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Internal Medicine (Tokyo, Japan) Jun 1996We report a patient who exhibited proteinuria and renal failure 93 months after receiving an allogeneic bone marrow transplantation (BMT) from his HLA-identical brother.... (Review)
Review
We report a patient who exhibited proteinuria and renal failure 93 months after receiving an allogeneic bone marrow transplantation (BMT) from his HLA-identical brother. A renal biopsy specimen revealed segmental sclerosis, mesangiolysis, subendothelial lucency in the glomeruli, fibrosis and small round cell infiltration in the interstitium, and hyaline droplets in the intimal spaces of arterioles and small arteries. These histological findings were consistent with late onset BMT nephropathy. This nephropathy may represent a more serious problem in the near future in Japan, since the number of BMT performed has been increasing with the establishment of a bone marrow bank.
Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Transplantation; Combined Modality Therapy; Cyclosporine; Graft vs Host Disease; Humans; Immunosuppressive Agents; Kidney; Kidney Failure, Chronic; Leukemia, Myeloid, Acute; Male; Proteinuria; Radiation Injuries; Time Factors; Transplantation Conditioning; Whole-Body Irradiation
PubMed: 8835602
DOI: 10.2169/internalmedicine.35.489 -
Kidney International Reports Apr 2021Although diabetic kidney disease (DKD) is responsible for more than half of all chronic and end-stage kidney disease (ESKD), the association of light (LM) and electron...
INTRODUCTION
Although diabetic kidney disease (DKD) is responsible for more than half of all chronic and end-stage kidney disease (ESKD), the association of light (LM) and electron microscopic (EM) structural changes with clinical parameters and prognosis in DKD is incompletely understood.
METHODS
This is an interim analysis of 62 patients diagnosed with biopsy-confirmed DKD from the multicenter TRIDENT (Transformative Research in Diabetic Nephropathy) study. Twelve LM and 8 EM descriptors, representing changes in glomeruli, tubulointerstitium, and vasculature were analyzed for their relationship with clinical measures of renal function. Patients were followed every 6 months.
RESULTS
Multivariable linear regression analysis revealed that estimated glomerular filtration rate (eGFR) upon enrollment correlated the best with interstitial fibrosis. On the other hand, the rate of kidney function decline (eGFR slope) correlated the most with glomerular lesions including global glomerulosclerosis and mesangiolysis. Unbiased clustering analysis based on histopathologic data identified 3 subgroups. The first cluster, encompassing subjects with the mildest histologic lesions, had the most preserved kidney function. The second and third clusters had similar degrees of kidney dysfunction and structural damage, but differed in the degree of glomerular epithelial cell and podocyte injury (podocytopathy DKD subtype). Cox proportional hazard analysis showed that subjects in cluster 2 had the highest risk to reach ESKD (hazard ratio: 17.89; 95% confidence interval: 2.13-149.79). Glomerular epithelial hyperplasia and interstitial fibrosis were significant predictors of ESKD in the multivariate model.
CONCLUSION
The study highlights the association between fibrosis and kidney function and identifies the role of glomerular epithelial changes and kidney function decline.
PubMed: 33912757
DOI: 10.1016/j.ekir.2021.01.025 -
Kidney International Feb 2003Increased expression of growth factors including platelet-derived growth factor (PDGF) and transforming growth factor-beta (TGF-beta) are thought to play pivotal roles...
BACKGROUND
Increased expression of growth factors including platelet-derived growth factor (PDGF) and transforming growth factor-beta (TGF-beta) are thought to play pivotal roles during mesangial expansion and glomerulosclerosis. Thymic stromal lymphopoietin (TSLP) transgenic mice develop mixed cryoglobulinemia and a membranoproliferative glomerulonephritis (MPGN). Here we describe the renal expression of isoforms of PDGF and TGF-beta in relation to changes in extracellular matrix (ECM) components and markers of cell proliferation and activation in this model.
METHODS
A total of 123 mice, including 61 TSLP transgenic mice and 62 wild-type controls, were sacrificed at defined intervals. PDGF-A chain, -B chain, PDGF alpha- and beta-receptor (beta-R) and TGF-beta1 mRNA were analyzed by in situ hybridization. Expression of alpha smooth muscle actin (alphaSMA), collagen type I, collagen type IV, laminin, and a marker of proliferating cells (PCNA) were assessed by immunohistochemistry. Slides also were studied by combined immunohistochemistry and in situ hybridization with an antibody that recognizes monocytes/macrophage and with riboprobes that detect PDGF B-chain, PDGF beta-R or TGF-beta1 mRNA.
RESULTS
Increased numbers of proliferating glomerular cells appeared early in the disease course, associated with de novo expression of alphaSMA. Expression of PDGF B-chain and beta-R mRNA was increased in the mesangium and in parietal epithelial cells of TSLP transgenic mice and correlated with the number of PCNA positive cells. Increased TGF-beta1 mRNA expression paralleled the deposition of type IV collagen. A significant proportion of Mac-2 positive macrophages expressed TGF-beta1 mRNA, while only a small percentage of glomerular macrophages expressed PDGF B-chain mRNA. No PDGF beta-R mRNA expression by macrophages was detected.
CONCLUSION
TSLP transgenic mice develop a membranoproliferative glomerulonephritis in which glomerular cell proliferation and matrix deposition are associated with an increased expression of PDGF B-chain, PDGF beta-R and TGF-beta1. These findings extend the paradigms covering these growth factors established in the rat Thy 1 model of mesangiolysis and repairs to a murine model of progressive glomerulonephritis closely resembling human MPGN.
Topics: Actins; Animals; Cell Division; Collagen Type IV; Cryoglobulinemia; Cytokines; Extracellular Matrix; Kidney Glomerulus; Laminin; Macrophages; Mice; Mice, Transgenic; Muscle, Smooth; Proto-Oncogene Proteins c-sis; RNA, Messenger; Receptor, Platelet-Derived Growth Factor beta; Transforming Growth Factor beta; Transforming Growth Factor beta1; Thymic Stromal Lymphopoietin
PubMed: 12631122
DOI: 10.1046/j.1523-1755.2003.00778.x -
TAFRO syndrome with renal biopsy successfully treated with steroids and cyclosporine: a case report.BMC Nephrology Jul 2022TAFRO syndrome is an acute or subacute systemic inflammatory disease with no apparent cause, presenting with fever, generalized edema, thrombocytopenia, renal damage,...
BACKGROUND
TAFRO syndrome is an acute or subacute systemic inflammatory disease with no apparent cause, presenting with fever, generalized edema, thrombocytopenia, renal damage, anemia, and organ enlargement. Interleukin-6, vascular endothelial growth factor, and other cytokines are thought to be the etiologic agents that increase vascular permeability and cause the resulting organ damage. Only few reports of renal biopsy performed in patients with TAFRO syndrome exist.
CASE PRESENTATION
A 61-year-old woman, with a history of Sjogren's syndrome, was admitted to our hospital with anasarca and abdominal distension. Based on the clinical course and various laboratory findings, we diagnosed TAFRO syndrome. Renal biopsy revealed thrombotic microangiopathy, including endothelial cell swelling, subendothelial space expansion, and mesangiolysis. She was treated with oral prednisolone and cyclosporine, with consequent resolution of anasarca, pleural effusion, and ascites, and improvement in renal function and urinary findings. The patient's platelet count also normalized after 2 months of treatment.
CONCLUSIONS
Given that only few reports of improvement in the systemic symptoms of TAFRO syndrome using steroids and cyclosporine exist, our study investigating the relationship between the pathogenesis of TAFRO syndrome and renal disorders, as well as treatment methods, provides valuable insights.
Topics: Biopsy; Castleman Disease; Cyclosporine; Edema; Female; Humans; Kidney Diseases; Middle Aged; Steroids; Thrombotic Microangiopathies; Vascular Endothelial Growth Factor A
PubMed: 35870879
DOI: 10.1186/s12882-022-02886-5 -
CEN Case Reports Aug 2022Glomerular capillary aneurysms are distinctly rare and specific glomerular lesions characterized by aneurysmal dilatation of the glomerular capillaries. This formation...
Glomerular capillary aneurysms are distinctly rare and specific glomerular lesions characterized by aneurysmal dilatation of the glomerular capillaries. This formation is associated with glomerular capillary injuries with focal mesangiolysis. Here, we report a case of proliferative glomerulonephritis with monoclonal immunoglobulin G deposits (PGNMID) presenting with multiple glomerular capillary microaneurysms. A 53-year-old woman presented with persistent proteinuria and microhematuria. She had no underlying diseases, such as hematopoietic or lymphoproliferative disorders. A renal biopsy showed diffuse membranoproliferative lesions with foam cell infiltration and multiple microaneurysms of the glomerular capillary on light microscopy. Immunofluorescence analysis showed granular deposits of monoclonal immunoglobulin G3 kappa (IgG3κ), C1q, C3, and C4 in the glomeruli. Electron microscopy revealed different sizes of non-organized electron-dense deposits in the mesangial, subendothelial, and subepithelial areas. In addition, glomerular endothelial cells showed swelling and loss of fenestra or diffuse formation of fenestrated diaphragms, accompanied by irregular thinning of the glomerular basement membrane. Furthermore, immunostaining for CD31 (a marker for endothelial cell) and low-vacuum scanning electron microscopy study identified loss of endothelial cells in microaneurysm, suggesting severe glomerular endothelial cell injury. After a renal biopsy, only the medication for dyslipidemia was continued because there were no physical symptoms, such as edema, and urinary abnormalities continued with stable renal function. Further studies are needed to elucidate the pathogenesis of glomerular capillary injury in PGNMID and clarify the clinical and pathological characteristics of PGNMID with glomerular capillary microaneurysms.
Topics: Antibodies, Monoclonal; Endothelial Cells; Female; Glomerular Basement Membrane; Glomerulonephritis; Humans; Immunoglobulin G; Immunoglobulin kappa-Chains; Microaneurysm; Middle Aged
PubMed: 35025059
DOI: 10.1007/s13730-021-00676-w -
Journal of the American Society of... Aug 2014VEGF-A and nitric oxide are essential for glomerular filtration barrier homeostasis and are dysregulated in diabetic nephropathy. Here, we examined the effect of excess...
VEGF-A and nitric oxide are essential for glomerular filtration barrier homeostasis and are dysregulated in diabetic nephropathy. Here, we examined the effect of excess podocyte VEGF-A on the renal phenotype of endothelial nitric oxide synthase (eNOS) knockout mice. Podocyte-specific VEGF(164) gain of function in eNOS(-/-) mice resulted in nodular glomerulosclerosis, mesangiolysis, microaneurysms, and arteriolar hyalinosis associated with massive proteinuria and renal failure in the absence of diabetic milieu or hypertension. In contrast, podocyte-specific VEGF(164) gain of function in wild-type mice resulted in less pronounced albuminuria and increased creatinine clearance. Transmission electron microscopy revealed glomerular basement membrane thickening and podocyte effacement in eNOS(-/-) mice with podocyte-specific VEGF(164) gain of function. Furthermore, glomerular nodules overexpressed collagen IV and laminin extensively. Biotin-switch and proximity ligation assays demonstrated that podocyte-specific VEGF(164) gain of function decreased glomerular S-nitrosylation of laminin in eNOS(-/-) mice. In addition, treatment with VEGF-A decreased S-nitrosylated laminin in cultured podocytes. Collectively, these data indicate that excess glomerular VEGF-A and eNOS deficiency is necessary and sufficient to induce Kimmelstiel-Wilson-like nodular glomerulosclerosis in mice through a process that involves deposition of laminin and collagen IV and de-nitrosylation of laminin.
Topics: Animals; Cell Culture Techniques; Collagen Type IV; Diabetic Nephropathies; Glomerular Basement Membrane; Laminin; Mice; Mice, Knockout; Nitric Oxide Synthase Type III; Podocytes; Proteinuria; Renal Insufficiency; Vascular Endothelial Growth Factor A
PubMed: 24578128
DOI: 10.1681/ASN.2013070752 -
Laboratory Investigation; a Journal of... Feb 2009Angiotensin II receptor blockade (ARB) suppresses the progression of chronic kidney disease. However, the renoprotective effect of ARB in the active phase of...
Angiotensin II receptor blockade (ARB) suppresses the progression of chronic kidney disease. However, the renoprotective effect of ARB in the active phase of glomerulonephritis (GN) has not been evaluated in detail. We examined the alteration of angiotensin II receptors' expression and the action of ARB on acute glomerular injuries in GN. Thy-1 GN was induced in rats that were divided into three groups (n=7, in each group); high dose (3 mg/kg/day) or low dose (0.3 mg/kg/day) olmesartan (Thy-1 GN+HD- or LD-ARB group), and vehicle (Thy-1 GN group). Renal function and histopathology were assessed by week 2. In the Thy-1 GN group, diffuse mesangiolysis and focal aneurysmal ballooning developed by day 3. Marked mesangial proliferation and activation progressed with glomerular epithelial injury. We confirmed that both angiotensin II type 1 receptor (AT1R) and type 2 receptor (AT2R) were expressed on glomerular endothelial, mesangial, epithelial cells, and macrophages, and increased 7 days after disease induction. However, ARB treatment caused a decrease in AT1R and a further increase in AT2R expression in glomeruli. ARB prevented capillary destruction and preserved eNOS expression after diffuse mesangiolysis. Mesangial proliferation and activation was suppressed markedly with low levels of PDGF-B expression. Glomerular desmin expression, which is a marker for injured glomerular epithelial cells, was diminished significantly with retained expression of nephrin and podoplanin. Glomerular macrophage infiltration was also inhibited. Proteinuria was suppressed significantly. Furthermore, these effects of ARB showed dose dependency. These results provide insights that ARB affects individual glomerular cells and macrophages through angiotensin II receptors, with the alteration of both AT1R and AT2R expressions, and leads to inhibition of the acute destructive and proliferative glomerular lesions in GN.
Topics: Angiotensin II; Angiotensin II Type 1 Receptor Blockers; Angiotensin II Type 2 Receptor Blockers; Animals; Becaplermin; Biomarkers; Blood Pressure; Cell Proliferation; Disease Models, Animal; Fluorescent Antibody Technique, Indirect; Glomerular Mesangium; Glomerulonephritis, Membranoproliferative; Imidazoles; Kidney Glomerulus; Male; Platelet-Derived Growth Factor; Proteinuria; Proto-Oncogene Proteins c-sis; RNA, Messenger; Rats; Rats, Wistar; Receptor, Angiotensin, Type 1; Receptor, Angiotensin, Type 2; Tetrazoles; Thy-1 Antigens
PubMed: 19139720
DOI: 10.1038/labinvest.2008.128 -
Diabetes Research and Clinical Practice May 2017Nodular lesions are one of the most characteristic pathological changes of advanced diabetic nephropathy (DN). Previous studies have demonstrated that the pattern of...
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.
Topics: Aged; Biopsy; Collagen Type IV; Diabetic Nephropathies; Female; Humans; Kidney; Kidney Failure, Chronic; Male; Middle Aged; Prognosis; Renal Dialysis; Staining and Labeling
PubMed: 28388509
DOI: 10.1016/j.diabres.2017.03.006 -
Journal of Lipid Research Oct 2014Lipoprotein glomerulopathy (LPG) is a renal disease often accompanied by dyslipidemia and increased serum apoE levels. apoESendai (Arg145Pro), a rare mutant based on the...
Lipoprotein glomerulopathy (LPG) is a renal disease often accompanied by dyslipidemia and increased serum apoE levels. apoESendai (Arg145Pro), a rare mutant based on the apoE3 sequence carrying an apoE2 charge, causes LPG in humans and transgenic mice, but its effects on the artery wall are unknown. Macrophage expression of apoESendai may also directly influence renal and arterial homeostasis. We investigated the effects of macrophage-expressed apoESendai in apoE(-/-) mice with or without LDL receptor (LDLR). Murine bone marrow transduced to express apoE2, apoE3, or apoESendai was transplanted into lethally irradiated mice. Macrophage apoESendai expression reduced aortic lesion size and inflammation by 32 and 28%, respectively, compared with apoE2 in apoE(-/-) recipients. No differences in lesion size or inflammation were found between apoESendai and apoE3 in apoE(-/-) recipients. Macrophage apoESendai expression also reduced aortic lesion size by 18% and inflammation by 29% compared with apoE2 in apoE(-/-)/LDLR(-/-) recipients. Glomerular lesions compatible with LPG with increased mesangial matrix, extracellular lipid accumulation, and focal mesangiolysis were only observed in apoE(-/-)/LDLR(-/-) mice expressing apoESendai. Thus, macrophage expression of apoESendai protects against atherosclerosis while causing lipoprotein glomerulopathy. This is the first demonstration of an apoprotein variant having opposing effects on vascular and renal homeostasis.
Topics: Animals; Apolipoproteins E; Atherosclerosis; Glomerular Mesangium; Hyperlipidemias; Inflammation; Kidney Diseases; Macrophages; Mice; Mice, Knockout; Receptors, LDL
PubMed: 25183802
DOI: 10.1194/jlr.M049874 -
Kidney International Apr 1998To study the glomerular morphological abnormalities in congestive heart failure (CHF), we analyzed 27 autopsy cases without other causes of renal disease. Their mean age...
To study the glomerular morphological abnormalities in congestive heart failure (CHF), we analyzed 27 autopsy cases without other causes of renal disease. Their mean age was 59 years, and they showed mild prerenal azotemia. They had generally been treated with digitalis and diuretics, and a few of them with captopril or nifedipine. The abnormal glomerular findings of enlargement, hyperemia, and mesangial thickening were observed at high frequencies (61%, 64%, and 57%, respectively). They characteristically showed mesangiolysis (ML) by the findings of microaneurysms (81%) and mesangial degeneration (70%) such as loose reticular matrix and poor matrix area. In addition, glomerular infiltration of mononuclear leukocytes including macrophages was noted in 70% of the cases. Glomerular enlargement was not correlated with the grade of hyperemia, but it was correlated with the grade of ML index of % glomeruli with microaneurysms (F = 7.22, p < 0.004). There was an inverse relationship between the grades of mesangial thickening and of the ML index (P < 0.005). The number of glomerular leukocytes was positively correlated with mean glomerular size (P < 0.002) and with the ML index (P < 0.03). Notably, the glomerular macrophage-positive cases showed a prominently higher mean ML index than the negative cases (P < 0.005). There was an inverse correlation between the mean glomerular size and the partial oxygen pressure in arterial blood (PaO2; P < 0.01), and a positive correlation between the mean glomerular size and hematocrit (Hct) levels (P < 0.02). The cases positive for mesangiolytic mesangial degeneration showed significantly lower PaO2 values than the cases negative for this lesion (P < 0.04). In the analysis of the various causes of CHF, the patients with congenital cardiac anomalies showed mean levels of the lowest PaO2 (P < 0.02) and the highest Hct (P < 0.03) and histologically the largest mean glomerular size (P < 0.04). There was no difference in the ML index and the glomerular leukocyte number among the subgroups classified by the causes. These results indicate that ML associated with glomerular enlargement is the major glomerular abnormality characteristic in patients with severe CHF and suggest that glomerular infiltration of leukocytes, especially of macrophages, should play an important role in the progression of both ML and glomerulomegaly. The contributions of persistent hypoxia and up-regulated angiotensin II as the causative factors of these glomerular abnormalities in congestive heart failure are discussed.
Topics: Adult; Aged; Angiotensin II; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Capillaries; Female; Glomerulonephritis, Membranoproliferative; Heart Failure; Hematocrit; Humans; Hypertension; Kidney Glomerulus; Macrophages; Male; Middle Aged; Oxygen; Periodic Acid-Schiff Reaction
PubMed: 9551394
DOI: 10.1111/j.1523-1755.1998.00830.x