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.

Nefropatía por tóxicos: la cocaína y su potente daño renal / Toxic nephropathy: cocaine and its potent kidney damage

Resumen El consumo de sustancias ilícitas en menores de 16 años y en adultos jóvenes se incrementa cada día en Colombia, por lo cual se presentan complicaciones asociadas que sería inusual encontrar en este grupo poblacional. El presente reporte de caso muestra cómo el uso de cocaína llevó a un paciente joven a desarrollar daño renal agudo con requerimiento de terapia de reemplazo renal, lo que en los hallazgos histológicos puede corresponder a una glomerulonefritis rápidamente progresiva o a una enfermedad tubulointersticial tipo necrosis tubular aguda o nefritis intersticial aguda.

Abstract In Colombia, the consumption of illicit substances increases daily. The increase and related consumption in the population involves both young people under 16 and young adults. Therefore, there are complications associated with the consumption of these substances that otherwise, would be unusual to find in this population group. In this case report, we will review how the use of cocaine led a young patient to the development acute kidney injury requiring renal replacement therapy, which in the histological findings may correspond to rapidly progressive glomerulonephritis, or tubulointerstitial disease either acute renal tubular necrosis or acute interstitial nephritis.

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 / 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.

Earlier renal fibrosis aggravates acute kidney injury induced by ischemia reperfusion in mice / 中华肾脏病杂志

Objective To investigate the influence of earlier renal fibrosis on ischemia and reperfusion induced acute kidney injury. Methods Male C57BL/6 mice at eight to twelve weeks old age were divided into 4 groups randomly: (1)Sham (n=3); (2)Unilateral ureter obstruction (UUO, n=6):UUO for 3 days (UUO3d, n=3) and UUO for 5 days (UUO5d, n=3);(3)Ischemia and reperfusion (IR, n=7): bilateral kidney ischemia for 40 minutes followed by 24 hours of reperfusion; (4)UUO for 3 days plus IR (UUO3d+IR, n=6): bilateral kidney ischemia after UUO 2 days for 40 minutes followed by 24 hours of reperfusion, and the real time for UUO was 3 days. Pathologic analysis for acute or chronic injury was performed on paraffin embedded kidney sections with hematoxylin and eosin (HE) or Masson staining. Apoptosis was detected by immunohistochemistry(IHC) and Western blotting with anti-caspase-3 antibody, and proliferation was observed by IHC with anti-ki67 antibody. Results On kidney sections with HE or Masson staining, it showed that the chronic kidney lesions and fibrosis got more severe as time of UUO prolonged from 3 days to 5 days; the area of matrix deposition increased in UUO5d and UUO3d mice significantly compared to Sham mice (P<0.05) and was smaller in UUO3d mice compared with UUO5d mice obviously (P<0.05). Acute kidney injury could be observed in UUO3d+IR mice, such as massive inflammatory cells infiltration, tubules dilation, brush border disappearance, tubular epithelial cells vacuolar degeneration, necrosis, casting formation, coexisting with chronic lesions: thinner cortex, broadened interstitial space, and increased blue stained matrix. Acute kidney injury score in UUO3d+IR mice was higher than that in IR mice significantly (P<0.05), and serum creatinine level increased significantly in UUO3d+IR mice compared to Sham mice (P<0.05). Caspase-3 expression increased and ki67 positive tubular cells decreased in UUO3d+IR mice than those in IR mice obviously (P<0.05). Conclusion Earlier renal fibrosis aggravates acute kidney injury induced by ischemia reperfusion in mice through increasing apoptosis and decreasing proliferation of tubular epithelial cells.

Histological evaluation and E-cadherin and ß-catenin expression in kidney of dogs submitted to renal ischemia and reperfusion after chlorpromazine administration / Avaliação histológica e imunomarcação de E-caderina e ß-catenina em rins de cães submetidos a isquemia e referfusão renal após administração de clorpromazina

Renal ischemia can be associated with some urological procedures, such as renovascular surgery or kidney transplantation, that are often followed by acute renal failure. The aim of this study was to verify the E-cadherin and ß-catenin localization in canine kidney in different times of renal ischemia and reperfusion after chlorpromazine application. Twelve dogs were randomly distributed equally into two groups. GroupA with ischemia and reperfusion without chlorpromazine and groupB with ischemia and reperfusion treated by chlorpromazine. GroupB received intravenous chlorpromazine, 15 min before the artery obstruction, which lasted 1 hour. After this period, the clamps in the renal arteries were released and the organ remained in reperfusion for 2 hours. In each group, anti-E-cadherin and anti-ß-catenin antibodies were made in six tissue samples from renal parenchyma. E-cadherin and ß-catenin are differentially expressed in segments from cortex and medulla in dog's kidneys and the use of chlorpromazine did not alter the expression of both proteins. Occlusion of the left renal artery in dogs causes morphological alterations mainly in proximal convoluted tubules, beginning 30min after the start of ischemia and being aggravated after two hours of reperfusion. These results reveal that chlorpromazine did not change kidneys' histological aspect nor E-cadherin and ß-catenin expression.(AU)

A lesão renal isquêmica pode estar associada a procedimentos urológicos, tais como cirurgia renovascular, cirurgia renal extracorpórea ou transplante renal. Essa injúria, muitas vezes, é seguida de insuficiência renal aguda. O objetivo deste trabalho foi observar a localização da E-caderina e da ß-catenina em rim de cães, além de relacionar a expressão dessas proteínas das junções de aderência em diferentes tempos de isquemia e reperfusão com ou sem a aplicação de clorpromazina. Para tanto, foram utilizados 12 cães, distribuídos aleatoriamente em dois grupos de seis indivíduos: grupo A, com isquemia e reperfusão sem tratamento por clorpromazina, e o grupo B, com isquemia e reperfusão tratado por clorpromazina. No procedimento cirúrgico, foi realizada uma incisão paracostal esquerda para identificação e isolamento do rim esquerdo e da artéria renal esquerda. Após o isolamento da artéria, os animais de todos os grupos tiveram o vaso ocluído. Os animais do grupo B receberam clorpromazina via endovenosa, na dose de 5mg/kg, 15min antes da clampagem do vaso, que durou uma hora. Após este período, as artérias renais foram desobstruídas e os órgãos permaneceram em reperfusão por duas horas. Em cada grupo, foram extraídas seis amostras de parênquima renal, com utilização de agulha tru-cut, para marcação com anticorpos anti-E-caderina e anti-ß-catenina por meio de imunoistoquímica. E-caderina e ß-catenina são diferencialmente expressas em segmentos do córtex e da medula em rim de cães e o uso da clorpromazina não alterou a expressão das duas proteínas.(AU)

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.

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.

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.

Acute tubular necrosis as a part of vancomycin induced drug rash with eosinophilia and systemic symptoms syndrome with coincident postinfectious glomerulonephritis / 소아과

Drug rash with eosinophilia and systemic symptoms (DRESS) syndrome is a rare and potentially fatal condition characterized by skin rash, fever, eosinophilia, and multiorgan involvement. Various drugs may be associated with this syndrome including carbamazepine, allopurinol, and sulfasalazine. Renal involvement in DRESS syndrome most commonly presents as acute kidney injury due to interstitial nephritis. An 11-year-old boy was referred to the Children's Hospital of Pusan National University because of persistent fever, rash, abdominal distension, generalized edema, lymphadenopathy, and eosinophilia. He previously received vancomycin and ceftriaxone for 10 days at another hospital. He developed acute kidney injury with nephrotic range proteinuria and hypocomplementemia. A subsequent renal biopsy indicated the presence of acute tubular necrosis (ATN) and late exudative phase of postinfectious glomerulonephritis (PIGN). Systemic symptoms and renal function improved with corticosteroid therapy after the discontinuation of vancomycin. Here, we describe a biopsy-proven case of severe ATN that manifested as a part of vancomycin-induced DRESS syndrome with coincident PIGN. It is important for clinicians to be aware of this syndrome due to its severity and potentially fatal nature.

Acute tubular necrosis as a part of vancomycin induced drug rash with eosinophilia and systemic symptoms syndrome with coincident postinfectious glomerulonephritis / 소아과

Drug rash with eosinophilia and systemic symptoms (DRESS) syndrome is a rare and potentially fatal condition characterized by skin rash, fever, eosinophilia, and multiorgan involvement. Various drugs may be associated with this syndrome including carbamazepine, allopurinol, and sulfasalazine. Renal involvement in DRESS syndrome most commonly presents as acute kidney injury due to interstitial nephritis. An 11-year-old boy was referred to the Children's Hospital of Pusan National University because of persistent fever, rash, abdominal distension, generalized edema, lymphadenopathy, and eosinophilia. He previously received vancomycin and ceftriaxone for 10 days at another hospital. He developed acute kidney injury with nephrotic range proteinuria and hypocomplementemia. A subsequent renal biopsy indicated the presence of acute tubular necrosis (ATN) and late exudative phase of postinfectious glomerulonephritis (PIGN). Systemic symptoms and renal function improved with corticosteroid therapy after the discontinuation of vancomycin. Here, we describe a biopsy-proven case of severe ATN that manifested as a part of vancomycin-induced DRESS syndrome with coincident PIGN. It is important for clinicians to be aware of this syndrome due to its severity and potentially fatal nature.

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.

Cost-effectiveness of iso- versus low-osmolality contrast media in outpatients with high risk of contrast medium-induced nephropathy / Costo-efectividad de medios de contraste isoosmolales e hiposmolales en pacientes con alto riesgo de nefropatía inducida por medio de contraste

Introduction. Contrast media can cause acute renal failure by direct toxic effects on the tubular cells and kidney ischemia. Diabetics and hospitalized patients have a greater risk of developing contrast-induced nephropathy than the general population. Objective. The cost effectiveness of iso and low-osmolality contrast media was assessed in high risk outpatients. Materials and methods. The analysis was based on a systematic literature review comparing the nephrotoxic effects of iso- to low-osmolality contrast media. Only direct costs were considered; these were obtained from the official tariff manual. Incremental cost-effectiveness ratios, efficiency curves and acceptability curves were calculated. Univariate sensitivity analyses were performed for costs and effects, as well as probabilistic analyses. Zero and 3% discounts were applied to results. The cost-effectiveness threshold was equal to the per capita GDP per life-year gained. Results. Alternatives with Iopamidol and Iodixanol are preferable to the others, because both reduce risk of contrast-induced nephropathy and are less costly. The incremental cost-effectiveness of the Iodixanol alternative compared to the Iopamidol alternative is US$ 14,660 per additional life year gained; this is more than twice the threshold. Conclusion. The low-osmolality contrast medium, Iopamidol, appears to be cost-effective when compared with Iohexol or other low-osmolality contrast media (Iopromide, Iobitridol, Iomeprol, Iopentol and Ioxilan) in contrast-induced nephropathy, high-risk outpatients. The choice of the iso-osmolality contrast medium, Iodixanol, depends on its cost per vial and on the willingness to pay.

Introducción. Los medios de contraste pueden provocar falla renal aguda por toxicidad directa sobre las células tubulares e isquemia medular renal. Los pacientes diabéticos y los hospitalizados presentan mayor riesgo de desarrollar nefropatía inducida por medios de contraste que la población general. Objetivo. Establecer el costo-efectividad de los medios de contraste isosmolales e hiposmolales en pacientes con alto riesgo. Materiales and métodos. El análisis se basó en una revisión sistemática de la literatura científica, comparando los efectos nefrotóxicos de los medios isosmolales e hipoosmolales. Se consideraron sólo los costos directos, obtenidos del manual tarifario. Se calcularon las tasas del incremento del costo-efectividad, las curvas de eficiencia y de aceptabilidad. Se hicieron análisis univariados de sensibilidad para costos y efectos, así como probabilísticos. Se aplicaron tasas de descuento de 0 y 3 % a los resultados. Se usó como umbral de costo-efectividad por año de vida ganado, el producto interno bruto per cápita. Resultados. Las alternativas con Iopamidol y Iodixanol dominan a las demás porque reducen el riesgo de nefropatía inducida por contraste a un menor costo. La razón del incremento del costo-efectividad del iodixanol comparado con el iopamidol es de US$ 14.660 por año de vida ganado que más que duplica el umbral. Conclusión. El medio de baja osmolalidad, iopamidol, parece ser costo-efectivo comparado con iohexol u otros medios hiposmolares (iopromide, iobitridol, iomeprol, iopentol y ioxilan), en pacientes con alto riesgo de nefropatía inducida por contraste. La elección del medio hiposmolar, depende de la disponibilidad a pagar o del costo por ampolleta.

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.

A Case of Biopsy-Proven Acute Tubular Necrosis Associated with Vancomycin Overdose / 대한신장학회지

Vancomycin has been associated with acute kidney injury, particularly in the concomitant treatment with aminoglycoside or in the presence of other risk factor such as preexisting renal disease, sepsis, or hemodynamic instability. Vancomycin-related nephrotoxicity typically manifests as acute tubulointerstitial nephritis. Biopsy-proven acute tubular necrosis associated with vancomycin intoxication in the absence of aminoglycoside has been reported only in very few cases. We report a case of biopsy-proven acute tubular necrosis associated with vancomycin intoxication that was treated by continuous venovenous hemodiafiltration. A 28-year-old male without preexisting renal disease received a massive overdose of vancomycin. The plasma vancomycin level was 440.3 microg/mL. Renal biopsy revealed acute tubular necrosis that there is marked thinning of the tubular epithelium with dilatation of the tubular lumens and severe foamy epithelial cell changes in tubules. Continuous venovenous hemodiafiltration resulted in efficient reduction of serum vancomycin levels, which was followed clinically by recovered of renal function.

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.

An Unusual Type of Acute Renal Failure due to Extensive Crystal Deposition in the Renal Tubular Epithelium and Interstitium: A Case Report

Acute tubular necrosis is a major cause of acute renal failure. Acute renal failure that is caused by crystal deposition can result from drug toxicity, lymphoplasmacytic neoplasms, ingestion of industrial organic solvents, or intratubular obstruction due to degenerated red blood cells and red blood cell casts. We herein present an uncommon case of acute renal failure in a 57-year-old woman showing an unusually massive accumulation of variable-sized, round, ellipsoid or rhomboid, pale-pink, refractile bodies in the proximal and distal tubular epithelial cells, interstitial macrophages and Bowman's spaces. These bodies were electron dense with a maximum diameter of 3 micrometer. The information we gathered from the patient history, the laboratory data and the various histochemical and immunohistochemical analyses failed to reveal the exact nature of these crystal-like structures.

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.

Apoptosis and Cell Proliferation in Experimental Acute Tubular Necrosis Induced by Intramuscular Glycerol Injection

BACKGROUND: Acute tubular necrosis (ATN) is the most common cause of acute renal failure. It is characterized by the destruction of tubular epithelial cells. To examine apoptosis and proliferative activity of tubular cells in the course of acute tubular necrosis, we induced acute renal failure by intramuscular hypertonic glycerol injection to New Zealand White rabbits. METHODS: The immunohistochemistry was done for Ki-67 and tissue-transglutaminase (tTG), and the terminal deoxynucleotidyl transferase mediated nick end labeling (TUNEL) method was performed using a total of 77 renal specimens including 29 gun biopsies and 48 nephrectomiy specimens. RESULTS: Widespread tubular injury with pigment casts and interstitial hemorrhage were noted. The tubular proliferation index was increased at 2 hours after glycerol injection, and the index peaked at 3 hours. The second cell proliferation peak was noted at 3 days. Apoptotic cells were identified by TUNEL and tTG staining. The apoptotic index was significantly increased, and it peaked at 24 hours after glycerol injection. There was a significant correlation between the proliferation index (MIB-1) the and the apototic index (TUNEL)(p= 0.001). A DNA ladder pattern was observed at 6 to 8 hours. CONCLUSIONS: Tubular cell proliferation and apoptosis occur in the early phase after the induction of acute tubular necrosis, and the excess hyperplastic epithelial cells appear to be eliminated by apoptosis.