Application progress in classification of puncture biopsy after kidney transplantation / 器官移植

Renal allograft biopsy (biopsy) remains the "gold standard" for the diagnosis of renal dysfunction after kidney transplantation. Puncture biopsy after kidney transplantation could be divided into indicative biopsy and protocol biopsy according to renal function of the patients. Indicative biopsy is mainly applied to diagnose postoperative complications of kidney transplantation, evaluate the severity of disease and guide subsequent treatment. Protocol biopsy is primarily employed to regular monitor renal allograft function of kidney transplant recipients and exclude subclinical rejection and other complications. Due to the willingness of patients and other reasons, protocol biopsy has not been widely applied in China. Currently, indicative biopsy is the main biopsy pattern. At present, the indications of puncture of indicative biopsy, the timing and necessity of puncture of protocol biopsy remain controversial. In this article, the classification of puncture biopsy after kidney transplantation and research progress on tissue biomarkers based on biopsy were reviewed, aiming to assist clinical diagnosis and targeted treatment of complications after kidney transplantation and provide reference for further improving the survival of renal allografts and recipients.

The use of intraoperative mannitol during the laparoscopic nephrectomy in living kidney donor and the prevention of delayed graft function / Uso de manitol intraoperatorio durante la nefrectomía por laparoscopia en donante vivo de riñón y la prevención de función retardada del injerto

Background and objectives: The administration of mannitol during laparoscopic hand-assisted nephrectomy in the living donor has been controversial with various recommendations about it. This study aims to evaluate the effect of the intraoperative mannitol in the living kidney donor and the incidence of delayed graft function (DGF). Methods: This study was a retrospective observational study with living kidney transplant recipients and donors who underwent laparoscopic hand-assisted nephrectomy at Colombiana de Trasplantes from January 2015 to September 2019. We assessed the impact of mannitol administration in living donors on the main transplant outcomes such as DGF, urinary volume, acute rejection, and mortality at 3 months of follow-up. We performed a descriptive analysis of demographics and clinical variables in our cohort. Results: A total of 367 recipients were evaluated. The incidence of DGF was 5.9% without mannitol versus 6.2% with mannitol (p = 0.99). The acute rejection episodes (12.2% without mannitol versus 4.7% with mannitol) had a trend difference between the comparative groups, but it was still not significant in the bivariate analysis (p = 0.06). The mortality rate in the recipient was not significant (p = 0.69). The mean serum creatinine did not have significant differences at 1 and 3 months of follow-up comparing both groups. Conclusion: The use of mannitol in living donors does not have a significant impact on the incidence of DGF in kidney recipients. A trend of association between mannitol administration and reduced acute rejection episodes was observed, though it was not statistically significant.

Antecedentes y objetivo: La administración de manitol durante la nefrectomía laparoscópica en el donante vivo ha sido discutida con diversas recomendaciones. El objetivo es evaluar la administración de manitol intraoperatorio en el donante vivo de riñón y la incidencia de función retardada del injerto en el receptor. Métodos: Estudio observacional retrospectivo con receptores de riñón y donantes vivos que tuvieron nefrectomía laparoscópica en Colombiana de Trasplantes entre enero de 2015 a septiembre de 2019. Evaluamos el impacto de administrar manitol en los principales desenlaces del trasplante: función retardada del injerto, volumen urinario, rechazo agudo y mortalidad del receptor a los 3 meses post-trasplante. Se realizó un análisis descriptivo de las características demográficas y clínicas. Resultados: Se evaluaron 367 receptores con una incidencia de función retardada del injerto de 5.9% sin manitol versus 6.2% con manitol (p = 0,99), el rechazo agudo (12,2% sin manitol versus 4,7% con manitol) tuvo una tendencia de diferencia entre ambos grupos no significativa (p = 0,06) y la mortalidad del receptor tampoco mostró diferencias significativas (p = 0,69). La media de creatinina sérica al mes y 3 meses no tuvo diferencias significativas en los grupos. Conclusión: El uso de manitol en los donantes vivos de riñón no impactó significativamente la incidencia de función retardada del injerto en los receptores de trasplante. Se encontró una tendencia de asociación en la administración de manitol intraoperatorio y la reducción de los episodios de rechazo agudo al tercer mes post-trasplante en los receptores. No obstante, esta tendencia no tuvo la suficiente relevancia estadística.

Predictive value of kidney injury markers for early DGF in kidney transplant recipients / 器官移植

Objective To evaluate the predictive values of serum neutrophil gelatinase-associated lipocalin (NGAL), urine NGAL, serum cystatin C (Cys-C) and serum creatinine (Scr) for early delayed graft function (DGF) in kidney transplant recipients. Methods Clinical data, blood and urine samples of 159 kidney transplant recipients were collected. All recipients were divided into the DGF group (n=42) and immediate graft function (IGF) group (n=117) according to the incidence of DGF. Clinical data of all recipients were analyzed. The changes of serum NGAL, urine NGAL, Cys-C and Scr levels were statistically compared between two groups. The predictive values of different markers for early DGF were assessed. Results Among 159 kidney transplant recipients, DGF occurred in 42 cases with an incidence rate of 26.4%. There were statistically significant differences in donor age, cold ischemia time of donor kidney and complement-dependent cytoxicity (CDC) between the two groups(all P < 0.05). Within postoperative 2 weeks, the serum NGAL levels in the DGF group were higher than those in the IGF group (all P < 0.05). The Cys-C, Scr and urine NGAL levels in the DGF group were higher compared with those in the IGF group within 3 weeks after kidney transplantation(all P < 0.001). Serum NGAL, urine NGAL, Cys-C and Scr levels had certain predictive values for early DGF in kidney transplant recipients. Cys-C yielded the highest predictive value with a cut-off value of 4.73 mg/L, sensitivity of 0.833, specificity of 0.812 and area under the curve (AUC) of 0.895. Conclusions Cys-C has higher predictive value for early DGF in kidney transplant recipients compared with serum NGAL, urine NGAL and Scr.

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.

Toxicological Evaluation of Nelumbo Nucifera Fruit Ethanol Extract

Nelumbo nucifera fruit (NNF) is frequently used for the treatment of many diseases in Asian countries withoutproper scientific evidence of its safety. The purpose of this study was to determine the toxicological effects ofNNF. Toxicity study was conducted on 28 male Wister rats weighing 180-230 g that were allocated equally to 4treatment groups; a control and 3 test groups. Parameters assessed were clinical signs, body weight,hematology, blood biochemistry and histopathology after administration of NNF to rats for 13 weeks. No majortoxicity was revealed throughout the study, though some biochemical changes were observed in hepatic andrenal tissues but these changes did not correspond with histopathology findings. There was no mortality andevidence of systemic toxicity following 13 weeks administration of NNF. Hematology and blood biochemistrydid not reveal any toxicity at any dose; however, histopathological evaluation of hepatic tissues of few animalstreated with 200 mg/kg showed areas of necrosis at lesser extent in few animals after 13 weeks exposure of fruit.Histopathology of renal tissues of group treated with 200 mg/kg revealed areas of moderate tubular disruptionand few foci of tubular necrosis. Although only few adverse effects were observed but NNF administration ifnecessary for a prolonged period, then it may be used in a dose rage of 50-100 mg/kg in order to avoidintractable effects. Additional studies are required to clinically evaluate the safety profile of NNF.

Injuria renal aguda secundaria a crisis hipercalcémica: a propósito de un caso / Acute renal injury secondary to hypercalcemic crisis: a case report / Lesão ou injúria renal aguda secundária a crise hipercalcêmica: relatório de caso clínico

La injuria renal aguda es una entidad clínica compleja, caracterizada por la disminución abrupta de la función renal. La hipercalcemia como etiología de la misma es poco frecuente. Los mecanismos involucrados en su desarrollo son múltiples y poco estudiados. Se presenta el caso de un paciente varón de 59 años que desarrolló un cuadro severo de falla renal aguda como complicación de crisis hipercalcémica por un adenoma de paratiroides. Se observó alteración en los marcadores de daño y función renal. La bioquímica urinaria mostró una necrosis tubular aguda. Los niveles de calcio, parathormona y calciuria se asociaron a endocrinopatía. La ecografía, el centellograma y la biopsia paratiroidea mostraron la presencia de un adenoma. Se presentaron otras complicaciones sistémicas concomitantes como pancreatitis y complicaciones cardíacas. El tratamiento paliativo fue la hemodiálisis y el definitivo la paratiroidectomía. El síndrome de hueso hambriento se presentó como una complicación postquirúrgica. Tras el alta, la recuperación de la función renal nunca fue total. El daño renal agudo asociado a disfunción sistémica por hipercalcemia puede llevar a una recuperación parcial de la función renal. Se debe considerar el desarrollo de enfermedad renal crónica posterior a la falla renal aguda por hipercalcemia como complicación de la misma.

Acute renal injury is a complex clinical entity, characterized by the abrupt worsening in renal function. Hypercalcemia as its etiology is rare. The mechanisms involved in its development are multiple and rarely studied. The case of a 59-year-old male patient who developed a severe acute renal failure as a complication of an hypercalcemic crisis due to a parathyroid adenoma is presented here. Alterations in markers of damage and renal function were observed. Urinary biochemistry showed acute tubular necrosis. Calcium, parathormone and urine calcium levels were associated with endocrinopathy. The ultrasound, the scintigraphy and the parathyroid biopsy showed the presence of an adenoma. There were other concomitant systemic complications such as pancreatitis and cardiac complications. Hemodialysis was the palliative treatment, while the definitive treatment was parathyroidectomy. The hungry bone syndrome occurred as a postoperative complication. After discharge, recovery of renal function was never complete. Acute renal damage associated with systemic dysfunction due to hypercalcemia can lead to a partial recovery of renal function. The development of chronic kidney disease after acute renal failure due to hypercalcemia should be considered one of its complications.

A Lesão renal aguda é uma entidade clínica complexa, caracterizada pela diminuição abrupta da função renal. A hipercalcemia como etiologia da mesma não é muito frequente. Os mecanismos que participam no seu desenvolvimento são múltiplos e pouco estudados. Apresenta-se o caso de um paciente, homem, de 59 anos, que desenvolveu um quadro severo de insuficiência renal aguda como complicação de crise hipercalcêmica por um adenoma da paratireóide. Foi observada alteração nos marcadores de dano e função renal. A bioquímica urinária mostrou uma necrose tubular aguda. Os níveis de cálcio, paratormona e calciúria foram associados a endocrinopatia. A ultra-sonografia, a cintilografia, e a biópsia da paratireóide mostraram a presença de um adenoma. Apresentaram-se outras complicações sistêmicas concomitantes como pancreatite e cardíacas. O tratamento paliativo foi hemodiálise e o definitivo, a paratireoidectomia. A síndrome do osso faminto apresentou-se como uma complicação pós-operatória. Após a alta, a recuperação da função renal nunca foi total. O dano renal agudo associado à disfunção sistêmica por hipercalcemia pode levar para uma recuperação parcial da função renal. Deve ser considerado o desenvolvimento da doença renal crônica posterior à insuficiência renal aguda por hipercalcemia como complicação da mesma.

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.

Etiology of graft dysfunction in renal transplant recipients

Background: Kidney transplantation is the preferred mode of renal replacement therapy for the endstage renal disease, with dramatic improvements in patient and graft survival over the last 50 years. In the modern era of immunosuppression, 1-year patient survival is close to 98%, and 1-year allograft survival rates have improved to 90% for deceased donor kidney transplants and 95 % for living donor kidney transplants with some inter-center variability. The aim of the study: To elucidate the etiology of graft dysfunction among renal transplant recipients. Materials and methods: A retrospective study was conducted among 155 patients who underwent both cadavers and live donor transplant from October 2009 to March 2011 at a tertiary care center in Chennai, South India. All the transplant recipients were regularly followed with serum urea and creatinine, urine routine, calcineurin inhibitor drug levels in the serum, USG Abdomen, urine culture depending on the graft status. Graft dysfunction defined by a rise in the creatinine more than 25% or 0.3 to 0.5 mg per dl from the baseline. Those who developed graft dysfunction were presented for graft biopsy and managed based on the report accordingly. S. Thirumavalavan, Krishna Kumar, S. A. K. Noor Mohamed, R Vijaya Kumar. Etiology of graft dysfunction in renal transplant recipients. IAIM, 2019; 6(3): 313-318. Page 314 Results: Among the 155 transplant recipient patients, 66 (44%) patients developed graft dysfunction and underwent renal biopsy. The graft dysfunction was due to chronic allograft dysfunction (interstitial fibrosis and tubular atrophy) in 24 (15.4%) patients, acute cellular rejection in 13 (8.4%) patients, acute antibody-mediated rejection in 2 (1.3%) patients, acute tubular necrosis in 9 (5.8%) patients, calcineurin toxicity in 6 (3.9%) patients, thrombotic microangiopathy in 6 (3.9%) patients, IgA nephropathy in 3 (1.9%) patients and transplant renal artery stenosis in 1(0.6%) patient. Conclusion: Among the various causes, acute cellular, acute antibody rejection and chronic allograft nephropathy holds nearly 25% of the incidence of graft dysfunction. It indicates appropriate immunological evaluation, appropriate immunosuppression, use of induction agents in high-risk patients and protocol renal biopsy to identify early rejection in high-risk patient and appropriate early intervention is important to improve long-term term graft and patient survival.

Renal damage associated with heavy metals: review work / Daño renal asociado a metales pesados: trabajo de revisión

Abstract Catheter-associated infection is an entity with multiple complications, a condition that alters the quality of life of all patients Chronic kidney disease (CKD) represents an important health problem in the entire global population, where knowledge of the environmental factors associated with this disease is currently essential for its prevention. Several heavy metals are recognized, including Cadmium (Cd), Lead (Pb), Arsenic (As) and Mercury (Hg), which are clearly associated with renal damage and progression of CKD. Studies in animals and humans primarily demonstrate a clear association between exposure to these metals and the presence of chronic renal damage, where the pathophysiology of each of these metals is important in understanding the mechanism of renal damage. The present review aims to analyze the pathophysiology and clinical manifestations of the nephrotoxicity associated with these metals, as well as the different studies in both humans and animals that have been performed.

Resumen La enfermedad renal crónica (ERC) representa un importante problema de salud en todo el globo. Actualmente, es esencial para su prevención el conocimiento de los factores ambientales asociados con la enfermedad. Se reconocen diversos metales pesados, entre los que destacan el cadmio (Cd), plomo (Pb), arsénico (As) y mercurio (Hg), que están claramente asociados con la lesión renal y la progresión de la ERC. Estudios en animales y humanos demuestran, principalmente, una clara asociación entre la exposición a estos metales y la presencia de daño renal crónico, donde la fisiopatologia de cada uno de ellos es importante para entender el mecanismo de daño renal. La presente revisión tiene como objetivo analizar, tanto la fisiopatología y manifestaciones clínicas de la nefrotoxicidad asociada a dichos metales, como los diferentes estudios que se han realizado en humanos y animales.

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.

Interstitial Nephritis Caused by Anorexia Nervosa in Young Male; A Case Report and Literature Review

Severe eating disorders characterized by repetitive episodes of purging and vomiting can occasionally trigger acute kidney injury. However, interstitial nephritis induced by episodes of repeated vomiting has rarely been reported, and the pathophysiology of this entity remains unknown. A 26-year-old man was admitted to our hospital because of known hypokalemia. His serum electrolyte profile showed: sodium 133 mEq/L, potassium 2.6 mEq/L, chloride 72 mEq/L, total carbon dioxide 50 mEq/L, blood urea nitrogen/creatinine ratio (BUN/Cr) 21.9/1.98 mg/dL, and magnesium 2.0 mg/dL. Arterial blood gas analysis showed: pH 7.557, partial pressure of carbon dioxide 65.8 mmHg, and bicarbonate 58.5 mEq/L. His urinary potassium concentration was 73.2 mEq/L, and Cr was 111 mg/dL. Renal biopsy revealed acute tubular necrosis and tubulointerstitial nephritis with a few shrunken glomeruli. Repeated psychogenic vomiting may precipitate acute kidney injury and interstitial nephritis secondary to volume depletion and hypokalemia. Serum electrolyte levels and renal function should be carefully monitored in patients diagnosed with eating disorders to prevent tubular ischemia and interstitial nephritis.

Lesión renal rápidamente progresiva como presentación de necrosis tubular aguda de origen incierto en un maratonista. Diagnóstico diferencial nо siempre sencillo / Rapidly progressive renal injury as a manifestation of acute tubular necrosis with an uncertain origin in a marathonist: A differential diagnosis is not always simple

Resumen El síndrome de deterioro rápidamente progresivo de la función renal, corresponde a una forma de lesión renal aguda que cursa con un decremento acelerado y progresivo de la tasa de filtrado glomerular en horas a días o semanas. Una vez descartadas las causas prerrenales, es necesario establecer el diagnóstico diferencial con causas glomerulares, vasculares renales (trombosis), obstructivas, nefritis intersticial y necrosis tubular aguda. Se presenta un caso de deterioro rápidamente progresivo de la función renal, que fue manejado con esteroide intravenoso y plasma fresco congelado, por la probabilidad diagnóstica de microangiopatía trombótica, nefritis intersticial y glomerulonefritis rápidamente progresiva (GNRP). Posteriormente, se confirmó el diagnóstico de necrosis tubularaguda mediante biopsia renal, sin habertenidoalgún antecedente evidente que sugiriera la presencia y etiología de dicha entidad.

Abstract The rapidly progressive renal failure syndrome corresponds to an acute kidney injury that causes an accelerated decrease of the glomerular filtration rate in hours to days or weeks. After pre-renal causes were dismissed, a differential diagnosis with glomerularcauses, vascularcauses (thrombosis), obstructive causes, interstitial nephritis and acute tubular necrosis must be established. We describe the case of a rapidly progressive decline of the renal function that was managed with intravenous steroids and freshly frozen plasma due to the diagnostic probability of thrombotic microangiopathy, interstitial nephritis and rapidly progressive glomerulonephritis. Subseguently, an acute tubular necrosis was confirmed by a renal biopsy without any previous clinical evidence suggesting a clear presence or etiology of this entity.

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)

Diagnóstico de necrosis tubular aguda en pacientes egresados fallecidos / Diagnosis of acute tubular necrosis in deceased patients

Introducción: el diagnóstico histopatológico de necrosis tubular aguda, generalmente de causa isquémica o nefrotóxica, se encuentra muy relacionado con el desarrollo de insuficiencia renal aguda. Objetivo: analizar la presencia de diagnóstico histopatológico de necrosis tubular aguda en los egresados fallecidos autopsiados y explorar la relación con posibles factores favorecedores. Métodos: estudio retrospectivo, observacional de las autopsias en el Hospital Militar Central Dr. Luis Díaz Soto, en el período 1962 al 2015. Se estableció en ellas el diagnóstico histopatológico de necrosis tubular aguda y se analizó el comportamiento de variables demográficas, clínicas y anatomopatológicas. Resultados: se registraron 843 341 egresados, de ellos 25 213 fallecidos (índice de mortalidad 3,0), se realizaron 18 630 autopsias (índice autopsia 75,3 por ciento), en estas se estableció diagnóstico de necrosis tubular aguda en 6.264 (33,6 por ciento). Predominaron los pacientes masculinos y los mayores de 45 años de edad. El shock (22,3 por ciento), la bronconeumonía (16,3 por ciento), la aterosclerosis coronaria(18,5 por ciento) y el edema pulmonar (11,3 por ciento) constituyeron las principales causas directas de muerte. La aterosclerosis coronaria (18,5 por ciento) fue la principal causa básica de muerte. Conclusiones: se registró un incremento sostenido de egresos, de fallecidos y de autopsias practicadas, así como del diagnóstico histopatológico de necrosis tubular aguda. Predominaron los pacientes del sexo masculino y aquellos mayores de 45 años de edad. Las principales causas directas de muerte en estos fueron el shock, la bronconeumonía y el edema pulmonar. La aterosclerosis fue la principal causa básica de muerte(AU)

Introduction: The histopathological diagnosis of acute tubular necrosis, usually of ischemic or nephrotoxic cause, is closely related to the development of acute renal failure. Objective: To analyze the presence of histopathological diganosis of acute tubular necrosis in deceased autopsied and to explore the relationship with possible favoring factors. Method: Retrospective, observational study, with descriptive statistical study of the autopsies at the Central Military Hospital Dr. Luis Díaz Soto in the period from 1962 to 2015. The histopathological diagnosis of acute tubular necrosis was done and demographic, clinical and anatomopathological variables were analyzed. Results: 843 341 discharged from hospital were recorded, of which 25 213 died (mortality rate 3.0), 18 630 autopsies were performed (autopsy rate 75.3 percent). In these cases a diagnosis of acute tubular necrosis was done in 6 264 (33.6 percent). Male patients and those over 45 years of age predominated. Shock (22.3 percent), bronchopneumonia (16.3 percent), coronary atherosclerosis (18.5 percent) and pulmonary edema (11.3 percent) were the main direct causes of death. Coronary atherosclerosis (18.5 percent) was the main underlying cause of death. Conclusions: There was a sustained increase in discharged patients, deaths and autopsies, as well as the histopathological diagnosis of acute tubular necrosis. Male patients predominated and those older than 45 years of age. The main direct causes of death in these were shock, bronchopneumonia and pulmonary edema. Atherosclerosis was the leading cause of death(AU)

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.

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.