Renal Pedicle Research Articles

Hypothermia During Partial Nephrectomy for Patients with Renal Tumors: A Randomized Controlled Trial.

Surgeons induce renal hypothermia during partial nephrectomy to preserve kidney function, without strong evidence of benefit. This trial examined the effectiveness and safety of renal hypothermia during partial nephrectomy. We conducted a parallel randomized controlled trial of hypothermia versus no hypothermia (control group) during partial nephrectomy at 6 academic hospitals. Eligible patients had a planned open partial nephrectomy for the treatment of a renal tumor. During surgery, after clamping the renal hilum, patients were randomized to the intervention or control arm in a 1:1 ratio using permuted blocks of variable lengths (2 and 4), stratified by institution, using a computer-based program. Surgeons and study coordinators were masked to treatment allocation until the renal hilum was clamped. Overall glomerular filtration rates were determined before, and 1-year after, surgery. The primary outcome was measured glomerular filtration rate (mGFR) assessed by the plasma clearance of 99mTc-DTPA. The trial (NCT01529658) was designed with 90% power to detect a minimal clinically important difference in mGFR of 10 ml/minute/1.73 m2 at a 5% significance level. Of the 184 patients randomized, hypothermia and control patients had similar baseline mean mGFR (87.1 vs 81.0 ml/minute/1.73 m2). One hundred and sixty-one (79 hypothermia, 82 control) were alive with primary outcome data 1 year after surgery. The change in mGFR 1 year after surgery was -6.6 ml/minute/1.73 m2 in the hypothermia group and -7.8 ml/minute/1.73 m2 in the control group (mean difference 1.2 ml/minute/1.73 m2, 95% CI -3.3 to 5.6). Operated-kidney change in mGFR was similar between groups (-5.8 vs -6.3 ml/minute/1.73 m2; mean difference 0.5 ml/minute/1.73 m2, 95% CI -2.9 to 3.8). No clinically significant difference in the mGFR was observed when patients were stratified by pre-planned subgroups. Renal hypothermia did not impact the secondary outcomes of surgical complications and patient reported quality of life. Renal hypothermia during partial nephrectomy does not preserve kidney function in patients with normal or mildly impaired renal function.

Protective effect of cordycepin on experimental renal ischemia/reperfusion injury in rats.

To date, various molecules have been investigated to reduce the effect of renal ischemia/reperfusion (I/R) injury. However, none have yet led to clinical use. The present study aimed to investigate the protective effect of cordycepin (C) on renal I/R injury in an experimental rat model. Twenty-four mature Sprague Dawley female rat was randomly divided into three groups: Sham, I/R, I/R+C. All animals underwent abdominal exploration. To induce I/R injury, an atraumatic vascular bulldog clamp was applied to the right renal pedicle for 60 minutes (ischemia) and later clamp was removed to allow reperfusion in all rats, except for the sham group. In the I/R + C group, 10 mg/kg C was administered intraperitoneally, immediately after reperfusion. After 4 hours of reperfusion, the experiment was terminated with right nephrectomy. Histological studies and biochemical analyses were performed on the right nephrectomy specimens. EGTI (endothelial, glomerular, tubulointerstitial) histopathology scoring and semi-quantitative analysis of renal cortical necrosis were used for histological analyses and superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA), total oxidant status (TOS) for biochemical analyses. Histopathological examination of the tissue damage revealed that all kidneys in the sham group were normal. The I/R group had higher histopathological scores than the I/R + C group. In the biochemical analysis of the tissues, SOD, MDA, TOS values were found to be statistically different in the I/R group compared to the I/R + C group (p: 0.004, 0.004, 0.001 respectively). Intraperitoneal cordycepin injection following ischemia preserve renal tissue against oxidative stress in a rat model of renal I/R injury.

Theaflavin ameliorates renal ischemia/reperfusion injury by activating the Nrf2 signalling pathway in vivo and in vitro

Studies have demonstrated that oxidaive stress-induced apoptosis may be the main pathogenic mechanism of renal ischemia/reperfusion (I/R) injury. Theaflavin, a polyphenolic compound extracted from black tea, has been proven to exert strong antioxidant biological function. The objective of the present study was to investigate the potential role of theaflavin on renal I/R injury and its potential molecular mechanism both in vitro and in vivo. C57/BL6 J mice were used to create a model of I/R injury wherein mice were ligated with bilateral renal pedicles for 45 min, and then reperfused for 24 h. A hypoxia/reoxygenation (H/R) model of TCMK-1 cells was used to simulate I/R in vitro. Theaflavin were administered to the treatment group first and then established the model. Kidney Injury Molecule-1 (KIM-1), serum creatinine, urea nitrogen, and 24-h urinary protein levels were evaluated and changes in mitochondrial membrane potential and the ultrastructure of mitochondria were observed. Cell viability, oxidative stress damage, and apoptosis were assessed. The expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream target genes HO-1 and NQO1 were evaluated. Our results revealed that pretreatment with theaflavin significantly inhibited I/R- and H/R-induced renal injury and cell apoptosis. Theaflavin improved mitochondrial dysfunction by attenuating mitochondrial damage and promoting mitochondrial membrane potential. Theaflavin pretreatment significantly reduced malondialdehyde content, while enhancing superoxide dismutase activity in vivo and in vitro. It also reduced oxidative stress and apoptosis mainly by upregulating Nrf2 and its downstream targets in TCMK-1 cells. Thus, theaflavin exerted a protective effect against renal I/R injury by inhibiting oxidative stress and apoptosis via activation of the Nrf2-NQO1/HO-1 pathway as well as correcting mitochondrial dysfunction, thereby presenting its potential as a clinical therapeutic in cases of acute kidney injury.

Activation of aryl hydrocarbon receptor by 6-formylindolo[3,2-b]carbazole alleviated acute kidney injury by repressing inflammation and apoptosis.

Acute kidney injury (AKI) is a multifactorial disease of various aetiologies. Aryl hydrocarbon receptor (AhR) is a ligand‐activated transcription factor that responds to ligands to induce or repress gene expressions, thereby regulating a diverse spectrum of biological or pathophysiologic effects. However, the effect of AhR on AKI remains unknown. A single intraperitoneal injection of 50% glycerol was performed to induce rhabdomyolysis in C57BL/6J mice. The bilateral renal pedicles were occluded for 30 minutes and then removed to stimulate renal I/R injury. 6‐formylindolo[3,2‐b]carbazole (FICZ), a photo‐oxidation product of tryptophan with a high affinity for AhR, was used. The in vitro study was performed on HK‐2 cells. Ferrous myoglobin and FICZ was dissolved in the medium in different cell groups. Treatment with AhR agonist FICZ significantly alleviated the elevation of serum creatinine and urea in AKI. AKI modelling‐induced renal damage was attenuated by FICZ. AhR mainly expressed in proximal tubular cells and could be activated by FICZ administration. Meanwhile, AKI triggered the production of pro‐inflammatory cytokines in injured kidneys, while FICZ inhibited their expressions. Furthermore, FICZ effectively reversed cell apoptosis in AKI models. Mechanistically, AKI stimulated the activation of NF‐κB and JNK pathways in the kidneys, while FICZ significantly suppressed these corresponding protein expressions. For the in vitro study, FICZ also inhibited inflammation and apoptosis in myoglobin or H/R‐stimulated HK‐2 cells. In summary, agonism of AhR by FICZ alleviated rhabdomyolysis and I/R‐induced AKI. FICZ inhibited inflammation and apoptosis via suppressing NF‐κB and JNK pathways in proximal tubular cells.

The role of open radical nephrectomy in contemporary management of renal cell carcinoma.

Radical nephrectomy (RN) remains a cornerstone of the management of localised renal cell carcinoma (RCC). RN involves the en bloc removal of the kidney along with perinephric fat enclosed within Gerota’s fascia. Key principles of open RN include appropriate incision for adequate exposure, dissection and visualisation of the renal hilum, and early ligation of the renal artery and subsequently renal vein. Regional lymph node dissection (LND) facilitates local staging but its therapeutic role remains controversial. LND is recommended in patients with high risk clinically localised disease, but its benefit in low risk node-negative and clinically node-positive patients is unclear. Concomitant adrenalectomy should be reserved for patients with large tumours with radiographic evidence of adrenal involvement. Despite a recent downtrend in utilisation of open RN due to nephron-sparing and minimally invasive alternatives, there remains a vital role for open RN in the management of RCC in three domains. Firstly, open RN is important to the management of large, complex tumours which would be at high risk of complications if treated with partial nephrectomy (PN). Secondly, open RN plays a crucial role in cytoreductive nephrectomy (CN) for metastatic RCC, in which the laparoscopic approach achieves similar results but is associated with a high reoperation rate. Finally, open RN is the current standard of care in the management of inferior vena caval (IVC) tumour thrombus. Management of tumour thrombus requires a multidisciplinary approach and varies with cranial extent of thrombus. Higher level thrombus may require hepatic mobilisation and circulatory support, whilst the presence of bland thrombus may warrant post-operative filter insertion or ligation of the IVC.

Vitamin D3 and erythropoietin protect against renal ischemia-reperfusion injury via heat shock protein 70 and microRNA-21 expression

Kidney ischemia reperfusion (IR) contributes to the development of acute kidney injury. The hypoxic conditions in ischemic damage lead to oxidative stress and apoptotic cell death. We investigated the effects of vitamin D3 (Vit D) and erythropoietin (EPO) on microRNA-21(miR-21) expression in renal IR. Wistar rats were divided into five groups including the control, vehicle + IR, Vit D + IR, EPO + IR, and Vit D + EPO + IR groups. The animals were unilaterally nephrectomized and subjected to 45 min of renal pedicle occlusion followed by 24 h reperfusion. Vitamin D3 and EPO were administered prior to ischemia. After 24 h reperfusion, the kidney samples were collected for the detection of miR-21, heat shock protein 70 (hsp70) and caspase-3 expression levels. Kidney IR significantly increased the expression of miR-21, hsp70 and capase-3 and blood urea nitrogen (BUN)-Cr levels. Treatment with vitamin D3 and EPO significantly decreased the BUN-Cr levels and hsp70 and caspase-3 expression. Also, the co-administration of two drugs significantly increased miR-21 expression. It seems that vitamin D3 or EPO administration could protect the kidney against IR injury. However, vitamin D3 and EPO co-treatment was the most effective compared with the other treatment groups.

Renal function after partial nephrectomy following intra-arterial embolization of renal tumors

Laparoscopic Partial Nephrectomy (LPN) after intra-arterial Embolization of renal tumors (LPNE) in a hybrid operating room allows renal tumor enucleation without dissection and clamping of the renal pedicle. The purpose was to assess the potential negative impact of embolization on the renal function. This prospective monocentric study included all patients treated with LPNE between May 2015 and June 2019. Clinical data was collected and incorporated into the UroCCR database (NCT03293563). Glomerular Filtration Rate (GFR) and Computed Tomography Renal Volume (CTRV) were compared before and after 6 months following LPNE. The mean post-operative GFR was 86.6 mL/min (SD 22.9). The mean GFR loss was 9.4% (SD 15.1) and the median renal parenchyma loss was 21 mL (SD 20.6). Using a threshold of 25% GFR loss, age was the only significant predictive factor of renal function impairment according to bivariate (59.5 vs 69.3 years, p = 0.017) and multivariable analysis (OR 1.075, CI 1–1.2], p = 0.05). Significant renal function impairment was not correlated with the renal parenchymal volume loss (OR 0.987, CI [0.95–1.02], p = 0.435). Renal function impairment after LPNE seems to be comparable to other techniques of partial nephrectomy.

Propofol reduces renal ischemia/reperfusion-induced acute lung injury by stimulating sirtuin 1 and inhibiting pyroptosis.

The activation of pyroptosis is an important feature of renal ischemia/reperfusion (rI/R)-induced acute lung injury (ALI). Propofol, a general anesthetic, is known to inhibit inflammation in I/R-induced ALI. We investigated whether propofol could suppress pyroptosis during rI/R-induced ALI by upregulating sirtuin 1 (SIRT1). We generated an in vivo model of rI/R-induced ALI by applying microvascular clamps to the renal pedicles of rats for 45 min. Pathological studies revealed that rI/R provoked substantial lung injury and inflammatory cell infiltration. The rI/R stimulus markedly activated pyroptotic proteins such as NLRP3, ASC, caspase 1, interleukin-1β and interleukin-18 in the lungs, but reduced the mRNA and protein levels of SIRT1. Propofol treatment greatly inhibited rI/R-induced lung injury and pyroptosis, whereas it elevated SIRT1 expression. Treatment with the selective SIRT1 inhibitor nicotinamide reversed the protective effects of propofol during rI/R-induced ALI. Analogous defensive properties of propofol were detected in vitro in rat alveolar macrophages incubated with serum from the rI/R rat model. These findings indicate that propofol attenuates rI/R-induced ALI by suppressing pyroptosis, possibly by upregulating SIRT1 in the lungs.

Fenofibrate attenuates ischemia reperfusion-induced acute kidney injury and associated liver dysfunction in rats.

Ischemia/reperfusion (I/R) is one of the common reasons for acute kidney injury (AKI) and we need to develop effective therapies for treating AKI. We investigated the role of fenofibrate against I/R-induced AKI and associated hepatic dysfunction in rats. In male wistar albino rats, renal pedicle occlusion for 40 min and 24 h reperfusion resulted in AKI. I/R-induced AKI was demonstrated by measuring serum creatinine, creatinine clearance, urea, uric acid, potassium, fractional excretion of sodium and urinary microproteins. Oxidative stress in rat kidneys was quantified by assaying superoxide anion generation, thiobarbituric acid reactive substances, and reduced glutathione levels. AKI-induced hepatic damage was quantified by assaying serum aminotransferases, alkaline phosphatase and bilirubin levels. Moreover, serum cholesterol, high density lipoprotein and triglycerides were quantified. Hematoxylin-eosin staining of renal and hepatic tissues was done and the kidney and liver injury scores were determined. Immunohistology of endothelial nitric oxide synthase (eNOS) was done in rat kidneys. Fenofibrate was administered for 1 week before subjecting rats to AKI. In separate group, the nitric oxide synthase inhibitor, L-nitroarginine methyl ester (L-NAME) was administered prior to fenofibrate treatment. In I/R group, significant alteration in the serum/urine parameters indicated AKI and hepatic dysfunction along with marked increase in kidney and liver injury scores. Treatment with fenofibrate attenuated AKI and associated hepatic dysfunction. Moreover, I/R-induced decrease in renal eNOS expression was abrogated by fenofibrate. Pre-treatment with L-NAME abolished fenofibrate mediated reno- and hepato-protective effects. In conclusion, fenofibrate attenuates I/R-induced AKI and associated hepatic dysfunction putatively through modulation of eNOS expression.

TOPOGRAPHIC-ANATOMICAL PECULIARITIES OF THE RENAL CALIXPELVIS SYSTEM IN THE FETAL PERIOD OF A HUMAN ONTOGENESIS

The study of the features of the topographic anatomy and individual anatomical variability of the renal calix-pelvis system (RCPS) during the fetal period of a human being intrauterine development (IUD) is important for elucidation and understanding of the complex transformations of their structure, syntopy and skeletotopy, in particular, to explain the causes and time of appearance of the structural variants, possible origin of the congenital malformations of the organ. Purpose of the work: to find out the dynamics of topographic and anatomical changes and anatomical variability of the renal calyx-pelvis system in the fetal period of human ontogenesis. Material and methods. 102 biomannequin of a human being fetuses of 160.0-480.0 mm parietal-coccygeal length (PCL) (4-10 months of IUD) were studied. A complex of methods of morphological research was applied, which included anthropometry, morphometry, injections of blood vessels with X-ray contrast mixtures, X-ray techniques, dissection, microscopy, three-dimensional reconstruction and statistical analysis. Results. It has been found that a lobar structure of the kidneys of human fetuses is observed on all specimens. Two main variants of their external structure were revealed – bean-shaped and oval-shaped. At the beginning of the fetal period of human ontogenesis, the oval shape of the kidney is most often observed, but from the 6th month of the IUD, the bean-shaped form begins to prevail, and from the 8th month of the IUD it is determined almost twice as often. Two variants of the structure of the renal hilum were observed – their open and compact forms. Until the 6th month of IUD, the open form of the renal hilum prevails, and from the end of the 7th month and at the beginning of the 8th months of IUD, a compact form of the organ hilus was revealed on most preparations. In 10-month-old human fetuses, the compact form occurs almost three times more often than the open one. Simultaneously with changes in the shape of the renal hilum, changes in their holotopy occur: in 4-7-month-old fetuses, the hilus is directed forward and medially, and from the 8th month of IUD they are reoriented and placed already on the medial surface of the kidney. Among the variants of the structure of the RCPS, we observed ampullar and branched types. During the study of the renal pelvis skeletotopy, it has been found that at the beginning of the fetal period (4-5-months-old fetuses), the right and left renal pelvis are located almost at the same level in relation to the spine – approximately at the level of the interval between the II and III lumbar vertebrae, but starting from the 6th month, they "rise" on the left to the level of the middle third of the II lumbar vertebra, and on the right, on the contrary, "descend" to the middle third of the III lumbar vertebra. Syntopy of the renal pelvis and pyelo-ureteral segment with renal vessels on the right and on the left is almost the same, and in the dynamics of the fetal period of IUD does not change significantly. Conclusions. 1. The topography of the renal calyx-pelvic system is largely determined by the peculiarities of the spatial structure of the kidney – its external shape, size, skeletotopy, individual features of the hilum of the organ, their syntopy with the renal vessels. 2. Close syntopy of the renal pelvis and pyelo-ureteral segment with renal vessels with a compact form of the renal hilum may be an anatomical prerequisite for impaired urodynamics, provided there are variants of renal vessels branching or the existence of an abnormal vessel in the renal hilum region. 3. Variants of the structure of the kidneys and their structures are clearly observed from the beginning of the fetal period of human intrauterine development, significantly affect the topography of the calyces and pelvis, and in some cases can cause impairment of urodynamics.

Effects and molecular mechanism of pachymic acid onferroptosis in renal ischemia reperfusion injury.

Acute kidney injury (AKI) is a common clinical disease. Ferropotosis, a new type of regulatory cell death, serves an important regulatory role in AKI. Pachymic acid (PA), a lanostane-type triterpenoid from Poria cocos, has been reported to be protective against AKI. However, the protective mechanism of PA in AKI is not yet fully understood. The present study aimed to investigate the effect and molecular mechanism of PA on ferroptosis in renal ischemia reperfusion injury in vivo. A total of 30 mice were intraperitoneally injected with 5, 10 and 20 mg/kg PA for 3 days. A bilateral renal pedicle clip was used for 40 min to induce renal ischemia-reperfusion injury and establish the model. The results demonstrated that treatment with PA decreased serum creatinine and blood urea nitrogen, and ameliorated renal pathological damage. Transmission electron microscopy revealed no characteristic changes in ferroptosis in the mitochondria of the renal tissue in the high-dose PA group, and only mild edema. Furthermore, treatment with PA increased glutathione expression, and decreased the expression levels of malondialdehyde and cyclooxygenase 2. Treatment with PA enhanced the protein and mRNA expression levels of the ferroptosis related proteins, glutathione peroxidase 4 (GPX4), solute carrier family 7 (cationic amino acid transporter, y+ system) member 11 (SLC7A11) and heme oxygenase 1 (HO-1) in the kidney, and increased the expression levels of nuclear factor erythroid derived 2 like 2 (NRF2) signaling pathway members. Taken together, the results of the present study suggest that PA has a protective effect on ischemia-reperfusion induced acute kidney injury in mice, which may be associated with the inhibition of ferroptosis in the kidneys through direct or indirect activation of NRF2, and upregulation of the expression of the downstream ferroptosis related proteins, GPX4, SLC7A11 and HO-1.

Opioid Preconditioning Modulates Repair Responses to Prevent Renal Ischemia-Reperfusion Injury.

Progression to renal damage by ischemia-reperfusion injury (IRI) is the result of the dysregulation of various tissue damage repair mechanisms. Anesthetic preconditioning with opioids has been shown to be beneficial in myocardial IRI models. Our main objective was to analyze the influence of pharmacological preconditioning with opioids in renal function and expression of molecules involved in tissue repair and angiogenesis. Experimental protocol includes male rats with 45 min ischemia occluding the left renal hilum followed by 24 h of reperfusion with or without 60 min preconditioning with morphine/fentanyl. We analyzed serum creatinine and renal KIM-1 expression. We measured circulating and intrarenal VEGF. Immunohistochemistry for HIF-1 and Cathepsin D (CTD) and real-time PCR for angiogenic genes HIF-1α, VEGF, VEGF Receptor 2 (VEGF-R2), CTD, CD31 and IL-6 were performed. These molecules are considered important effectors of tissue repair responses mediated by the development of new blood vessels. We observed a decrease in acute renal injury mediated by pharmacological preconditioning with opioids. Renal function in opioid preconditioning groups was like in the sham control group. Both anesthetics modulated the expression of HIF-1, VEGF, VEGF-R2 and CD31. Preconditioning negatively regulated CTD. Opioid preconditioning decreased injury through modulation of angiogenic molecule expression. These are factors to consider when establishing strategies in pathophysiological and surgical processes.

Laparoscopic nephrectomy for giant benign renal schwannoma: a case report and review of literature

Benign giant renal schwannoma is rarely found and the diagnosis difficulty only depends on physical and imagological examination. Pathological examination is essential to confirm the diagnosis of renal schwannoma. Nephrectomy and tumorectomy are primary treatments for renal schwannoma. Although most of the reported patients present satisfactory outcome, however, there is still not sufficient evidence to reveal the biological characteristics and post-operation recurrence rate of renal schwannoma. Herein, we report a rare case of giant and complicated renal schwannoma. A 56-years-old female patient was admitted to the urology department due to left lower back pain for approximately 5 days. No positive signs and other special abnormalities were found. CT scan presented a soft tissue tumor with inhomogeneous enhanced in the renal hilum. Surgery was performed to excise the tumor and left renal. Renal schwannoma was confirmed by pathological examination. At the 6-month follow-up, no evidence of recurrence was found. Our present report could provide more material for further study.

Rats with congenital hydronephrosis show increased susceptibility to renal ischemia-reperfusion injury.

Many drug candidates have shown significant renoprotective effects in preclinical models; however, there is no clinically used effective pharmacotherapy for acute kidney injury. The failure to translate from bench to bedside could be due to misleading results from experimental animals with undetected congenital kidney defects. This study was performed to assess the effects of congenital hydronephrosis on the functional capacity of tubular renal transporters as well as kidney sensitivity to ischemia‐reperfusion (I‐R)‐induced injury in male Wistar rats. Ultrasonography was used to distinguish healthy control rats from rats with hydronephrosis. L‐carnitine or furosemide was administered, and serial blood samples were collected and analyzed to assess the effects of hydronephrosis on the pharmacokinetic parameters. Renal injury was induced by clamping the renal pedicles of both kidneys for 30 min with subsequent 24 hr reperfusion. The prevalence of hydronephrosis reached ~30%. The plasma concentrations after administration of L‐carnitine or furosemide were similar in both groups. I‐R induced more pronounced renal injury in the hydronephrotic rats than the control rats, which was evident by a significantly higher kidney injury molecule‐1 concentration and lower creatinine concentration in the urine of the hydronephrotic rats than the control rats. After I‐R, the gene expression levels of renal injury markers were significantly higher in the hydronephrotic kidneys than in the kidneys of control group animals. In conclusion, our results demonstrate that hydronephrotic kidneys are more susceptible to I‐R‐induced damage than healthy kidneys. Unilateral hydronephrosis does not affect the pharmacokinetics of substances secreted or absorbed in the renal tubules.

MYELOLIPOMA IN THE ADRENAL GLAND OF A CANINE

O presente relato visa descrever os achados macroscópicos e histopatológicos de um canino com mielolipoma em glândula adrenal esquerda. Tumores de glândula adrenal são neoplasias frequentes em cães, porém mielolipomas são geralmente encontrados em bovinos ou primatas sendo infrequente em outras espécies. Um cadáver de um canino, sem raça definida, com diagnóstico clínico de doença renal aguda foi encaminhado ao Laboratório de Patologia para a realização da necropsia. Na abertura da cavidade abdominal foi encontrada uma massa crânio-medial ao rim esquerdo que circundava o hilo renal. O rim esquerdo apresentava leve aumento de volume. A massa foi diagnosticada microscopicamente como Mielolipoma e no rim esquerdo foram encontradas alterações que sugeriam isquemia renal. O diagnóstico de mielolipoma de adrenal foi considerado um achado incidental de necropsia, sendo a causa da morte deste canino uma doença renal bilateral de origem não determinada. Porém, apesar deste tumor não estar relacionado ao óbito do animal lesões compatíveis com isquemia no rim esquerdo foram encontradas, demonstrando, que tumores benignos de adrenal, como o mielolipoma, podem gerar lesões por compressão no rim.

Clusterin regulates macrophage expansion, polarization and phagocytic activity in response to inflammation in the kidneys.

Clusterin (CLU) is a multifunctional protein localized extracellularly and intracellularly. Although CLU‐knockout (KO) mice are more susceptible to renal ischemia‐reperfusion injury (IRI), the mechanisms underlying the actions of CLU in IRI are not fully understood. Macrophages are key regulators of IRI severity and tissue repair. Therefore, we investigated the role of CLU in macrophage polarization and phagocytosis. Renal IRI was induced in wild‐type (WT) or CLU‐KO C57BL/6 mice by clamping the renal pedicles for 30 min at 32°C. Peritoneal macrophages were activated via an intraperitoneal injection of lipopolysaccharide (LPS). Renal tissue damage was examined using histology, whereas leukocyte phenotypes were assessed using flow cytometry and immunohistochemistry. We found that monocytes/macrophages expressed the CLU protein that was upregulated by hypoxia. The percentages of macrophages (F4/80+, CD11b+ or MAC3+) infiltrating the kidneys of WT mice were significantly less than those in CLU‐KO mice after IRI. The M1/M2 phenotype ratio of the macrophages in WT kidneys decreased at day 7 post‐IRI when the injury was repaired, whereas that in KO kidneys increased consistently as tissue injury persisted. In response to LPS stimulation, WT mice produced fewer M1 macrophages, but not M2, than the control did. Phagocytosis was stimulated by CLU expression in macrophages compared with the CLU null controls and by the exogenous CLU protein. In conclusion, CLU suppresses macrophage infiltration and proinflammatory M1 polarization during the recovery period following IRI, and enhances phagocytic activity, which may be partly responsible for tissue repair in the kidneys of WT mice after injury.

Characterization of the Oxidative Stress in Renal Ischemia/Reperfusion-Induced Cardiorenal Syndrome Type 3.

In kidney disease (KD), several factors released into the bloodstream can induce a series of changes in the heart, leading to a wide variety of clinical situations called cardiorenal syndrome (CRS). Reactive oxygen species (ROS) play an important role in the signaling and progression of systemic inflammatory conditions, as observed in KD. The aim of the present study was to characterize the redox balance in renal ischemia/reperfusion-induced cardiac remodeling. C57BL/6 male mice were subjected to occlusion of the left renal pedicle, unilateral, for 60 min, followed by reperfusion for 8 and 15 days, respectively. The following redox balance components were evaluated: catalase (CAT), superoxide dismutase (SOD), total antioxidant capacity (FRAP), NADPH oxidase (NOX), nitric oxide synthase (NOS), hydrogen peroxide (H2O2), and the tissue bioavailability of nitric oxide (NO) such as S-nitrosothiol (RSNO) and nitrite (NO2−). The results indicated a process of renoprotection in both kidneys, indicated by the reduction of cellular damage and some oxidant agents. We also observed an increase in the activity of antioxidant enzymes, such as SOD, and an increase in NO bioavailability. In the heart, we noticed an increase in the activity of NOX and NOS, together with increased cell damage on day 8, followed by a reduction in protein damage on day 15. The present study concludes that the kidneys and heart undergo distinct processes of damage and repair at the analyzed times, since the heart is a secondary target of ischemic kidney injury. These results are important for a better understanding of the cellular mechanisms involved in CRS.

Mucinous tubular and spindle cell carcinoma of the kidney: Five case reports and review of the literature.

Mucinous tubular and spindle cell carcinoma (MTSCC) of the kidney is a rare and polymorphic tumor, which has been previously considered to be a low-grade malignancy, predominantly occurring in women. To the best of our knowledge, MTSCC with bladder metastasis has never been reported. The current study presents five adult cases of MTSCC that included three male and two female patients. Among the male cases, two were of advanced stage, one with MTSCC and renal chromophobe cell carcinoma with bladder metastasis and the other with MTSCC with invasion of the renal vein. The other three cases with small masses were at an early stage. All five cases had a good prognosis and were without recurrence after several years of follow-up. A 70-year-old male with intermittent gross hematuria, intermittent renal colic, and groin radiation pain for a year (case 1), was incidentally detected to have a left renal density mass by total abdominal enhanced computed tomography scans. In the other four cases, renal masses were found by B-ultrasound. The patient in case 1 underwent a retroperitoneal laparoscopic radical nephroureterectomy with bladder cuff resection and transurethral resection of the bladder tumor, and received gemcitabine hydrochloride via intravesical instillation therapy plus cisplatin chemotherapy every 3 months. The patient in case 2 underwent an open left radical nephrectomy and renal pedicle lymph node dissection. The other three patients underwent a laparoscopic radical nephrectomy. All five patients had no recurrence or new metastasis in other organs after follow-up. In conclusion, the incidence of MTSCC in men and women is not as disparate as reported in previous publications. The characteristics of the images of the five adult cases in the present study showed a considerable consistency, with only minor differences. The malignancy and prognosis of MTSCC are still controversial, and thus inclusion and review of more cases is required to reach a definite final conclusion. Sunitinib and gemcitabine chemotherapy in combination with cisplatin may be effective for the therapy of MTSCC patients with metastasis, but a larger range of treatments needs to be identified.

Knockout of Trpa1 Exacerbates Renal Ischemia-Reperfusion Injury With Classical Activation of Macrophages.

Classically activated macrophages contribute to the development of renal ischemia-reperfusion injury (IRI). This study aimed to investigate the role of transient receptor potential ankyrin 1 (Trpa1), a regulator of macrophage activation, in IRI-induced acute kidney injury (AKI) by using the Trpa1 gene knockout (Trpa1-/-) mouse model. Male 8-week-old Trpa1-/- mice and wild-type (WT) littermates were subjected to renal ischemia for 35 minutes by clamping bilateral renal pedicles under isoflurane anesthesia, and blood and tissue samples were collected 24 hours after reperfusion and analyzed with histological and molecular measurements. Following IRI, Trpa1-/- mice developed more deteriorated biochemical and morphological signs of AKI when comparing with WT mice. More classically activated M1 macrophages were found in the kidneys of Trpa1-/- mice comparing with WT mice after IRI, while the counts of alternatively activated M2 macrophages in the kidney were similar between the 2 strains after IRI. Furthermore, significantly higher expression levels of proinflammatory markers including interleukin-1 beta and tumor necrosis factor alpha were detected in the kidney of Trpa1-/- mice compared with WT mice after IRI. The levels of TRPA1 protein in the kidney of WT mice were also decreased after IRI. Our results show that ablation of Trpa1 exacerbates infiltration of classically activated macrophages, renal inflammation, and renal injury in mice after IRI. These findings suggest that activation of TRPA1 may protect against IRI-induced AKI via regulation of macrophage-mediated inflammatory pathway.

PREventive effect of FENestration with and without clipping on post-kidney transplantation lymphatic complications (PREFEN): study protocol for a randomised controlled trial

IntroductionPeritoneal fenestration is an effective preventive method for reducing the rate of lymphatic complications in kidney transplantation (KTx). The size of the fenestration plays an important role in its effectiveness....