Can paricalcitol increase the effectiveness of n-acetylcysteine in contrast induced acute kidney prophylaxis in rats? A biochemical and histopathological study / ¿Puede el paricalcitol aumentar la eficacia de la n-acetilcisteína en la profilaxis renal aguda inducida por contraste en ratas? Un estudio bioquímico e histopatológico

SUMMARY: N-Acetylcysteine (NAC) is used for contrast induced acut kidney injury (CI-AKI) prophylaxis because of its antioxidant effects. Paricalcitol, which has reno-protective effects, is likely to provide a more effective prophylaxis when added to NAC treatment. The study was designed based on this hypothesis. The study was organised to include 4 groups each consisting of 7 rats. Group 1 was the control group, and Group 2 included rats with CI-AKI. Rats in Group 3 were administered NAC at a dose of 100 mg/kg via oral gavage once a day for 5 days. Rats in group 4 were administered paricalcitol at a dose of 0.4 mcg/kg once a day for 5 days in addition to NAC. CI-AKI was induced after the treatments in both groups. The study was terminated on the sixth day. Samples were collected from the rats' sera and kidney tissues to study oxidant and antioxidant parameters; kidney function tests were also studied. There were significant differences between the contrast nephropathy group (Group 2) and NAC and NAC+paricalcitol groups with respect to serum urea and creatinine levels. When the same groups were compared regarding oxidant (TOS-MDA) and antioxidant (TAC-Paraoxonase) parameters, we observed that the oxidant parameters increased in serum and kidney tissue samples with NAC use, and that effect was strengthened by the addition of paricalcitol to NAC treatment. However, despite increased antioxidant effectiveness, we observed no decrease in urea and creatinine levels when paricalcitol was added for CI-AKI in rats. There was no significant difference between Group 3 and Group 4. Paricalcitol provides a more potent antioxidant effect in both serum and kidney tissue samples when added to NAC treatment in rats with CI-AKI. Despite increased antioxidant parameters, however, paricalcitol does not provide a significant decrease in urea and creatinine levels.

RESUMEN: Debido a sus efectos atioxidantes la N- acetilcisteína (NAC) se usa para la profilaxis de la lesión renal aguda inducida por contraste (CI-AKI). Es probable que el paricalcitol, que tiene efectos renoprotectores, proporcione una profilaxis más eficaz cuando se agrega al tratamiento con NAC. En base a esta hipótesis el estudio fue diseñado para incluir cuatro grupos cada uno compuesto por siete ratas. El grupo 1 fue el grupo control y el grupo 2 incluyó ratas con CI-AKI. A las ratas del Grupo 3 se les administró NAC con una dosis de 100 mg/kg por sonda oral una vez al día, durante 5 días. A las ratas del grupo 4 se les administró paricalcitol a una dosis de 0,4 mcg/kg una vez al día durante 5 días, además de NAC. Se indujo CI-AKI después de los tratamientos en ambos grupos. El estudio finalizó el sexto día. Se recolectaron muestras de suero y tejidos renales de ratas para estudiar los parámetros oxidantes y antioxidantes; También se estudiaron las pruebas de función renal. Hubo diferencias significativas entre el grupo de nefropatía por contraste (Grupo 2) y los grupos NAC y NAC+paricalcitol con respecto a los niveles séricos de urea y creatinina. Cuando se compararon los mismos grupos con respecto a los parámetros oxidantes (TOS-MDA) y antioxidantes (TAC-Paraoxonase), observamos que los parámetros oxidantes aumentaron en muestras de suero y tejido renal con el uso de NAC, y ese efecto se vio reforzado por la adición de paricalcitol a tratamiento NAC. Sin embargo, a pesar de una mayor eficacia antioxidante, no observamos una disminución en los niveles de urea y creatinina cuando se agregó paricalcitol para CI-AKI en ratas. No hubo diferencias significativas entre el Grupo 3 y el Grupo 4. El paricalcitol proporciona un efecto antioxidante más potente tanto en muestras de suero como de tejido renal cuando se agrega al tratamiento con NAC en ratas con CI-AKI. Sin embargo, a pesar del aumento de los parámetros antioxidantes, el paricalcitol no proporciona una disminución sig- nificativa en los niveles de urea y creatinina.

Evaluation of the effect of intraperitoneal etanercept administration on oxidative stress and inflammation indicators in the kidney and blood of experimental sepsis-induced rats.

INTRODUCTION: Sepsis is an important cause of mortality and morbidity, and inflammatory response and oxidative stress play major roles underlying its pathophysiology. Here, we evaluated the effect of intraperitoneal etanercept administration on oxidative stress and inflammation indicators in the kidney and blood of experimental sepsis-induced rats. METHODS: Twenty-eight adult Sprague Dawley rats were classified into Control (Group 1), Sepsis (Group 2), Sepsis+Cefazolin (Group 3), and Sepsis+Cefazolin+Etanercept (Group 4) groups. Kidney tissue and serum samples were obtained for biochemical and histopathological investigations and examined for the C reactive protein (CRP), tumor necrosis factor-alpha (TNF-α), triggering receptor expressed on myeloid cells (TREM), and malondialdehyde (MDA) levels. RESULTS: The levels of TNF-α, TREM, and MDA in serum and kidney samples were significantly higher in rats from sepsis group than in rats from control group (p < 0.05). Group 3 showed a significant reduction in serum levels of TNF-α, CRP, and TREM as compared with Group 2 (p < 0.05). Serum TNF-α, CRP, TREM, and MDA levels and kidney TNF-α and TREM levels were significantly lower in Group 4 than in Group 2 (p < 0.05). Serum TNF-α and TREM levels in Group 4 were significantly lower than those in Group 3, and histopathological scores were significantly lower in Group 3 and Group 4 than in Group 2 (p < 0.05). Histopathological scores of Group 4 were significantly lower than those of Group 3 (p < 0.05). CONCLUSIONS: Etanercept, a TNF-α inhibitor, may ameliorate sepsis-induced oxidative stress, inflammation, and histopathological damage.

Evaluation of the effect of intraperitoneal etanercept administration on oxidative stress and inflammation indicators in the kidney and blood of experimental sepsis-induced rats

Abstract INTRODUCTION: Sepsis is an important cause of mortality and morbidity, and inflammatory response and oxidative stress play major roles underlying its pathophysiology. Here, we evaluated the effect of intraperitoneal etanercept administration on oxidative stress and inflammation indicators in the kidney and blood of experimental sepsis-induced rats. METHODS: Twenty-eight adult Sprague Dawley rats were classified into Control (Group 1), Sepsis (Group 2), Sepsis+Cefazolin (Group 3), and Sepsis+Cefazolin+Etanercept (Group 4) groups. Kidney tissue and serum samples were obtained for biochemical and histopathological investigations and examined for the C reactive protein (CRP), tumor necrosis factor-alpha (TNF-α), triggering receptor expressed on myeloid cells (TREM), and malondialdehyde (MDA) levels. RESULTS: The levels of TNF-α, TREM, and MDA in serum and kidney samples were significantly higher in rats from sepsis group than in rats from control group (p < 0.05). Group 3 showed a significant reduction in serum levels of TNF-α, CRP, and TREM as compared with Group 2 (p < 0.05). Serum TNF-α, CRP, TREM, and MDA levels and kidney TNF-α and TREM levels were significantly lower in Group 4 than in Group 2 (p < 0.05). Serum TNF-α and TREM levels in Group 4 were significantly lower than those in Group 3, and histopathological scores were significantly lower in Group 3 and Group 4 than in Group 2 (p < 0.05). Histopathological scores of Group 4 were significantly lower than those of Group 3 (p < 0.05). CONCLUSIONS: Etanercept, a TNF-α inhibitor, may ameliorate sepsis-induced oxidative stress, inflammation, and histopathological damage.

Hypersensitivity and tumor lysis syndrome associated with cetuximab treatment: should we be afraid?

The majority of the chemotherapy agents in use today cause various infusion reactions, from mild flushing to life-threatening events. The frequency of the reported hypersensitivity reactions induced by cetuximab varies between 3% and 22%. It is recommended in the literature to stop the infusion and replace cetuximab with panitumumab in case of hypersensitivity reactions observed during the treatment of colon cancer. Tumor lysis syndrome (TLS) may occur in colorectal cancers with heavy tumor load. Tumor lysis syndrome may be life-threatening. In our patient with widespread bone and liver metastases, treatment continued with cetuximab as a combination therapy with irinotecan in spite of the hypersensitivity and TLS led to a complete treatment response. The complete response observed after 3 months through continued therapy in our patient may present an example supporting treatment with cetuximab in spite of severe reactions.

Acoustic radiation force impulse imaging for evaluation of renal parenchyma elasticity in diabetic nephropathy.

OBJECTIVE. The goal of this study is to evaluate the changes in the elasticity of the renal parenchyma in diabetic nephropathy using acoustic radiation force impulse imaging. SUBJECTS AND METHODS. The study included 281 healthy volunteers and 114 patients with diabetic nephropathy. In healthy volunteers, the kidney elasticity was assessed quantitatively by measuring the shear-wave velocity using acoustic radiation force impulse imaging based on age, body mass index, and sex. The changes in the renal elasticity were compared between the different stages of diabetic nephropathy and the healthy control group. RESULTS. In healthy volunteers, there was a statistically significant correlation between the shear-wave velocity values and age and sex. The shear-wave velocity values for the kidneys were 2.87, 3.14, 2.95, 2.68, and 2.55 m/s in patients with stage 1, 2, 3, 4, and 5 diabetic nephropathy, respectively, compared with 2.35 m/s for healthy control subjects. Acoustic radiation force impulse imaging was able to distinguish between the different diabetic nephropathy stages (except for stage 5) in the kidneys. The threshold value for predicting diabetic nephropathy was 2.43 m/s (sensitivity, 84.1%; specificity, 67.3%; positive predictive value, 93.1%; negative predictive value 50.8%; accuracy, 72.1%; positive likelihood ratio, 2.5; and negative likelihood ratio, 0.23). CONCLUSION. Acoustic radiation force impulse imaging could be used for the evaluation of the renal elasticity changes that are due to secondary structural and functional changes in diabetic nephropathy.

A rare cause of secondary amyloidosis: common variable immunodeficiency disease.

The common variable immunodeficiency disease (CVID) is the most common symptomatic primary antibody deficiency. It is the most frequently observed cause of panhypogammaglobulinemia in adults. Here, we present a case of systemic amyloidosis that developed secondary to the common variable immunodeficiency disease causing recurrent infections in a young female patient. A 24-year-old female patient, who was under treatment at the gynecology and obstetrics clinic for pelvic inflammatory disease, was referred to our clinic when she was observed to have swellings in her legs, hands, and face. She had proteinuria at a rate of 3.5 gr/day, and her serum albumin was 1.5 gr/dl. The levels of immunoglobulins are IgG: 138 mg/dl, IgA: 22,6 mg/dl, and IgM: 16,8 mg/dl. The renal USG revealed that the kidneys were observed to be enlarged. Since the patient had recurrent infections, hypogammaglobulinemia, nephrotic range proteinuria, and enlarged kidneys in the renal USG, she was thought to have type AA amyloidosis and therefore underwent a renal biopsy. The kidney biopsy revealed amyloid (+). So the patient was diagnosed with AA type of amyloidosis secondary to common variable immunodeficiency disease. A treatment regimen (an ACE inhibitor and a statin) with monthly administration of intravenous immunoglobulin was started.

Epidemiological and clinical aspects of liver cirrhosis in adult patients living in Southeastern Anatolia: leading role of HBV in 505 cases.

BACKGROUND/AIMS: Liver cirrhosis is the terminal condition of liver disorders resulting from various causes. Literature lacks data on epidemiological and clinical aspects of liver cirrhosis in Turkey. We aimed to evaluate the main features of liver cirrhosis in this study. METHODOLOGY: We included in the study a total of 505 patients referred to Dicle University Hospital in the last five years and evaluated retrospectively. Demographic features, etiology, clinical findings, disease severity, complications and mortality rates were all recorded. RESULTS: Of the patients, 136 (27%) were female and 369 were (73%) male. Mean age was 50.4. The etiologic spectrum consisted of 368 HBV (72.9%), 41 HCV (8.1%), 12 alcohol (2.4%). Rate for cryptogenic cirrhosis (CC) was 11.1% with mean age of 45.4. HDV superinfection was present in 17.8%. Most of the patients were in Child-Pugh class B. Number of decompensated cirrhosis cases was 278 (55%). Hepatocellular cancer (HCC) was seen in 8.9% of patients and 88% had HBV with a mean age of 60. HCC was seen more commonly in HDV superinfected patients (p = 0.035). In-patient mortality was observed in 13.2%. CONCLUSIONS: HBV is the leading etiological factor of liver cirrhosis in Southeastern Anatolia and strict measures must be taken against perinatal or horizontal transmission of contagious pathogens. Alcohol had a marginal role in cirrhosis in our region. Although HDV superinfection is decreasing with time, it may increase HCC risk. Patients with cryptogenic cirrhosis were younger and had lower Child-Pugh scores.

Acute oligo-anuric renal failure during the course of non-fulminant hepatitis A in a patient with anorexia nervosa.

Acute renal failure is a very rare complication seen during the course of non- fulminant hepatitis A. Several mechanisms have been postulated in the pathogenesis of renal failure. Firstly, there is insufficiency of renal blood flow due to developing endotoxemia or cryoglobulinemia, secondly mesangial proliferative glomerulonephritis or interstitial nephritis occurs due to immune complexes and finally there is acute tubular necrosis caused by the direct cytopathic effect of the virus or due to immune complexes. The following case report describes a 17 year old male patient admitted with complaints of appetite loss and severe weight loss due to anorexia nervosa. During the second week of admission, he developed hepatitis A infection which was complicated by acute renal failure requiring hemodialysis therapy. Hepatorenal parameters returned to normal values by the fifth week of admission in this case of biopsy proven acute tubular necrosis. In this case, the possible negative effects of malnutrition on the liver and kidneys were not observed. The present authors emphasize that during the course of non- fulminant hepatitis A, renal functions should be closely monitored and renal biopsy should be performed if acute renal failure occurs.