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.

     

Early diagnosis of contrast-induced renal damage and the protective effect of hydration therapy

Objective To investigate the diagnostic value of urine neutrophil gelatinase apolipoprotein (NGAL) and kidney injury molecule 1 (KIM-1) as markers of CIN, and the effectiveness of hydration therapy in the prevention of CIN. Methods One hundred and twenty patients were randomly divided into control group and treatment group. The patients of treatment group received hydration therapy through intravenous fluid infusion. Urine samples were taken for detecting the value of albumin (mAlb), NGAL, and KIM-1 before surgery (T0), after surgery 12 h (T1), 24 h (T2), 48 h (T3), 72 h (T4) by ELISA assay. The levels of urinary mAlb, Scr, BUN and cystatin C were detected at the same time. Results ⑴ The urine NGAL/Cr and KIM-1/Cr significantly increased and were more than twice the baseline value at the time of 12 h after PCI in 87 of 120 cases of the participants. There are eight cases occurred CIN (6.67%) and one case occurred in hydration treatment group (1.7%), seven cases were in control group (11.7%). The difference was statistically significant. ⑵ There were no significant difference in BUN, Scr, mAlb/Cr, Cys-C and GFR between two groups (P＞0.05). ⑶ NGAL/Cr, KIM-1/Cr were elevated at T1 in both groups (P＜0.01). In hydration treatment group, levels of NGAL/Cr and KIM-1/Cr decreased substantially to the level of T0 at T4(P＜0.01), while in the control group they didn't. ⑷ Area under the ROC curve (AUC) of NGAL/Cr and KIM-1/Cr 12 h after PCI were 0.931 [95% CI (0.889, 0.973)] and 0.811 [95% CI(0.736, 0.886)] respectively (all P＜0.05). Conclusions NGAL and KIM-1 are sensitive and specific indicators for predicting early renal injury induced by contrast medium and can be used for early diagnosis of CIN. Hydration therapy can prevent the contrast agent-induced renal damage.     

Tubular markers do not predict the decline in glomerular filtration rate in type 1 diabetic patients with overt nephropathy

Recent studies have shown that both glomerular and tubulointerstitial damage are important factors in the pathophysiology and progression of diabetic nephropathy. To examine whether markers of tubular damage are useful in monitoring the progression of disease, we measured urinary levels of neutrophil gelatinase-associated lipocalin (NGAL), liver-fatty acid-binding protein (LFABP), and kidney injury molecule-1 (KIM-1) in a 3-year intervention study of 63 type 1 diabetic patients with kidney disease. The baseline mean glomerular filtration rate (GFR) was 87?ml/min per 1.73?m(2) and urinary albumin excretion 1141?mg/24?h. Patients with the highest compared with the lowest quartile of urinary NGAL at baseline had higher urinary KIM-1 levels and a significant decrease in their GFR each year. Using linear regression analysis, we found that elevated urinary NGAL and KIM-1 concentrations were associated with a faster decline in GFR, but not after adjustment for known promoters of progression. Urinary LFABP was not related to decline in GFR. Losartan treatment (100?mg/day) reduced urinary KIM-1 by 43% over a 12-month period. Thus, urine biomarker measurements in patients with type 1 diabetic nephropathy did not provide additional prognostic information to that of known progression promoters.     

Urinary kidney injury molecule-1 levels in renal stone patients

Objective

To study kidney injury molecule-1 (KIM-1) biomarker levels, indicating renal tubular damage, in patients with kidney stones and in those who underwent minimally invasive method stone treatment.

Patients and methods

Sixty patients with renal stones between 10 and 20 mm were included into the present study. Patients who were divided into three cohorts underwent micropercutaneous nephrolithotomy (microperc), retrograde intrarenal stone surgery (RIRS), and percutaneous nephrolithotomy (PNL). Urine samples were obtained from all participants before, 4 h and 14 days after the procedure. In all the samples obtained, urinary KIM-1 and creatinine (Cr) levels were measured and KIM-1/Cr ratios (ng/mg creatinine) were calculated.

Results

Preoperative urine KIM-1/Cr ratio was higher than postoperative 14th day. The bigger the renal stone size, the higher was the ratio (correlation coefficient 0.353, p = 0.006). According to preferred treatment procedure, there was a statistically significant decrease in preoperative and postoperative 4th hour and 14th day urine KIM-1/Cr rates in the RIRS and PNL, yet none in the microperc group (p = 0.010, p = 0.001, p = 0.212, respectively).

Conclusion

In renal stone patients, the elevated urine KIM-1/Cr ratio levels increase further according to stone size. KIM-1/Cr ratio is a promising marker might be helpful in monitoring the damage created by stone disease.

     

Urinary kidney injury molecules in children with febrile seizures

Objective: Hypoxia occurs following convulsions, and hypoxia is one of the most common causes of acute renal damage. The aim of this study was to investigate urinary levels of kidney injury molecules, including neutrophil gelatinase-associated lipocalin (NGAL), N-acetyl-β-D-glucosaminidase (NAG), and liver-type fatty acid-binding protein (L-FABP) in children with febrile seizures (FS) for the first time.

Methods: The study included 28 children with FS and 34 age and gender matched healthy children. Serum biochemistry and blood gases were measured in the serum samples. Estimated glomerular filtration rate (eGFR) was calculated. NGAL, NAG, L-FABP, and creatinine (Cr) were measured in the urine samples. The ratios of kidney injury markers to urinary Cr were used for comparisons.

Results: There were no significant differences in eGFR and serum chemistry values between the FS and the control group (p?>?0.05). Hypoxia was detected in 67.9% of the FS patients. The FS group had significantly higher urinary kidney injury molecules to Cr ratios compared to the controls, including NGAL/Cr (17.9?±?9.8; 6.7?±?4.0, respectively; p?p?p?Conclusion: Increased urinary NGAL/Cr, NAG/Cr, and L-FABP/Cr values, in patients with FS compared to healthy controls, suggest a possible subclinical renal damage in these patients.     

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.     

Are there any new reliable markers to detect renal injury in obese children?

Aim: The aim of this study was to examine the serum and urine levels of kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), osteopontin (OPN), matrix metalloproteinase-9 (MMP-9), and serum Cystatin-C to determine the renal effect of obesity in obese children.

Methods: Seventy-two obese and 35 non-obese healthy children were included in this study. Blood pressure (BP) was evaluated with office measurement. Creatinine, cystatin C, lipids, fasting glucose, and insulin levels were measured, and homeostasis model assessment -insulin resistance (HOMA-IR) was calculated. The urine albumin/creatinine ratio was calculated. The serum and urine KIM-1, NGAL, OPN, and MMP-9 levels were measured.

Results: Serum cystatin-C, triglyceride, and homeostasis model assessment-insulin resistance (HOMA-IR) index were found to be significantly higher in the obese group (p?=?.0001), and high-density lipoprotein (HDL) cholesterol was found to be significantly lower (p?=?.019) in the obese group. No significant differences were found in serum KIM-1, NGAL, OPN or MMP-9 levels between groups (p?>?.05). No significant differences were found in urine KIM-1 and MMP-9 levels (p?>?.05), Urine NGAL, and OPN levels were found significantly higher in obese groups (p?Conclusions: According to our results, although serum KIM-1, NGAL, OPN, MMP-9, and urine MMP-9, urine KIM-1 do not appear to be ideal markers to evaluate renal injury in the early period of obesity, the serum levels of cystatin C and urine NGAL, urine OPN can be used as a good marker for assessing the renal effect of obesity which can lead end stage renal disease in pediatric population.     

Effect of percutaneous nephrolithotomy on renal functions in children: assessment by quantitative SPECT of 99mTc-DMSA uptake by the kidneys

Abstract

Objective: To determine the impact of percutaneous nephrolithotomy (PNL) on global and regional renal function in children. Methods: In total, 40 children (41 renal units) undergoing PNL were included in this prospective study. All patients were evaluated using quantitative single-photon emission computed tomography (QSPECT) with technetium-99?m-dimercaptosuccinic acid (^99mTc-DMSA) examinations before and 3 months after surgery. Results: The mean age was 9.5 years (range, 3–16), and the mean stone size was 3.4?cm (range, 2–6.5). Of the cases, 39 (95%) were managed as being stone-free after a single session of PNL. After additional treatment procedures, 40 (97.5%) of the cases were managed as being stone-free. Of the 41 renal units, new focal cortical defects on ^99mTc-DMSA scans were seen in 4 (9.7%) patients. Total relative uptake in the treated kidneys increased from 42.3% to 44.1%. The mean creatinine level before PNL was 1.18?±?0.45 (0.8–1.6)?mg/dL compared with 1.16 (0.7–1.5)?mg/dL by the end of the follow-up period (not statistically significantly different, p?>?0.05). Conclusions: PNL in children is a safe and feasible method for the maximal clearance of stones. QSPECT of ^99mTc-DMSA confirmed that renal function is preserved or even improved after percutaneous stone removal.     

Comparing different markers of tubular dysfunction in transfusion-dependent thalassemia patients

Background

Renal tubular dysfunction was reported in transfusion-dependent thalassemia (TDT) patients and ranges from mild to severe. The objectives of our study were identification of the best marker of early renal tubular dysfunction in TDT patients among the three most commonly used urinary biomarkers, named neutrophil gelatinase-associated lipocalin (NGAL), retinol-binding protein (RBP) and N-acetyl-D-glucosaminidase (NAG) and correlation of these biomarkers with different patient variables.

Methodology

Sixty-one TDT patients and another 62 healthy children were enrolled in a cross-sectional study. Morning urine samples were taken for measurement of calcium, phosphorus, creatinine, microalbumin and markers of tubular dysfunction (NGAL, NAG and RBP). Urine NGAL/creatinine (UrNGAL/Cr), urine NAG/creatinine (UrNAG/Cr) and urine RBP/creatinine (UrRBP/Cr) ratios were used for accuracy. Patients were classified into 2 groups: group A, with tubular dysfunction and group b, without tubular dysfunction.

Results

Group A showed statistically significant higher UrNGAL/Cr (p < 0.001), UrRBP/Cr (p < 0.001) and UrNAG/Cr (p <0.001) than group B. In group A, microalbuminuria was detected only in 7 patients (28%) while it was detected in 12 patients (33.3%) in group B. By using ROC curve analysis, the diagnostic cutoff values for UrNGAL/Cr, UrRBP/Cr and UrNAG/Cr were 3713.38, 1614.85 and 56.56 ng/g, respectively. We found a statistically significant superiority of UrNGAL/Cr over UrRBP/Cr (p < 0.001) and UrRBP/Cr over UrNAG/Cr (p < 0.001).

Conclusion

Evaluation of UrNGAL/Cr, UrRBP/Cr and UrNAG/Cr could early discriminate tubular dysfunction TDT patients from those with normal tubular function. UrNGAL/Cr is more accurate in early detection of tubular dysfunction when compared with the other two biomarkers.

     

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.     

Urine NGAL and KIM-1 in children and adolescents with hyperuricemia

Background

The aim of this study was to test the hypothesis that urine levels of neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) are enhanced in pediatric patients with hyperuricemia.

Methods

The study included 88 children and adolescents (60 males, 28 females) with a median age of 16 (range 11–18.5) years who had been referred to our department to rule out or confirm hypertension. The subjects were divided into two groups: the hyperuricemic (HU) group comprising 59 subjects with hyperuricemia (defined as serum uric acid?>4.8 and?>5.5 mg/dl in girls and boys, respectively) and the reference group comprising 29 patients with normouricemia. Urine NGAL and KIM-1 levels were evaluated using a commercially available kit.

Results

Concentrations of the examined biomarkers [urine NGAL, NGAL/creatinine (cr.) ratio, urine KIM-1, KIM-1/cr. ratio] were increased in the HU group compared with the reference group (p?<?0.01). There were positive correlations between the serum uric acid and urine NGAL/cr. ratio (R?=?0.67, p?<?0.001) and the urine KIM-1/cr. ratio (R?=?0.36, p?<?0.001). In the multiple regression models, serum uric acid, systolic blood pressure and cholesterol accounted for more than 49 % of the variation in the NGAL/cr. ratio (R?=?0.702, p?<?0.001). In the second model, serum uric acid, gender, age and systolic blood pressure accounted for more than 36 % of the variation in the KIM-1/cr. ratio (R?=?0.604, p?<?0.001).

Conclusion

We demonstrated that male, obese, hypertensive adolescents with hyperuricemia have higher urine NGAL and KIM-1 levels relative to a reference group with normouricemia.     

Protective effect of L-glutamine against diabetes-induced nephropathy in experimental animal: Role of KIM-1, NGAL,TGF-β1, and collagen-1

Diabetic nephropathy is a serious microvascular complication and one of the main causes of end-stage renal disease. L-Glutamine (LG) is naturally occurring amino acids with antidiabetic and antioxidant potential. The aim of present investigation was to evaluate the potential of LG against streptozotocin (STZ)-induced diabetic nephropathy (DN) in laboratory rats. DN was induced in male Wistar rats (200–220?g) by intraperitoneal administration of STZ (55?mg/kg). Animals were treated orally with either distilled water (10?mg/kg) or LG (250, 500, and 1000?mg/kg) or Sitagliptin (5?mg/kg). Various biochemical, molecular, and histological (hematoxylin–eosin and Masson’s trichrome stain) parameters were assessed. Administration of LG (500 and 1000?mg/kg) significantly inhibited (p?<?.05) STZ-induced alterations in serum and urine biochemistry (urine creatinine, uric acid, albumin, and BUN). It also significantly increased creatinine clearance rate. STZ induced increase in renal oxidonitrosative stress was significantly decreased (p?<?.05) by LG (500 and 1000?mg/kg) treatment. Upregulated renal KIM-1, NGAL, TGF-β1, and collagen-1 mRNA expression after STZ administration was significantly inhibited (p?<?.05) by LG (500 and 1000?mg/kg) treatment. Correlation analysis also revealed that antidiabetic potential of LG attenuates STZ-induced elevated renal KIM-1, NGAL, TGF-β1, and collagen-1 mRNA expression. Histopathological alteration induced by STZ in renal tissue was ameliorated by LG treatment. In conclusion, results of present investigation suggest that treatment with LG ameliorated STZ-induced DN via the inhibition of oxidonitrosative stress as well as downregulation of KIM-1, NGAL, TGF-β1, and collagen-1 mRNA expressions.     

Combination of biomarkers for diagnosis of acute kidney injury after cardiopulmonary bypass

Abstract

Novel acute kidney injury (AKI) biomarkers offer promise of earlier diagnosis and risk stratification, but have yet to find widespread clinical application. We measured urinary α and π glutathione S-transferases (α-GST and π-GST), urinary l-type fatty acid-binding protein (l-FABP), urinary neutrophil gelatinase-associated lipocalin (NGAL), urinary hepcidin and serum cystatin c (CysC) before surgery, post-operatively and at 24?h after surgery in 93 high risk patient undergoing cardiopulmonary bypass (CPB) and assessed the ability of these biomarkers alone and in combination to predict RIFLE-R defined AKI in the first 5 post-operative days. Twenty-five patients developed AKI. π-GST (ROCAUC?=?0.75), lower urine Hepcidin:Creatine ratio at 24?h (0.77), greater urine NGAL:Cr ratio post-op (0.73) and greater serum CysC at 24?h (0.72) best predicted AKI. Linear combinations with significant improvement in AUC were: Hepcidin:Cr 24?h?+?post-operative π-GST (AUC?=?0.86, p?=?0.01), Hepcidin:Cr 24?h?+?NGAL:Cr post-op (0.84, p?=?0.03) and CysC 24?h?+?post-operative π-GST (0.83, p?=?0.03), notably these significant biomarkers combinations all involved a tubular injury and a glomerular filtration biomarker. Despite statistical significance in receiver–operator characteristic (ROC) analysis, when assessed by ability to define patients to two groups at high and low risk of AKI, combinations failed to significantly improve classification of risk compared to the best single biomarkers. In an alternative approach using Classification and Regression Tree (CART) analysis a model involving NGAL:Cr measurement post-op followed by Hepcidin:Cr at 24?h was developed which identified high, intermediate and low risk groups for AKI. Regression tree analysis has the potential produce models with greater clinical utility than single combined scores.     

The effects of intraoperative infusion of dexmedetomidine on early renal function after percutaneous nephrolithotomy

Background: Percutaneous nephrolithotomy (PCNL) may interfere with renal function because of continuous fluid irrigation and compression. The aim of this study was to evaluate the effects of an intraoperative infusion of dexmedetomidine on renal function in patients undergoing PCNL. Methods: This study included 40 patients between the ages of 18 and 65 years who underwent PCNL. After induction of anesthesia, we administered 100 ml of normal saline to the patients in the control group (n=20) and 1 mcg/kg dexmedetomidine in 100 ml of normal saline to the patients in the dexmedetomidine group (n=20) over 10 min. Throughout the surgery, 1 mcg/kg/h dexmedetomidine and 1 ml/kg/h normal saline infusions were given to the dexmedetomidine and control groups, respectively. Renal function, electrolytes, serum levels of neutrophil gelatinase‐associated lipocalin (NGAL) and cystatin C were analyzed after induction and post‐operatively at 2, 8 and 24 h. Renin levels and blood gas analyses were performed after induction and before extubation. Results: No statistically significant differences were found between the two groups with regard to renal function, creatinine clearance (CrCl), NGAL, cystatin C and serum electrolyte levels at 0, 2, 8 and 24 h post‐operatively. End‐surgery renin levels in the dexmedetomidine group were significantly lower than the baseline levels in the control group. Conclusion: In PCNL, an intraoperative infusion of dexmedetomidine was not found to have beneficial effects on CrCl, NGAL or cystatin C levels early after the procedure; however, it reduced renin levels.     

Urine kidney injury molecule-1: a potential non-invasive biomarker for patients with renal cell carcinoma

Background

KIM-1 staining is upregulated in proximal tubule-derived renal cell carcinoma (RCC) including clear renal cell carcinoma and papillary renal cell carcinoma, but not in chromophobe RCC (distal tubular tumor). This study was designed to prospectively examine urine KIM-1 level before and 1 month after removal of renal tumors.

Patients and design

A total of 19 patients were eventually enrolled in the study based on pre-operative imaging studies. Pre-operative and follow-up (1 month) urine KIM-1 levels were measured. The urine KIM-1 levels (uKIM-1) were then normalized to urine creatinine levels (uCr). Renal tumors were also stained for KIM-1 using immunohistochemical techniques.

Results

The KIM-1-negative staining group included 7 cases, and the KIM-1-positive group consisted of 12 cases. The percentage of KIM-1-positive staining RCC cells ranged from 10 to 100 %, and the staining intensity ranged from 1+ to 3+. In both groups, serum creatinine levels were both significantly elevated after nephrectomy. In the KIM-1-negative group, uKIM-1/uCr remained at a similar level before (0.37 ± 0.1 ng/mg Cr) and after nephrectomy (0.32 ± 0.01 ng/mg Cr). However, in the KIM-1-positive group, elevated uKIM-1/uCr at 1.20 ± 0.31 ng/mg Cr was significantly reduced to 0.36 ± 0.1 ng/mg Cr, which was similar to the pre-operative uKIM-1/uCr (0.37 ± 0.1 ng/mg Cr) in the KIM-1-negative group.

Conclusion

Our small but prospective study showed significant reduction in uKIM-1/uCr after nephrectomy in the KIM-1 positive group, suggesting that urine KIM-1 may serve as a surrogate biomarker for kidney cancer and a non-invasive pre-operative measure to evaluate the malignant potential of renal masses.     

全麻下泌尿外科后腹腔镜手术对患者尿NAG、血β2-微球蛋白的影响

目的探讨全麻下泌尿外科后腹腔镜手术对尿N-乙酰-β-D-氨基葡萄糖苷酶（NAG）、血β2-微球蛋白（β2-MG）的影响。方法 33例气管内插管全身麻醉下行后腹腔镜非肾切除手术患者,对术前和术后0h、24h、48h及72h的血β2-MG、尿NAG指标进行检测,应用统计学方法分析指标动态变化规律,并且比较不同气腹时间与术后各指标变化情况。结果与手术前相比,术后24～48h血β2-MG、尿NAG均有不同程度的增高,术后24～48h达到最高值;术后72h其水平下降明显降低,术前后变化差异具有显著性意义;比较不同气腹时间与各指标变化发现,气腹时间大于60min对血β2-MG、尿NAG、尿肌酐（Cr）影响较明显。结论全麻下实施泌尿外科保留肾脏后腹腔镜手术,可导致患者术后早期血β2-MG、尿NAG水平增高,但这种改变是可逆的,提示泌尿外科后腹腔镜手术可能对肾小球滤过功能及肾小管重吸收功能有一定影响。     

Prospective comparative study of miniperc and standard PNL for treatment of 1 to 2 cm size renal stone

Study Type – Therapy (case series) Level of Evidence 4 What’s known on the subject? and What does the study add? Standard PNL is known to have higher clearance rates for stones 1–2 cm. However, it is not promoted because of its associated morbidity, especially bleeding. Minitiarization of the PNL has spawned a new interest in this modality for treating small bulk urolithiasis. The study adds to a growing body of evidence in a prospective manner that smaller tract PNL “miniperc” is associated with a similiar efficacy of achieving stone‐clearance rates while decreasing the invasiveness of the procedure and associated morbidity.

OBJECTIVE

? To evaluate the results of miniperc vis‐à‐vis standard PNL in the treatment of stones of 1–2 cm in size. Miniperc may represent a reasonable procedure in patients with nonbulky urolithiasis offering a similar outcome as standard percutaneous nephrolithotomy (PNL) with advantage of reduced morbidity.

PATIENTS AND METHODS

? 55 procedures including 27 miniperc and 28 standard PNL were performed for renal stones 1–2 cm in size. Pediatric patient, active urinary tract infection, renal malformation, uncorrected coagulopathy and morbid obesity patients were excluded from the study. ? The parameters studied were demography, operative time, postoperative analgesic requirement, hemoglobin drop, complications and stone clearance.

RESULTS

? Mean tract size was 18.2 ± 2 F (15–20) and 26.8 ± 2 F (24–30), P value <0.0001 in the miniperc and standard PNL, respectively. Holmium LASER and pneumatic lithotripter were the main energy sources used in miniperc and standard PNL, respectively. ? Miniperc operative time was longer than that of standard PNL (45.2 ± 12.6 vs 31 ± 16.6 min, P= 0.0008 respectively). ? Conversely, there was an advantage of miniperc over standard PNL in terms of a significantly reduced hemoglobin drop (0.8 ± 0.9 vs 1.3 ± 0.4 gram%, P= 0.01), analgesic requirement (55.4 ± 50 vs 70.2 ± 52 mg tramadol, P= 0.29) and hospital stay (3.2 ± 0.8 vs 4.8 ± 0.6 days, P≤ 0.001), respectively. ? Intra‐ operative conversion of the procedure into a tubeless PNL was significantly more in the miniperc group (P≤ 0.001). The miniperc and standard PNL group had clearance rates of 96% and 100%, respectively at 1 month follow up.

CONCLUSIONS

? This study demonstrated significant advantages of the miniperc procedure in terms of reduced bleeding leading to a tubeless procedure and reduced hospital stay. ? The stone free rates and the complications were similar in either group.     

Urinary netrin-1 and KIM-1 as early biomarkers for septic acute kidney injury

Background: Acute kidney injury (AKI) during sepsis is associated with poor outcome. However, diagnosis of AKI with serum creatinine (SCr) level change is neither highly sensitive nor specific. Therefore, identification of novel biomarkers for early diagnosis of AKI is desirable. Aims: To evaluate the capacity of combining urinary netrin-1 and human kidney injury molecule type 1 (KIM-1) in the early diagnosis of septic AKI. Methods: We prospectively recruited 150 septic patients from Jun 2011 to Jun 2013 at Zhejiang Provincial People's Hospital, China. SCr, urinary netrin-1, and KIM-1 levels were recorded at 0, 1, 3, 6, 24, and 48?h of ICU admission and compared between AKI and non-AKI patients. In addition, we investigated the prognostic value of netrin-1 and KIM-1 between non-survivors and survivors in septic AKI patients. Results: SCr levels started to show elevation after 24?h of ICU admission. However, netrin-1 levels increased significantly as early as 1?h, peaked at 3–6?h and remained elevated up to 48?h of ICU admission in septic AKI patients. KIM-1 increased significantly by 6?h, peaked at 24?h and remained significantly elevated until 48?h of ICU admission. Furthermore, we observed significant higher urinary KIM-1 levels at 24?h and 48?h in non-survivors compared to survivors in AKI patients. Conclusions: Our results suggest that both netrin-1 and KIM-1 are clinically useful as early biomarkers in the diagnosis of septic AKI. In addition, persistent elevation of urinary KIM-1 level may be associated with poor prognosis.     

Tubular biomarkers to assess progression of diabetic nephropathy

Despite aggressive management, many patients with diabetic nephropathy still develop end-stage renal disease. Accompanying tubulointerstitial damage is important in the progression of diabetic nephropathy. Markers of tubular damage, such as NGAL, KIM-1, and LFABP, have been proposed for monitoring the effectiveness of therapy. However, Nielsen et al. report a lack of an independent correlation between these biomarkers and glomerular filtration rate. Therefore, these markers seem to offer no improvement in the management of diabetic nephropathy.     

A study on acute renal damage from percutaneous nephrolithotomy assessed by urinary NAG and gamma-GTP activities

We performed percutaneous nephrolithotomy (PNL) on 49 patients between May, 1986 and March, 1987. To investigate acute renal damage from PNL, we measured urinary NAG (N-acetyl-beta-D-glucosaminidase) and gamma-GTP (gamma-glutamyl transpeptidase) activities before PNL and for 6 days after PNL in 24 patients. The NAG activities elevated beyond normal level in 23 patients and gamma-GTP activities in 15 patients. NAG activities showed a peak level in the third day after PNL and gamma-GTP activities in the next day of PNL. After the peak both enzyme activities got down gradually. There was no difference in NAG and gamma-GTP activities between nephrostomy and lithotripsy in 2 staged patients. And the intrapelvic pressure during operation was at the normal level in 5 patients. Therefore, we think that the cause of NAG and gamma-GTP activity elevation is a mechanical damage, not an influence of the irrigation fluid. Large stones, long operation time and 2 stage procedure were the factors that produced high enzyme activities, because, we guess, the frequency of mechanical damages to the kidney increase in such cases. Postoperative pyrexia caused a slight increase in enzyme activities but preoperative hydronephrosis exerted no influence on both enzyme activities. We also measured creatinine clearance before and after PNL but no significant change was obtained. PNL causes only slight mechanical damage to the operated kidney which is reversible when assessed by NAG and gamma-GTP activities and the glomerular function is not affected. Therefore, we conclude that PNL is a safe treatment for upper urinary tract stones.