Inflammatory milieu as an early marker of kidney injury in offspring rats from diabetic mothers

The present study investigated the early presence of inflammatory response in renal tissue of young offspring from diabetic mothers. The effect of L-arginine (L-arg) supplementation was also investigated. The offspring was divided into four groups: group CO (controls); group DO (diabetic offspring); group CA (CO receiving 2% L-arg solution) and group DA (DO receiving the 2% L-arg solution). Glycemia, arterial pressure and renal function were evaluated; gene and protein expression of pro-inflammatory cytokines were also measured. Blood pressure levels were significantly increased in 2 and 6 month-old DO rats, whereas L-arg administration caused a significant decrease in the DA group, at both ages. DO rats showed a significantly blunted glycemic response to exogenous insulin. In 2 month-old DO animals, renal protein expression of pro-inflammatory molecules was significantly increased. At six months of age, we also observed an increase in gene expression of pro-inflammatory molecules, whereas L-arg supplementation prevented this increase at both ages. Our data suggest that activation of inflammatory pathways is present early in the kidney of DO rats, and that L-arg can attenuate the expression of these markers of tissue inflammation. Our results also reinforce the concept that intrauterine environmental factors are a fundamental determinant in the development of metabolic and vascular diseases later in life. (C) 2012 Elsevier B.V. All rights reserved.

TLR2, TLR4 and the MYD88 Signaling Pathway Are Crucial for Neutrophil Migration in Acute Kidney Injury Induced by Sepsis

The aim of this study was to investigate the role of TLR2, TLR4 and MyD88 in sepsis-induced AKI. C57BL/6 TLR2(-/-), TLR4(-/-) and MyD88(-/-) male mice were subjected to sepsis by cecal ligation and puncture (CLP). Twenty four hours later, kidney tissue and blood samples were collected for analysis. The TLR2(-/-), TLR4(-/-) and MyD88(-/-) mice that were subjected to CLP had preserved renal morphology, and fewer areas of hypoxia and apoptosis compared with the wild-type C57BL/6 mice (WT). MyD88(-/-) mice were completely protected compared with the WT mice. We also observed reduced expression of proinflammatory cytokines in the kidneys of the knockout mice compared with those of the WT mice and subsequent inhibition of increased vascular permeability in the kidneys of the knockout mice. The WT mice had increased GR1(+low) cells migration compared with the knockout mice and decreased in GR1(+high) cells migration into the peritoneal cavity. The TLR2(-/-), TLR4(-/-), and MyD88(-/-) mice had lower neutrophil infiltration in the kidneys. Depletion of neutrophils in the WT mice led to protection of renal function and less inflammation in the kidneys of these mice. Innate immunity participates in polymicrobial sepsis-induced AKI, mainly through the MyD88 pathway, by leading to an increased migration of neutrophils to the kidney, increased production of proinflammatory cytokines, vascular permeability, hypoxia and apoptosis of tubular cells.

Functional independence in patients with chronic kidney disease being treated with haemodialysis

Purpose: This study has described and analysed the functional independence of the patients served in the haemodialysis services of a countryside town in the State of Sao Paulo, Brazil, using the Functional Independence Measure (FIM). Method: The population considered was that of 214 patients being treated with haemodialysis, assessed in 2011, by means of a social, demographic and clinical report, a Mini-Mental State Examination (MMSE) and also the FIM. Results: The mean age of the population under study was 58.01 years, while the mean FIM point score was 118.38 points, showing a level of complete or modified independence within this population. Even though the level of dependence found has been low, this can be highlighted, within the locomotion domain, in the activity of going up and down stairs (10.28%). Age, complications arising from haemodialysis, and comorbidities show a negative correlation with FIM. Conclusion: Awareness of the level of functional independence of the patients being subjected to treatment with haemodialysis is essential in order to back up intervention for the improvement of nursing assistance provided to this population.

N-acetylcysteine (NAC) Protects Against Acute Kidney Injury (AKI) Following Prolonged Pneumoperitoneum in the Rat

Background. Acute kidney injury (AKI) following prolonged laparoscopy is a documented phenomenon. Carbon dioxide pneumoperitoneum induces oxidative stress. Previous experimental studies have shown that the antioxidant, N-acetylcysteine, protects the rat from AKI following ischemia-reperfusion. The aim of this study was to evaluate the effects of N-acetylcysteine (NAC) on rat renal function after prolonged pneumoperitoneum. Methods. Normal rats treated or not with NAC were submitted to abdominal CO2 insufflation of 10 mmHg, at short and long periods of time of 1 and 3 h, respectively, and evaluated at 24, 72 h, and 1 wk after deinsufflation. Glomerular filtration rate (GFR) was measured by inulin clearance and oxidative stress was evaluated by serum thiobarbituric acid reactive substances (TBARS) Results. No significant alterations in GFR were observed in normal animals submitted to the pneumoperitoneum of 1 h and evaluated after 24 h desufflation. With 3 h of pneumoperitoneum, a significant and progressive decrease in GFR occurred 24 and 72 h after desufflation with an increase in serum TBARS. GFR returned to normal levels a week later. In the NAC-treated rats, a complete protection against GFR drops was observed 24 and 72 h following 3 h of pneumoperitoneum associated with a decrease in TBARS. Conclusion. These results suggest that NAC protects against acute kidney injury following prolonged pneumoperitoneum. These findings have significant clinical implications. (C) 2012 Elsevier Inc. All rights reserved.

Ethanol consumption increases the expression of endothelial nitric oxide synthase, inducible nitric oxide synthase and metalloproteinases in the rat kidney

Objectives The effects of longterm ethanol consumption on the levels of nitric oxide (NO) and the expression of endothelial NO synthase (eNOS), inducible NO synthase (iNOS) and metalloproteinase-2 (MMP-2) were studied in rat kidney. Methods Male Wistar rats were treated with 20% ethanol (v/v) for 6 weeks. Nitrite and nitrate generation was measured by chemiluminescence. Protein and mRNA levels of eNOS and iNOS were assessed by immunohistochemistry and quantitative real-time polymerase chain reaction, respectively. MMP-2 activity was determined by gelatin zymography. Histopathological changes in kidneys and indices of renal function (creatinine and urea) and tissue injury (mitochondrial respiration) were also investigated. Results Chronic ethanol consumption did not alter malondialdehyde levels in the kidney. Ethanol consumption induced a significant increase in renal nitrite and nitrate levels. Treatment with ethanol increased mRNA expression of both eNOS and iNOS. Immunohistochemical assays showed increased immunostaining for eNOS and iNOS after treatment with ethanol. Kidneys from ethanol-treated rats showed increased activity of MMP-2. Histopathological investigation of kidneys from ethanol-treated animals revealed tubular necrosis. Indices of renal function and tissue injury were not altered in ethanol-treated rats. Conclusions Ethanol consumption increased renal metalloproteinase expression/activity, which was accompanied by histopathological changes in the kidney and elevated NO generation. Since iNOS-derived NO and MMPs contribute to progressive renal injury, the increased levels of NO and MMPs observed in ethanol-treated rats might contribute to progressive renal damage.

Somatotroph pituitary adenoma with acromegaly and autosomal dominant polycystic kidney disease: SSTR5 polymorphism and PKD1 mutation

A 39-year-old woman with autosomal dominant polycystic kidney disease (ADPKD) presented with acromegaly and a pituitary macroadenoma. There was a family history of this renal disorder. She had undergone surgery for pituitary adenoma 6 years prior. Physical examination disclosed bitemporal hemianopsia and elevation of both basal growth hormone (GH) 106 ng/mL (normal 0-5) and insulin-like growth factor (IGF-1) 811 ng/mL (normal 48-255) blood levels. A magnetic resonance imaging scan disclosed a 3.0 cm sellar and suprasellar mass with both optic chiasm compression and left cavernous sinus invasion. Pathologic, cytogenetic, molecular and in silico analysis was undertaken. Histologic, immunohistochemical and ultrastructural studies of the lesion disclosed a sparsely granulated somatotroph adenoma. Standard chromosome analysis on the blood sample showed no abnormality. Sequence analysis of the coding regions of PKD1 and PKD2 employing DNA from both peripheral leukocytes and the tumor revealed the most common PKD1 mutation, 5014_5015delAG. Analysis of the entire SSTR5 gene disclosed the variant c.142C > A (p.L48M, rs4988483) in the heterozygous state in both blood and tumor, while no pathogenic mutations were noted in the MEN1, AIP, p27Kip1 and SSTR2 genes. To our knowledge, this is the fourth reported case of a GH-producing pituitary adenoma associated with ADPKD, but the first subjected to extensive morphological, ultrastructural, cytogenetic and molecular studies. The physical proximity of the PKD1 and SSTR5 genes on chromosome 16 suggests a causal relationship between ADPKD and somatotroph adenoma.

Recipient of kidney from donor with asymptomatic infection by Paracoccidioides brasiliensis

The increase in solid organ transplantations may soon create a rise in the occurrence of endemic fungal diseases, such as paracoccidioidomycosis, due to the lack of rigorous screening of donors from endemic areas. Here we present the first case of an immunocompetent and asymptomatic kidney donor who had Paracoccidioides brasiliensis infected-adrenal tissue but no glandular dysfunction.

Leptin as a link between the immune system and kidney-related diseases: leading actor or just a coadjuvant?

Food intake and nutritional status modify the physiological responses of the immune system to illness and infection and regulate the development of chronic inflammatory processes, such as kidney disease. Adipose tissue secretes immune-related proteins called adipokines that have pleiotropic effects on both the immune and neuroendocrine systems, linking metabolism and immune physiology. Leptin, an adipose tissue-derived adipokine, displays a variety of immune and physiological functions, and participates in several immune responses. Here, we review the current literature on the role of leptin in kidney diseases, linking adipose tissue and the immune system with kidney-related disorders. The modulation of this adipose hormone may have a major impact on the treatment of several immune- and metabolic-related kidney diseases.

Physicochemical analysis of blood and urine in the course of acute kidney injury in critically ill patients: a prospective, observational study

Abstract Background Sequential physicochemical alterations in blood and urine in the course of acute kidney injury (AKI) development have not been previously described. We aimed to describe these alterations in parallel to traditional renal and acid–base parameters. Methods One hundred and sixty eight consecutive critically ill patients with no previous kidney disease, who had an indwelling urinary catheter at ICU admission and who remained with the catheter for at least two days without dialysis were included. A sample of blood and spot urine were collected simultaneously, once daily, until catheter removal or dialysis requirement. Traditional acid–base and renal parameters were sequentially evaluated in parallel to blood and urinary physicochemical parameters. Patients were classified during this period as having or not AKI and, for patients with AKI, duration (transient or persistent) and severity (creatinine-based AKIN stage) were evaluated. Results One hundred and thirteen patients (67.3%) had AKI: 92 at ICU admission and 21 during the observation period. AKI development was characterized in blood by increased values of phosphate and unmeasured anions (SIG), decreased albumin, and in urine by decreased values of sodium (NaU), chloride (ClU) as well as high urinary strong ion difference (SIDu). These alterations began to occur before AKI diagnosis, and they reverted in transient AKI but remained in persistent AKI. NaU, ClU and albumin decreased, and phosphate, SIG and SIDu increased with AKI severity progression. NaU and ClU values increased again when AKIN stage 3 was reached. Conclusions Simultaneous physicochemical analysis of blood and urine revealed standardized alterations that characterize AKI development in critically ill patients. These alterations paralleled AKI duration and severity. Future studies should consider including sequential evaluation of urine biochemistry as part of the armamentarium for AKI diagnosis and management.

The imaging and pathological features of a mucinous tubular and spindle cell carcinoma of the kidney: a case report

A mucinous tubular and spindle cell carcinoma (MTSCC) is a rare and recently described kidney neoplasm with distal nephron differentiation. It can affect patients of all ages and is more prevalent among women. In this case report, we present a 50-year-old woman who had a renal mass, which was accidently discovered during an investigation for chronic anemia. The final diagnosis of MTSCC was made after the lesion was removed and a pathology work-up was performed. The clinical, pathological and imaging findings of this rare neoplasm are described in this report.

Does long-term creatine supplementation impair kidney function in resistance-trained individuals consuming a high-protein diet?

Abstract Background The aim of this study was to determine the effects of creatine supplementation on kidney function in resistance-trained individuals ingesting a high-protein diet. Methods A randomized, double-blind, placebo-controlled trial was performed. The participants were randomly allocated to receive either creatine (20 g/d for 5 d followed by 5 g/d throughout the trial) or placebo for 12 weeks. All of the participants were engaged in resistance training and consumed a high-protein diet (i.e., ≥ 1.2 g/Kg/d). Subjects were assessed at baseline (Pre) and after 12 weeks (Post). Glomerular filtration rate was measured by 51Cr-EDTA clearance. Additionally, blood samples and a 24-h urine collection were obtained for other kidney function assessments. Results No significant differences were observed for 51Cr-EDTA clearance throughout the trial (Creatine: Pre 101.42 ± 13.11, Post 108.78 ± 14.41 mL/min/1.73m2; Placebo: Pre 103.29 ± 17.64, Post 106.68 ± 16.05 mL/min/1.73m2; group x time interaction: F = 0.21, p = 0.64). Creatinine clearance, serum and urinary urea, electrolytes, proteinuria, and albuminuria remained virtually unchanged. Conclusions A 12-week creatine supplementation protocol did not affect kidney function in resistance-trained healthy individuals consuming a high-protein diet; thus reinforcing the safety of this dietary supplement. Trial registration ClinicalTrials.gov NCT01817673

Common bile duct stones: analysis of the videolaparoscopic surgical treatment

CONTEXT: About 9% of the Brazilian population has gallstones and the incidence increases significantly with aging. The choledocholithiasis is found around 15% of these patients, and a third to half of these cases presented as asymptomatic. Once the lithiasis in the common bile duct is characterized through intraoperative cholangiography, the laparoscopic surgical exploration can be done through the transcystic way or directly through choledochotomy. OBJECTIVE: To evaluate the results and outcomes of the laparoscopic treatment of common bile duct lithiasis. METHODS: Seventy consecutive patients were evaluated. They prospectively underwent the treatment of the lithiasis in the common bile duct and the exploration ways were compared according to the following parameters: criteria on their indication, success in the clearance, surgical complications. It was verified that about ½ of the choledocholithiasis carriers did not show any expression of predictive factors (clinical antecedents of jaundice and/or acute pancreatitis, compatible sonographic data and the pertaining lab tests). The laparoscopic exploration through the transcystic way is favored when there are no criteria for the practice of primary choledochotomy, which are: lithiasis in the proximal bile duct, large (over 8 mm) or numerous calculi (multiple calculosis). RESULTS: The transcystic way was employed in about 50% of the casuistic and the choledochotomy in about 30%. A high success rate (around 80%) was achieved in the clearance of the common bile duct stones through laparoscopic exploration. The transcystic way, performed without fluoroscopy or choledochoscopy, attained a low rate of success (around 45%), being 10% of those by transpapilar pushing of calculi less than 3 mm. The exploration through choledochotomy, either primary or secondary, if the latter was performed after the transcystic route failure, showed high success rate (around 95%). When the indication to choledochotomy was primary, the necessity for choledochoscopy through choledochotomy to help in the removal of the calculi was 55%. However, when choledochotomy was performed secondarily, in situations where the common bile duct diameter was larger than 6 mm, the use of choledochoscopy with the same purpose involved about 20% of the cases. There was no mortality in this series. CONCLUSION: The laparoscopic exploration of the common bile duct was related to a low rate of morbidity. Therefore, the use of laparoscopy for the treatment of the lithiasis in the common bile duct depends on the criteria for the choice of the best access, making it a safe procedure with very good results.

Functional independence in patients with chronic kidney disease being treated with haemodialysis¹

PURPOSE: This study has described and analysed the functional independence of the patients served in the haemodialysis services of a countryside town in the State of São Paulo, Brazil, using the Functional Independence Measure (FIM). METHOD: The population considered was that of 214 patients being treated with haemodialysis, assessed in 2011, by means of a social, demographic and clinical report, a Mini-Mental State Examination (MMSE) and also the FIM. RESULTS: The mean age of the population under study was 58.01 years, while the mean FIM point score was 118.38 points, showing a level of complete or modified independence within this population. Even though the level of dependence found has been low, this can be highlighted, within the locomotion domain, in the activity of going up and down stairs (10.28%). Age, complications arising from haemodialysis, and comorbidities show a negative correlation with FIM. CONCLUSION: Awareness of the level of functional independence of the patients being subjected to treatment with haemodialysis is essential in order to back up intervention for the improvement of nursing assistance provided to this population.

Hepatocyte nuclear factors 1α/4α and forkhead box A2 regulate the solute carrier 2A2 (Slc2a2) gene expression in the liver and kidney of diabetic rats

AIMS: Solute carrier 2a2 (Slc2a2) gene codifies the glucose transporter GLUT2, a key protein for glucose flux in hepatocytes and renal epithelial cells of proximal tubule. In diabetes mellitus, hepatic and tubular glucose output has been related to Slc2a2/GLUT2 overexpression; and controlling the expression of this gene may be an important adjuvant way to improve glycemic homeostasis. Thus, the present study investigated transcriptional mechanisms involved in the diabetes-induced overexpression of the Slc2a2 gene. MAIN METHODS: Hepatocyte nuclear factors 1α and 4α (HNF-1α and HNF-4α), forkhead box A2 (FOXA2), sterol regulatory element binding protein-1c (SREBP-1c) and the CCAAT-enhancer-binding protein (C/EBPβ) mRNA expression (RT-PCR) and binding activity into the Slc2a2 promoter (electrophoretic mobility assay) were analyzed in the liver and kidney of diabetic and 6-day insulin-treated diabetic rats. KEY FINDINGS: Slc2a2/GLUT2 expression increased by more than 50% (P<0.001) in the liver and kidney of diabetic rats, and 6-day insulin treatment restores these values to those observed in non-diabetic animals. Similarly, the mRNA expression and the binding activity of HNF-1α, HNF-4α and FOXA2 increased by 50 to 100% (P<0.05 to P<0.001), also returning to values of non-diabetic rats after insulin treatment. Neither the Srebf1 and Cebpb mRNA expression, nor the SREBP-1c and C/EBP-β binding activity was altered in diabetic rats. SIGNIFICANCE: HNF-1α, HNF-4α and FOXA2 transcriptional factors are involved in diabetes-induced overexpression of Slc2a2 gene in the liver and kidney. These data point out that these transcriptional factors are important targets to control GLUT2 expression in these tissues, which can contribute to glycemic homeostasis in diabetes.