There was however, a significant increase in kidney weight to body weight ratio in STZ/hyperglycemic groups versus controls (e.g., kidney weight to body weight ratio [mg/g] 4.8 ± 0.3089 for HSRA‐S vs 7.8 ± 1.204 for HSRA‐S+STZ, p=0.02). STZ/hyperglycemic groups also exhibited significant decreases in creatinine clearance (e.g., creatinine clearance [μL/min/g] 719.0 ± 44.81 for HSRA‐S vs. 455.2 ± 72.91 for HSRA‐S+STZ, p=0.009). Targeted RNA sequencing was performed on isolated glomeruli using a custom panel of 42 genes involved in maintenance of glomerular function. In support of the physiological data stated above, few genes were observed to be dysregulated; however, Nphs1 and Nphs2 genes (associated with the protein nephrin) were increased in two‐kidney rats (HSRA‐C and HSRA‐C+ STZ) versus either one kidney group, regardless of glycemic status. In total, the data indicates that hyperglycemia does not have a significant impact on the onset and progression of injury in young HSRA‐S animals. We are currently investigating a mixed model of hypertension + hyperglycemia in the HSRA, which represents a large cohort of patients that are susceptible to CKD. Animals will be provided a low dose of DOCA+salt (35 mg) to induce moderate hypertension at ten weeks of age, along with 45mg/kg of STZ to induce hyperglycemia. In summary, establishing a role of nephron deficiency as a risk factor for hyperglycemia‐associated CKD will contribute to the growing knowledge of the relationship between nephron number and disease.

Crescent-Like Lesions as an Early Signature of Nephropathy in a Rat Model of Prediabetes Induced by a Hypercaloric Diet.

Diabetic nephropathy (DN) is a major microvascular complication of diabetes. Obesity and hyperlipidemia, fueled by unhealthy food habits, are risk factors to glomerular filtration rate (GFR) decline and DN progression. Several studies recommend that diabetic patients should be screened early (in prediabetes) for kidney disease, in order to prevent advanced stages, for whom the current interventions are clearly inefficient. This ambition greatly depends on the existence of accurate early biomarkers and novel molecular targets, which only may arise with a more thorough knowledge of disease pathophysiology. We used a rat model of prediabetes induced by 23 weeks of high-sugar/high-fat (HSuHF) diet to characterize the phenotype of early renal dysfunction and injury. When compared with the control animals, HSuHF-treated rats displayed a metabolic phenotype compatible with obese prediabetes, displaying impaired glucose tolerance and insulin sensitivity, along with hypertriglyceridemia, and lipid peroxidation. Despite unchanged creatinine levels, the prediabetic animals presented glomerular crescent-like lesions, accompanied by increased kidney Oil-Red-O staining, triglycerides content and mRNA expression of IL-6 and iNOS. This model of HSuHF-induced prediabetes can be a useful tool to study early features of DN, namely crescent-like lesions, an early signature that deserves in-depth elucidation.

Elevated neutrophil gelatinase-associated lipocalin levels before contrast media administration among ST-segment elevation myocardial infarction patients treated with primary percutaneous coronary intervention.

Neutrophil gelatinase-associated lipocalin (NGAL) is a glycoprotein released by renal tubular cells upon nephrotoxic or ischemic events and is considered an early marker of tubular damage. We aimed to demonstrate the presence of early renal injury detected by elevated NGAL levels taken before contrast administration in ST-segment elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PCI). We prospectively included 88 patients with STEMI treated with PCI. Blood samples for plasma NGAL were drawn immediately before PCI (baseline NGAL; NGAL1) and 24 h after PCI (NGAL2). Abnormal elevations in NGAL levels were defined using the cardiac surgery associated NGAL score (NGAL score) with NGAL levels at least 100 ng/ml, suggesting renal tubular damage. Patients were also assessed for the dynamics between NGAL2 and NGAL1 levels. The mean age of the patients was 62 ± 13 years and 78% were men. A total of 50/88 (56%) patients had baseline NGAL level of at least 100, suggesting possible tubular damage before PCI. Only 10 patients progressed to clinical acute kidney injury during hospitalization, all of whom had baseline NGAL level of at least 100 (P < 0.001). Among patients with baseline NGAL at least 100, 28/50 (56%) showed a decrease in the NGAL level within 24 h, whereas only 9/50 (18%) showed an elevation in the NGAL level. In contrast, only 7/38 (19%) patients with baseline NGAL level less than 100 showed an elevation in NGAL levels within 24 h. Elevated NGAL levels before primary PCI suggesting renal tubular damage are common among STEMI patients. Further trials are needed to assess the complex cardio-renal interactions.

Effect of Shenfu Injection on Porcine Renal Function after Cardiopulmonary Resuscitation.

Objective To comprehensively evaluate the protective effect of Shenfu injection (SFI) on renal ischaemia/reperfusion injury (IRI) after cardiopulmonary resuscitation (CPR) through neutrophil gelatinase-associated lipocalin (NGAL) and to explore effective monitoring of early renal injuries after CPR. Methods Thirty healthy minipigs were randomly divided into 3 groups: sham operation (SO) (n = 6), control (n = 12), and SFI (n = 12). The SO group underwent only catheterization, whereas the control and SFI groups were subjected to program-controlled electrical stimulation to establish a cardiac arrest (CA) model due to ventricular fibrillation. After CPR, the return of spontaneous circulation was achieved. Each animal in the SFI group was intravenously injected with SFI after resuscitation. Haemodynamic parameters were monitored at baseline and 2, 6, 12, and 24 hr after CPR. At each time point, venous blood samples were collected for NGAL, creatinine, and ATPase screening. Results After CA, the MAP, CPP, and CO of the animals in the control and SFI groups decreased significantly. However, at 6 hr after CPR, the MAP, CPP, and CO of the animals in the SFI group began to recover gradually; the differences between the control and SFI groups were significant (P < 0.005). The renal damage immediately after CPR appeared to be significant in the pathological examinations. However, the degree of renal injury in the SFI group improved significantly, and the apoptosis index was also notably reduced. The blood and urine NGAL levels were clearly elevated after CPR. The greatest increase in NGAL was found in the control group, which was significantly different from that of the SFI group (P < 0.001). SFI can significantly increase the ATPase activity of kidney tissues after CPR and improve abnormal caspase-3 protein expression. Conclusion SFI can effectively prevent acute kidney injuries caused by CPR through improving energy metabolism and inhibiting apoptosis.

Evaluation of Injury Degree of Adriamycin-Induced Nephropathy in Rats Based on Serum Metabolomics Combined with Proline Marker.

Nephrotic syndrome (NS) is one of the leading causes of end-stage renal failure. Unfortunately, reliable surrogate markers for early diagnosing and monitoring the entire progression of NS are as yet absent. A method using UPLC-Q exactive HR-MS was established for the serum metabolomic study of adriamycin-induced nephropathy in rats. Two rat nephropathy models induced by adriamycin were adopted to reflect different degrees of renal damage of early and advanced stages. Then two MPC5 cell models were used to verify the role of proline in the progression of kidney injury. The results showed that seven metabolites such as 14S-HDHA, DPA, and DHA were associated with early renal injury, while 12 metabolites such as tryptophan, linoleyl carnitine, and LysoPC (18:3) reflected the advanced renal disease. At the same time, metabolites including LPE (22:6), LysoPC (22:5), and proline that changed during the whole process of NS were defined as progressive markers. Pathway analysis results showed that fatty acid metabolism, glycerophospholipid metabolism, and amino acids metabolism participated in the occurrence and development of NS. In addition, the change trend of intracellular proline content was consistent with that in serum, and the results were further supported by the detection of the crucial gene PYCRL. This study provides an important basis for searching for diagnostic markers of NS and also provides a methodological reference for early diagnosing and monitoring the pathogenesis of other progressive diseases.

Machine learning distilled metabolite biomarkers for early stage renal injury.

With chronic kidney disease (CKD), kidney becomes damaged overtime and fails to clean blood. Around 15% of US adults have CKD and nine in ten adults with CKD do not know they have it. Early prediction and accurate monitoring of CKD may improve care and decrease the frequent progression to end-stage renal disease. There is an urgent demand to discover specific biomarkers that allow for monitoring of early-stage CKD, and response to treatment. To discover such biomarkers, shotgun high throughput was applied to the detection of serum metabolites biomarker discovery for early stages of CKD from 703 participants. Ultra performance liquid chromatography coupled with high-definition mass spectrometry (UPLC-HDMS)-based metabolomics was used for the determination of 703 fasting serum samples from five stages of CKD patients and age-matched healthy controls. We discovered a set of metabolite biomarkers using a series of classic and neural network based machine learning techniques. This set of metabolites can separate early CKD stage patents from normal subjects with high accuracy. Our study illustrates the power of machine learning methods in metabolite biomarker study.

Urinary proteome of dogs with kidney injury during babesiosis

BackgroundAcute kidney injury is the most frequent complication of babesiosis in dogs and may provide a natural model for identifying early and specific markers of kidney injury in this species. There are limited data on urine proteomics in dogs, and none of the effect of babesiosis on the urine proteome. This study aimed to identify urinary proteins of dogs with kidney injury during the natural course of babesiosis caused by Babesia canis, and to compare them with proteins in a control group to reveal any potential biomarkers predicting renal injury before the presence of azotemia.Urine samples were collected from 10 dogs of various breeds and sex with naturally occurring babesiosis, and 10 healthy dogs. Pooled urine samples from both groups were separated by 2D (two-dimensional) electrophoresis, followed by protein identification using MALDI-TOF (matrix-assisted laser desorption ionization time of flight) mass spectrometry.ResultsIn total, 176 proteins were identified in the urine samples from healthy dogs, and 403 proteins were identified in the urine samples from dogs with babesiosis. Of the 176 proteins, 146 were assigned exclusively to healthy dogs, and 373 of the 403 proteins were assigned exclusively to dogs with babesiosis; 30 proteins were common for both groups. Characteristic analysis of 373 proteins found in dogs with babesiosis led to the isolation of 8 proteins associated with 10 metabolic pathways involved in immune and inflammatory responses.ConclusionsIt was hypothesized that epithelial-mesenchymal transition might play an important role in the mechanisms underlying pathological changes in renal tissue during babesiosis, as indicated by a causal relationship network built by combining 5 of the 10 selected metabolic pathways, and 4 of the 8 proteins associated with these pathways; this network included cadherins, gonadotropin releasing hormone receptors, inflammatory responses mediated by chemokine and cytokine signalling pathways, integrins, interleukins, and TGF-β (transforming growth factor β) pathways. Those pathways were linked by interleukin-13, bone morphogenetic protein 7, α2(1) collagen, and tyrosine protein kinase Fer, which are potential biomarkers of damage during babesiosis in dogs, that might indicate early renal injury.

Clinical value of early renal damage index in children hydronephrosis

Objective To explore urinary NAG, Cr, MA, α1-MG andβ2-MG as the early renal damage index in children hydronephrosis. Methods The clinical data of 206 patients in the Bayi Children′s Hospital Affiliated to the Seventh Medical Center of Chinese PLA General Hospital from May 2018 to January 2019 were analyzed retrospectively. Among them, 152 children with hydronephrosis were set as observation group, 54 children without hydronephrosis were set as control group. In the observation group, the age ranged from 1 month to 18 years old, and the median age was 2 years old. There were 123 cases of hydronephrosis caused by ureteropelvic junction obstruction (UPJO) and 29 cases of posterior urethral valve complicated with hydronephrosis. In the control group, the age ranged from 1 month to 15 years old, with a median age of 5 years. There were 18 hypospadias cases, 15 occult penis cases and 21 phimosis. All children with hydronephrosis underwent nuclear medicine renal dynamic imaging. Urine specimens were tested for urinary NAG, Cr, MA, α1-MG, and β2-MG. According to renal dynamic results, the observed components were the renal function injury group and the normal renal function group. The above indicators analyzed to judge the clinical value to find the early renal damage. Results The expression levels of urinary NAG, MA, α1-MG and β2-MG in the observation group were higher than those in the control group, and the difference was statistically significant. The expression of urinary Cr and the abnormal rate were no significant difference between any two groups(P=0.647, P=0.572). The expression levels of urinary NAG, MA, α1-MG and β2-MG were not significantly different between the normal renal hydronephrosis group and the renal function impairment group (P=0.365, P=0.448, P=0.379, P=0.338). The abnormal expression rate of Urine MA and β2-MG was not statistically significant in the patients with normal renal hydronephrosis and the renal function impairment group (P=0.436, P=0.478). MA got the highest sensitivity of (58.8%), and NAG had the highest specificity of 89.3% to detect early renal demage. Four indexes combined analysis, sensitivity, negative predictive rate, diagnostic coincidence rate improved obviously. Joint analysis of posterior urethral valves combined with hydronephrosis, the abnormal rate was 89.7%(26/29). The renal dysfunction of the posterior urethral valve showed that the renal dynamics dysfunction rate was only 37.9%(11/29). Conclusions The combined analysis of urinary NAG, MA, α1-MG and β2-MG can accurately predict early renal injury. The index of early renal loss may be the early evidence to judge whether the posterior urethral valve is complicated with upper urinary tract function injury. Key words: Hydronephrosis; Children; Early renal damage index; Clinical application

Evaluation of renal markers of T1D in Sprague-Dawley exposed to 2-aminoanthracene.

The incidence of type 1 diabetes (T1D) and its associated risks of chronic kidney disease or end-stage renal disease development are on the rise. T1D is an autoimmune disease in which insulin-producing beta cells are destroyed. Increased incidence of T1D has been suggested to be a result of environmental factors such as exposure to polycyclic aromatic hydrocarbons (PAHs). 2-aminoanthracene (2AA) is a PAH that has been associated with the onset of early diabetic symptoms. This study was conducted to assess if 2AA dietary ingestion would induce T1D renal injuries. To accomplish study goals, Sprague-Dawley rats were assigned into three 2AA dietary (0, 50, and 100 mg/kg-2AA) ingestion groups for 12 weeks. Animals were evaluated for various morphometric indices, clinical markers, and gene expression. The rats in the 100 mg/kg group lost 5% less weight than the other treatment groups and converted roughly 3% more of their food intake into body mass. Renal histopathology indicated no significant difference between groups. The kidney weight per bodyweight of the 100 mg/kg treatment group was 30.1% greater than the control group. Creatinine concentration of the 100 mg/kg group was 46.2% greater than the control group. Serum glucose levels were significantly elevated in rats exposed to 2AA. On the contrary, serum albumin concentration was significantly reduced in 2AA-treated rats. T1D and genetic markers of renal injury such as FABP1, SPP1, IL-1B, and IL-7 were elevated in treated groups. These results suggest that 2AA may induce the early diabetic renal injuries.

Evaluation of Renal Function Disorder With Urinary Neutrophil Gelatinase-associated Lipocalin Level in Patients With β-Thalassemia Major.

Neutrophil gelatinase-associated lipocalin (NGAL) is found in the granules of human neutrophils, with many diverse functions. Expression of NGAL is induced under various pathophysiological conditions, for example, infection, inflammation, kidney injury, cardiovascular disease, burn injury, and intoxication, and it has an important antiapoptotic and anti-inflammatory role. A total of 37 patients with thalassemia disease β-thalassemia major (24 male and 13 female individuals) and 37 healthy controls (17 male and 20 female) were enrolled in this study. All patients were regularly transfused, and all of them were using oral chelator, deferasirox. NGAL and cystatin C levels were significantly higher in the case group than in the control group. In patients with β-thalassemia major, renal damage can occur owing to regular blood transfusion. Urinary NGAL levels in these patients may be considered as a marker for early renal injury.

The significance of combined detection of CysC, urinary mAlb and β2-MG in diagnosis of the early renal injury in pregnancy-induced hypertension syndrome.

ObjectiveTo elaborate the significance of combined detection of cystatin C, urinary micro-albumin (mAlb) and β2-microglobulin (β2-MG) in diagnosis of the early renal injury in pregnancy-induced hypertension syndrome.MethodsA total of 120 patients with pregnancy-induced hypertension syndrome who were admitted to this hospital for treatment between November 2015 and October 2018 were enrolled as subjects, and divided into the control group (without complication of renal injury, n = 76) and the observation group (with complication of renal injury, n = 44) according to the complications of early renal injury. Furthermore, 60 patients who participated in the antenatal care in this hospital were enrolled as the normal subjects (normal group). Automatic biochemistry analyzer was utilized to measure CysC, urinary mAlb and β2-MG in serum to evaluate the specificity, sensitivity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) of single or combined measurements of these indexes in diagnosis of the early renal injury in pregnancy-induced hypertension syndrome.ResultsIn the observation group, the levels of CysC, urinary mAlb and β2-MG were higher than those in the control group, while the levels in the normal group were the lowest (P < 0.05). Combined measurement of CysC, urinary mAlb and β2-MG showed a higher accuracy (90.0%) in diagnosis of the early renal injury in pregnancy-induced hypertension syndrome than the single measurements, and the difference had statistical significance (P < 0.05). Besides, the sensitivity, specificity, PPV and NPV of the combined measurements were 94.59%, 87.30%, 81.40% and 94.49%, slightly higher than the single measurements, with no statistical significance in differences (P > 0.05).ConclusionCysC, urinary mAlb and β2-MG can reflect the renal injury effectively, and the combined measurements shows potent accuracy in diagnosis of the early renal injury in pregnancy-induced hypertension syndrome, thereby providing the scientific evidence for early diagnosis and stipulation of rational therapeutic regimen and improving the pregnancy outcome.

Acute renal impairment characterization using diffusion magnetic resonance imaging: Validation by histology.

Diffusion magnetic resonance imaging has been demonstrated to be a simple, noninvasive and accurate method for the detection of renal microstructure and microcirculation, which are closely linked to renal function. Moreover, serum endothelin-1 (ET-1) was also reported as a good indicator of early renal injury. The aim of this study was to evaluate the feasibility and capability of diffusion MRI and ET-1 to detect acute kidney injury by an operation simulating high-pressure renal pelvic perfusion, which is commonly used during ureteroscopic lithotripsy. Histological findings were used as a reference. Fourteen New Zealand rabbits in an experimental group and 14 in a control group were used in this study. Diffusion tensor imaging and intravoxel incoherent motion diffusion-weighted imaging were acquired by a 3.0T MRI scanner. Significant corticomedullary differences were found in the values of the apparent diffusion coefficient (ADC), pure tissue diffusion, volume fraction of pseudo-diffusion (fp) and fractional anisotropy (FA) (P<0.05 for all) in both preoperation and postoperation experimental groups. Compared with the control group, the values of cortical fpmean , medullary ADCmean and FAmean decreased significantly (P<0.05) after the operation in the experimental group. Also, the change rate of medullary ADCmean in the experimental group was more pronounced than that in the control group (P=0.018). No significant change was found in serum ET-1 concentration after surgery in either the experimental (P=0.80) or control (P=0.17) groups. In the experimental group, histological changes were observed in the medulla, while no visible change was found in the cortex. This study demonstrated the feasibility of diffusion MRI to detect the changes of renal microstructure and microcirculation in acute kidney injury, with the potential to evaluate renal function. Moreover, the sensitivity of diffusion MRI to acute kidney injury appears to be superior to that of serum ET-1.