Is the urinary biomarkers assessment a non-invasive approach to tubular lesions of the solitary kidney?

Abstract

Introduction: The solitary kidney (SK) is currently debated in the literature, as living kidney donation is extensively used and the diagnosis of congenital SK is frequent. Tubulointerstitial lesions associated with adaptive phenomena may occur early within the SK. Aims: Analysis of the significance of urinary biomarkers in the assessment of tubulointerstitial lesions of the SK. Methods: A cross-sectional study of 37 patients with SK included 18 patients—acquired SK (mean age 56.44?±?12.20 years, interval from nephrectomy 10.94?±?9.37 years), 19 patients—congenital SK (mean age 41.52?±?10.54 years). Urinary NAG, urinary alpha-1-microglobulin, albuminuria, eGFR (CKD-EPI equation) were measured. Results: In acquired SK, NAG increased in 60.66%, urinary alpha 1-microglobulin in 16.66%, albuminuria in 55.55% of patients. Inverse correlation with eGFR presented NAG (R^2?=?0.537, p?=?0.022), urinary alpha 1-microglobulin (R^2?=?0.702, p?=?0.001), albuminuria (R^2?=?0.655, p?=?0.003). In congenital SK, NAG increased in 52.63%, urinary alpha 1-microglobulin in 5.26%, albuminuria in 47.36% of patients. In this group, urinary biomarkers correlated inversely with eGFR: NAG (R^2?=?0.743, p?<?0.001), urinary alpha 1-microglobulin (R^2?=?0.701, p?=?0.001), albuminuria (R^2?=?0.821, p?<?0.001). Significant correlations were found between the urinary biomarkers in both groups. Conclusions: Urinary biomarkers allow a non-invasive, sensitive, early assessment of the tubular lesions of the SK. Urinary biomarkers of PT injury parallel renal function decline, thus complementing the estimation of GFR. Monitoring of PT dysfunction is mandatory in patients with SK.     

NGAL and NT-proBNP levels in diabetic patients with macroproteinuria

Abstract

Background: In patients with heart failure plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) levels are correlated to urine neutrophil gelatinase-associated lipocalin (NGAL) levels. We prospectively evaluated the relationship among glomerular filtration rate (eGFR), urine albumin-to-creatinine ratio (ACR), urine and serum NGAL and NT-proBNP levels in 20 type II diabetic patients with macroalbuminuria at 4-month intervals. Results: Compared with 20 age, gender-matched healthy controls, diabetic patients had higher urine and serum NGAL, serum NT-proBNP and lower eGFR. The eGFR of the patients at the baseline, the 4th and the 8th month were 29.6?±?12.0, 27.8?±?13.7 and 22.9?±?10.4?mL/min/1.73?m², respectively. No significant change in urine NGAL levels was detected (p?>?0.05), whereas there were significant increases in NT-proBNP, serum NGAL and urine ACR and significant decrease in eGFR as the study progressed (p?<?0.05). Both the baseline and the 4th month urine ACR were positively correlated to NT-proBNP levels measured at the same periods (r: 0.451; p: 0.046; r: 0.489; p: 0.029 respectively). In all measurements, urine ACR was negatively correlated to serum albumin levels measured at the same periods (r: ?0.792; p: 0.000; r: ?0.716; p: 0.000; r: ?0.531; p: 0.016 respectively). None of eGFR measurements was correlated with NT-proBNP (p?>?0.05). Neither serum NGAL nor urinary NGAL levels are associated with NT-proBNP (p?>?0.05). Conclusion: Our findings show an association between NT-proBNP and proteinuria in type II diabetic patients with macroalbuminuria but not with serum and urine NGAL.     

Amelioration of cisplatin-induced acute kidney injury by recombinant neutrophil gelatinase-associated lipocalin

We investigated the protective effect and mechanism of neutrophil gelatinase-associated lipocalin (NGAL) in a murine model of cisplatin-induced nephrotoxicity. Male Swiss-Webster mice were assigned to four groups (n?=?10 in each group). Control mice received vehicle only. Mice in the experimental group were given a single intraperitoneal injection of cisplatin (20?mg/kg) to induce nephrotoxicity, and were divided into three groups. The first group received 100?μL of saline only via tail vein at the time of cisplatin administration. The second group was given biologically active recombinant NGAL via tail vein (250?μg/100?μL solution). The third group was injected with a 250?μg/100μL solution of inactivated NGAL. After 4 days, we measured serum creatinine and urinary N-acetyl-β-d-glucosaminidase (NAG), and performed histologic studies. Biologically active NGAL significantly blunted the rise in serum creatinine (NGAL plus cisplatin 1.33?±?0.31 versus cisplatin alone 2.43?±?0.31?mg/dL, p?<?.001) as well as the increase in urine NAG (NGAL plus cisplatin 60.7?±?14.2 versus cisplatin alone 120.5?±?22.5 units/gm creatinine, p?<?.005). In addition, NGAL conferred a marked reduction in tubule cell necrosis and apoptosis (NGAL plus cisplatin 6.9?±?1.2 versus cisplatin alone 15.1?±?3.4 TUNEL positive nuclei per 100 cells, p?<?.001). These beneficial effects were completely abolished when heat-inactivated NGAL was administered instead of the biologically active form. Since induction of NGAL in kidney tubules is a known physiologic response to cisplatin, the pharmacologic use of NGAL to prevent cisplatin nephrotoxicity is likely to be safe and effective.     

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.

     

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.

     

Liver fatty-acid-binding protein in heart and kidney allograft recipients in relation to kidney function

Mammalian intracellular fatty-acid-binding proteins (FABPs), a large multigene family, encode 14-kD proteins that are members of a superfamily of lipid-binding proteins. FABPs are tissue specific. Liver-type FABP (L-FABP) can be filtered through the glomerulus owing to its small molecular size, similar to cystatin C, but it is reabsorbed by proximal tubule epithelial cells like other small proteins. In the human kidney, L-FABP is expressed predominantly in proximal tubules. It had been suggested that the presence of L-FABP in urine reflects hypoxic conditions resulting from decreased peritubular capillary flow, serving as a marker of acute kidney injury. The aim of this study was to assess urinary L-FABP in 111 heart and 76 kidney transplant recipients in relation to kidney function.Complete blood count, urea, fasting glucose, creatinine, and the N-terminal fragment of brain natriuretic protein were studied by standard laboratory methods; L-FABP and cystatin C, by ELISA using commercially available kits.Kidney transplant recipients displayed significantly higher L-FABP than heart recipients. Upon univariate analysis, urinary L-FABP correlated, with serum creatinine, cystatin C and estimated glomerular filtration ratio (eGFR) in kidney allograft recipients. However, in heart transplant recipients it was not related to kidney function, as reflected by creatinine or eGFR; was strongly related to cystatin C (r = 0.34; P < .001) and urinary creatinine (r = −0.29; P < .01), and NGAL (r = 0.29; P < .01). Upon multiple regression analysis, the best predictor of urinary L-FABP in kidney allograft recipients, was eGFR whereas in heart recipients, no parameter independently predicted L-FABP.Successful heart transplantation is associated with kidney injury as reflected by a reduced eGFR; however, in this population, L-FABP did not serve as a marker of kidney function. In contrast, in kidney allograft recipients, L-FABP may be a potential early marker for impaired kidney function/injury.     

Serum Neutrophil Gelatinase-Associated Lipocalin as a Marker of Renal Function in Non-Diabetic Patients with Stage 2–4 Chronic Kidney Disease

The current Kidney Disease Outcomes Quality Initiative (K/DOQI) guidelines advocate creatinine-based equations for estimating GFR to identify patients with potential kidney disease and classify them into different stages due to the fact that serum creatinine is very insensitive to changes in the glomerular filtration rate. Very few biomarkers exist for monitoring chronic kidney disease. The aim of the study was to assess whether NGAL could represent a novel, sensitive marker of kidney function in adult patients with CKD. The study was performed on 92 non-diabetic patients with CKD stages 2–4. Serum and urinary NGAL as well as serum cystatin C were measured using commercially available kits. Serum NGAL was related, in univariate analysis, to serum creatinine, urinary NGAL, hemoglobin, hematocrit, leukocyte count, eGFR, and cystatin C. Urinary NGAL correlated with age, hemoglobin, hematocrit, serum creatinine, and eGFR. In multiple regression analysis, predictors of serum NGAL were creatinine (beta value = 0.97, p = 0.005), cystatin C (beta = 0.34, p = 0.01), and eGFR (beta value = 1.77, p = 0.001). In the healthy volunteers, serum NGAL correlated with age, serum creatinine, eGFR, leukocyte count, and cystatin C. Taking into consideration the fact that the recent DOQI (Dialysis Outcomes Quality Initiative) states that individuals with reduced GRF (glomerular filtration rate) are at greater risk for CVD and cardiac deaths, precise evaluation of renal function is important in order to select the appropriate strategy to reduce the cardiovascular risk. NGAL should be investigated as a potential early and sensitive marker of kidney impairment/injury.     

Urinary biomarkers in assessing the nephrotoxic potential of gentamicin in solitary kidney patients after 7 days of therapy

Introduction: The solitary kidney (SK) may present increased vulnerability to nephrotoxicity because of adaptive phenomena. Aims: Assessing the vulnerability of the SK with urinary tract infections (UTI) to gentamicin by means of urinary biomarkers (N-acetyl-beta-D-glucosaminidase (NAG) and urinary alpha-1-microglobulin), as well as glomerular filtration rate (GFR). Methods: We studied 14 patients with SK with UTI (group A) (mean age 58.07?±?13.61 years, mean duration of SK 13.55?±?12.33 years) who were administered gentamicin for 7 days. Group B consisted by 17 patients with SK without any other associated renal pathology (average age 51.17?±?9.39 years, average existence period of a single kidney 33.23?±?21.73 years). We also included a third group (group C) represented by nine healthy individuals, with two kidneys. Results: Increased values of urinary NAG were found in group B as compared to group C and alpha-1 microglobulin in group A as compared to group B. During treatment with gentamicin, increased values of both NAG and alpha-1-microglobulin in group A were found on day 7 as compared to values before treatment (day 7 NAG?=?18.99?±?14.07?U/g creat versus day 0, NAG?=?5.15?±?6.54?U/g creat, p?=?0.004; day 7 alpha-1-microglobulin?=?20.88?±?18.84?mg/g creat versus day 0, urinary alpha-1-microglobulin?=?4.96?±?6.57?mg/g creat, p?=?0.003). No statistically significant alterations of GFR were noticed after 7 days of treatment. Conclusions: We found the nephrotoxic effects of gentamicin at tubular level, but not at glomerular level. The nephrotoxic potential of gentamicin in patients with a SK can be monitored by assessing urinary biomarkers during treatment of UTI.     

Potential biomarkers for the early detection of acute kidney injury after percutaneous nephrolithotripsy

This study aims to investigate the role of urinary biomarkers in the determination of the potential risks of renal parenchymal tubular damage in adult patients who underwent percutaneous nephrolithotomy (PNL) with the indication of renal stone. A randomized and prospective controlled study was performed between June and December 2013. We enrolled 29 consecutive patients with renal calculi?>?2?cm and who underwent PNL, as well as 47 healthy control subjects. Urine samples, including 2 h before surgery, 2 and 24 h after surgery were collected from the patient group. Freshly voided urine samples were collected from the control group. Kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), N-acetyl-glucosaminidase (NAG), and liver-type fatty acid binding protein (LFABP) levels were measured from these urine samples. The mean KIM-1/Cr value that measured 24 h after the operation was statistically significant, higher than its preoperative (preop) level (p?= 0.045). A significant difference was detected between the mean preop and postoperative (postop) 24 h NAG/Cr values (p?< 0.001). Also, postop 24 h NGAL/Cr levels were statistically significant, higher than its preop levels (p?= 0.013). According to the comparison of preop and postop levels, an increase in LFABP/Cr values secondary to surgical intervention was observed without any statistically significant difference. Besides the LFABP/Cr levels do not change after percutaneous kidney surgery, KIM-1/Cr, NAG/Cr, and NGAL/Cr levels increase postop period, especially at 24 h. Further studies with a larger series and repeated measurements should be performed to clarify if they can be used to demonstrate renal damage after percutaneous surgery or not.     

Urinary markers of acute kidney injury in newborns with perinatal asphyxia*

Background: Acute kidney injury (AKI) affects up to 60% of severely asphyxiated neonates. The diagnosis of AKI can be and is further challenged by a lack of good biomarkers. We studied the role of novel markers for AKI, neutrophil gelatinase-associated lipocalin (NGAL), interleukin-8 (IL-18), Netrin-1 (NTN-1), and sodium hydrogen exchanger isoform 3 (NHE3) on development and early diagnosis of AKI in newborns with perinatal asphyxia (PA). Methods: Forty-one newborns with a diagnosis of PA (15 with AKI and 26 without AKI) and 20 healthy matched controls were involved to the study. Urinary samples were obtained on postnatal days 1 and 4 for patients with PA and on postnatal day 1 for the control subjects. AKI was defined using a serum creatinine-based modification of the acute kidney injury network criteria. Results: The levels of NGAL, NTN-1, NHE3, and IL-18 on the first postnatal day urine samples were higher in patients compared to controls (p?<?0.001, p?<0.001, p <0.02, p <0.001, respectively). In patients with AKI, the levels of NGAL and IL-18 were higher when compared to patients without AKI (p?=?0.002, p <0.001, respectively). The levels of NTN-1 and NHE3 were similar in both groups. For the samples obtained on postnatal day 4, only NGAL levels were significantly higher in patients with AKI (p?=?0.004) compared to those without AKI. Conclusion: To our knowledge, this is the largest study, which evaluated the utility of urinary biomarkers in the diagnosis of AKI in newborns with PA. First day, urine NGAL and IL-18 levels have an important diagnostic power in such patients.     

Assessment of fractional excretion of urea for early diagnosis of cardiac surgery associated acute kidney injury

Abstract

Background: Acute kidney injury (AKI) is a common complication after cardiac surgery (CS). Recently, neutrophil gelatinase-associated lipocalin (NGAL) was shown to predict AKI development earlier than serum creatinine, but it is not widely used in clinical practice. Fractional excretion of urea (FeU) has been referred to as a useful tool to discriminate between prerenal and established AKI. The aim of our study is to evaluate the sensitivity and specificity of FeU, in the early diagnosis of AKI in patients undergoing CS. Methods: We performed a prospective study on adults undergoing CS. AKI was defined by AKIN criteria. Individuals suffering from CKD, were excluded. Sensitivity and specificity of FeU, fractional excretion of sodium (FeNa) and urine NGAL, measured at 1, 6 and 24?h following CS, were assessed. Results: We included 66 patients (26% female) aging 68?±?11 years. AKI prevalence was 24% and mortality was 3.28%. Patients with AKI had a significantly lower FeU compared to those without AKI (23.89?±?0.67% vs. 34.22?±?0.58%; p?<?0.05) 6?h after CS, but not at the 1- and 24-h time points. NGAL was also statistically significant between both groups. FeU showed a 75% sensitivity and 79.5% specificity; the AUC was 0.786. ROC analysis of FeU and NGAL yielded similar values (p?=?NS). Conclusion: FeU is useful as an early biomarker to predict AKI after CS and it is comparable to the new biomarker NGAL.     

A retrospective analysis of kidney function and risk factors by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation in elderly Chinese patients

Abstract

Chronic kidney disease accounts for much of the increased mortality, especially in the elder population. The prevalence of this disease is expected to increase significantly as the society ages. Our aim was to evaluate the kidney function and risk factors of reduced renal function among elderly Chinese patients. This study retrospectively collected clinical data from a total of 1062 inpatients aged 65 years or over. Estimated glomerular filtration rate (eGFR) was calculated with the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. Renal function and risk factors were also analyzed. For all 1062 subjects, the mean eGFR was 71.0?±?24.8?mL/min/1.73?m², and the incidence rates of reduced renal function, proteinuria, hematuria and leukocyturia were 31.1%, 11.8%, 6.6% and 8.7%, respectively. The eGFR values were 83.4?±?28.4, 72.2?±?22.9, 67.8?±?24.3 and 58.8?±?29.1?mL/min/1.73?m² in the groups of 60–69, 70–79, 80–89 and ≥90 years age group (F?=?15.101, p?=?0.000), respectively; while the incidences of reduced renal function were 12.8%, 27.0%, 37.8% and 51.7% (χ²?=?36.143, p?=?0.000). Binary logistic regression analysis showed that hyperuricemia (OR?=?4.62, p?=?0.000), proteinuria (OR?=?3.96, p?=?0.000), urinary tumor (OR?=?2.92, p?=?0.015), anemia (OR?=?2.45, p?=?0.000), stroke (OR?=?1.96, p?=?0.000), hypertension (OR?=?1.83, p?=?0.006), renal cyst (OR?=?1.64, p?=?0.018), female (OR?=?1.54, p?=?0.015), coronary artery disease (OR?=?1.53, p?=?0.008) and age (OR?=?1.05, p?=?0.000) were the risk factors of reduced renal function. In conclusion, eGFR values decreased by age, while the incidence of reduced renal function, proteinuria, hematuria and leukocyturia increased with age. Treatment and control of comorbidities may slow the decline of renal function in elderly patients.     

Higher urine heat shock protein 70/creatinine ratio in type 1 diabetes mellitus

Insidious progressive renal damage caused by type 1 diabetes mellitus (T1DM) begins in childhood before it becomes manifest in adult ages. Heat shock proteins (HSPs) regulate the cell response to any hazardous factors to prevent cell structure. The aim of the study is to determine whether urine levels of HSPs increase in diabetic children with time and indicate a progressive renal injury in T1DM. Thirty-three patients with T1DM and 24 healthy children were enrolled in the study. Renal function was normal in all patients. Urine levels of HSP27, HSP40, HSP60, HSP70, and HSP90 were measured by enzyme-linked immunosorbent assay at two consecutive years (2012 and 2013). The results were evaluated as urine HSP/creatinine ratios (uHSP/Cr). Mean urine HSP27/Cr, HSP40/Cr, HSP60/Cr, HSP70/Cr, HSP90/Cr in patient group were significantly higher than in controls in 2012 (uHSP27/Cr 460.12?±?217.64 versus 270.02?±?136.83?pg/mgCr; uHSP40/Cr 180.89?±?118.59 versus 99.44?±?62.49?pg/mgCr; uHSP60/Cr 114.40?±?64.91 versus 70.50?±?43.70?pg/mgCr; uHSP70/Cr 41.17?±?28.42 versus 16.47?±?7.32?pg/mgCr; uHSP90/Cr 175.64?±?102.22 versus 107.61?±?75.85?pg/mgCr) (p?p?=?0.001), whereas uHSP60/Cr level decreased and uHSP27/Cr, uHSP40/Cr, uHSP90/Cr levels remained stable (p?>?0.05). Area under the curve (AUC) for uHSP70/Cr (0.957) was significantly higher than the others. Using a cutoff 22.59?pg/mgCr for uHSP70/Cr to predict of diabetic damage, sensitivity and specificity were 85% and 96%, respectively. Our results suggest that uHSP70/Cr increases over time and may indicate early phases of progressive kidney damage in diabetic children.     

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.

     

Urinary markers in the early stage of nephropathy in patients with childhood-onset type 1 diabetes

Background

The aim of this study was to evaluate the association of a urinary tubular marker, liver-type fatty acid binding protein (L-FABP) and an inflammatory marker, serum/urinary YKL-40, with albuminuria in patients with childhood-onset type 1 diabetes (T1D).

Methods

Twenty-nine patients with childhood-onset T1D and 32 controls were enrolled. Serum and urinary concentrations of YKL-40 and urinary concentrations of L-FABP were measured.

Results

The serum levels of YKL-40 were not significantly different between the control group and the patient groups. However, the levels of urinary YKL-40/creatinine (Cr) were higher in the patients, even those with normoalbuminuria than in the controls (p?<?0.001). The levels of urinary L-FABP/Cr were not different between the control group and the patient groups. However, the level of urinary L-FABP/Cr in the microalbuminuria group was higher than that in the normoalbuminuria group (p?=?0.03). There were no associations between the levels of urinary albumin-to-creatinine ratio and urinary L-FABP/Cr or YKL-40/Cr. However, the urinary L-FABP/Cr level was significantly correlated with the hemoglobin A1C level (p?=?0.005) and the urinary YKL-40/Cr level (p?=?0.043).

Conclusions

Urinary L-FABP/Cr and YKL-40/Cr may reflect renal injury in early stages of nephropathy in patients with childhood-onset T1D, even in the normoalbuminuric state.

     

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 effect of renal artery-only or renal artery–vein clamping during partial nephrectomy on short and long-term functional results: Is clamping technique important?

Purpose

To evaluate the effect of artery-only (AO) and artery–vein (AV) clamping during partial nephrectomy (PN) on short- and long-term renal function outcome.

Methods

Medical records of 154 patients in the AO group and 192 patients in the AV group who underwent open and minimally invasive (laparoscopic/robotic) PN between January 2011 and January 2018 were retrospectively assessed. Preoperative patient and tumor-specific characteristics in addition to perioperative factors and renal function outcomes were compared. The change in the estimated glomerular filtration rate (eGFR) from postoperative 1–3 days, 12 and 24 months after surgery was calculated. Acute kidney injury (AKI) was defined a as a?>?25% reduction in eGFR.

Results

There were no statistically significant differences between the clamping techniques in terms of postoperative 1–3 days, 12 and 24 months eGFR change percentage and risk of progression to chronic kidney disease (CKD). No significant difference in short- and long-term renal functions was found between the minimally invasive or open AO and AV clamping subgroups at any time point. In multivariate analysis, the R.E.N.A.L score (AO group p?=?0.026, AV group p?<?0.001) and preoperative eGFR (AO group p?<?0.001, AV group p?=?0.010) were strong predictors of the acute kidney injury in both groups. Older age (AO group p?=?0.045, AV group p?=?0.010) and preoperative eGFR (AO group p?=?0.008, AV group p?=?0.002) were significantly associated with CKD progression at 2-year follow-up in both groups.

Conclusion

AV clamping does not adversely affect postoperative renal function compared to AO clamping. Preoperative patient- and tumor-related factors are more important for renal function regardless of the clamping technique.

     

Could urinary kidney injury molecule-1 be a good marker in subclinical acute kidney injury in mild to moderate COVID-19 infection?

Purpose

To evaluate urinary kidney injury molecule-1 (uKIM-1), which is a proximal tubule injury biomarker in subclinical acute kidney injury (AKI) that may occur in COVID-19 infection.

Methods

The study included proteinuric (n?=?30) and non-proteinuric (n?=?30) patients diagnosed with mild/moderate COVID-19 infection between March and September 2020 and healthy individuals as a control group (n?=?20). The uKIM-1, serum creatinine, cystatin C, spot urine protein, creatinine, and albumin levels of the patients were evaluated again after an average of 21 days.

Results

The median (interquartile range) uKIM-1 level at the time of presentation was 246 (141–347) pg/mL in the proteinuric group, 83 (29–217) pg/mL in the non-proteinuric group, and 55 (21–123) pg/mL in the control group and significantly high in the proteinuric group than the others (p?<?0.001). Creatinine and cystatin C were significantly higher in the proteinuric group than in the group without proteinuria, but none of the patients met the KDIGO-AKI criteria. uKIM-1 had a positive correlation with PCR, non-albumin proteinuria, creatinine, cystatin C, CRP, fibrinogen, LDH, and ferritin, and a negative correlation with eGFR and albumin (p?<?0.05). In the multivariate regression analysis, non-albumin proteinuria (p?=?0.048) and BUN (p?=?0.034) were identified as independent factors predicting a high uKIM-1 level. After 21?±?4 days, proteinuria regressed to normal levels in 20 (67%) patients in the proteinuric group. In addition, the uKIM-1 level, albuminuria, non-albumin proteinuria, and CRP significantly decreased.

Conclusions

Our findings support that the kidney is one of the target organs of the COVID-19 and it may cause proximal tubule injury even in patients that do not present with AKI or critical/severe COVID-19 infection.