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Introduction: Post hematopoietic stem cell transplant (HSCT), kidney can be subjected to injury by various causes. Of these, graft versus host disease (GvHD) affecting the kidney is an under-recognized entity with no clear guidelines on its diagnosis, clinicopathological manifestations, and outcomes. Material and Methods: Out of 2,930 patients who underwent HSCT at our center between 2005 and 2020, kidney biopsy was performed in 19 allogenic and 5 autologous recipients. Results: The mean age of the cohort at transplant was 33.2 ± 7 years, and 15 (62%) were males. Median time to kidney biopsy from HSCT was 14 (IQR, 9–30) months. Aplastic anemia was the most common underlying hematological disease (54.2%). All 19 allogenic recipients were classified based on clinicopathological manifestations into either thrombotic microangiopathy (TMA, 12/19 [63%]) or nephrotic syndrome (NS, 7/19 [37%]) pattern. Glomerular tuft “mesangiolysis” was the dominant pattern of injury noted in 9/12 cases of TMA pattern. There was a predominance of acute microangiopathic changes restricted primarily to the glomerular compartment. Of the 7 patients with NS pattern, membranous nephropathy was seen in 4 (57%) and minimal change disease in 3 (43%) patients. Thirty-nine percent (7/18) stained positive for C4d which was predominantly glomerular. Allogenic recipients who did not receive immunosuppression (IS) for renal disease had a lower eGFR at biopsy, a longer latency between withdrawal of GvHD prophylaxis and biopsy, and were significantly at a higher risk of kidney failure (IS: 2/11, 18.1% vs. no IS: 2/6, 33.3%, p = 0.04). “Associated extra-renal GvHD” occurred in 11/19 (57.9%) allogenic recipients. Patients with “associated extra-renal GvHD” had significantly more deaths (6/11, 60% vs. 0, p = 0.02) but comparable renal outcomes. Conclusion: Renal GvHD can present with or without “associated extra-renal GvHD” after a prolonged period of withdrawal of GvHD prophylaxis, requiring careful diagnostic vigilance and consideration of IS.

Abstract Background Atypical hemolytic uremic syndrome (aHUS) is a life-threatening disease that leads to end-stage kidney disease if only a poor response to plasma exchanges (PEs) or eculizumab therapy is achieved. Case presentation A 58-year-old Japanese man presented with thrombocytopenia, anemia, and kidney failure requiring dialysis without any underlying disease. A kidney biopsy revealed marked mesangiolysis in all glomeruli, compatible with thrombotic microangiopathy (TMA). Based on the positive anti- factor H antibody and negative result for secondary TMA, we diagnosed him as aHUS. Despite eculizumab administration after eight sessions of PE, neither platelet normalization nor kidney recovery was achieved. Eight months later, we discontinued eculizumab therapy due to anaphylactic reaction. At 15 months after the onset of TMA, his platelet count increased gradually from 40 to 150 × 103/μL with a decreased serum creatinine level and increased urine output, eventually allowing the withdrawal of dialysis therapy. A second kidney biopsy showed mesangial widening compatible with the healing of TMA. Conclusions This case indicates that aHUS with PEs and eculizumab therapy has the potential for renal recovery even if over 1 year has passed.

Abstract Background Post-transplant diabetes mellitus (PTDM) is an emerging problem in kidney transplantation, representing an important risk factor for kidney function loss. Diabetic nephropathy (DN) occurrence in transplanted kidneys is poorly investigated. Current knowledge describes DN recurrence in graft 5.9 years from kidney transplantation however there is little data about PTDM and DN. Here, we report a clinical case peculiar for an early appearance of advanced glomerular diabetic lesions, after kidney transplantation. Case presentation A 45-year-old Caucasian male affected by autosomal polycystic kidney disease was transplanted with a cadaveric-kidney-donor from 58-year-old male. Induction immunosuppressive therapy included basiliximab and steroids while the maintenance treatment included, tacrolimus, mofetil micophenolate and methylprednisolone. One month after transplantation the patient developed diabetes requiring treatment with repaglinide quickly replaced with insulin to obtain an acceptable glycemic control (HbA1c 52 mmol/mol). Glycosuria was detected persistently during the first six months after transplantation. To achieve further improvement in glycemic control, a shift from tacrolimus to cyclosporine (CyA) was made and steroids were rapidly tapered and stopped. To minimize calcineurin inhibitors toxicity, which was revealed in the 1-year-protocol-biopsy, everolimus was introduced thereby lowering CyA through levels. Moderate hypertension was well controlled with doxazosin. Thirty months after transplantation a second graft biopsy was performed owing to renal function decline and microalbuminuria appearance. Histological analysis surprisingly showed mesangiolysis and microaneurysms; glomerular sclero-hyalinosis and basal membrane thickness and typical nodular glomerulosclerosis. C4d staining was negative and no evidence of immune deposits were detected. Donor Specific Antibodies, serum C3 and C4 levels and autoimmunity tests were negative. Retrospective analysis on donor history didn’t show diabetes or insulin resistance and no diabetic lesions were found in kidney pre-implant biopsy. Conclusions In our knowledge, this is the first report describing a very early onset of advanced diabetic glomerular lesions in a graft biopsy after PTDM. We hypothesize that additional factors such as everolimus and hypertension, may have contribute to kidney damage.

Background Chronic hypoxia may play a pivotal role in the development of diabetic nephropathy (DN). However, the precise mechanisms underlying progressive hypoxia-induced glomerular injury remain unclear. Methods We housed db/db mice in a hypoxia chamber (12% O2) for up to 16 weeks beginning at 8 weeks of age. Various urine, serum and kidney abnormalities and glomerular messenger RNA (mRNA) expression were compared with those in age-matched db/db mice housed under normoxia. Results Levels of urinary albumin and podocalyxin (PCX) were significantly higher in hypoxic mice early during hypoxia. Ultracentrifugation of urine samples revealed that podocytes in the hypoxic mice shed PCX-positive microparticles into the urine. After 16 weeks of hypoxia, the mice also had higher hematocrits with lower serum glucose and various degrees of mesangiolytic glomerulosclerosis with microaneurysms and the infrequent occurrence of nodular lesions. Immunohistologically, hypoxic mice showed significantly decreased endothelial cell densities early during hypoxia and decreased podocyte densities later. In both hypoxic and normoxic mice, glomerular macrophage and transforming growth factor-β1 (TGF-β1) staining significantly increased with aging, without changes in vascular endothelial growth factor or endothelial nitric oxide synthase (eNOS). Glomerular mRNA expression of monocyte chemoattractant protein-1, eNOS and TGF-β1 was significantly enhanced in the hypoxic mice. Conclusions These results indicate that chronic hypoxia induces advanced glomerulosclerosis with accelerated albuminuria triggered by mesangiolysis and podocyte injury in a murine model of DN. [ABSTRACT FROM AUTHOR]

Background: Atypical hemolytic uremic syndrome (aHUS) is a life-threatening disease that leads to end-stage kidney disease if only a poor response to plasma exchanges (PEs) or eculizumab therapy is achieved.Case Presentation: A 58-year-old Japanese man presented with thrombocytopenia, anemia, and kidney failure requiring dialysis without any underlying disease. A kidney biopsy revealed marked mesangiolysis in all glomeruli, compatible with thrombotic microangiopathy (TMA). Based on the positive anti- factor H antibody and negative result for secondary TMA, we diagnosed him as aHUS. Despite eculizumab administration after eight sessions of PE, neither platelet normalization nor kidney recovery was achieved. Eight months later, we discontinued eculizumab therapy due to anaphylactic reaction. At 15 months after the onset of TMA, his platelet count increased gradually from 40 to 150 × 103/μL with a decreased serum creatinine level and increased urine output, eventually allowing the withdrawal of dialysis therapy. A second kidney biopsy showed mesangial widening compatible with the healing of TMA.Conclusions: This case indicates that aHUS with PEs and eculizumab therapy has the potential for renal recovery even if over 1 year has passed. [ABSTRACT FROM AUTHOR]

Background: The Japanese classification of diabetic nephropathy reflects the risks of mortality, cardiovascular events and kidney prognosis and is clinically useful. Furthermore, pathological findings of diabetic nephropathy are useful for predicting prognoses. In this study, we evaluated the characteristics of pathological findings in relation to the Japanese classification of diabetic nephropathy and their ability to predict prognosis.Methods: The clinical data of 600 biopsy-confirmed diabetic nephropathy patients were collected retrospectively from 13 centers across Japan. Composite kidney events, kidney death, cardiovascular events, all-cause mortality, and decreasing rate of estimated GFR (eGFR) were evaluated based on the Japanese classification of diabetic nephropathy.Results: The median observation period was 70.4 (IQR 20.9-101.0) months. Each stage had specific characteristic pathological findings. Diffuse lesions, interstitial fibrosis and/or tubular atrophy (IFTA), interstitial cell infiltration, arteriolar hyalinosis, and intimal thickening were detected in more than half the cases, even in Stage 1. An analysis of the impacts on outcomes in all data showed that hazard ratios of diffuse lesions, widening of the subendothelial space, exudative lesions, mesangiolysis, IFTA, and interstitial cell infiltration were 2.7, 2.8, 2.7, 2.6, 3.5, and 3.7, respectively. Median declining speed of eGFR in all cases was 5.61 mL/min/1.73 m2/year, and the median rate of declining kidney function within 2 years after kidney biopsy was 24.0%.Conclusions: This study indicated that pathological findings could categorize the high-risk group as well as the Japanese classification of diabetic nephropathy. Further study using biopsy specimens is required to clarify the pathogenesis of diabetic kidney disease. [ABSTRACT FROM AUTHOR]

The homeostatic chemokine receptor CCR7 serves as key molecule in lymphocyte homing into secondary lymphoid tissues. Previous experiments from our group identified CCR7 also to be expressed by human mesangial cells. Exposing cultured human mesangial cells to the receptor ligand CCL21 revealed a positive effect on these cells regarding proliferation, migration, and survival. In the present study, we localized CCR7 and CCL21 during murine nephrogenesis. Analyzing wild-type and CCR7 deficient (CCR7–/–) mice, we observed a retarded glomerulogenesis during renal development and a significantly decreased mesangial cellularity in adult CCR7–/– mice, as a consequence of less mesangial cell proliferation between embryonic day E17.5 and week 5 postpartum. Cell proliferation assays and cell-wounding experiments confirmed reduced proliferative and migratory properties of mesangial cells cultured from CCR7–/– kidneys. To further emphasize the role of CCR7 as important factor for mesangial biology, we examined the chemokine receptor expression in rats after induction of a mesangioproliferative glomerulonephritis. Here, we demonstrated for the first time that extra- and intraglomerular mesangial cells that were CCR7-negative in control rats exhibited a strong CCR7 expression during the phase of mesangial repopulation and proliferation. [ABSTRACT FROM AUTHOR]

Aims: Nodular lesions are one of the most characteristic pathological changes of advanced diabetic nephropathy (DN). Previous studies have demonstrated that the pattern of both routine and collagen staining of nodular lesions changes during their development. However, the association between such changes of staining and the renal prognosis remains unclear.Methods: Among 252 patients with biopsy-proven DN, 67 met the selection criteria and were enrolled to investigate this relationship. In all patients, nodular lesions were stained with periodic acid Schiff, periodic acid methenamine silver, and Masson trichrome stains, and immunostaining was done for type I, III, IV, V, and VI collagen. The endpoint was commencement of dialysis due to end-stage renal disease.Results: At least one mesangiolytic nodular lesion (MNL) that showed faint staining for PAS and PAM was found in 61% of the patients. MNLs were negative for type IV collagen staining, unlike the strong positivity of non-MNLs, while type V and VI collagen staining were strongly positive in all nodular lesions. Cox proportional hazards regression analysis revealed that the hazard ratio (HR) for the endpoint was significantly higher in patients with at least one MNL than in patients with no MNLs after adjustment for known promoters of renal progression (HR: 2.94; 95% confidence interval: 1.24-7.07).Conclusions: MNLs may reflect characteristic differences of collagen production and could be a useful prognostic indicator in patients with nodular lesions. Further investigation of the mechanism underlying these differences of collagen production could contribute to finding new therapeutic targets for DN. [ABSTRACT FROM AUTHOR]

A 58-year-old normotensive male with normal renal function and gastric cancer underwent total gastrectomy and received adjuvant chemotherapy with mitomycin C (MMC) for 10 months. He developed anemia, hypertension, and renal function impairment 9 months after initiation of chemotherapy. Kidney biopsy showed thrombotic microangiopathy with marked mesangiolysis and expansion of the subendothelial space resulting in cystic dilation of the glomerular capillaries, and cellular atypia in the tubular cells. His renal function deteriorated gradually then stabilized after treatment with plasma exchange, antihypertensive agents, and antiplatelet agents. He had no sign of tumor recurrence after 3 years of follow-up. We suggest that patients receiving MMC should have their blood pressure and renal function closely monitored for the possibility of development of drug-induced renal insufficiency.

Introduction: This study aimed to determine if immune or nonimmune and acute or chronic lesions associated with mesangiolysis (MGLS) occurred in biopsy-proven pathological chronic active antibody-mediated rejection (P-CAABMR) in kidney transplant biopsies., Methods: We evaluated MGLS in 41 patients with biopsy findings of P-CAABMR from January 2016 to December 2019. Histological scoring was evaluated by Banff classification. Multivariate logistic regression analysis was performed using a forward selection method., Results: Fifteen of the 41 P-CAABMR biopsies (36.6%) cases showed MGLS. The estimated glomerular filtration rate (eGFR) was significantly lower in the MGLS-positive compared with the MGLS-negative group, and proteinuria was significantly higher in the MGLS-positive compared with the MGLS-negative group. In the clinical model, multivariate analysis was performed using covariates of eGFR and duration after transplantation significantly correlated with MGLS by simple analysis, in addition to type of calcineurin inhibitor use (tacrolimus or cyclosporine), donor-specific antibodies, diabetes, and hypertension grade defined by use of antihypertensive therapy or/and blood pressure level. Only hypertension grade was significantly correlated with MGLS. In the pathological model, multivariate analysis was performed using the presence of FSGS and the aah and cg scores significantly correlated with MGLS by simple analysis, in addition to g and ptc scores. The cg score was significantly correlated with hypertension grade, duration after transplantation, g, ah, and aah., Conclusion: Lower graft function and higher proteinuria was observed in MGLS of P-CAABMR. The Banff cg score was independently related to MGLS in multivariate analysis. Sustained glomerulitis, calcineurin inhibitor nephrotoxicity, and hypertension may cause Banff cg lesions, leading to MGLS in P-CAABMR., (© 2023 S. Karger AG, Basel.)

Diabetic nephropathy is a leading cause of end-stage renal failure all over the world. Advanced human diabetic nephropathy is characterized by the presence of specific lesions including nodular lesions, doughnut lesions, and exudative lesions. Thus far, animal models precisely mimicking advanced human diabetic nephropathy, especially nodular lesions, remain to be fully established. Animal models with spontaneous diabetic kidney diseases or with inducible kidney lesions may be useful for investigating the pathogenesis of diabetic nephropathy. Based on pathological features, we previously reported that diabetic glomerular nodular-like lesions were formed during the reconstruction process of mesangiolysis. Recently, we established nodular-like lesions resembling those seen in advanced human diabetic nephropathy through vascular endothelial injury and mesangiolysis by administration of monocrotaline. Here, in this review, we discuss diabetic nodular lesions and its animal models resembling human diabetic kidney lesions, with our hypothesis that endothelial cell injury and mesangiolysis might be required for nodular lesions. [ABSTRACT FROM AUTHOR]

23-year-old Japanese man who had undergone hematopoietic stem cell transplantation for acute lymphocytic leukemia from an HLA-identical sibling 6 years earlier developed proteinuria and impaired kidney function. Kidney biopsy revealed thrombotic microangiopathy with a moderate increase in mesangial matrices and glomerular microaneurysm featuring retention of red blood cells. The patient's kidney function gradually deteriorated, requiring the institution of treatment with angiotensin II receptor blockers and angiotensin-converting enzyme inhibitors, and progressing to continuous ambulatory peritoneal dialysis 4 years after the initial kidney biopsy. Eventually, kidney transplantation was performed with his mother as the donor. His kidney function is stable on immunosuppressive drugs at 2 years after transplantation. This report reflects the growing number of patients with chronic kidney disease with thrombotic microangiopathy all over the world. [ABSTRACT FROM AUTHOR]

The vascular endothelium expresses endothelial nitric oxide synthase (eNOS) that generates nitric oxide (NO) to help maintain vascular integrity due to its anti-inflammatory, antiproliferative, and antithrombogenic effects. Pharmacological blockade of NO production has been shown to exacerbate renal injury in chronic renal disease and induces endothehal cell loss. However, pharmacological inhibition of NO nonspecifically blocks other types of NOS and therefore does not define the specific role of eNOS in kidney disease. We hypothesized that a lack of endothehial eNOS can induce a loss of glomerular and peritubular capillary endothehium and exacerbate renal injury in progressive renal disease. We tested out this hypothesis using remnant kidney (RK) in eNOS knockout (eNOS KO) mice. Systolic blood pressure was significantly higher, and renal function was worse in RK-eNOS KO mice compared with those in RK-C57BL6 mice. eNOS deficiency resulted in more severe glomerulosclerosis, mesangiolysis, and tubular damage. Glomerular and tubular macrophage infiltration and collagen deposition were also greater in RK-eNOS KO mice. Renal injuries in the RK-eNOS KO mice were accompanied by a greater loss of endothelial cells that was shown to be due to both a decrease in endothehial cell proliferation and an increase in apoptosis. A lack of eNOS accelerates both glomerular and tubulointerstitial injury with a loss of glomerular capillaries and peritubular capillaries. Impaired endothehial function is likely a direct risk factor for renal disease. [ABSTRACT FROM AUTHOR]

Background/Aims: α8β1-Integrin is expressed in mesangial cells. In vitro studies suggest a role for α8-integrin in the regulation of cell proliferation and apoptosis. We tested the hypothesis that α8-integrin is essential for the healing process after mesangioproliferative glomerulonephritis. Methods: Mice homozygous for a deletion of the α8-integrin chain were compared with wild-type mice. To study glomerular healing, we used the habu toxin model of reversible mesangioproliferative glomerulonephritis. Animals received 6 mg/kg habu toxin intravenously; controls received saline only. Results: Early mesangiolysis occurred in wild-type and α8-integrin-deficient mice. However, mesangiolysis was no longer detectable after 7 days in wild types but persisted after 14 days in α8-integrin-deficient animals. Mesangial activation marker α-smooth muscle actin was detectable only at day 7 in wild-type mice but persisted until day 14 in α8-integrin-deficient mice. In wild types, glomerular cell proliferation and apoptosis peaked at day 7 and decreased thereafter but remained elevated in α8-integrin-deficient mice until day 28. In cultivated mesangial cells, α8-integrin expression was associated with increased cell survival. Conclusion: Interactions between α8-integrin and the mesangial matrix may contribute to healing of glomerular injury by influencing cell proliferation and apoptosis. Copyright © 2007 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Chronic progressive renal failure is a well-recognized complication in hematopoietic stem cell transplantation (HSCT) recipients. Although thrombotic microangiopathy or chemotherapeutic agents are frequently associated, total body irradiation might also be one of the suspected etiologic factors. This study describes a 38-year-old female patient with acute lymphoblastic leukemia treated with HSCT who developed chronic renal dysfunction after transplantation. Renal biopsy revealed focal and diffuse glomerulosclerosis with extensive mesangiolytic lesions. Her clinical course implied that pretransplant irradiation might have the most impact on the expression of this glomerular lesion. [ABSTRACT FROM AUTHOR]

A 46-year-old woman developed nephrotic syndrome at the age of 16 in 1973. On the basis of the histological findings of the first renal biopsy, she was diagnosed as having minimal change nephrotic syndrome. Initial treatment with steroid was effective, but she had several relapses during tapering of the daily dose of steroid. The second renal biopsy, performed in 1997, disclosed glomerular lobulation, mesangial proliferation, nodular mesangial lesions, and mesangiolysis. From 2001, the degree of proteinuria increased, with urinary protein being 5 g/day in January 2003, when a third renal biopsy was performed. On light microscopy, the glomerular lesions were similar to those observed in 1997. Immunofluorescence microscopy revealed coarse granular stainings for IgG, IgA, IgM, κ, λ, and C3 in the mesangial area and along the capillary walls. On electron microscopy, fingerprint structures were observed in the mesangial and subendothelial deposits. There were no characteristic fibers in the nodular lesions. On the basis of clinical and laboratory findings in this patient, we excluded disease entities in which nodular mesangial lesions, mesangiolysis, and fingerprint deposits had been reported. To our knowledge, such a unique combination of glomerular lesions has not been described previously in the literature. [ABSTRACT FROM AUTHOR]

Presents a case of HIV-associated thrombotic microangiopathy. Renal biopsy microscopic description; Pathogenesis; Therapy.

Dissociation of mesangial cell migration and proliferation in experimental glomerulonephritis. Background. Recently, we documented that following in vivo mesangial cell (MC) ablation in the Thy1 model, reconstitution of the mesangium occurs by a coordinated proliferation and migration of Thy1 (OX-7)-positive cells originating from the hilus and extraglomerular mesangium. We investigated the role of basic fibroblast growth factor (bFGF) in the mediation of these events. Methods. Rats were injected with antithymocyte serum and 48 hours later were pulsed with 3H-thymidine to label proliferating cells. Ninety minutes later, a baseline renal biopsy was obtained, and rats were injected with neutralizing anti-bFGF antibodies or control IgG. Sacrificial biopsies were obtained at 96 hours of disease. Using computer image analysis, biopsies from both time points were quantitated for the number of radiolabeled MC (proliferation) and their mean distance from the hilus (migration). The effect of bFGF on the migration of MCs in culture was examined using a chemotactic assay. Results. At sacrifice, autoradiographs of rats receiving anti-bFGF had significantly fewer radiolabeled MCs as compared with rats receiving control IgG (8.7 ± 1.9 vs. 14.7 ± 3.5, P = 0.0001), yielding an overall 40% reduction in proliferation. There was no difference, however, in the final distance of radiolabeled MCs from the glomerular hilus in the two groups, indicating that the administration of anti-bFGF did not effect MC migration in this model. In an in vitro chemotactic assay, MCs migrated in response to platelet-derived growth factor (PDGF) BB (20 ng/ml), but did not migrate in response to bFGF at a wide range of concentrations (0.5 to 50 ng/ml). Conclusions. These studies demonstrate that bFGF is an important mediator of MC proliferation but that it does not significantly influence MC migration. This is the first demonstration showing that the mediators effecting... [ABSTRACT FROM AUTHOR]

We report three autopsy cases of patients with renal symptoms related to intravascular malignant lymphomatosis (IML) exclusively involving both kidneys. The patients were one woman and two men, aged 64, 65, and 82 years, respectively. Their presenting symptoms included fever, anemia, thrombocytopenia, icterus, dyspnea, weight loss, and enlarged adrenal glands. All patients presented with acute renal dysfunction, with creatinine ranging from 2.0 to 6.5 mg/dl, or with modest proteinuria. One patient had an underlying bilateral disease, chronic pyelonephritis. Another patient also had an autoimmune disease. None of the three patients were aggressively treated. All died of progressive disease 2 weeks to 2 months after the onset of their renal symptoms. The diagnosis of the lymphomas was confirmed by morphological and immunohistochemical studies of the postmortem material. The lymphomas were subclassified as large-cell, characterized by angiotropism. Immunophenotyping revealed that all were B-lineage neoplasms. Renal involvement by IML was characterized histologically by a unique pattern of multifocal neoplastic disseminations within the glomerular and peritubular capillaries, with relative sparing of the interstitum. In one patient, glomerular mesangiolysis in association with embolic proliferations of lymphoma cells was a striking feature. All patients had bilateral renal involvement by IML which occurred in a setting of widespread disease. Our studies indicate that IML is an unusual subset of secondary renal lymphomas with bilateral diseases, and, rarely, may produce renal symptomatology early in the course. [ABSTRACT FROM AUTHOR]

The goal of this study has been to characterize the process of glomerular microaneurysm formation and to separate it from capillary ballooning. In the Habu venom model glomerular capillary ballooning and glomerular microaneurysm formation are seen regularly. The sequence of glomerular lesions leading to a glomerular microaneurysm has been examined and it is clear that the process starts with local mesangiolysis. This may proceed to mesangial expansion and/or ballooning of glomerular capillaries but in contrast to ballooning the formation of a glomerular microaneurysm is based on endothelial defects. The process occurs as follows: once initiated by mesangial failure lesions extend along the mesangial axis. As long as the extension of the lesion encroaches on divergent capillary branches, capillary ballooning by "coalescence" is the result. This process comes to an end when convergent capillary branching is reached and two capillaries join. At this point endothelial disruptions occur, blood and mesangial spaces merge and a glomerular microaneurysm is established. Further growth of the microaneurysm occurs following damage spreading along the lobular axis. The entire process has been reconstructed and is presented in a three-dimensional model. [ABSTRACT FROM AUTHOR]

A 72 year old man with rectal adenocarcinoma developed chronic renal failure when treated by surgery and subsequent chemotherapy (5-fluorouracil, Mitomycin C and Cytosine arabinoside) and immunotherapy. Light microscopy provided evidence of severe glomerular changes with extensive mesangiolysis and vascular damage. Electron microscopy confirmed the mesangiolysis and showed nuclear changes in mesangial cells with nuclear pockets, chromatin loss and margination. There was further indirect evidence of endothelial cell damage. It is suggested that the glomerular changes should be attributed to a direct cytotoxic effect on the mesangial cells. [ABSTRACT FROM AUTHOR]

Sequential changes in the kidney during the generalized Shwartzman reaction were studied electron microscopically. The first anatomical change was infiltration of neutrophils into the glomerular capillaries. Endothelial damage was not noticeable until the capillaries were filled with fibrin deposits. Fibrin appeared in the mesangium at almost the same time as in the capillary lumina, traversing through the endothelial fenestrae. Endothelial damage was more common in the mesangial portion than in the peripheral portion of the capillaries. Severe mesangiolysis developed after loss of endothelial cells had been followed by massive penetration of intracapillary contents. Later, signs of repair were evident in some parts of the damaged endothelium. The development of cortical necrosis coincided with the appearance of mesangiolysis and arteriolar thrombotic lesions. [ABSTRACT FROM AUTHOR]

Electron microscopic analysis was performed on the development of irreversible glomerular distortion in experimental serum sickness nephritis in the rabbit. In the animals showing transient albuminuria, glomerular hypercellularity was due to the accumulation of monocytes and polymorphonuclear leukocytes and was seen to recover to nearly normal glomerulus. In this condition the glomerular structure was observed to be well preserved throughout the inflammation. In contrast, in the animals showing persistent proteinuria, a disorganizing process was found in their glomeruli. Mesangial disintegration resulted in collapsed scarring or circumferential mesangial interposition of the glomeruli. Extracapillary exudation, sometimes with the rupture of the glomerular basement membrane, was often associated with grannlomatous glomerular lesions or crescent formation. The results showed that the structural disintegration is a fundamental event in the development of progressive glomerulonephritis. [ABSTRACT FROM AUTHOR]

Thy-1.1 nephritis is a widely used model of proliferative glomerulonephritis. Lesions are characterized by diffuse mesangiolysis and prominent ballooning of capillary loops, followed by severe mesangial proliferation. However, such severe lesions are not common in human mesangial proliferative nephritis. We analyzed mild-to-moderate mesangial proliferative nephritis induced by a lower dose of anti-Thy-1.1 antibody. We administered a low intravenous dose (0.02 mg/mL) of antibody to Wislar rats, and the histologic changes were observed by light and electron microscopy and by various immunopathologic methods. The serum complement level and distribution of polymorphonuclear leukocytes were also examined. Diffuse mesangial-cell lysis occurred at day 1, but mesangial-matrix lysis was mild, and ballooning of capillary loops was rare. Mesangial cell proliferation appeared at day 2 and reached its maximum at day 5, but it was milder than that seen in the usual dose (0.2 mg/mL) model. The glomerulus was repaired to almost normal structure by day 14. Residual mesangial matrices and endothelial cells seemed to prevent ballooning by making bridges with capillary basement membranes. In the healing stage, this low-dose model demonstrated mild vascular remodeling without active angiogenesis, while the usual-dose model of Thy-1 nephritis showed prominent angiogenic activity to reconstruct capillary tufts. The low-dose model of Thy-1 nephritis, which does not require prominent angiogenesis, may be more useful in analyzing the mechanism of glomerulonephritis than the usually adopted Thy-1 nephritis model, which showed drastic glomerular destruction and prominent angiogenesis. [ABSTRACT FROM AUTHOR]

Severe ballooning of the glomerular tufts was observed in a 65-year-old man who was treated with mitomycin C (MMC) and had typical MMC-induced renal lesions. He developed renal failure and severe anaemia 6 months after initiation of chemotherapy. Ballooned tufts were caused by enormous expansion of the sub-endothelial space simultaneously associated with mesangiolysis. Glomerular cysts, described in a variety of disorders including thrombotic microangiopathy and diabetes mellitus, are derived from cystically dilated and united capillary luminae secondary to mesangiolysis. The morphogenesis of this unusual lesion when induced by MMC differs from that of the glomerular cysts previously reported. [ABSTRACT FROM AUTHOR]

We report a 2-year-old girl with nephrotic syndrome, microcephaly, seizures and psychomotor retardation. Histological studies of a renal biopsy revealed focal glomerular sclerosis with mesangiolysis and capillary microaneurysms. Dysmorphic features were remarkable: abnormal-shaped skull, coarse hair, narrow forehead, large low-set ears, almond-shaped eyes, low nasal bridge, pinched nose, thin lips and micrognathia. Cases with this rare combination of microcephaly and early onset of nephrotic syndrome with various neurological abnormalities have been reported. However, clinical manifestations and histological findings showed a wide variation, and there is a lot of confusion in this syndrome. We therefore reviewed the previous reports and propose a new clasification of this syndrome. [ABSTRACT FROM AUTHOR]

A paediatric case of lipoprotein glomerulopathy, a new kidney disease characterized by glomerular lipoprotein thrombi, is reported. The patient had massive proteinuria from the age of 8 years, when the nephrotic syndrome was first detected. This was resistant to conventional treatment for more than 10 years. During the course of the disease, the hyperlipidaemia characteristic of hyper-pre-β-lipoproteinaemia and elevation of apoprotein E persisted, and renal function gradually deteriorated. The renal histopathological findings from four biopsies were essentially the same, with storage of β-lipoprotein in dilated, balloon-like glomerular capillary lumina. However, the number of glomeruli showing global sclerosis increased and tubulo-interstitial changes progressed in parallel with the gradual clinical deterioration. As in other cases reported in Japan some familial involvement has been noted. [ABSTRACT FROM AUTHOR]

A wide variety of glomerular lesions express circumferential mesangial interposition (CMI). The pathomorphogenesis of CMI involves low-grade mesangiolysis and subsequent passive dislocation of mesangial cells towards the lateral wall of glomerular capillaries through a high hydraulic pressure of blood flow penetrating the lytic mesangium. This is in contrast to the previous theories which advocate an active movement of mesangial cells. Moreover, circumferential mesangial interposition can disappear spontaneously or after treatment, suggesting that mesangial cells may return to the original site with their inherent contractility after the insults are removed, in order to restore handicapped filtering surfaces. But the precise mechanisms of its regression will be a subject for future investigation. [ABSTRACT FROM PUBLISHER]