Biomarkers of acute kidney injury in patients with nephrotic syndrome / Biomarcadores de lesão renal aguda em pacientes com síndrome nefrótica

ABSTRACT Introduction: Emergence of acute kidney injury (AKI) in patients with nephrotic syndrome (NS) requires prompt diagnosis and differentiation between acute tubular necrosis (ATN) and proliferative glomerulonephritis. We studied the potential use of commercial urinary biomarkers' tests in the diagnosis of AKI in patients with NS. Methods: A cross sectional estimate of urinary concentrations of KIM-1 and NGAL was performed in 40 patients with NS: 9 with proliferative glomerulopathy, being 4 with AKI and 31 without proliferative glomerulopathy, being 15 with AKI. AKI was defined using the KDIGO criteria. Results: The mean age was 35 ± 16 years. The main diagnoses were focal and segmental glomerulosclerosis (10, 25%), membranous glomerulopathy (10, 25%), minimal change disease (7, 18%), lupus nephritis (6, 15%), and proliferative glomerulonephritis (3, 8%). Patients with ATN had higher levels of urinary KIM-1 (P = 0.0157) and NGAL (P = 0.023) than patients without ATN. The urinary concentrations of KIM-1 (P= 0.009) and NGAL (P= 0.002) were higher in patients with AKI than in patients without AKI. Urinary NGAL and KIM-1 levels were significantly higher in patients with ATN without proliferative glomerulonephritis than in patients with proliferative glomerulonephritis (P = 0.003 and P=0.024, respectively). Conclusions: Neutrophil gelatinase associated lipocalin (NGAL) and kidney injury molecule 1 (KIM-1) estimates correlated with histological signs of ATN and were able to discriminate patients with AKI even in conditions of NS. Furthermore, urinary levels of NGAL and KIM-1 may be useful in the differential diagnosis of acute tubular necrosis and exudative glomerulonephritis in patients with nephrotic syndrome.

RESUMO Introdução: O surgimento de lesão renal aguda (LRA) em pacientes com síndrome nefrótica (SN) requer diagnóstico imediato e diferenciação entre necrose tubular aguda (NTA) e glomerulonefrite proliferativa. Avaliamos o uso potencial de testes de biomarcadores urinários comerciais no diagnóstico de LRA em pacientes com SN. Métodos: Uma estimativa transversal das concentrações urinárias de KIM-1 e NGAL foi realizada em 40 pacientes com SN: 9 com glomerulopatia proliferativa, sendo 4 com LRA e 31 sem glomerulopatia proliferativa, sendo 15 com LRA. A LRA foi definida usando os critérios da KDIGO. Resultados: A média de idade foi de 35 ± 16 anos. Os principais diagnósticos foram glomeruloesclerose segmentar e focal (10, 25%), glomerulopatia membranosa (10, 25%), doença por lesão mínima (7, 18%), nefrite lúpica (6, 15%) e glomerulonefrite proliferativa (3, 8 %). Os pacientes com NTA apresentaram níveis mais elevados de KIM-1 urinário (P = 0,0157) e NGAL (P = 0,023) do que pacientes sem NTA. As concentrações urinárias de KIM-1 (P = 0,009) e NGAL (P = 0,002) foram maiores em pacientes com LRA do que em pacientes sem LRA. Os níveis urinários de NGAL e KIM-1 foram significativamente maiores em pacientes com NTA sem glomerulonefrite proliferativa do que em pacientes com glomerulonefrite proliferativa (P = 0,003 e P = 0,024, respectivamente). Conclusões: As estimativas de lipocalina associada a gelatinase de neutrófilos (NGAL) e molécula de lesão renal 1 (KIM-1) se correlacionaram com sinais histológicos de NTA, e foram capazes de discriminar pacientes com LRA mesmo em condições de SN. Além disso, os níveis urinários de NGAL e KIM-1 podem ser úteis no diagnóstico diferencial de necrose tubular aguda e glomerulonefrite exsudativa em pacientes com síndrome nefrótica.

Clinical Significance of Urinary Neutrophil Gelatinase-associated Lipocalin Levels in Defining the Various Etiologies of Acute Kidney Injury in Liver Cirrhosis Patients / 대한소화기학회지

BACKGROUND/AIMS: A diagnosis of hepatorenal syndrome (HRS) is based on a differential evaluation of acute kidney injury (AKI), which may aggravate the clinical course. This study assessed the clinical significance of the urinary neutrophil gelatinase-associated lipocalin (u-NGAL) levels in a differential diagnosis of AKI in patients with liver cirrhosis (LC).METHODS: Patients with LC who developed AKI were enrolled prospectively. Clinically, patients with AKI were classified into prerenal azotemia (PRA), HRS, and acute tubular necrosis (ATN) groups.RESULTS: Fifty-five patients (male, 74.5%) with LC who exhibited AKI upon admission were enrolled; 28, 9, and 18 patients were included in the PRA, HRS, and ATN groups, respectively. The baseline model for end-stage liver disease (MELD) scores was similar in the subgroups. The median event creatinine level, measured at the time of the AKI diagnosis, was similar in the HRS and ATN subgroups. On the other hand, the median event u-NGAL level differed significantly between the three subgroups (PRA, HRS, and ATN: 37 vs. 134 vs. 2,625 ng/mL, p=0.003). In particular, the median u-NGAL level of the HRS group was clearly different from those of the PRA (p<0.001) and ATN (p<0.001) groups. Multivariable analysis revealed the natural logarithm of the u-NGAL level (hazard ratio [HR] 1.77, p=0.031) and the MELD score (HR 1.17, p=0.027) to be independent prognostic factors for in-hospital mortality in patients with LC and AKI.CONCLUSIONS: The median u-NGAL level differentiated HRS from ATN and served as a clinical indicator of in-hospital mortality for patients with LC and AKI.

Clinical Significance of Urinary Neutrophil Gelatinase-associated Lipocalin Levels in Defining the Various Etiologies of Acute Kidney Injury in Liver Cirrhosis Patients / 대한소화기병학회잡지

BACKGROUND/AIMS: A diagnosis of hepatorenal syndrome (HRS) is based on a differential evaluation of acute kidney injury (AKI), which may aggravate the clinical course. This study assessed the clinical significance of the urinary neutrophil gelatinase-associated lipocalin (u-NGAL) levels in a differential diagnosis of AKI in patients with liver cirrhosis (LC). METHODS: Patients with LC who developed AKI were enrolled prospectively. Clinically, patients with AKI were classified into prerenal azotemia (PRA), HRS, and acute tubular necrosis (ATN) groups. RESULTS: Fifty-five patients (male, 74.5%) with LC who exhibited AKI upon admission were enrolled; 28, 9, and 18 patients were included in the PRA, HRS, and ATN groups, respectively. The baseline model for end-stage liver disease (MELD) scores was similar in the subgroups. The median event creatinine level, measured at the time of the AKI diagnosis, was similar in the HRS and ATN subgroups. On the other hand, the median event u-NGAL level differed significantly between the three subgroups (PRA, HRS, and ATN: 37 vs. 134 vs. 2,625 ng/mL, p=0.003). In particular, the median u-NGAL level of the HRS group was clearly different from those of the PRA (p<0.001) and ATN (p<0.001) groups. Multivariable analysis revealed the natural logarithm of the u-NGAL level (hazard ratio [HR] 1.77, p=0.031) and the MELD score (HR 1.17, p=0.027) to be independent prognostic factors for in-hospital mortality in patients with LC and AKI. CONCLUSIONS: The median u-NGAL level differentiated HRS from ATN and served as a clinical indicator of in-hospital mortality for patients with LC and AKI.

Delayed acute kidney injury recognition is not associated with poor short-term outcomes: a propensity score matched study / 中华肾脏病杂志

Objective Acute kidney injury (AKI) is common but usually under-diagnosed in hospitalized patients,of the impact of which on patients is still unclear.The paper was aimed to investigate the impact of delayed recognition of AKI on short-time prognosis of patients through a propensity score matched study.Methods From Oct 2013 to Sep 2014,1401 adult hospitalized patients with AKI in the First Affiliated Hospital of Nanjing Medical University were divided into delayed recognition group and timely-diagnosed group according to propensity score matching (1∶ 1) without replacement method.Primary endpoint was 30-day all-cause mortality,and secondary endpoints included recovery of kidney at discharge,length of hospitalization,length of intensive care unit stay and hospital costs.Results There were significant differences in age,department distribution,complications,stage of AKI,Charlson index,APACHE Ⅱ score,SOFA score between the two groups before matching.After matching,there were no significant difference in demographic data,department distribution,complications,stage of AKI,Charlson index,APACHE Ⅱ score,SOFA score between the two groups except in blood urea nitrogen (P=0.039) and use of diuretics (P=0.018).Delayed recognition of acute kidney injury was not associated with 30-day all-cause mortality in univariate (P=0.711) and multivariate Logistic regression analyses.The secondary endpoints did not differ in two groups.Conclusion Delayed acute kidney injury recognition did not associate with poor short-term outcomes in adult hospitalized patients.

Diagnostic value of serum cystatin C for acute kidney injury in patients with liver cirrhosis / 中华肝脏病杂志

Objective@#To determine the diagnostic value of serum cystatin C (Cys C) for acute kidney injury (AKI) in patients with liver cirrhosis.@*Methods@#Serum Cys C levels in 150 liver cirrhosis patients (88 AKI and 62 non-AKI patients) were measured by the Particle-Enhanced Nephelometric Immuno-Assay. The accuracy of serum Cys C for the diagnosis of AKI in liver cirrhosis was evaluated by the ROC curve.@*Results@#Liver cirrhosis patients with AKI had significantly higher serum Cys C levels [2.37 (1.75-2.83) mg/L] than those without AKI [0.97 (0.85-1.09) g/L] (P <0.001). Serum Cys C level was highest in the acute tubular necrosis group [5.41 (2.77-6.19) mg/L], followed by the hepatorenal syndrome group [2.55 (2.28-3.59) mg/L] and prerenal azotemia group [2.07 (1.70-2.41) mg/L], and the serum Cys C level was significantly different between the three groups (P <0.001). In addition, patients with AKI were further divided into infection group and non-infection group. Serum Cys C level was significantly higher in the infection group than in the non-infection group (P <0.05). The area under the ROC curve of serum Cys C for the diagnosis of AKI in liver cirrhosis was 0.99 (0.98-1.00) at a cut-off value of 1.36 mg/L, and the sensitivity and specificity were 97% and 95%, respectively.@*Conclusion@#Serum Cys C is a good marker for detecting AKI in liver cirrhosis, and the different levels of increase in Cys C may be useful in differentiating the different types of AKI.

A Case Report of a Middle East Respiratory Syndrome Survivor with Kidney Biopsy Results

A 68-year old man diagnosed with Middle East Respiratory Syndrome-Coronavirus (MERS-CoV) presented with multiple pneumonic infiltrations on his chest X-ray, and the patient was placed on a mechanical ventilator because of progressive respiratory failure. Urinary protein excretion steadily increased for a microalbumin to creatinine ratio of 538.4 mg/g Cr and a protein to creatinine ratio of 3,025.8 mg/g Cr. The isotope dilution mass spectrometry traceable serum creatinine level increased to 3.0 mg/dL. We performed a kidney biopsy 8 weeks after the onset of symptoms. Acute tubular necrosis was the main finding, and proteinaceous cast formation and acute tubulointerstitial nephritis were found. There were no electron dense deposits observed with electron microscopy. We could not verify the virus itself by in situ hybridization and confocal microscopy (MERS-CoV co-stained with dipeptidyl peptidase 4). The viremic status, urinary virus excretion, and timely kidney biopsy results should be investigated with thorough precautions to reveal the direct effects of MERS-CoV with respect to renal complications.

Quantitative analysis of contrast-enhanced ultrasonography in differentiating acute rejection from acute tubular necrosis of transplant kidney / 中华超声影像学杂志

Objective To evaluate the value of quantitative analysis of contrast‐enhanced ultrasonography (CEUS) in differentiating acute rejection(AR) from acute tubular necrosis(ATN) of transplant kidney. Methods Total of 67 kidney recipients were examined with conventional US and CEUS. Biopsies were performed in 37 patients, 26 patients were with AR, 11 with ATN, 30 patients as control group. The hemodynamic parameters (PSV and RI) were measured on infrarenal artery with conventional US, while CEUS quantitative analysis was performed on the cortex, pyramid and interlobar artery by time‐intensity curve (TIC). TIC parameters including rise time (RT ), time to peak (TTP), mean transit time (mTT ) were compared among three groups. In addition, the reproducibility of TIC parameters was evaluated. Results The RI in AR group was significantly higher than that in control group, but there were no significant differences of RI between AR and ATN groups. TIC parameters including RT, TTP were with high reproducibility (ICC> 0 7.5). Compared to the other two groups, the RT and TTP of the pyramid, ΔRTm‐c, and ΔTTPm‐c were significantly longer in AR group, the receiver operating curves (ROC) analysis demonstrated that ΔRTm‐c had the highest accuracy and RI had the lowest accuracy for detecting AR(areas under the curve were 0 7.86, 0 7.56, 0 7.49, 0 7.36 and 0 4.98, respectively). High sensitivity and specificity(78 3.% and 73 5.%, respectively) were shown when using 4 6.2 s as a cutoff point of ΔRTm‐c to diagnose AR. Conclusions Quantitative analysis of CEUS could detected the changes of the microcirculation perfusion in kidney grafts with AR and ATN, which might be superior in the diagnosis of AR compared with conventional US.

Role of renal progenitor-like tubular cells in the repair of acute renal tubular necrosis / 中华肾脏病杂志

Objective To elucidate the role of renal progenitor-like tubular cells in the repair process after acute tubular necrosis(ATN)induced by ischemia. Methods Rat ATN was developed by clamping left kidney artery for 60 minutes,and bromodeoxyuridine(BrdU),a cell division and proliferation marker,was administrated one hour before rats were sacrificed.Kidneys were isolated at 1,3,5,7,14,21,28 days after injury.The proliferative and apoptotic cells were determined by immunostaining using anti-BrdU,Pax2(an embryonic renal marker),vimentin(an immature mesenchymal cell marker),and activated caspase-3(a cell apoptosis marker). Results Cell death was found in tubules at day 1 after ischemia and reperfusion injury.BrdU-positive cells were dramatically increased and reached peak at day 3 after injury.In addition,the number of BrdU positive cells in the contralateral kidney was significantly increased compared to sham operated group.Double immunostaining showed that BrdU-positive cells co-expressed Pax2 or vimentin,but not activated caspase-3. Conclusions Renal progenitor-like tubular cells may play a predominant role in repair process following ATN in rats.They may dedifferentiate,proliferate,and then redifferentiate into mature tubular cells.Growth factors may regulate the repair process.

Nephroprotective effects of subcapsular transplantation of metanephric mesenchymal cells on acute tubular necrosis rats / 中华肾脏病杂志

ObjectiveTo evaluate the nephroprotective effects of transplanting metanephric mesenchymal cells (MMCs) into the renal subcaspsule of rats with acute tubular necrosis (ATN) induced by gentamicin. MethodsMMCs were expanded in culture and immunocytochemistry was used to characterize the cells. After gentamicin-induced ATN, fluorescence-labeled cells were transplanted and traced in kidney tissues by fluorescence microscopy. Serum creatinine (Scr) and N-acetyl-b-D-glucosaminidase (NAG) were tested. Kidney pathology was studied by hematoxylin-eosin staining. Apoptosis was examined by the TUNEL assay. Ki-67 and Bcl-2 expression was examined by immunohistochemistry. ResultsMMCs were expanded in culture and the phenotype of the cells was vimentin-positive and keratin-negative. Compared with other ATN groups, in the MMCs-treated group, Scr and NAG clearly decreased[14d Scr: (101.38±20.46) μmol/L vs (248.78±23.15), (252.98±33.52), (229.08±18.18) μmol/L;NAG: (14.83±7.74) U/L vs (33.33±14.88), (29.62±10.54), (30.22±10.94) U/L, P<0.05, respectively];the histopathoiogic lesion scores were lower (P<0.05);the Ki-67 antibody and apoptosis of renal tubular epithelial cells were improved or reduced respectively;the expression of Bcl-2 protein was up-regulated (P<0.05). ConclusionThe subcapsular transplantation of MMCs can ameliorate renal function and repair kidney injury.

Diagnosis of acute tubular necrosis in renal allograft with contrast ultrasound: an experimental study / 中华超声影像学杂志

Objective To investigate the diagnostic feasibility of acute tubular necrosis(ATN) in renal allograft using time intensity curves by intravenous contrast ultrasound.Methods The canine models of acute tubular necrosis in renal allograft were established,and examined subsequently with intravenous contrast ultrasound using auto control,and also the parameters of time intensity curves were analyzed,tracking the renal biopsies simultaniously.Results After ATN occured, the curve peak was ante displaced.And parameters of TIC (except peak intensity,PI),area under the curve(AUC),half time of descent(HT),mean transit time(MTT),the ratio of AUC were decreased dramatically.Conclusions Contrast ultrasound combined with TIC quantitative analysis could reflect the variation of blood perfusion objectively,and it is a potential new method for diagnosis of ATN in renal allograft.