A child with crescentic glomerulonephritis following SARS-CoV-2 mRNA (Pfizer-BioNTech) vaccination.

BACKGROUND: There are few reports on kidney complications after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) messenger RNA (mRNA) vaccination, especially in the pediatric population. We report a pediatric case diagnosed with crescentic glomerulonephritis (CrGN) after the second dose of the SARS-CoV-2 mRNA vaccine. CASE-DIAGNOSIS/TREATMENT: A 16-year-old girl was admitted due to dyspnea and headache approximately 6 weeks after receiving the second SARS-CoV-2 mRNA vaccine (Pfizer-BioNTech). She had previously experienced fever, nausea, vomiting, and dyspnea after the first vaccination, which persisted for a week. On admission, her blood pressure was 155/89 mmHg with a 7 kg weight gain in a month. She had microhematuria and proteinuria. Laboratory findings were as follows: blood urea nitrogen/creatinine, 66/9.57 mg/dL; and brain natriuretic peptide, 1,167 pg/mL. Anti-neutrophil cytoplasmic antibody (ANCA), anti-glomerular basement membrane (GBM) antibody, and antinuclear antibody findings were negative. Kidney doppler sonography revealed swelling and increased echogenicity of both kidneys with increased resistive index. Cardiac magnetic resonance imaging results showed early minimal fibrosis of myocarditis. We then started hemodialysis. Kidney biopsy showed diffuse extra capillary proliferative glomerulonephritis with diffuse crescent formation. We treated the patient with methylprednisolone pulse therapy with subsequent oral steroids and mycophenolate mofetil. Although dialysis was terminated, the patient remained in the chronic kidney disease stage. CONCLUSIONS: This is the first case of ANCA-negative CrGN after SARS-CoV-2 mRNA vaccination in the pediatric population. As children are increasingly vaccinated with SARS-CoV-2 mRNA vaccines, monitoring for kidney complications is warranted.

Membranoproliferative glomerulonephritis after intravitreal vascular growth factor inhibitor injections: A case report and review of the literature.

Systemic administration of agents that inhibit vascular endothelial growth factor (VEGF) and therefore vascular proliferation is often used to treat various cancers. However, these agents are associated with a number of side effects, including proteinuria and renal injury. Intravitreal injection of anti-VEGF agents has become the cornerstone of macular disease treatment. Since these agents cross the blood-retina barrier and enter the circulation, systemic side effects have been reported. We report the novel case of a 57-year-old patient who presented with macular oedema secondary to central retinal vein occlusion, underwent three monthly loading-dose injections with the anti-VEGF agent ranibizumab, and 2 weeks after the second injection presented with biopsy-verified membranoproliferative glomerulonephritis. Twelve weeks after presenting with renal failure and 10 weeks after his last anti-VEGF injection, the patient demonstrated spontaneous recovery of his kidney function. The patient had a history that promoted renal fragility, including hypertension, liver transplantation 6 years earlier for alcohol-related cirrhosis and new-onset diabetes mellitus after transplant. Our literature review and case suggest that although adverse renal events after intravitreal anti-VEGF injections are very rare, ophthalmologists and nephrologists should be aware of this risk.

Membranoproliferative Glomerulonephritis Type I Associated with Intravenous Immunoglobulin Administration Arising in a Child with X-Linked Agammaglobulinemia: A Case Report and a Reappraisal.

In 1952, X-linked agammaglobulinemia (XLA) was discovered as a rare inherited disorder. It markedly compromises the ability of the body to combat infectious microorganisms. Membranoproliferative glomerulonephritis (MPGN) Type I is characterized by subendothelial immune complex deposits. Patients with XLA can rarely develop immune-complex-induced diseases. Here, we report a case of MPGN Type I in a 12-year-old male patient with a past and family history of XLA. The patient presented with fever, productive cough, vomiting, and lower limb edema. Clinical and radiological examinations established a diagnosis of bronchopneumonia. The laboratory findings revealed proteinuria and hematuria, and a renal biopsy was performed. The histological examination of this biopsy revealed mesangial hypercellularity and thickened basement membranes. Immunofluorescence studies showed mesangiocapillary staining for Complement 3 and Immunoglobulin (Ig) G and, to a lesser extent, for IgA, IgM, and Complement 1q. Ultrastructural studies revealed partly thick, double-contoured glomerular basement membranes, glomerular endothelial cells with swollen cell bodies, and podocytes with effaced foot processes. Small subendothelial and mesangial eosinophilic deposits were identified. The diagnosis of MPGN type I was established. The patient was started on prednisolone. To the best of our knowledge, this is a rare case of MPGN Type I in a patient with XLA. The pathogenetic mechanisms underlying the development of MPGN Type I were not apparent in our patient. However, residual humoral immunity may play a role in the development of MPGN.

A case report of pre-eclampsia-like endothelial injury in the kidney of an 85-year-old man treated with ibrutinib.

BACKGROUND: Glomerular endotheliosis is the pathognomonic glomerular lesion in pre-eclampsia that has also been described in those taking tyrosine kinase inhibitors for cancer treatment. Ibrutinib is a Bruton's tyrosine kinase inhibitor used to treat chronic lymphocytic leukemia (CLL). We report the first known case of glomerular endotheliosis on kidney biopsy in a patient on ibrutinib monotherapy. CASE PRESENTATION: The patient presented with acute on chronic kidney disease, proteinuria, low C3 and C4 and a high rheumatoid factor titer. A kidney biopsy was performed to confirm a preliminary diagnosis of membranoproliferative glomerulonephritis (MPGN), the most common glomerular disease in patients with CLL. Unexpectedly, the kidney biopsy showed pre-eclampsia-like lesions on light and electron microscopy: occlusion of glomerular peripheral capillary lumens by swollen reactive endothelial cells. Findings of glomerulonephritis were not seen, and there were no specific glomerular immune deposits by immunofluorescence or electron microscopy. CONCLUSIONS: CLL is known to cause glomerular lesions, mainly MPGN. There is increasing evidence that ibrutinib, a major treatment for CLL, can cause kidney disease, but the precise pathology is not characterized. We present a patient with CLL on ibrutinib with signs of glomerular endotheliosis. Based on the absence of CLL-induced kidney pathologies typically seen on the kidney biopsy and the non-selectivity of ibrutinib, we attributed the glomerular endotheliosis to ibrutinib. In pre-eclampsia, increased soluble fms-like tyrosine kinase 1 (sFlt1) levels induce endothelial dysfunction by decreasing vascular endothelial growth factor (VEGF). Ibrutinib has been demonstrated to have non-selective tyrosine kinase inhibition, including inhibition of VEGF receptor (VEGFR) and epidermal growth factor receptor (EGFR). VEGFR and EGFR inhibitors have recently been described in the literature to cause hypertension, proteinuria, and glomerular endotheliosis. Kidney biopsy should be performed in CLL patients on ibrutinib that present with acute kidney injury (AKI) or proteinuria to determine whether the clinical picture is attributable to the disease itself or a complication of the therapy.

Bevacizumab-associated glomerular microangiopathy.

Bevacizumab is a humanized monoclonal IgG1 antibody, which neutralizes vascular endothelial growth factor and is used for treating multiple cancer types. As a known and frequent adverse event, this therapy can lead to renal damage including proteinuria and nephrotic syndrome. In a retrospective approach, we analyzed 17 renal biopsies from patients receiving bevacizumab treatment. We observed a distinctive histopathological pseudothrombotic pattern different from the previously reported thrombotic microangiopathy. Since this pattern includes some features similar to acute and chronic thrombotic microangiopathy, focal segmental glomerulosclerosis and cryoglobulinemic membranoproliferative glomerulonephritis, biopsies with these diagnoses were included for comparison. Clinical, laboratory, light microscopic, immunohistochemical (including a proximity ligation assay), proteomic and electron microscopic features were assessed. Nephrotic syndrome was present in 15 of the 17 bevacizumab-treated patients. All 17 displayed a patchy pattern of variably PAS-positive hyaline pseudothrombi occluding markedly dilated glomerular capillaries in their biopsies. Mass spectrometry-based proteome analysis revealed a special protein pattern demonstrating some features of thrombotic microangiopathy and some of cryoglobulinemic glomerulonephritis, including a strong accumulation of IgG in the pseudothrombi. Proximity ligation assay did not show interaction of IgG with C1q, arguing for accumulation without classic pathway complement activation. In contrast to thrombi in thrombotic microangiopathy cases, the hyaline pseudothrombi did not contain clusters of CD61-positive platelets. Electron microscopy of bevacizumab cases did not show fibrin polymers or extensive loss of podocyte foot processes. Even though cases of bevacizumab-associated microangiopathy share some features with thrombotic microangiopathy, its overall histopathological pattern is quite different from acute or chronic thrombotic microangiopathy cases. We conclude that bevacizumab therapy can lead to a unique hyaline occlusive glomerular microangiopathy, likely arising from endothelial leakage followed by subendothelial accumulation of serum proteins. It can be diagnosed by light microscopy and is an important differential diagnosis in cancer patients with nephrotic syndrome.

Filgrastim-Induced Crescentic Transformation of Recurrent IgG2λ GN.

Proliferative GN with monoclonal IgG deposits is an increasingly recognized form of GN, but its relation to hematologic malignancy remains poorly understood. Filgrastim, an analog for granulocyte colony-stimulating factor produced by recombinant DNA technology, is frequently used to stimulate bone marrow release of hematopoietic progenitor cells in preparation for stem cell transplant. We report an exceptional case of proliferative GN with monoclonal IgG2λ deposits in a young man whose disease progressed slowly to CKD, which was followed by a preemptive kidney transplant. The patient developed recurrent GN in the allograft and clinically detectable plasma cell neoplasm 9 years after the first renal manifestations. Contemporaneous with filgrastim administration for stem cell mobilization, the patient's slowly progressive GN underwent severe crescentic transformation, leading to rapidly progressive and irreversible allograft failure. This report explores the spectrum of GN with monoclonal IgG deposits and the pathophysiologic role of granulocyte colony-stimulating factor in exacerbation of preexisting GN.

Aldosterone mediates glomerular inflammation in experimental mesangial proliferative glomerulonephritis.

BACKGROUND: The renoprotection of the mineralocorticoid receptor antagonist (MRA) is considered to be mainly via its antifibrotic activity, and the possibility that it may also have antiinflammatory effects has not been studied. We tested the hypothesis that MRA might influence the inflammatory changes that accompany experimental glomerular injury. METHODS: Administration of vehicle (control) or a selective MRA, eplerenone (50 mg/kg x 2 times/day) was started 7 days (-7d) before induction of anti-Thy-1.1 glomerulonephritis. Kidney samples were evaluated serially over a 12-day period for the presence of cell proliferation, macrophage infiltration, mesangial cell phenotypic activation and expression of the chemokine monocyte chemoattractant protein-1 (MCP-1). RESULTS: MRA did not prevent the mesangiolysis associated with anti-Thy-1 antibody. However, MRA significantly inhibited MCP-1 expression, glomerular macrophage infiltration and mesangial phenotypic activation (alpha-smooth muscle actin expression). CONCLUSION: MRA alters glomerular inflammation and mesangial cell activation in experimental glomerular injury. MRA may be a novel way to treat acute glomerular diseases.

Membranoproliferative glomerulonephritis possibly associated with over-vaccination in a cocker spaniel.

Membranoproliferative glomerulonephritis was observed in a seven-month-old male cocker spaniel dog. The clinical, microbiological, biochemical, radiographic and ultrasonographic examinations ruled out neoplasia, congenital disease and infectious disease. The anamnesis revealed that the owner had vaccinated the dog seven times, one vaccination per month, without veterinarian supervision. In both kidneys, severe thickening of the glomerular capillary walls was observed. Electron microscope examination revealed a large number of electron-dense deposits that were primarily in the glomerular subendothelial spaces and the basal membrane, which is compatible with antigen-antibody complexes. The immunohistochemical examination revealed that the antigen present in the glomeruli corresponded with the antigen present in the vaccine. We report a type III hypersensitivity nephropathy in a young dog, which was possibly caused by over-vaccination.

Endothelin signaling via guanine exchange factor C3G in renal glomerular mesangial cells.

The guanine nucleotide exchange factor C3G is one of the mediators of endothelin-1 (ET-1) intracellular signaling cascades and is vital for kidney development and homeostasis. The aim of the current study was to analyze the specificity of ET-1-induced signaling via C3G in rat glomerular mesangial cells (GMC) and to investigate the biological significance of C3G during mesangioproliferative glomerulonephritis. In GMC, C3G expression was increased (1) in vivo after induction of the anti-Thy1 model of glomerulonephritis and (2) in cell culture experiments after fetal bovine serum incubation. To examine the consequences of C3G up-regulation, adenovirus-mediated gene transfer of C3G into cultured glomerular cells was done, and the GTP loading of the small G proteins Rap1 and R-Ras was analyzed. Overexpression of C3G in mesangial cells resulted in enhanced activation of Rap1, but failed to affect the GTP-bound status of R-Ras in ET-1-stimulated cells. C3G overexpression led to significant changes in GMC spreading and migration patterns in response to ET-1 stimulation and increased stress fiber formation, which was mimicked by Rap1A overexpression. Together, these findings suggest (1) the existence of regulatory mechanisms resulting in disease-related up-regulation of C3G in GMC and (2) that an increase in the C3G protein level may contribute to the resolution stage of mesangioproliferative glomerulonephritis by reducing GMC sensitivity to ET-1, modulating cellular motility, and actin dynamics.

Signal transduction involved in protective effects of 15(R/S)-methyl- lipoxin A(4) on mesangioproliferative nephritis in rats.

Studies have shown that lipoxin A(4) (LXA(4)) inhibited proliferation of mesangial cells in vitro induced by platelet-derived growth factor, epidermal growth factor, leukotriene D(4) or tumor necrosis factor-alpha. In this study, we investigated the protective effects of 15(R/S)-methyl-LXA(4) on mesangioproliferative nephritis in rats and the signal transduction involved in actions of 15(R/S)-methyl-LXA(4). Mesangioproliferative nephritis was induced by a single intravenous injection of the mouse monoclonal anti-Thy1.1 antibodies. The nephritic rats were treated by intravenous injection of 15(R/S)-methyl-LXA(4) every 8h until the rats were sacrificed. There were increments in glomerular infiltration of leukocytes, expressions of protein and mRNA of interleukin (IL)-1beta and IL-6, activities of nuclear factor-kappaB (NF-kappaB) in nephritic rats from day 1 to 4 after induction of nephritis. The enhanced proteinuria, proliferation score of mesangial cells, glomerular proliferating cell nuclear antigen (PCNA) positive cells, activities of phosphorylated phosphoinositide 3-kinase (PI3-K), Akt(1), alpha-smooth muscle actin (alpha-SMA) and signal transducer and activator of transcription 3(STAT(3)), and reduced expression of p27(kip1) were found on day 4 after induction of nephritis. Treatment of nephritic rats with 15(R/S)-methyl-LXA(4) significantly reduced the protenuria, glomerular infiltration of leukocyte, expressions of protein and mRNA of IL-1beta and IL-6, proliferation score of mesangial cells, glomerular PCNA positive cells, activities of phosphorylated PI3-K, Akt(1), alpha-SMA, NF-kappaB and STAT(3), and ameliorated the decrement in p27(kip1) induced by anti-Thy1.1 antibodies. Protective effects of 15(R/S)-methyl-LXA(4) on nephritis induced by anti-Thy1.1 antibodies were related to PI3-K/Akt(1)/p27(kip1)/cyclin pathway, STAT(3) and NF-kappaB pathway-dependent signal transduction.

[Preventive effect of multi-glycoside of tripterygium Wilfordii Hook. f. on proteinuria and mesangial injury in experimental mesangial proliferative glomerulonephritis].

OBJECTIVE: To observe the preventive effect of multi-glycoside of Tripterygium Wilfordii Hook. f. (GYW) on proteinuria and mesentery injury in experimental mesangial proliferative glomerulonephritis in vivo. METHODS: The reversible anti-Thyl.1 antibody glomerulo nephritis model of rats was established with monoclonal antibody 1-22-3 and intervened with GTW, and a control group was set up in the same time. Changes of 24h urinary protein excretion, serum creatinine (Scr), blood urea nitrogen (BUN), total plasma protein (TP) and glomerular morphology were observed, and the level of mRNA expression of proliferative factors, including platelet-derived growth factor-BB (PDGF-BB) and transforming growth factor-beta (TGF-beta), in renal tissue was determined. RESULTS: GTW could inhibit proteinuria and mesangial injury in anti-Thyl. 1 antibody nephritis model. The PDGF-BB and TGF-beta mRNA expression in the anti-Thy1.1 antibody nephritis model rats were increased for 2.84 and 1.64 times respectively to those in the normal control group. GTW could down-regulate the over-expression of PDGF-BB mRNA by 33.1%, it was significantly different to that in the control group (P < 0.05). CONCLUSION: GTW could reduce the proteinuria and inhibit mesangial cells proliferation and extracellular matrix deposition, these effects maybe related to the down-regulating of PDGF-BB mRNA expression.

Chronic overexposure to cadmium fumes associated with IgA mesangial glomerulonephritis.

BACKGROUND: Cadmium is a metal used in the zinc, copper and steel industries, and in the manufacture of electric batteries and solar cells. Acute cadmium poisoning is characterized by irritation of the respiratory tract, while in chronic poisoning the main target organ is the renal tubule. AIMS: We report a patient with chronic work overexposure to cadmium, who presented a IgA mesangial glomerulonephritis with no respiratory or renal tubule involvement. Case report A 39-year-old patient was referred to our hospital for evaluation of a glomerular nephropathy. For the past 12 years he had worked as a welder, using cadmium electrodes. The patient had no respiratory symptoms and the chest X-ray was normal. Tests showed a proteinuria of 2 g in 24 h with microhaematuria [150 red blood cells/high power field (rbc/hpf)], with preservation of the renal function (creatinine clearance of 137 ml/min). The concentrations of cadmium in blood and urine were 45 micro g/l and 25 micro g/g creatinine, and an environmental study showed that levels of cadmium in the workplace were 52 micro g/m(3). A renal biopsy showed an IgA mesangial glomerulonephritis. The patient ceased to work with cadmium, and 1 year later cadmium levels had decreased and renal function was found to be stable. CONCLUSIONS: IgA mesangial glomerulonephritis is a disease of unknown aetiology which has been associated with other diseases. Chronic overexposure to cadmium may contribute to the development of this nephrophathy.

[Pathogenesis of rat mesangial proliferative glomerulonephritis induced by anti-Thy1 antibody].

OBJECTIVE: To probe into the pathogenesis of rat mesangial proliferative glomerulonephritis (MsPGN) induced by anti-Thy1 antibody. METHODS: Anti-Thy1 serum was produced, and then intravenously injected into Wistar rats for establishing an experimental model of MsPGN. The control group received intravenous injection of normal saline. Urinary volume and urinary protein were examined every other day. The IL-1, IL-6 and TNF contents of serum were detected by radioimmunoassay. Pathologic morphology of renal section was observed with micrscope and BI2000 Image Analysis System. The rats of model group were killed on the 1st, 3rd, 5th and 7th days. RESULTS: No significant difference was seen between the model group and control group in regard to the volume of urine and in-take water (P > 0.05). The levels of urinary protein, IL-1, IL-6 and TNF in model group were significantly higher than those in control group at all time points (P < 0.001-0.005). Glomerular mesangium cells and matrix in the model group were obviously proliferative, compared with those in control group. CONCLUSION: It is suggested that cytokine plays an important role in the onset of MsPGN.

Heterogeneity of macrophage activation in anti-Thy-1.1 nephritis.

Macrophages infiltrating glomeruli in telescoped nephrotoxic nephritis are programmed. The purpose of this study was to assess whether macrophages infiltrating glomeruli of rats with passively induced injury become similarly programmed, and to determine whether macrophage commitment is an early event. Glomerular macrophages isolated from rats with resolving and proliferative anti-Thy-1 nephritis were examined for nitric oxide (NO) generation and expression of lysosomal hydrolases. After a single injection of Thy-1 antibody the cells generated large amounts of NO that was attenuated ex vivo by transforming growth factor-beta and other anti-inflammatory cytokines. In contrast macrophages infiltrating glomeruli immediately after a second injection of Thy-1 antibody generated NO spontaneously and were unresponsive to alternative activation. beta-Glucuronidase expression was used as a second independent assay for macrophage activation and the results confirmed the observations made for NO. Furthermore, macrophages infiltrating the glomerulus after the second antibody injection exhibited a striking dichotomy in that 70% of the cells behave as programmed by interferon-gamma and 30% by transforming growth factor-beta. The results show that macrophage commitment occurs very early after monocyte migration and that infiltration itself does not invariably induce macrophage programming. It demonstrates that macrophages infiltrating inflamed glomeruli at the same time do not respond uniformly, but are capable of engaging different activation programs. This emphasizes the critical importance of the underlying disease process for macrophage functional development in an inflamed environment.

In vitro effects of Habu snake venom on cultured mesangial cells.

BACKGROUND: Habu snake venom (HSV)-induced glomerulonephritis is a unique model showing a progressive course of mesangial proliferation. To elucidate the in vitro effects of HSV, we examined whether HSV itself could have direct effects on the cultured mesangial cells, such as cell proliferation and activation of chemokine gene expression. METHODS: The incorporation of 5-[(125)I]iodo-2'-deoxyuridine was measured with a gamma-counter, and gene expressions of growth factors, chemokines and cytokines were evaluated by a real time quantitative PCR. RESULTS: We demonstrated that excessive or continuous HSV stimulation decreased a mesangial cell viability. However, adequate and temporary HSV stimulation induced proliferation of mesangial cells in vitro along with a significant elevation of monocyte chemoattractant protein-1 (MCP-1) mRNA levels. In addition to these in vitro results, we showed that MCP-1 mRNA levels increased in renal cortices of glomerulonephritis induced by HSV. Immunohistochemistry also showed a positive staining for MCP-1 in the marginal area of glomerulus with mesangiolysis. CONCLUSIONS: These data suggest that HSV itself may elicit direct biological effects on mesangial cells which may participate in pathophysiology of glomerulonephritis induced by HSV.

Suppressive effects of rosmarinic acid on mesangioproliferative glomerulonephritis in rats.

BACKGROUND: Rosmarinic acid is known to be a natural phenolic compound widely distributed in Labiatae herbs such as rosemary, sweet basil, and perilla. In the present study, we evaluated the suppressive effects of rosmarinic acid on mesangioproliferative glomerulonephritis in vivo, which was induced by intravenous injection of rabbit anti-rat thymocyte serum (ATS) to rats. METHODS: Rosmarinic acid was orally administered to the rats at a dose of 100 mg/kg/day from the day of ATS injection (day 0) to day 8 when rats were sacrificed. The degree of mesangial cell proliferation and matrix accumulation were evaluated by trichrome staining and by immunostaining for proliferating cell nuclear antigen (PCNA), fibronectin, type IV collagen and fibrin. Superoxide dismutase (SOD)-activity in the homogenate of renal cortex was also evaluated. RESULTS: The number of PCNA-positive cells, staining areas of trichrome, fibronectin, collagen IV and fibrin in the glomerulus were significantly decreased, and SOD-activity of renal cortex homogenate was significantly augmented in rosmarinic acid-treated group. CONCLUSION: Rosmarinic acid would suppress the proliferation of mesangial cells and glomerular matrix expansion in vivo by its fibrinolytic and anti-oxidative activity.

MPGN type I induced by granulocyte colony stimulating factor.

We report a girl with severe congenital neutropenia who has received long-term granulocyte-colony stimulating factor (G-CSF) therapy and has developed macroscopic hematuria, proteinuria, and decreased renal function associated with biopsy-proven membranoproliferative glomerulonephritis (MPGN) type I. Temporary discontinuation of G-CSF therapy as well as the use of glycosylated G-CSF has resulted in improvement in renal manifestations. We postulate that the MPGN was G-CSF-induced. Long-term G-CSF therapy should be used with great caution and close surveillance of kidney function.

Effects of antioxidants on kidney disease.

Kidney mesangial cells (MCs) and vascular smooth muscle cells (VSMCs) are closely related in terms of origin, microscopic anatomy, histochemistry, and contractility. This relationship suggests a similarity between kidney glomerular sclerosis and atherosclerosis. Vitamin E appears beneficial in the prevention and treatment of coronary disease and also inhibits the proliferation of VSMCs in vitro. We used vitamin E and probucol to treat glomerular sclerosis and MC-proliferative glomerulonephritis (GN) in two animal models of glomerular disease. Using rats, a remnant kidney model accelerated with hyperlipidemia was employed to reflect progressive glomerular sclerosis leading to chronic renal failure, and an anti-thymocyte serum treatment was used to model acute MC-proliferative GN. Supplemental dietary antioxidants suppress MC proliferation and glomerular sclerosis in models of glomerular disease in rats. These results suggest that treatment with antioxidants may be a promising intervention to prevent progression of kidney disease.

Glucocorticoid diminishes vascular endothelial growth factor and exacerbates proteinuria in rats with mesangial proliferative glomerulonephritis.

Glucocorticoids are widely prescribed for renal diseases. It is believed that glucocorticoids attenuate immune-mediated renal diseases by suppressing the cell-mediated immune system. However, there is evidence that glucocorticoids influence the expression of such growth factors as vascular endothelial growth factor (VEGF), transforming growth factor-beta1 (TGF-beta1), and connective tissue growth factor (CTGF), which are known to influence the development or progression of renal diseases. Therefore, we undertook this study to determine whether glucocorticoids regulate proteinuria or extracellular matrix (ECM) production by altering these growth factors. Mesangial proliferative glomerulonephritis was induced in rats by intravenous injection of monoclonal antibody (OX-7), and dexamethasone (20 mg/kg) was administered intraperitoneally from the third to seventh disease day. Glomerular expression of VEGF, TGF-beta1, and CTGF, the amount of urinary protein, and glomerular ECM were measured on the seventh disease day. The nephritic group showed proteinuria and greater VEGF, TGF-beta1, and ECM production. Dexamethasone aggravated proteinuria (protein, 0.4 +/- 0.1 mg/mg creatinine in the NC group, 6.3 +/- 2.0 mg/mg creatinine in the DC group, and 21.1 +/- 1.9 mg/mg creatinine in the D-Dex group; P < 0.05) and diminished VEGF release (22 +/- 3 pg/mg total protein in the NC group, 292 +/- 26 pg/mg total protein in the DC group, and 198 +/- 23 pg/mg total protein in the D-Dex group; P < 0.05). Expression of TGF-beta1, CTGF, and ECM was not altered significantly by dexamethasone treatment. We found that glucocorticoid diminishes VEGF release and at the same time exacerbates proteinuria in rats with this type of glomerulonephritis.