Sociological genealogy of a non-teleological concept of evolution.

The aim of this article is to carry out a sociological-conceptual genealogy of the evolutionist perspective (non-teleological) of approaching social reality. While during the first phases of modernity, a teleological and progressive conception of evolution was imposed, clearly manifested in the proposals of Auguste Comte or Herbert Spencer, in the last decades important bifurcations, processes, and developments have emerged that question the linearity and the finalist character of these positions. We consider that these approaches are closer to the nature of change and social phenomena, so it seems important to us to analyze some of the most outstanding contributions-in the form of sociological genealogy, as we have already mentioned-that have developed this perspective. In order to carry out our task, we have organized four sections: In the first, we make a critique of the sociological evolutionism represented by Comte, Spencer, and Parsons, focusing on the limits of their proposals and the blind spots associated with them. Second, we will analyze the anti-teleological cognitive approaches of Donald and the importance they attach to cultural transmission as a key element for understanding the evolution of both cognition and human societies. In a third moment, we will analyze the coexistence in Weber's work between the dynamics of 'disenchantment' and 're-enchantment' of the world in modern societies, understood as the two sides of the same coin that are in constant dynamic tension and that break with the evolutionary vision that goes from magic through religion to science, or from belief to knowledge. In a fourth moment, we analyze the relevance of approaches focused on what we have called 'multiple evolutions' (plural) that collide with each other-the conflicting simultaneity of the non-simultaneous-of their rhythms and directions, inspired by the works of Knöbl, Koselleck, Luhmann, Rosa, Eisenstadt, Abbott, and Zerubavel, which pave the way for the construction of a non-teleological approach to evolution.

Evolution of kidney allograft loss causes over 40 years (1979-2019).

INTRODUCTION: The improvement of kidney allograft recipient and graft survival showed a decrease over the last 40 years. Long-term graft loss rate remained stable during a 25-year time span. Knowing the changing causes and the risk factors associated with graft loss requires special attention. The present study aimed to assess the causes of graft loss and kidney allograft recipient death. Also, we aimed to compare two different periods (1979-1999 and 2000-2019) to identify changes in the characteristics of the failed allografts and recipient and donors profile. METHODS AND PATIENTS: We performed a single-center cohort study. We included all the kidney transplant recipients at the Hospital del Mar (Barcelona) between May 1979 and December 2019. Graft loss was defined as recipient death with functioning graft and as loss of graft function (return to dialysis or retransplantation). We assessed the causes of graft loss using clinical and histological information. We also analyzed the results of the two different transplant periods (1979-1999 and 2000-2019). RESULTS: Between 1979 and 2019, 1522 transplants were performed. The median follow-up time was 56 (IQR 8-123) months. During follow-up, 722 (47.5%) grafts were lost: 483 (66.9%) due to graft failure and 239 (33.1%) due to death with functioning graft. The main causes of death were cardiovascular (25.1%), neoplasms (25.1%), and infectious diseases (21.8%). These causes were stable between the two periods of time. Only the unknown cause of death has decreased in the last period. The main cause of graft failure (loss of graft function) was the allograft chronic dysfunction (75%). When histologic information was available, antibody-mediated rejection (ABMR) and interstitial fibrosis/tubular atrophy (IF/TA) were the most frequent specific causes (15.9% and 12.6%). Of the graft failures, 213 (29.5%) were early (<1 year of transplantation). Vascular thrombosis was the main cause of early graft failure in the second period (2000-2019) (46.7%) and T-cell-mediated rejection (TCMR) was the main cause (31.3%) in the first period (1979-1999). The causes of late graft loss were similar between the two periods. CONCLUSIONS: The causes of kidney allograft recipient death are still due to cardiovascular and malignant diseases. Vascular thrombosis has emerged as a frequent cause of early graft loss in the most recent years. The evaluation of the causes of graft loss is necessary to improve kidney transplantation outcomes.

Evolución de las causas de pérdida del injerto en trasplante renal durante 40 años (1979-2019) / Evolution of kidney allograft loss causes over 40 years (1979-2019)

Introducción: La mejoría en la supervivencia del receptor y del injerto renal sufre un proceso de deceleración. La tasa de pérdida del injerto a medio y largo plazo permanece estable desde hace 25 años. Es fundamental conocer las causas de pérdida del injerto y los factores relacionados, así como identificar si se han producido cambios en las causas de pérdida del injerto en los últimos años. El objetivo del presente estudio fue evaluar las causas de pérdida del injerto según fallecimiento del receptor o pérdida del injerto con vuelta a diálisis/retrasplante, y analizar las causas específicas de pérdida del injerto en 2 épocas (1979-1999 y 2000-2019) para identificar cambios en el perfil de los injertos perdidos. Pacientes y métodos: Estudio retrospectivo de todos los trasplantes renales (TR) realizados en el Hospital del Mar (Barcelona) entre mayo-1979 y diciembre-2019. Consideramos pérdida del injerto el fallecimiento del paciente con injerto funcionante o el re-inicio de diálisis o retrasplante. Revisamos las causas de pérdida mediante información clínica e histológica, y analizamos los resultados en 2 periodos (1979-1999 y 2000-2019). (AU)

Introduction: The improvement of kidney allograft recipient and graft survival showed a decrease over the last 40 years. Long-term graft loss rate remained stable during a 25-year time span. Knowing the changing causes and the risk factors associated with graft loss requires special attention. The present study aimed to assess the causes of graft loss and kidney allograft recipient death. Also, we aimed to compare two different periods (1979-1999 and 2000-2019) to identify changes in the characteristics of the failed allografts and recipient and donors profile. Methods and patients: We performed a single-center cohort study. We included all the kidney transplant recipients at the Hospital del Mar (Barcelona) between May 1979 and December 2019. Graft loss was defined as recipient death with functioning graft and as loss of graft function (return to dialysis or retransplantation). We assessed the causes of graft loss using clinical and histological information. We also analyzed the results of the two different transplant periods (1979-1999 and 2000-2019). (AU)

THSD7A-positive membranous nephropathy after kidney transplantation: A case report.

Membranous nephropathy (MN) is a common cause of nephrotic syndrome after kidney transplantation (KT); however, scarce is known regarding post-KT thrombospondin type-1 domain-containing 7A (THSD7A)-positive MN. Herein, we report on a 72-year-old woman with end-stage kidney disease due to chronic interstitial nephritis (1996). In February 2020, she received a second deceased-donor KT, achieving optimal kidney function but presenting early post-KT proteinuria, reaching up to 1800mg/24h six months after transplantation, controlled with renin-angiotensin-aldosterone system (RAAS) blockade. In July 2021, a kidney allograft biopsy revealed features consistent with MN. Immunohistochemical stains showed diffuse and granular THSD7A and C4d deposition in glomerular capillary walls and negative PLA2R and IgG4 staining. No anti-THSD7A antibodies were detected in the serum. The pre-implantation biopsy showed no MN-associated lesions and negative THSD7A staining. Secondary triggers such as malignancy were discarded. The present report illustrates a THSD7A-positive MN in a KT recipient. Despite lacking native kidney biopsy and early presentation, a recurrent MN seemed unprovable due to documented native kidney disease and a long time span between native kidney disease and MN diagnosis. We, therefore, presumed primary de novo disease. Two years after KT, kidney function remains stable, and the patient has reached complete remission of proteinuria.

Microvascular inflammation in the absence of human leukocyte antigen-donor-specific antibody and C4d: An orphan category in Banff classification with cytotoxic T and natural killer cell infiltration.

Isolated microvascular inflammation (iMVI) without HLA donor-specific antibodies or C4d deposition in peritubular capillaries remains an enigmatic phenotype that cannot be categorized as antibody-mediated rejection (ABMR) in recent Banff classifications. We included 221 kidney transplant recipients with biopsies with ABMR (n = 73), iMVI (n = 32), and normal (n = 116) diagnoses. We compared peripheral blood leukocyte distribution by flow cytometry and inflammatory infiltrates in kidney transplant biopsies among groups. Flow cytometry showed fewer lymphocytes and total, CD4+, and CD8+ peripheral T cells in iMVI compared with ABMR and normal cases. ABMR and iMVI had fewer total natural Killer (NK) cells but more NKG2A+ NK cells. Immunohistochemistry indicated that ABMR and iMVI had greater CD3+ and CD68+ glomerular infiltration than normal biopsies, whereas CD8+ and TIA1+ cells showed only increased iMVI, suggesting they are cytotoxic T cells. Peritubular capillaries displayed more CD3+, CD56+, TIA1+, and CD68+ cells in both ABMR and iMVI. In contrast, iMVI had less plasma cell infiltration in peritubular capillaries and interstitial aggregates than ABMR. iMVI displayed decreased circulating T and NK cells mirrored by T cell and NK cell infiltration in the renal allograft, similar to ABMR. However, the lesser plasma cell infiltration in iMVI may suggest an antibody-independent underlying stimulus.

Phosphorylation of S6RP in peritubular capillaries of kidney grafts and circulating HLA donor-specific antibodies.

Antibody-mediated rejection (ABMR) caused by donor-specific HLA-antibodies (DSA) is a mediator of allograft loss after kidney transplantation (KT). DSA can activate microvascular endothelium damage through the mTOR pathway. In this study we assessed the mTOR pathway activation by DSA in KT with ABMR (ABMR + DSA+) compared to controls (ABMR-DSA-), biopsies with ABMR changes without DSA (ABMR + DSA-) and DSA without ABMR changes (ABMR-DSA+), and the potential modulation by mTOR inhibitors (mTORi). We evaluated 97 biopsies: 31 ABMR + DSA+, 33 controls ABMR-DSA-, 16 ABMR + DSA-, and 17 ABMR-DSA+ cases. Regarding immunosuppression of full ABMR + DSA+ and controls, 21 biopsies were performed under mTORi treatment (11 of them ABMR + DSA+ cases) and 43 without mTORi (20 of them ABMR + DSA+) so as to explore its effect on the mTOR pathway. Biopsies were stained for C4d, Ki67, and phosphorylated (p) S6RP, ERK, and mTOR by immunohistochemistry. Labeling was graded according to peritubular capillary staining. ABMR biopsies showed significantly higher C4d, p-S6RP, and Ki67 staining in peritubular capillaries (PTC) compared to controls, and light differences in p-ERK or p-mTOR. mTORi treatment did not modify p-S6RP, p-mTOR, and p-ERK staining. Diffuse p-S6RP in PTC in the biopsies significantly associated with circulating HLA-DSA independently of graft rejection, and with worse death-censored graft survival. These findings suggest that activation of endothelium through the mTOR pathway evidence different mechanisms of damage in ABMR + DSA+ and ABMR + DSA- despite similar histological injury.

Podocytopathy in patients with monoclonal gammopathy: three patients and literature review.

BACKGROUND: Renal manifestations of monoclonal gammopathies are of increasing interest among nephrologists. Typical manifestations include light chain cast nephropathy, amyloidosis or renal damage mediated by monoclonal immunoglobulin deposition. Podocytopathies in the setting of an underlying monoclonal gammopathy constitute a rare manifestation of these diseases and, although being described in the literature, remain a challenge since most data derive from case reports. METHODS: A retrospective review of the clinical data of Hospital del Mar and Hospital Vall d'Hebron was performed to identify patients with minimal change disease (MCD) or focal and segmental glomerulosclerosis (FSGS) in the setting of neoplasms that produce monoclonal (M) protein. Additionally, a literature review on this topic was performed. This study aims to describe the clinical characteristics and outcomes of these patients. RESULTS: Three patients were identified to have podocytopathy and monoclonal gammopathy between the years 2013 and 2020. All three were males and  >65 years of age. Two patients were diagnosed with MCD and one patient was diagnosed with FSGS. All patients underwent a kidney biopsy and light and electron microscopic studies were performed. The underlying causes of monoclonal gammopathy were multiple myeloma in two cases and Waldeström macroglobulinemia in one case. Two patients developed nephrotic syndrome during the follow-up. All patients were under active hematological treatment. One patient presented a complete remission of proteinuria whereas the other two presented a partial remission. CONCLUSIONS: Podocytopathies may infrequently be found in patients with monoclonal gammopathies. Patients with overt glomerular proteinuria and hematological disorders with M protein should undergo a kidney biopsy for prompt diagnosis and to specify a prognosis. In addition, further study on this matter must be done to understand the pathophysiology and treat these patients appropriately.

Redefining the Role of ADAM17 in Renal Proximal Tubular Cells and Its Implications in an Obese Mouse Model of Pre-Diabetes.

Acute and chronic kidney lesions induce an increase in A Disintegrin And Metalloproteinase domain 17 (ADAM17) that cleaves several transmembrane proteins related to inflammatory and fibrotic pathways. Our group has demonstrated that renal ADAM17 is upregulated in diabetic mice and its inhibition decreases renal inflammation and fibrosis. The purpose of the present study was to analyze how Adam17 deletion in proximal tubules affects different renal structures in an obese mice model. Tubular Adam17 knockout male mice and their controls were fed a high-fat diet (HFD) for 22 weeks. Glucose tolerance, urinary albumin-to-creatinine ratio, renal histology, and pro-inflammatory and pro-fibrotic markers were evaluated. Results showed that wild-type mice fed an HFD became obese with glucose intolerance and renal histological alterations mimicking a pre-diabetic condition; consequently, greater glomerular size and mesangial expansion were observed. Adam17 tubular deletion improved glucose tolerance and protected animals against glomerular injury and prevented podocyte loss in HFD mice. In addition, HFD mice showed more glomerular macrophages and collagen accumulation, which was prevented by Adam17 deletion. Galectin-3 expression increased in the proximal tubules and glomeruli of HFD mice and ameliorated with Adam17 deletion. In conclusion, Adam17 in proximal tubules influences glucose tolerance and participates in the kidney injury in an obese pre-diabetic murine model. The role of ADAM17 in the tubule impacts on glomerular inflammation and fibrosis.

Non-HLA Antibodies and Epitope Mismatches in Kidney Transplant Recipients With Histological Antibody-Mediated Rejection.

Background: Correlation between antibody-mediated rejection (ABMR) and circulating HLA donor-specific antibodies (HLA-DSA) is strong but imperfect in kidney transplant (KT) recipients, raising the possibility of undetected HLA-DSA or non-HLA antibodies contributing to ABMR. Detailed evaluation of the degree of HLA matching together with the identification of non-HLA antibodies in KT may help to decipher the antibody involved. Methods: We retrospectively assessed patients with transplant biopsies scored following Banff'15 classification. Pre- and post-transplant serum samples were checked for HLA and non-HLA antibodies [MICA-Ab, angiotensin-II type-1-receptor (AT1R)-Ab, endothelin-1 type-A-receptor (ETAR)-Ab and crossmatches with primary aortic endothelial cells (EC-XM)]. We also analyzed HLA epitope mismatches (HLA-EM) between donors and recipients to explore their role in ABMR histology (ABMRh) with and without HLA-DSA. Results: One-hundred eighteen patients with normal histology (n = 19), ABMRh (n = 52) or IFTA (n = 47) were studied. ABMRh patients were HLA-DSApos (n = 38, 73%) or HLA-DSAneg (n = 14, 27%). Pre-transplant HLA-DSA and AT1R-Ab were more frequent in ABMRh compared with IFTA and normal histology cases (p = 0.006 and 0.003), without differences in other non-HLA antibodies. Only three ABMRhDSAneg cases showed non-HLA antibodies. ABMRhDSAneg and ABMRhDSApos cases showed similar biopsy changes and graft-survival. Both total class II and DRB1 HLA-EM were associated with ABMRhDSApos but not with ABMRhDSAneg. Multivariate analysis showed that pre-transplant HLA-DSA (OR: 3.69 [1.31-10.37], p = 0.013) and AT1R-Ab (OR: 5.47 [1.78-16.76], p = 0.003) were independent predictors of ABMRhDSApos. Conclusions: In conclusion, pre-transplant AT1R-Ab is frequently found in ABMRhDSApos patients. However, AT1R-Ab, MICA-Ab, ETAR-Ab or EC-XM+ are rarely found among ABMRhDSAneg patients. Pre-transplant AT1R-Ab may act synergistically with preformed or de novo HLA-DSA to produce ABMRhDSApos but not ABMRhDSAneg. HLA epitope mismatch associates with ABMRhDSApos compared with ABMRhDSAneg, suggesting factors other than HLA are responsible for the damage.

Activation of final complement components after kidney transplantation as a marker of delayed graft function severity.

BACKGROUND: Ischaemia-reperfusion (I/R) damage is a relevant cause of delayed graft function (DGF). Complement activation is involved in experimental I/R injury, but few data are available from kidney transplant (KT) patients. We studied the dynamics of membrane attack complex (C5b-9) as a soluble fraction (SC5b-9) and the histological deposit pattern of C3b, complement Factor H (FH) and C5b-9 in DGF patients. METHODS: We evaluated SC5b-9 levels in 59 recipients: 38 with immediate graft function and 21 with DGF. The SC5b-9 was measured at admission for KT and 7 days after KT. DGF-kidney biopsies (n = 12) and a control group of 1-year protocol biopsies without tissue damage (n = 4) were stained for C5b-9, C3b and FH. RESULTS: SC5b-9 increased significantly in DGF patients (Day 0: 6621 ± 2202 mAU/L versus Day 7: 9626 ± 4142 mAU/L; P = 0.006), while it remained stable in non-DGF patients. Days 0-7 increase >5% was the better cut-off associated with DGF versus non-DGF patient discrimination (sensitivity = 81%). In addition, SC5b-9 increase was related to DGF duration and worse graft function, and independently associated with DGF occurrence. SC5b-9, C3b and FH stains were observed in tubular epithelial cells basal membrane. DGF-kidney biopsies showed a more frequently high-intensity stain, a higher number of tubules with positive stain and larger perimeter of tubules with positive stains for SC5b-9, C3b and FH than control patients. CONCLUSIONS: Both SC5b-9 levels and SC5b-9, C3b and FH deposits in tubular epithelial cells basal membrane are highly expressed in patients experiencing DGF. SC5b-9 levels increase could be useful as a marker of DGF severity.

Role of C5aR1 and C5L2 Receptors in Ischemia-Reperfusion Injury.

The role of C5a receptors (C5aR1 and C5L2) in renal ischemia-reperfusion injury (IRI) is uncertain. We generated an in vitro model of hypoxia/reoxygenation with human proximal tubule epithelial cells to mimic some IRI events. C5aR1, membrane attack complex (MAC) and factor H (FH) deposits were evaluated with immunofluorescence. Quantitative polymerase chain reaction evaluated the expression of C5aR1, C5L2 genes as well as genes related to tubular injury, inflammation, and profibrotic pathways. Additionally, C5aR1 and C5L2 deposits were evaluated in kidney graft biopsies (KB) from transplant patients with delayed graft function (DGF, n = 12) and compared with a control group (n = 8). We observed higher immunofluorescence expression of C5aR1, MAC and FH as higher expression of genes related to tubular injury, inflammatory and profibrotic pathways and of C5aR1 in the hypoxic cells; whereas, C5L2 gene expression was unaffected by the hypoxic stimulus. Regarding KB, C5aR1 was detected in the apical and basal membrane of tubular epithelial cells, whereas C5L2 deposits were observed in endothelial cells of peritubular capillaries (PTC). DGF-KB showed more frequently diffuse C5aR1 staining and C5L2 compared to controls. In conclusion, C5aR1 expression is increased by hypoxia and IRI, both in vitro and in human biopsies with an acute injury. C5L2 expression in PTC could be related to endothelial cell damage during IRI.

Podocyte and tubular involvement in AngioJet-induced kidney injury.

The AngioJet technique combines localized thrombolysis and percutaneous mechanical thrombectomy (PMT). However, PMT may cause acute kidney injury (AKI), which has been ascribed to severe mechanical haemolysis, although no renal biopsies have been reported. We now report the first renal biopsy in a patient with AKI following PMT. There is histological evidence of haemoglobin (Hb)-induced tubular injury and podocyte stress characterized by intracellular Hb and staining for ferritin and hemo-oxygenase-1, suggestive of an adaptive response to oxidative stress. This confirms that Hb is involved in kidney cell injury and supports the existence of several different kidney cellular targets.

Endothelial ADAM17 Expression in the Progression of Kidney Injury in an Obese Mouse Model of Pre-Diabetes.

Disintegrin and metalloproteinase domain 17 (ADAM17) activates inflammatory and fibrotic processes through the shedding of various molecules such as Tumor Necrosis Factor-α (TNF-α) or Transforming Growht Factor-α (TGF-α). There is a well-recognised link between TNF-α, obesity, inflammation, and diabetes. In physiological situations, ADAM17 is expressed mainly in the distal tubular cell while, in renal damage, its expression increases throughout the kidney including the endothelium. The aim of this study was to characterize, for the first time, an experimental mouse model fed a high-fat diet (HFD) with a specific deletion of Adam17 in endothelial cells and to analyse the effects on different renal structures. Endothelial Adam17 knockout male mice and their controls were fed a high-fat diet, to induce obesity, or standard rodent chow, for 22 weeks. Glucose tolerance, urinary albumin-to-creatinine ratio, renal histology, macrophage infiltration, and galectin-3 levels were evaluated. Results showed that obese mice presented higher blood glucose levels, dysregulated glucose homeostasis, and higher body weight compared to control mice. In addition, obese wild-type mice presented an increased albumin-to-creatinine ratio; greater glomerular size and mesangial matrix expansion; and tubular fibrosis with increased galectin-3 expression. Adam17 deletion decreased the albumin-to-creatinine ratio, glomerular mesangial index, and tubular galectin-3 expression. Moreover, macrophage infiltration in the glomeruli of obese Adam17 knockout mice was reduced as compared to obese wild-type mice. In conclusion, the expression of ADAM17 in endothelial cells impacted renal inflammation, modulating the renal function and histology in an obese pre-diabetic mouse model.

Numerical Analysis of Urea to Ammonia Conversion in Automotive Selective Catalytic Reduction Realistic Conditions.

The selective catalytic reduction (SCR) is a technology employed for NO x reduction purposes which is based on the injection of an Urea Water Solution (UWS) into the exhaust line. Conversion of this injected urea into ammonia is a key step to ensure high SCR efficiency. In order to study this phenomenon, a three-dimensional model of the urea-water injection process has been created to recreate realistic conditions. A Lagrangian-Eulerian approach has been followed to model liquid and gas phases, respectively. Droplet evaporation as well as relevant chemical processes have been included to recreate the thermolysis and hydrolysis phenomena, and the results have been validated against literature data. Then, the validated model has been applied to recreate an in-house experimental facility that measured spray macroscopic and microscopic characteristics by means of diffused back illumination (DBI) visualization. Probability density functions of the UWS droplet sizes as well as the velocity distributions have been obtained at three different regions of interest to be compared with the experimental data set. Contours of isocyanic acid and ammonia mass fractions have been included to show the chemical transformation from urea into its products. The model accurately replicates the experimental results, and it stands as a good methodology to predict the main spray characteristics as well as the chemical processes that take place in actual SCR systems.

Angiotensin-converting enzyme 2 influences pancreatic and renal function in diabetic mice.

Type 1 diabetes is a T-cell mediated autoimmune disease characterized by pancreatic beta cells destruction. Angiotensin-converting enzyme 2 (ACE2), a component of renin-angiotensin system (RAS) has been identified in pancreas from type 2 diabetic mice and its overexpression prevents beta cell dysfunction. We studied the effect of ACE2 deletion on pancreatic and renal function in the nonobese diabetic mice, a model that mimics type 1 diabetes. ACE2-deficient NOD mice and the respective controls were generated. Pancreas function and immunohistochemistry studies were performed. Renal function and RAS gene expression were also analyzed. Renal proximal tubular cells were obtained from these animals to dissect the effect of ACE2 deficiency in these cells. In NOD mice, ACE2 deletion significantly worsened glucose homeostasis, decreased islet insulin content, increased beta cell oxidative stress, and RIPK1-positive islets as compared with control mice. Angiotensin-converting enzyme and angiotensin II type 1 receptor (AT1R) were also increased in ACE2-deficient mice. In kidneys of 30-day diabetic mice, ACE2 deletion decreased podocyte number within the glomeruli, and altered renal RAS gene expression in tubules. ACE2 deletion influenced the expression of fibrosis-related genes in isolated primary renal proximal tubular cells before diabetes onset in NOD mice. Our findings suggest that ACE2 deletion may have a deleterious impact on beta cell and renal function, by promoting oxidative stress and increasing necroptosis mediators. In addition, this effect is accompanied by RAS alterations in both pancreas and renal proximal tubular cells, indicating that ACE2 may exert a renopancreatic protective effect on type 1 diabetes, which is activated before diabetes starts.

Risk Factors Associated with Major Complications after Ultrasound-Guided Percutaneous Renal Biopsy of Native Kidneys.

INTRODUCTION: Percutaneous renal biopsy (PRB) of native kidneys is an important tool for diagnosis and management of renal disease. In this study, we analyzed the success, safety, and risk complications of PRB in our center. METHODS: A retrospective review of ultrasound-guided PRB done at our institution from January 1998 to December 2017 was performed. Clinical and laboratory data were collected for 661 PRBs. Statistical analysis was performed using the Mann-Whitney U test for continuous variable and chi-square test for categorical variables. Multivariate analysis using logistic regression was performed to assess factors associated with increased risk of complications after PRB. RESULTS: The median age was 56 (42-68) years old, the majority were male (64%) and white (82%). Ten glomeruli were present in 63.5% of PRBs. Overall, the rate of complications was 16.6%, where 15.1% of them were minor complications and 1.5% were major complications. Perinephritic hematoma accounted for the minor complication that occurred most frequently, whereas the need of a blood transfusion was the prevalent for major complications. By multivariate analysis, increased activated partial thromboplastin time (aPTT; OR 1.11, 95% CI 1.035-1.180) and prebiopsy lower hemoglobin (Hgb; OR 1.61, 95% CI 1.086-2.304) were identified as independent risk factors for major complications. In addition, older patients (OR 1.057, 95% CI 1.001-1.117) were identified as an independent risk factor for blood transfusion requirement. CONCLUSION: The current risk of complications after native PRB is low. Major complications are most common in case of increased aPTT and decreased Hgb baseline level.

A Myxoid Fibrotic Reaction Pattern is Associated with Metastatic Risk in Cutaneous Squamous Cell Carcinoma.

Although desmoplasia has been associated with poor prognoses in cutaneous squamous cell carcinoma, little attention has been paid to the patterns of fibrosis. This study aimed to examine the different stromal fibrotic patterns as markers of metastatic risk. We performed a multicenter retrospective study that included 102 cutaneous squamous cell carcinomas (52 non-metastatic and 50 metastatic carcinomas). Clinical and histopathological data were registered. The fibrotic reaction pattern was classified as mature, intermediate or immature depending on the presence of keloid-like collagen and myxoid stroma. The immature pattern (areas characterized by myxoid changes with no inflammation) was observed in 18 samples and its presence was significantly associated with immunosuppression, budding, desmoplasia, perineural invasion, anatomic level, tumoural depth and metastatic risk in the multivariate analysis. Our findings suggest that the presence of an immature myxoid fibrotic pattern, which can be easily identified by routine hematoxylin-eosin staining, is strongly associated with metastatic risk.

Membrane Attack Complex and Factor H in Humans with Acute Kidney Injury.

BACKGROUND AND AIMS: Complement system seems to play an important role in the pathogenesis of Acute Kidney Injury (AKI). The aim of this study was to investigate the role of complement system in the pathogenesis of human AKI. For this purpose, we studied Membrane Attack Complex (MAC) and factor H in plasma and kidney tissue in AKI. METHODS: Plasmatic concentrations of MAC and Factor H were studied in patients with hospital-acquired AKI and their respective controls. MAC and Factor H expression and localization within the kidney were studied by immunohistochemistry in kidney tissue samples from autopsies. Demographical, past medical, and laboratory data in patients on admission and 3 years after discharge were recorded. RESULTS: Plasmatic MAC concentrations were significantly higher in AKI-patients (5848±3604 vs 3703±1483 mAU/mL, p< 0.01), mainly in the severe cases, as measured by the need of renal replacement therapy, non-recovery of renal function, RIFLE classification and CKD development. MAC deposition was observed in tubular epithelial cell basal membranes, showing a larger number of tubules with MAC deposition, larger perimeter of affected tubules and greater intensity of MAC immunostaining in AKI patients. Factor H concentrations were higher in AKI patients (0.86±0.05 vs 0.60±0.04 mg/mL, p=0.007), showing a strong positive association with plasmatic MAC (r=0.7, p< 0.01)). Factor H immunostaining showed a tubular cytoplasmic pattern, with significant variations in the staining intensity, associated with the severity of histologic damage. CONCLUSION: Our data confirm that complement system is involved in human AKI, through the lytic action of MAC in tubular epithelial cells. These results suggest that complement system activation in AKI could be related with CKD development.