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.

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.

Anatrophic Nephrotomy as Nephron-Sparing Approach for Complete Removal of Intraparenchymal Renal Tumors

Objective: Partial nephrectomy for small kidney tumors has increased in the last decades, and the approach to non-palpable endophytic tumors became a challenge, with larger chances of positive margins or complications. The aim of this study is to describe an alternative nephron-sparing approach for small endophytic kidney tumors through anatrophic nephrotomy. Patients and Methods: A retrospective analysis of patients undergoing partial nephrectomy at our institution was performed and the subjects with endophytic tumors treated with anatrophic nephrotomy were identified. Patient demographics, perioperative outcomes and oncological results were evaluated. Results: Among the partial nephrectomies performed for intraparenchymal tumors between 06/2006 and 06/2010, ten patients were submitted to anatrophic nephrotomy. The mean patient age was 42 yrs, and the mean tumor size was 2.3 cm. Mean warm ischemia time was 22.4 min and the histopathological analysis showed 80% of clear cell carcinomas. At a mean follow-up of 36 months, no significant creatinine changes or local or systemic recurrences were observed. Conclusion: The operative technique described is a safe and effective nephron-sparing option for complete removal of endophytic renal tumors.

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.

Annexin-A1 peptide down-regulates the leukocyte recruitment and up-regulates interleukin-10 release into lung after intestinal ischemia-reperfusion in mice

Abstract Background Intestinal ischemia/reperfusion (IR) injury is a serious and triggering event in the development of remote organ dysfunction, from which the lung is the main target. This condition is characterized by intense neutrophil recruitment, increased microvascular permeability. Intestinal IR is also responsible for induction of adult respiratory distress syndrome, the most serious and life-threatening form of acute lung injury. The purpose of this study was to investigate the effect of annexin-A1 protein as an endogenous regulator of the organ remote injury induced by intestinal ischemia/reperfusion. Male C57bl/6 mice were subjected to intestinal ischemia, induced by 45 min occlusion of the superior mesenteric artery, followed by reperfusion. Results The intestinal ischemia/reperfusion evoked a high intensity lung inflammation as indicated by the number of neutrophils as compared to control group. Treatment with annexin-A1 peptidomimetic Ac2-26, reduced the number of neutrophils in the lung tissue and increased its number in the blood vessels, which suggests a regulatory effect of the peptide Ac2-26 in the neutrophil migration. Moreover, the peptide Ac2-26 treatment was associated with higher levels of plasma IL-10. Conclusion Our data suggest that the annexin-A1 peptidomimetic Ac2-26 treatment has a regulatory and protective effect in the intestinal ischemia/reperfusion by attenuation of the leukocyte migration to the lung and induction of the anti-inflammatory cytokine IL-10 release into the plasma. The anti-inflammatory action of annexin-A1 and its peptidomimetic described here may serve as a basis for future therapeutic approach in mitigating inflammatory processes due to intestinal ischemia/reperfusion.

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

Sinvastatina e lesão renal aguda isquêmica em ratos

OBJETIVOS: O estudo visou verificar a ação renoprotetora da sinvastatina em modelo animal de isquemia/reperfusão por 30 minutos. MÉTODOS: A isquemia foi obtida por meio do clampeamento dos pedículos renais bilaterais por 30 minutos, seguida de reperfusão. Ratos Wistar, machos foram usados pesando entre 250-300g, distribuídos nos seguintes grupos: SHAM (controle, sem clampeamento renal); Isquemia (isquemia renal por 30 minutos); Isquemia+Estatina (sinvastatina 0,5 mg/kg, via oral durante três dias). A função renal (clearance de creatinina, método de Jaffé), a osmolalidade urinária, os peróxidos urinários foram avaliados. RESULTADOS: Os resultados mostraram que a estatina melhorou a função renal, a osmolalidade urinária e reduziu a excreção de PU. CONCLUSÃO: Em síntese, o estudo confirmou o efeito renoprotetor da estatina, com ação antioxidante de proteção renal.

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.

Robotic-assisted laparoscopic partial nephrectomy: initial experience in Brazil and a review of the literature

CONTEXT AND PURPOSE: Partial nephrectomy has become the standard of care for renal tumors less than 4 cm in diameter. Controversy still exists, however, regarding the best surgical approach, especially when minimally invasive techniques are taken into account. Robotic-assisted laparoscopic partial nephrectomy (RALPN) has emerged as a promising technique that helps surgeons achieve the standards of open partial nephrectomy care while offering a minimally invasive approach. The objective of the present study was to describe our initial experience with robotic-assisted laparoscopic partial nephrectomy and extensively review the pertinent literature. MATERIALS AND METHODS: Between August 2009 and February 2010, eight consecutive selected patients with contrast enhancing renal masses observed by CT were submitted to RALPN in a private institution. In addition, we collected information on the patients' demographics, preoperative tumor characteristics and detailed operative, postoperative and pathological data. In addition, a PubMed search was performed to provide an extensive review of the robotic-assisted laparoscopic partial nephrectomy literature. RESULTS: Seven patients had RALPN on the left or right sides with no intraoperative complications. One patient was electively converted to a robotic-assisted radical nephrectomy. The operative time ranged from 120 to 300 min, estimated blood loss (EBL) ranged from 75 to 400 mL and, in five cases, the warm ischemia time (WIT) ranged from 18 to 32 min. Two patients did not require any clamping. Overall, no transfusions were necessary, and there were no intraoperative complications or adverse postoperative clinical events. All margins were negative, and all patients were disease-free at the 6-month follow-up. CONCLUSIONS: Robotic-assisted laparoscopic partial nephrectomy is a feasible and safe approach to small renal cortical masses.Further prospective studies are needed to compare open partial nephrectomy with its minimally invasive counterparts.