Glomerular Capillary Endothelium Research Articles

Non-voltage-gated Ca2+ channel signaling in glomerular cells in kidney health and disease.

Positioned at the head of the nephron, the renal corpuscle generates a plasma ultrafiltrate to initiate urine formation. Three major cell types within the renal corpuscle, the glomerular mesangial cells, podocytes, and glomerular capillary endothelial cells, communicate via endocrine- and paracrine-signaling mechanisms to maintain the structure and function of the glomerular capillary network and filtration barrier. Ca2+ signaling mediated by several distinct plasma membrane Ca2+ channels impacts the functions of all three cell types. The past two decades have witnessed pivotal advances in understanding of non-voltage-gated Ca2+ channel function and regulation in the renal corpuscle in health and renal disease. This review summarizes the current knowledge of the physiological and pathological impact of non-voltage-gated Ca2+ channel signaling in mesangial cells, podocytes and glomerular capillary endothelium. The main focus is on transient receptor potential and store-operated Ca2+ channels, but ionotropic N-methyl-d-aspartate receptors and purinergic receptors also are discussed. This update of Ca2+ channel functions and their cellular signaling cascades in the renal corpuscle is intended to inform the development of therapeutic strategies targeting these channels to treat kidney diseases, particularly diabetic nephropathy.

STRUCTURE AND PROPERTIES OF THE GLOMERULAR FILTRATION BARRIER OF VERTEBRATES: ROLE OF CHARGE FOR FILTERING PROTEINS

The renal glomerulus is a unique structure that distinguishes the nephrons of vertebrates from the nephridia of invertebrate animals, providing a direct connection between the circulatory and excretory systems and the most effective control of the composition of the internal environment due to the significant intensification of filtration. The modern ideas about the structure of the glomerular filtration barrier in representatives of all major groups of vertebrates (cyclostomes, fishes, amphibians, reptiles and birds, mammals) were reviewed. Emphasis is placed on the role of the charge of the glomerular barrier structures for its selective properties; approaches to studying the contribution of the anionic components of the renal filter to preventing the loss of plasma proteins are described. The main models of the glomerular filter functioning presented in the literature are considered. Negative charge has been demonstrated to be a distinctive feature of the glomerular filter in all vertebrates. It was shown that a multiple increase of the glomerular filtration rate (from lower vertebrates to birds and mammals) was accompanied by a number of structural changes that ensured the passage of a significant volume of water and dissolved low-molecular substances through the glomerular filter: an increase in the number and ordering of fenestrae in the endothelium of glomerular capillaries, thinning of the glomerular basement membrane and complete exclusion of cellular elements from it. It has been shown that comparative physiological data on the glomerular filter in different groups of vertebrates most strongly confirm the electrokinetic model of the glomerular filtration, since it explains the importance of the evolutionarily conservative structure of podocytes and the role of a set of fixed anionic charges in the filter wall to prevent the loss of macromolecules (primarily proteins) from blood at different intensities of the ultrafiltration.

Effects of calcitriol on peripheral endothelial progenitor cells and renal renovation in rats with chronic renal failure

BackgroundThe role of calcitriol (1,25-dihydroxyvitamin D3 or 1,25-(OH)2D3) in physiological processes, such as anti-fibrosis, anti-inflammation, and immunoregulation is known; however, its role in the remodeling of the glomerular capillary endothelium in rats with chronic renal failure (CRF) remains unclear. MethodsHere, we analyzed the role/number of endothelial progenitor cells (EPCs), renal function, and pathological alterations in rats with CRF, and compared the results before and after supplementation with calcitriol in vivo. ResultsAmongst the three experimental groups (sham group, CRF group, and calcitriol-treated group (0.03 μg/kg/d), we observed substantially elevated cell adhesion and vasculogenesis in vivo in the calcitriol-treated group. Additionally, lower levels of serum creatinine (Scr) and blood urea nitrogen (BUN) was recorded in the calcitriol-treated group than the CRF group (p > 0.05). Calcitriol treatment also resulted in an improvement in renal pathological injury. ConclusionsThus, calcitriol could ameliorate the damage of glomerular arterial structural and renal tubules vascular network integrity, maybe through regulating the number and function of EPCs in the peripheral blood of CRF rats. Treatment with it may improve outcomes in patients with renal insufficiency or combined cardiac insufficiency.Calcitriol could ameliorate CRF-induced renal pathological injury and renal dysfunction by remodeling of the glomerular capillary endothelium, thus, improving the function of glomerular endothelial cells.

MO070NEW ASPECTS OF THE PATHOMORPHOLOGIC SEQUENCE OF NEPHRON LOSS IN DIABETIC NEPHROPATHY

Abstract Background and Aims Diabetic nephropathy (DN) is the leading cause of end-stage-renal disease in western countries. Despite of innumerable studies undertaken to elucidate the pathogenesis of DN the underlying morphologic alterations have been insufficiently analyzed. Method Re-evaluation of more than 800 biopsies was done showing several unknown features. Results: 1. Matrix accumulation in the mesangium: Thickening of the glomerular basement membrane (GBM) and expansion of the mesangial matrix are hallmarks of DN, generally considered to emerge from different sites of overproduction: GBM components from podocytes and mesangial matrix from mesangial cells. We show, that the accumulation of matrix in the mesangium emerges from an overproduction of GBM material by podocytes and endothelial cells and an impaired degradation by mesangial cells. The progressing deposition of worn-out GBM material into the mesangium accounts for the advancement from diffuse mesangial sclerosis (DMS) to nodular sclerosis (NS) and to the herniation of the tuft through the glomerular vascular pole to the outside; the latter is associated with the outgrowth of glomerular capillaries into the peri-glomerular space leading to the destruction of the juxtaglomerular apparatus. 2.The role of podocytes Podocytes have frequently been accused to play a central role in DN. This is correct, but in another way than generally assumed. Damage to podocytes cannot be seen in DMS. The albuminuria regularly seen during this stage derives, as previously suggested by others, from an increased leakiness of the glomerular capillary endothelium based on a deranged glycocalyx. Podocyte detachments start at the transition from DMS to NS, based on the loss of cross talk signals with the capillary endothelium: the increasing deposition of matrix leads to the collapse of many capillaries. These podocytes contribute little to the further progression of the damage: they are lost into primary urine or they undergo cell lysis.In addition to their role in increased matrix production, podocytes take an active role in the formation of tuft adhesions to Bowman’s capsule (BC), starting the progression to NS. Expansion of the matrix within the mesangium has led to expansion of the tuft (frequently associated with nodules) towards Bowman’s capsule (BC) or towards the urinary orifice. Podocytes on the surface of these expansions are in their majority structurally intact, exhibiting an intact pattern of foot processes. These podocytes come into contact with parietal epithelial cells and initiate DN-specific tuft adhesions to BC allowing the proliferation of glomerular capillaries into BC. There they deliver an exudate into BC that spreads around the entire circumference of the glomerulus presenting as giant insudative spaces. Moreover, this process encroaches via the glomerulo-tubular junction onto the tubule constituting the major pathway of glomerular damage extending to the tubulointerstitium. 3. Tubulointerstitial fibrosisIt is current opinion that the tubulointerstitial fibrosis may start from tubular damage resulting in an own, glomerular-independent pathway to nephron loss. However, there is scant evidence for such a mechanism. Studying 162 glomerulo-tubular transitions, we did not see a tubular epithelial or interstitial damage in those biopsies without any evidence of a glomerulo-tubular damage transfer. The only exception consists of the well-known prominent thickening of the tubular basement membrane, which may result in functional loss but does not lead to structural epithelial damage. Conclusion We consistently found that tubulo-interstitial damage develops after encroachment of the glomerular damage onto the tubule, leading first to a gradual degeneration of tubules which subsequently initiate the process of interstitial fibrosis.

Pathogenetic and morphological features in certain types of primary glomerulonephritis

The kidney, as an organ, quite often appears as the target of immune system dysregulation in the context of a primary or systemic disease. Glomerulonephritis (GL) is the most common clinical and pathological manifestation of this process. Currently, there is no unified view on the classification of GN. However, the study and recognition of the pathophysiological mechanisms of GN made it possible to determine the immunological features, biomarkers and genetic aspects of the disease. In the review, we update modern ideas about the genetic factors, etiology, immunopathogenesis of primary GN, and the variety of damage to each of the components of the glomerular filtration barrier, including the endothelium of glomerular capillaries, glomerular basement membrane and podocytes. Special attention is paid to the pathogenesis of various morphological forms of primary GN, diagnostic and prognostic biomarkers of the disease (markers of blood, urine, histopathological and genetic markers).

Kidney transplant dysfunction in a patient with COVID \u2212\u200919 infection: role of concurrent Sars-Cov 2 nephropathy, chronic rejection and vitamin C-mediated hyperoxalosis: case report

BackgroundCOVID-19 infection in kidney transplant recipients often lead to allograft dysfunction. The allograft injury has various histopathological manifestations. Our case illustrates the unusual combination of allograft rejection, acute kidney injury secondary to oxalate nephropathy and SARS CoV-2 nephropathy as the cause of irreversible allograft failure.Case presentationA 56 year old renal allograft recipient presented with a history of fever and diarrhoea for the preceding 4 weeks, tested positive for Sars-CoV2 on nasal swab and was found to have severe allograft dysfunction, necessitating haemodialysis. He subsequently underwent an allograft biopsy, which demonstrated antibody mediated rejection along with the presence of extensive oxalate deposition in the tubules. Ultrastructural examination demonstrated spherical spiked particles in the glomerular capillary endothelium and the presence of tubulo-reticular inclusions suggestive of an active COVID-19 infection within the kidney. The intra-tubular oxalate deposition was considered to be the result of high dose, supplemental Vitamin C used as an immune booster in many patients with COVID − 19 infection in India.ConclusionsThis case highlights the complex pathology that may be seen in following COVID-19 disease and the need for kidney biopsies in these patients to better understand the aetiology of disease.

The structural and ultrastructural organization of the cellular constituents of the trunk kidney of grass carp (Ctenopharyngodon idella).

The trunk kidney of grass carp mainly consisted of renal tubules with a few interstitial hematopoietic tissues. The component structure of fish nephron markedly varies between different species of fish. The nephron of grass carp consisted of morphologically distinct segments; renal corpuscles, neck segment, proximal, intermediate, distal, and collecting tubules. The glomerulus of renal corpuscles mainly composed of mesangial cells and well-developed podocytes that extended their processes to the endothelium of glomerular capillaries forming the filtration barrier. The podocytes expressed both α-SMA and the transforming growth factor gene, TGF-β. The proximal convoluted tubules (PCTs) expressed α-SMA iNOS2, and TGF-β. The cytoplasm of PCT was rich in mitochondria and rER, in addition to the presence of well-developed basolateral tubular system and apical brush borders. Collecting tubules distributed throughout the kidney and lined by principal and flask cells. The interstitial hemopoietic tissues contained iNOS2 -positive polymorphic granulocytes, CD3-positive T lymphocytes, rodlet cells, dendritic cells, macrophages, melanomacrophage centers, and telocytes. This study described for the first time the cellular components of the nephron and its associated hemopoietic tissues that can act as a basis for studying the structural changes that may occur in the kidney of grass carp during water salinitiy, environmental, or experimental conditions.

Simulations of Glomerular Shear and Hoop Stresses in Diabetes, Hypertension, and Reduced Renal Mass using a Network Model of a Rat Glomerulus

A novel anatomically accurate model of rat glomerular filtration is used to quantify shear stresses on the glomerular capillary endothelium and hoop stresses on the glomerular capillary walls. Plasma, erythrocyte volume, and plasma protein mass are distributed at network nodes using pressure differentials calculated taking into account volume loss to filtration, improving on previous models which only took into account blood apparent viscosity in calculating pressures throughout the network. Filtration is found to be heterogeneously distributed throughout the glomerular capillary network and is determined by concentration of plasma proteins and surface area of the filtering capillary segments. Hoop stress is primarily concentrated near the afferent arteriole, whereas shear stress is concentrated near the efferent arteriole. Using parameters from glomerular micropuncture studies, conditions of diabetes mellitus (DM), 5/6‐Nephrectomy (5/6‐Nx), and Angiotensin II‐induced hypertension (HTN) are simulated and compared to their own internal controls to assess the changes in mechanical stresses. Hoop stress is increased in all three conditions, while shear stress is increased in 5/6‐Nx, decreased in HTN, and maintained at control levels in DM by the hypertrophic response of the glomerular capillaries. The results indicate that these alterations in mechanical stresses and the consequent release of cytokines by or injury of the glomerular cells may play a significant role in the progression of glomerulopathy in these disease conditions.

Influence of Hydrolyzed Polyacrylamide Hydrogel Stiffness on Podocyte Morphology, Phenotype, and Mechanical Properties.

Chronic kidney disease is characterized by a gradual decline in renal function that progresses toward end-stage renal disease. Podocytes are highly specialized glomerular epithelial cells which form with the glomerular basement membrane (GBM) and capillary endothelium the glomerular filtration barrier. GBM is an extracellular matrix (ECM) that acts as a mechanical support and provides biophysical signals that control normal podocytes behavior in the process of glomerular filtration. Thus, the ECM stiffness represents an essential characteristic that controls podocyte function. Hydrolyzed Polyacrylamide (PAAm) hydrogels are smart polyelectrolyte materials. Their biophysical properties can be tuned as desired to mimic the natural ECM. Therefore, these hydrogels are investigated as new ECM-like constructs to engineer a podocyte-like basement membrane that forms with cultured human podocytes a functional glomerular-like filtration barrier. Such ECM-like PAAm hydrogel construct will provide unique opportunity to reveal podocyte cell biological responses in an in vivo-like setting by controlling the physical properties of the PAAm membranes. In this work, Hydrolyzed PAAm scaffolds having different stiffness ranging between 0.6-44 kPa are prepared. The correlation between the hydrogel structural and mechanical properties and Podocyte morphology, elasticity, cytoskeleton reorganization, and podocin expression is evaluated. Results show that hydrolyzed PAAm hydrogels promote good cell adhesion and growth and are suitable materials for the development of future 3D smart scaffolds. In addition, the hydrogel properties can be easily modulated over a wide physiological range by controlling the cross-linker concentration. Finally, tuning the hydrogel properties is an effective strategy to control the cells function. This work addressed the complexity of podocytes behavior which will further enhance our knowledge to develop a kidney-on-chip model much needed in kidney function studies in both healthy and diseased states.

SAT-125 Proteoglycans are glomerular endothelial glycocalyx components playing a major role in permselectivity and prevention of proteinuria

The loss of permselectivity resulting in proteinuria is a critical step during kidney disease progression. The luminal surface layer of the glomerular capillary endothelium (ESL) consists of a glycocalyx and an endothelial cell coat, which together form a stagnant mucosal layer hindering leakage of macromolecules such as albumin from blood to urine. We have investigated the composition and possible role for the ESL in glomerular kidney disease.

Disorders of club filtration barrier as the cause of proteinuria in the nephrotic syndrome

The review is devoted to the causes and mechanisms of proteinuria in various diseases associated with the development of the nephrotic syndrome. The contribution of damage to the main components of the glomerular filtration barrier, including the endothelium of glomerular capillaries, glomerular basement membrane, and podocytes, was analyzed. It is shown that the induction of proteinuria may be a consequence of disorders of the structure and function of each of these layers of the filter, as well as its combined damage. Special attention is given to the role of the glycocalyx and its components as well as reactive oxygen species and endothelial growth factor in the pathogenesis of disorders of the selective permeability of the capillary endothelium of the glomeruli in minimal change disease, focal segmental glomerulosclerosis, pre-eclampsia, diabetogenic nephropathy. The significance of such genetic disorders of the glomerular membrane as Pearson and Alport syndromes is discussed. Gene mutations causing disorders of the structure and functioning of the main proteins of the actinic cytoskeleton of podocytes are considered separately.

Engineering the vasculature of decellularized rat kidney scaffolds using human induced pluripotent stem cell-derived endothelial cells

Generating new kidneys using tissue engineering technologies is an innovative strategy for overcoming the shortage of donor organs for transplantation. Here we report how to efficiently engineer the kidney vasculature of decellularized rat kidney scaffolds by using human induced pluripotent stem cell (hiPSCs)-derived endothelial cells (hiPSC-ECs). In vitro, hiPSC-ECs responded to flow stress by acquiring an alignment orientation, and attached to and proliferated on the acellular kidney sections, maintaining their phenotype. The hiPSC-ECs were able to self-organize into chimeric kidney organoids to form vessel-like structures. Ex vivo infusion of hiPSC-ECs through the renal artery and vein of acellular kidneys resulted in the uniform distribution of the cells in all the vasculature compartments, from glomerular capillaries to peritubular capillaries and small vessels. Ultrastructural analysis of repopulated scaffolds through transmission and scanning electron microscopy demonstrated the presence of continuously distributed cells along the vessel wall, which was also confirmed by 3D reconstruction of z-stack images showing the continuity of endothelial cell coverage inside the vessels. Notably, the detection of fenestrae in the endothelium of glomerular capillaries but not in the vascular capillaries was clear evidence of site-specific endothelial cell specialisation.

Association of Soluble TNFR-1 Concentrations with Long-Term Decline in Kidney Function: The Multi-Ethnic Study of Atherosclerosis.

TNF receptor-1 (TNFR-1), which plays a causative role in endothelial cell dysfunction and inflammation, is expressed on the cell surface in glomerular and peritubular capillary endothelium of the kidneys. Higher soluble TNF receptor-1 (sTNFR-1) concentrations are associated with kidney disease progression among persons with established diabetic kidney disease. However, no studies have assessed sTNFR-1's role in long-term kidney function changes in a multiethnic population without cardiovascular disease at baseline. We tested associations between baseline sTNFR-1 concentrations and 10-year decline in eGFR (incident ≥40% decline and annual proportional decline) among 2548 participants in the Multi-Ethnic Study of Atherosclerosis (MESA), a prospective cohort study. Serum creatinine concentrations were determined at enrollment and study years 3, 5, and 10. Mean age of participants was 61 years old, 53% were women, and mean baseline eGFR was 79 ml/min per 1.73 m2. Serum sTNFR-1 was inversely associated with baseline eGFR. Over median follow-up of 9.3 years, 110 participants developed ≥40% decline in eGFR; each SD higher concentration of sTNFR1 was associated with higher risk of 40% eGFR decline (adjusted hazard ratio, 1.43; 95% confidence interval [95% CI], 1.16 to 1.77; P<0.001). The highest sTNFR-1 tertile was associated with adjusted annualized decline in eGFR of 1.94% (95% CI, 1.79 to 2.09). Associations persisted across subgroups defined by demographics, hypertension, diabetes, and baseline CKD status. Elevated serum sTNFR-1 concentrations are associated with faster declines in eGFR over the course of a decade in a multiethnic population, independent of previously known risk factors for kidney disease progression.

A comparative study on the efficacy of a retrograde perfusion technique and an antegrade perfusion technique for donor kidney recovery in transplantation in pigs

BackgroundDonor organ shortage is a significant problem in kidney transplantation. Improvement of perfusion techniques can increase the number of available organs. The aim of this study is to investigate the efficiency and safety of retrograde perfusion (RP) of kidney grafts during organ recovery after transplantation in pigs.MethodsTen pigs were divided into two groups, six in the study group for the RP technique and four in the control group for standard antegrade perfusion (AP). The left kidney was removed and perfused by the RP or AP method according to the study group. The perfused left kidney was auto-transplanted to the right groin location. The right kidney was removed and perfused in the same manner and then stored at 4 °C for 24 h prior to histopathological analysis. Data in both groups were observed and recorded.ResultsAll kidneys perfused by both the RP and AP methods were satisfactory in appearance. All grafts showed diuresis from the first postoperative day onward. On postoperative day 7, the mean serum creatinine (Scr) and blood urea nitrogen (BUN) levels were 174 ± 9.7 ìmol/L and 27.7 ± 2.5 mg/dL in the RP group, and they were 168 ± 13.7 ìmol/L and 26.5 ± 4.3 mg/dL, respectively, in the AP group (p = 0.483 for Scr and p = 0.646 for BUN). The mean peak Scr levels in the RP group (570 ìmol/L) and the AP group (530 ìmol/L) were similar. All pigs survived with adequate renal function throughout the study period. There was minimal interstitial and tubular edema, and there was endothelial cell swelling in some specimens before revascularization in both groups. At postoperative day 7, the auto-transplanted kidneys showed normal glomerular and tubular structure with little interstitial edema and inflammatory cell infiltration in the grafts. No differences were identified between the two groups. Under electron microscopy, the tubular epithelial cells, glomeruli, and glomerular capillary endothelium of the grafts appeared normal in both groups after 24 h in cold storage.ConclusionsKidney grafts in pigs perfused by RP had normal function after transplantation compared with the AP control group. Therefore,retrograde perfusion is potentially an efficient, safe kidney perfusion method for organ recovery.

Does Olive Oil Attenuate Ciprofloxacin-Induced Renal Cortical Toxicity? Light and Electron Microscopic Study

Introduction: Ciprofloxacin (CPFX) is a broad spectrum antibiotic used for treatment of many infections. Olive oil is rich in compounds that have strong antioxidant activity.Aim: To assess CPFX-induced renal cortical structural changes in albino rats and to evaluate whether or not olive oil could attenuate such changes.Materials and Methods: Thirty two male albino rats were used and divided into 4 groups. Control group received distilled water, OO group received olive oil (5ml/kg/day), CPFX group received CPFX (20 mg/kg/day) and CPFX+OO group received both CPFX and olive oil as the previous groups. All medications were continued for 14 days. Renal cortex specimens were processed for light and electron microscopy. Morphometric study and statistical analysis for the results were also performed.Results: CPFX group revealed irregularity and shrinkage of renal corpuscles with loss of vascular component and capsular space obliteration. The mesangial cells were significantly increased. The renal tubules showed dilatation with significant increase in proximal convoluted tubules diameter, marked degeneration, significant increase in the darkly stained nuclei of their lining cells and intraluminal casts. Congested glomerular capillaries and peritubular blood vessels were also observed. Ultrastructurally, there were thickening of glomerular basement membrane, fusion of glomerular capillary endothelium and podocyte pedicles. Cytoplasmic empty areas and vacuolations, swollen mitochondria, nuclear changes were also found in the tubules. CPFX + OO group showed less structural changes.Conclusion: Olive oil has ameliorating effect on ciprofloxacin-induced renal cortical toxicity.

Occurrence of fenestral diaphragms and knots in renal glomerular endothelia of diabetic mutant MafA-/-MafK+ mice as revealed in embedment-free transmission electron microscopy.

Using the advantages (high contrast and transparency and efficient 3D viewing) of embedment-free section transmission electron microscopy (TEM), the occurrence of numerous fenestral diaphragms was clearly shown in 3D en-face viewing of the renal glomerular capillary endothelium of severe overt diabetes mellitus mice, which were generally MafA-deficient and simultaneously MafK-overexpressed specifically in pancreatic β-cells. This presents another example of nephritis-induced diaphragmed fenestrae in the renal glomerular endothelium. In addition, knot-/umbilicus-like structures discrete from and larger than the central knots of regular diaphragms of fenestrated endothelium were clearly demonstrated to occur randomly in the renal glomerular endothelial fenestrae of mutant mice and wild ones. The knot-structures were revealed to be protrusions of underlining basement lamina in conventional TEM by section-tilting observation.

Interleukin-1β increases permeability and upregulates the expression of vascular endothelial-cadherin in human renal glomerular endothelial cells.

The renal glomerular capillary endothelium is part of the glomerular filtration barrier and is involved in acute and chronic inflammation of the glomerulus. Glomerular endothelial cells are a unique type of microvascular cell, which remain to be fully characterized. The aim of the present study was to examine the permeability of glomerular endothelial cells and their responses to interleukin (IL)‑1β, a pro‑inflammatory cytokine. Human glomerular endothelial cell (HRGEC) and human umbilical vein endothelial cell (HUVEC) monolayers were examined using a Transwell permeability assay, transendothelial electrical resistance (TEER) and by determining the expression of the adhesion molecule, vascular endothelial (VE)‑cadherin, in the absence or presence of 10 ng/ml IL‑1β. Compared with the HUVECs, the HRGECs demonstrated higher permeability, lower TEER and reduced expression of VE‑cadherin. IL‑1β induced an increase in the permeability and a decrease in the TEER of the HRGECs, however, to a lesser extent compared with the HUVECs. Following IL‑1β treatment, the expression of VE‑cadherin was increased in the HRGECs and decreased in the HUVECs. These results suggested that HRGECs have distinct biological properties and specific gene expression features in response to IL‑1β.

O papel de imunoglobulinas na nefropatia da leptospirose em suínos

A leptospirose é uma antropozoonose endêmica em todo o mundo, que afeta o homem e várias espécies de animais domésticos e silvestres. No início da infecção há produção de IgM para o controle da infecção e após alguns dias, IgG são produzidas e provocam lise das leptospiras circulantes. Objetivou-se neste estudo identificar depósitos de antígeno de leptospiras e imunoglobulinas no tecido renal, para avaliar o papel de imunoglobulinas na patogênese da nefropatia da leptospirose em suínos. Foram colhidas 139 amostras de sangue e rim de suínos das cidades de Teresina/PI e Timon/MA, que foram avaliadas pela SAM, imunoistoquímica e PCR. Nefrite intersticial, fibrose, vasculite, tumefação do tufo glomerular e hipercelularidade difusa foram as principais alterações histopatológicas encontradas. A imunoistoquímica detectou antígeno de leptospira em 60 suínos. Depósitos de IgG, IgM e IgA foram observados no endotélio de capilares glomerulares, dos capilares intertubulares e na cápsula de Bowman, com marcação focal, difusa, global e segmentar. A deposição de IgM e IgA foi significantemente maior nos suínos infectados. Estranhamente depósitos de IgG foi significantemente maior nos suínos não infectados, onde não havia presença de antígeno de leptospiras e nem lesão túbulo-intersticial. Concluímos que antígeno de leptospiras no rim de suínos está relacionado a depósitos de IgM e IgA mas não a depósitos de IgG.

Ultrastructural study of the kidney in the coelacanth Latimeria chalumnae (Rhipidistia: Coelacanthini).

The morphology of the nephrons of the coelacanth Latimeria chalumnae was investigated by electron microscopy. Each nephron is composed of a large renal corpuscle with well vascularized glomerulus, ciliated neck segment, proximal tubule divided into first and second proximal segments, ciliated intermediate segment, distal tubule, collecting tubule, and duct. The podocytes of visceral epithelium contain large bi-lobed nuclei and their surface membranes pinch off vesicles into the cytoplasm. The processes of the podocytes give rise to pedicels that enclose narrow filtration slits. The endothelium of glomerular capillaries is attenuated and fenestrated. The short cytoplasmic processes of mesangial cells do not penetrate deeply into the sub-endothelial lamina. The glomerular basement membrane is about 286 nm in thickness. The pedicels also arise from podocyte cell bodies, and are connected by diaphragms and enclose slits, which open into narrow urinary spaces between podocytes. The cuboidal cells of the short neck segment display cilia with a characteristic pattern of 9+2 microtubules. The first proximal tubule segment differs from the second proximal segment in having densely packed microvilli, prominent endocytotic-lysosomal apparatus, and numerous basal membrane infoldings associated with mitochondria. The lateral cell membranes like those of other segments are straight and joined by desmosomes and apical adhering and tight junctions. The distal tubules display few short luminal microvilli and numerous basal mitochondria. The distal tubule, collecting tubule and duct are devoid of intercalated cells. The ultrastructure of the L chalumnae nephrons correlates well with their osmoregulatory function and resembles that of freshwater rainbow trout.

Beyond C4d: the ultrastructural appearances of endothelium in ABO-incompatible renal allografts

ABO incompatibility is no longer a barrier in kidney transplantation. C4d is frequently positive in ABO-incompatible (iABO) biopsies without further signs of microcirculation injury. This phenomenon is assumed to represent graft accommodation. However, ultrastructural examination of glomerular and peritubular capillary endothelium might reveal subtle endothelial damage. We studied the ultrastructural appearance of the endothelium in 67 biopsies from 21 patients with iABO allografts and compared it with 20 patients (29 biopsies) with ABO-compatible (cABO) grafts with C4d positivity and 25 ABO-compatible control patients (25 biopsies) without serological or histological evidence of humoral rejection (C4d negative). Ten ultrastructural parameters indicative of chronic and acute glomerular and peritubular capillary damage in transmission electron microscopy (TEM) were semi-quantitatively graded and expressed in a sum score. Clinico-pathological data were compared as well as graft function at the time of biopsy and follow-up. Ultrastructural parameters did not significantly differ between iABO and controls. In contrast, C4d-positive cABO had the highest TEM sum score (P = 0.001 versus iABO, P = 0.002 versus controls). The sum score did not differ between C4d-positive and C4d-negative iABO but did differ between patients with and without anti-HLA donor-specific antibodies (DSA). Graft function in iABO at the time of biopsy and at follow-up was similar to controls. Our ultrastructural observations support the concept of endothelial accommodation in iABO renal transplants. C4d positivity in the ABO-incompatible situation does not indicate injurious activation of the complement cascade and does not seem to impact on the graft function, in contrast to C4d deposition in cABO with antibody-mediated rejection.