Urinary syndecan-1 in dogs anesthetized with isoflurane or sevoflurane: A randomized, prospective study.

BACKGROUND: Syndecan-1 (SDC1) is an established marker of endothelial glycocalyx shedding. Most research on SDC1 has focused on plasma or serum concentrations, and little is known about urine concentrations. OBJECTIVES: Measure urinary SDC1 concentrations in dogs undergoing anesthesia with either sevoflurane or isoflurane and assess the effects of anesthesia duration and IV crystalloids on urinary SDC1 concentrations. ANIMALS: Thirty-one client-owned dogs undergoing anesthesia for magnetic resonance imaging (MRI) with or without surgery for suspected intervertebral disk disease (IVDD) were used. METHODS: Dogs with suspected IVDD were randomized to undergo anesthesia with either sevoflurane or isoflurane. Urine was collected before and immediately after anesthesia for the analysis of SDC1. Urinary creatinine concentrations also were measured, and the ratio of urinary SDC1 to urinary creatinine (USCR) was used to account for dilution. RESULTS: Median (range) USCR was significantly higher after anesthesia compared with baseline for all groups combined (P < .05). No significant difference was found between the groups for age, sex, weight, and type of anesthesia. Multiple regression analysis of the effect of the independent variables inhalant type, age, weight, sex, anesthesia time, surgery, and quantity of IV fluids on the dependent variable SDC1 found that only the quantity of IV fluids significantly predicted a change (P < .001). CONCLUSIONS AND CLINICAL IMPORTANCE: The total volume of lactated Ringer's solution administered to anesthetized dogs may affect USCR. Further investigations are warranted to evaluate the relationship between IV fluids and SDC1.

Urinary Neutrophil Gelatinase Associated Lipocalins (NGALs) predict acute kidney injury post liver transplant.

BACKGROUND: Acute Kidney Injury, a common complication of liver transplant, is associated with a significant increase in the risk of morbidity, mortality and graft loss. Current diagnostic criteria leaves a delay in diagnosis allowing further potential irreversible damage. Early biomarkers of renal injury are of clinical importance and Neutrophil Gelatinase Associated Lipocalins (NGALs) and Syndecan-1 were investigated. METHODS: AKI was defined according to the Acute Kidney Injury Network criteria. Urine and blood samples were collected pre-operatively, immediately post-op and 24 h post reperfusion to allow measurement of NGAL and Syndecan-1 levels. RESULTS: 13 of 27 patients developed an AKI. Patients who developed AKI had significantly higher peak transaminases. Urinary NGAL, plasma NGAL and Syndecan-1 levels were significantly elevated in all patients post reperfusion. Urinary NGAL levels immediately post-op were significantly higher in patients who developed an AKI than those that didn't [1319 ng/ml vs 46.56 ng/ml, p ≤ 0.001]. ROC curves were performed and urinary NGAL levels immediately post-op were an excellent biomarker for AKI with an area under the curve of 0.948 (0.847-1.00). CONCLUSIONS: Urinary NGAL levels measured immediately post-op accurately predict the development of AKI and their incorporation into clinical practise could allow early protocols to be developed to treat post transplant AKI.

Urinary Syndecan-1 and acute kidney injury after pediatric cardiac surgery.

INTRODUCTION: Acute kidney injury (AKI) is a common occurrence after pediatric cardiac surgery. Plasma syndecan-1 is a biomarker of endothelial glycocalyx damage and it is associated with AKI. Syndecan-1 is also expressed in renal tubular cells but there is no study evaluating urinary syndecan-1 in predicting AKI. METHODS: Prospective cohort study with 86 patients ≤18 years submitted to cardiac surgery at one reference institution. Postoperative urinary syndecan-1 was collected within the first 2 h after cardiac surgery. Severe AKI - defined according to KDIGO as stage 2 or 3 - doubling of serum creatinine from the preoperative value or need for dialysis during hospitalization was the main outcome. Analyses were adjusted for clinical cofounders. RESULTS: Postoperative urinary syndecan-1 levels were higher in patients with severe AKI and even after adjustment for several clinical variables; the fourth quartile was significantly associated with severe AKI. The AUC-ROC for postoperative urinary syndecan-1 showed good discriminatory capacity (AUC-ROC = 0.793). The addition of urinary syndecan-1 improved the discrimination capacity of a clinical model (0.78 to 0.84). It also improved risk prediction, as measured by net reclassification improvement (NRI). CONCLUSION: Urinary syndecan-1 predicts severe AKI after pediatric cardiac surgery. Moreover, it appears to add capacity to predict severe AKI into a clinical model.

Association between syndecan-1 and renal function in adolescents with excess weight: evidence of subclinical kidney disease and endothelial dysfunction.

Excess weight (overweight and obesity) is associated with kidney and cardiovascular disease. The aim of this study was to investigate the association between syndecan-1 and renal function among adolescents with excess weight. A total of 56 students from a public school at Fortaleza, CE, Brazil, were investigated. The adolescents were submitted to anthropometric evaluation, including weight, height, blood pressure and body mass index. Blood and urine samples were collected for the determination of serum lipids (total cholesterol, high density lipoprotein cholesterol, low density lipoprotein cholesterol, triglycerides), and the endothelial injury biomarker syndecan-1. Participants' mean age was 16±1 years (range 14-19 years), and 68% were females. Overweight was observed in 4 cases (7.1%) and obesity in 7 (12.5%). Changes in serum lipid levels were more frequent in the overweight group. A positive correlation between syndecan-1 and serum creatinine (r=0.5, P=0.001) and triglycerides (r=0.37, P=0.004), and a negative correlation with glomerular filtration rate (r=-0.33, P=0.02) were found. These findings suggest that adolescents with excess weight present incipient changes at the cellular level that make them more vulnerable to the development of kidney and cardiovascular diseases.

Association between syndecan-1 and renal function in adolescents with excess weight: evidence of subclinical kidney disease and endothelial dysfunction

Excess weight (overweight and obesity) is associated with kidney and cardiovascular disease. The aim of this study was to investigate the association between syndecan-1 and renal function among adolescents with excess weight. A total of 56 students from a public school at Fortaleza, CE, Brazil, were investigated. The adolescents were submitted to anthropometric evaluation, including weight, height, blood pressure and body mass index. Blood and urine samples were collected for the determination of serum lipids (total cholesterol, high density lipoprotein cholesterol, low density lipoprotein cholesterol, triglycerides), and the endothelial injury biomarker syndecan-1. Participants' mean age was 16±1 years (range 14-19 years), and 68% were females. Overweight was observed in 4 cases (7.1%) and obesity in 7 (12.5%). Changes in serum lipid levels were more frequent in the overweight group. A positive correlation between syndecan-1 and serum creatinine (r=0.5, P=0.001) and triglycerides (r=0.37, P=0.004), and a negative correlation with glomerular filtration rate (r=-0.33, P=0.02) were found. These findings suggest that adolescents with excess weight present incipient changes at the cellular level that make them more vulnerable to the development of kidney and cardiovascular diseases.

Minimal shedding of the glycocalyx layer during abdominal hysterectomy.

BACKGROUND: Surgery with and without hypervolaemia may cause shedding (breakdown) of the endothelial glycocalyx layer, but the severity of this problem is unclear. METHODS: In this preliminary report of a larger clinical trial, the plasma and urine concentrations of three biomarkers of glycocalyx shedding (syndecan-1, hyaluronic acid and heparan sulfate) were measured in seven patients before, during, and after open hysterectomy. The fluid therapy consisted of 25 ml/kg (approximately 2 l) of Ringer's lactate, which was infused over 30 min when the surgery started. The resulting plasma volume expansion at the end of the infusion was estimated from the haemodilution. RESULTS: The mean plasma concentration of syndecan-1 was 21.7 ng/ml before surgery and averaged 19.7 ng/ml during and after the surgery. The plasma concentration of hyaluronic acid decreased from 38.0 to 27.7 ng/ml (P < 0.05), while heparan sulfate increased from 3.4 to 5.5 µg/ml (P < 0.05). The urine concentrations of syndecan-1 decreased significantly, while they increased for hyaluronic acid and heparan sulfate. Despite the vigorous fluid load, the urine flow did not exceed 1 ml/min. CONCLUSIONS: No clear evidence was found for shedding of the endothelial glycocalyx layer when 2 l of Ringer's lactate was infused over 30 min during abdominal hysterectomy. Urine analyses yielded patterns of changes that differed from those in plasma. TRIAL REGISTRATION: ISRCTN81005631 . Registered May 17, 2016.

Tubulointerstitial heparan sulfate proteoglycan changes in human renal diseases correlate with leukocyte influx and proteinuria.

Heparan sulfate proteoglycans (HSPGs) are well known for their proposed role in glomerular filtration. In addition, HSPGs can bind the leukocyte adhesion molecule l-selectin and chemokines, suggesting a role in inflammation. We examined a panel of biopsies representing different human primary kidney diseases for l-selectin and monocyte chemoattractant protein-1 (MCP-1) binding. In various renal diseases, l-selectin and MCP-1 binding to interstitial perivascular matrix HSPGs is increased, which is significantly associated with leukocyte influx. In proteinuric diseases, including membranous glomerulopathy, minimal change disease, but also IgA nephropathy and lupus nephritis, increased binding of l-selectin and MCP-1 to tubular epithelial cell (TEC) HSPGs is observed, which colocalizes with increased basolateral syndecan-1 and anti-heparan sulfate 10E4 staining. Short-hairpin RNA-mediated silencing demonstrates that syndecan-1 on TECs indeed mediates l-Selectin binding. Increased TEC expression of IL-8 in biopsies of proteinuric patients suggests that the increase in luminal protein may activate TECs to increase expression of l-selectin and MCP-1 binding syndecan-1. Strikingly, urinary syndecan-1 from proteinuric patients is less capable of binding l-selectin compared with urinary syndecan-1 from healthy controls, although syndecan-1 concentrations are similar in both groups. Together, our data show pronounced tubulointerstitial HSPG alterations in primary kidney disease, which may affect the inflammatory response.