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CEN Case Reports Nov 2020Parvovirus B19 (PVB19) has been known to cause acute glomerulonephritis and nephrotic syndrome with various renal histologic patterns, such as endocapillary...
Parvovirus B19 (PVB19) has been known to cause acute glomerulonephritis and nephrotic syndrome with various renal histologic patterns, such as endocapillary glomerulonephritis and collapsing glomerulopathy. Remission is achieved spontaneously or by treatment with steroid and/or immunosuppressants in most patients, except those with sickle cell anemia or two APOL1 risk alleles. In this study, we report the case of a previously healthy 5-year-old boy with infection-related glomerulonephritis (IRGN) associated with PVB19 that progressed to end-stage renal disease (ESRD). He presented with macrohematuria, nephrotic-range proteinuria, and progressive renal dysfunction despite treatment with methylprednisolone pulse therapy, plasmapheresis, and intravenous immunoglobulin. The kidney biopsy specimens exhibited endocapillary infiltration and mesangiolysis with cellular crescent formation. Immunofluorescence analysis revealed that IgA was dominantly positive in the glomeruli, with some co-localized with KM55, which is a specific monoclonal antibody for galactose-deficient IgA1 (Gd-IgA1). The intensity of the KM55 signal in the present patient was weaker than that in patients with IgA nephropathy. To our knowledge, this is the first report of IRGN associated with PVB19 that progressed to ESRD without any underlying diseases. Further investigations are needed to determine the significance of IgA and Gd-IgA1 deposition in IRGN associated with PVB19.
Topics: Antibodies, Monoclonal; Biopsy; Child, Preschool; Disease Progression; Fluorescent Antibody Technique; Galactose; Glomerulonephritis, IGA; Hematuria; Humans; Immunoglobulin A; Kidney; Kidney Failure, Chronic; Kidney Glomerulus; Male; Parvovirus B19, Human; Proteinuria
PubMed: 32621069
DOI: 10.1007/s13730-020-00501-w -
BMJ Case Reports Jun 2020TAFRO (thrombocytopenia, anasarca, fever, reticulin myelofibrosis or renal dysfunction and organomegaly) syndrome is a systemic inflammatory disease characterised by...
TAFRO (thrombocytopenia, anasarca, fever, reticulin myelofibrosis or renal dysfunction and organomegaly) syndrome is a systemic inflammatory disease characterised by thrombocytopenia, anasarca, fever or inflammatory syndrome, reticulin myelofibrosis or renal dysfunction and organomegaly. It was first described as a subtype of idiopathic multicentric Castleman disease. Here, we report the case of a 42-year-old woman presenting with thrombocytopenia, anasarca, inflammatory syndrome, renal insufficiency, reticulin myelofibrosis at bone marrow biopsy and cervical and axillary lymph nodes. Kidney biopsy showed double contours of the glomerular basement membrane, mesangiolysis and endothelial swelling compatible with thrombotic microangiopathy (TMA) as well as with TAFRO syndrome. She was successfully treated by corticosteroids, tocilizumab and rituximab. This new case description of TAFRO syndrome underlines three features of this disease rarely described in the literature and never simultaneously in the same patient: the association to severe hypothyroidism, the presence of TMA-like lesions on kidney biopsy and the treatment by the association of steroids, tocilizumab and rituximab.
Topics: Adult; Antibodies, Monoclonal, Humanized; Antirheumatic Agents; Biopsy; Castleman Disease; Edema; Female; Glucocorticoids; Humans; Hypothyroidism; Kidney; Positron-Emission Tomography; Renal Insufficiency; Rituximab; Thrombotic Microangiopathies; Tomography, X-Ray Computed; Treatment Outcome
PubMed: 32606113
DOI: 10.1136/bcr-2019-234155 -
BMC Nephrology Jun 2020Atypical 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...
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 × 10/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.
Topics: Antibodies, Monoclonal, Humanized; Atypical Hemolytic Uremic Syndrome; Complement Inactivating Agents; Humans; Kidney Failure, Chronic; Male; Middle Aged; Plasma Exchange; Recovery of Function; Renal Dialysis; Time Factors
PubMed: 32571244
DOI: 10.1186/s12882-020-01897-4 -
Journal of Diabetes Research 2020Diabetic nephropathy (DN) is the main factor leading to end-stage renal disease (ESRD) and subsequent morbidity and mortality. Importantly, the prevalence of DN is... (Review)
Review
Diabetic nephropathy (DN) is the main factor leading to end-stage renal disease (ESRD) and subsequent morbidity and mortality. Importantly, the prevalence of DN is continuously increasing in developed countries. Many rodent models of type 1 and type 2 diabetes have been established to elucidate the pathogenesis of diabetes and examine novel therapies against DN. These models are developed by chemical, surgical, genetic, drug, and diet/nutrition interventions or combination of two or more methods. The main characteristics of DN including a decrease in renal function, albuminuria and mesangiolysis, mesangial expansion, and nodular glomerulosclerosis should be exhibited by an animal model of DN. However, a rodent model possessing all of the abovementioned features of human DN has not yet been developed. Furthermore, mice of different genetic backgrounds and strains show different levels of susceptibility to DN with respect to albuminuria and development of glomerular and tubulointerstitial lesions. Therefore, the type of diabetes, development of nephropathy, duration of the study, cost of maintaining and breeding, and animals' mortality rate are important factors that might be affected by the type of DN model. In this review, we discuss the pros and cons of different rodent models of diabetes that are being used to study DN.
Topics: Animals; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Disease Models, Animal; Disease Progression; Humans; Kidney Failure, Chronic; Mice; Rats; Rodentia
PubMed: 32566684
DOI: 10.1155/2020/9416419 -
BMJ Open Diabetes Research & Care Jun 2020The speed of declining kidney function differs among patients with diabetic nephropathy. This study was undertaken to clarify clinical and pathological features that...
INTRODUCTION
The speed of declining kidney function differs among patients with diabetic nephropathy. This study was undertaken to clarify clinical and pathological features that affect the speed of declining kidney function in patients with diabetic nephropathy.
RESEARCH DESIGN AND METHODS
This study was design as multicenter retrospective study. The subjects (377 patients with diabetic nephropathy diagnosed by kidney biopsy at 13 centers in Japan) were classified into three groups based on the estimated glomerular filtration rate (eGFR) declining speed. The eGFR increasing group, the control group, and the eGFR declining group were divided at 0 and 5 mL/min/1.73 m/year, respectively. Characteristics of clinicopathological findings of declining kidney function were evaluated.
RESULTS
The mean observation period of this study was 6.9 years. The control group, the eGFR increasing group, and the eGFR declining group included 81, 66, and 230 patients, respectively. The incidences of composite kidney events represented by 100 persons/year were 25.8 in the eGFR declining group and 2.0 in the eGFR increasing group. After adjustment for age, sex, systolic blood pressure, hemoglobin, and urinary albumin levels, three clinicopathological findings (urinary albumin levels, presence of nodular lesion, and mesangiolysis) were risk factors for inclusion in the eGFR declining group (the ORs were 1.49, 2.18, and 2.08, respectively). In contrast, the presence of subendothelial space widening and polar vasculosis were characteristic findings for inclusion in the eGFR increasing group (the ORs were 0.53 and 0.41, respectively).
CONCLUSIONS
As well as urinary albumin elevation, nodular lesion and mesangiolysis were characteristic pathological features of patients with fast declining kidney function.
Topics: Diabetes Mellitus, Type 2; Diabetic Nephropathies; Glomerular Filtration Rate; Humans; Japan; Retrospective Studies
PubMed: 32503809
DOI: 10.1136/bmjdrc-2019-001157 -
American Journal of Physiology. Renal... May 2020Podocyte loss and proteinuria are both key features of human diabetic nephropathy (DN). The leptin-deficient BTBR mouse strain with the mutation develops progressive...
Podocyte loss and proteinuria are both key features of human diabetic nephropathy (DN). The leptin-deficient BTBR mouse strain with the mutation develops progressive weight gain, type 2 diabetes, and diabetic nephropathy that has many features of advanced human DN, including increased mesangial matrix, mesangiolysis, podocyte loss, and proteinuria. Selective antagonism of the endothelin-1 type A receptor (ETR) by atrasentan treatment in combination with renin-angiotensin-aldosterone system inhibition with losartan has been shown to have the therapeutic benefit of lowering proteinuria in patients with DN, but the underlying mechanism for this benefit is not well understood. Using a similar therapeutic approach in diabetic BTBR mice, this treatment regimen significantly increased glomerular podocyte number compared with diabetic BTBR controls and suggested that parietal epithelial cells were a source for podocyte restoration. Atrasentan treatment alone also increased podocyte number but to a lesser degree. Mice treated with atrasentan demonstrated a reduction in proteinuria, matching the functional improvement reported in humans. This is a first demonstration that treatment with the highly selective ETR antagonist atrasentan can lead to restoration of the diminished podocyte number characteristic of DN in humans and thereby underlies the reduction in proteinuria in patients with diabetes undergoing similar treatment. The benefit of ETR antagonism in DN extended to a decrease in mesangial matrix as measured by a reduction in accumulations of collagen type IV in both the atrasentan and atrasentan + losartan-treated groups compared with untreated controls.
Topics: Angiotensin II Type 1 Receptor Blockers; Animals; Atrasentan; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Disease Models, Animal; Drug Therapy, Combination; Endothelin A Receptor Antagonists; Female; Losartan; Mice; Phosphorylation; Podocytes; Proteinuria; Renin-Angiotensin System; Ribosomal Protein S6 Kinases; TOR Serine-Threonine Kinases
PubMed: 32249614
DOI: 10.1152/ajprenal.00498.2019 -
BMC Nephrology Oct 2019TAFRO syndrome is a systemic inflammatory disorder that manifests as thrombocytopenia (T), anasarca (A), fever (F), reticulin fibrosis (R), and organomegaly (O). Renal... (Review)
Review
BACKGROUND
TAFRO syndrome is a systemic inflammatory disorder that manifests as thrombocytopenia (T), anasarca (A), fever (F), reticulin fibrosis (R), and organomegaly (O). Renal dysfunction is frequently complicated with TAFRO syndrome, however, it is challenging to perform kidney biopsy in patients with TAFRO syndrome in the presence of thrombocytopenia. Renal histology in TAFRO syndrome mainly shows membranoproliferative glomerulonephritis (MPGN)-like lesions or thrombotic microangiopathy (TMA)-like glomerulopathy. We review our case and previous reports of TAFRO syndrome with kidney biopsy findings and discuss the renal pathophysiology of TAFRO syndrome.
CASE PRESENTATION
We describe a previously healthy 48- year-old woman with TAFRO syndrome. Kidney biopsy performed before the treatment showed diffuse global endocapillary proliferative changes with endothelial cell swelling, double contours of partial capillary walls, and mesangiolysis, consistent with TMA-like glomerulopathy. Glucocorticoid therapy including steroid pulse was ineffective and she developed anasarca, renal dysfunction and oliguria. Hemodialysis was required. However, the anti-Interleukin (IL)-6 receptor antibody (tocilizumab) therapy was very effective. An increase in urinary volume was achieved about 2 weeks after the tocilizumab therapy and hemodialysis was discontinued. To investigate the renal pathophysiology of TAFRO syndrome, we performed immunohistological staining of vascular endothelial growth factor (VEGF)-A, CD34, and D2-40, in our case and a normal control kidney. Glomerular VEGF-A was especially positive in podocytes both, in the control and in the case, with no significant difference and there was a significant increase of VEGF-A staining area in the cortical peritubular capillaries in the case. Both glomerular and renal cortical CD34 expression were significantly decreased in our case. D2-40 expression in cortex was not significantly different.
CONCLUSIONS
We reviewed our case and other 10 previous reports about renal biopsy findings in TAFRO syndrome and found that glomerular microangiopathy was a common finding. IL-6-VEGF-axis-induced glomerular microangiopathy may play a crucial role in developing acute kidney injury in TAFRO syndrome and the anti-IL-6 receptor antibody therapy may be useful for TAFRO syndrome refractory to glucocorticoids. About the pathophysiology of VEGF in TAFRO syndrome, VEGF balance in the glomerulus and perhaps in the peritubular capillary system as well may be critical. Further investigation is needed.
Topics: Antibodies, Monoclonal, Murine-Derived; Antigens, CD34; Capillaries; Castleman Disease; Female; Humans; Kidney Diseases; Kidney Glomerulus; Middle Aged; Podocytes; Vascular Endothelial Growth Factor A
PubMed: 31623576
DOI: 10.1186/s12882-019-1574-9 -
Biology of Blood and Marrow... Jan 2020Transplantation-associated thrombotic microangiopathy (TA-TMA) is an important complication of hematopoietic stem cell transplantation. To date, information regarding... (Clinical Trial)
Clinical Trial Comparative Study
Transplantation-associated thrombotic microangiopathy (TA-TMA) is an important complication of hematopoietic stem cell transplantation. To date, information regarding the organs that are affected by TA-TMA as confirmed histologically remains limited; the clinicopathologic differences between renal TA-TMA and intestinal TA-TMA have not been examined despite being the well-known and commonly affected sites of TA-TMA. We therefore examined 165 autopsied patients after hematopoietic stem cell transplantation and compared the clinicopathologic factors of renal and intestinal TA-TMA. It was clear that 38 (23%) of our patients had TA-TMA. In the TA-TMA cases, the kidney (61%) and intestine (53%) were commonly affected, and the ileum and right colon were vulnerable. Other organs that we found to be affected by TA-TMA included the stomach (8%), gallbladder (5%), and oral cavity, pharynx, esophagus, liver, heart, urinary bladder, and ureter (all at 3%), and symptoms thought to be caused by TA-TMA of these organs were not observed in any patient. Histologically, TA-TMA only affected the arteriole, or small arteries, regardless of the organ, and the veins or larger arteries were not affected at all. In the kidney, the glomerular capillary was also affected, and mesangiolysis and double contours of the basement membranes were often in evidence. The histologic overlap of renal and intestinal TA-TMA was rare (13%), and the patients in the intestinal TA-TMA group exhibited more frequency of a history of intestinal acute graft-versus-host disease (GVHD) during the clinical course compared with that of the renal TA-TMA group (80% versus 22%, P = .0016). Although TA-TMA can affect many other organs, the frequency of these ancillary events was low, and the clinical effect may have been small. Our results suggest that in comparison to renal TA-TMA, intestinal GVHD could be more closely associated with intestinal TA-TMA as a risk factor.
Topics: Acute Disease; Adult; Autopsy; Child; Female; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Intestinal Diseases; Male; Middle Aged; Thrombotic Microangiopathies
PubMed: 31491486
DOI: 10.1016/j.bbmt.2019.08.025 -
Journal of the American Society of... Oct 2019A glycocalyx envelope consisting of proteoglycans and adhering proteins covers endothelial cells, both the luminal and abluminal surface. We previously demonstrated that...
BACKGROUND
A glycocalyx envelope consisting of proteoglycans and adhering proteins covers endothelial cells, both the luminal and abluminal surface. We previously demonstrated that short-term loss of integrity of the luminal glycocalyx layer resulted in perturbed glomerular filtration barrier function.
METHODS
To explore the role of the glycocalyx layer of the endothelial extracellular matrix in renal function, we generated mice with an endothelium-specific and inducible deletion of hyaluronan synthase 2 (Has2), the enzyme that produces hyaluronan, the main structural component of the endothelial glycocalyx layer. We also investigated the presence of endothelial hyaluronan in human kidney tissue from patients with varying degrees of diabetic nephropathy.
RESULTS
Endothelial deletion of Has2 in adult mice led to substantial loss of the glycocalyx structure, and analysis of their kidneys and kidney function showed vascular destabilization, characterized by mesangiolysis, capillary ballooning, and albuminuria. This process develops over time into glomerular capillary rarefaction and glomerulosclerosis, recapitulating the phenotype of progressive human diabetic nephropathy. Using a hyaluronan-specific probe, we found loss of glomerular endothelial hyaluronan in association with lesion formation in tissue from patients with diabetic nephropathy. We also demonstrated that loss of hyaluronan, which harbors a specific binding site for angiopoietin and a key regulator of endothelial quiescence and maintenance of EC barrier function results in disturbed angiopoietin 1 Tie2.
CONCLUSIONS
Endothelial loss of hyaluronan results in disturbed glomerular endothelial stabilization. Glomerular endothelial hyaluronan is a previously unrecognized key component of the extracelluar matrix that is required for glomerular structure and function and lost in diabetic nephropathy.
Topics: Animals; Endothelium; Humans; Hyaluronic Acid; Kidney Glomerulus; Mice; Urothelium
PubMed: 31308073
DOI: 10.1681/ASN.2019020192 -
CEN Case Reports Nov 2019TAFRO syndrome (thrombocytopenia, anasarca, fever, reticulin fibrosis, and organomegaly) is thought of as an atypical type of idiopathic multicentric Castleman's...
TAFRO syndrome (thrombocytopenia, anasarca, fever, reticulin fibrosis, and organomegaly) is thought of as an atypical type of idiopathic multicentric Castleman's disease. Interleukin-6, vascular endothelial growth factor (VEGF), and other cytokines are considered etiological factors. A 45-year-old woman was admitted to hospital with unknown fever and abdominal pain. She had thrombocytopenia, anasarca, proteinuria/hematuria, and slight hepatosplenomegaly. Based on her clinical course and laboratory data, she was diagnosed as having TAFRO syndrome. Kidney biopsy showed a membranoproliferative glomerulonephritis (MPGN)-like lesion containing lobulations of glomeruli, endothelial cell swelling, double contours of the glomerular basement membrane, and mesangiolysis. She was treated with methylprednisolone pulse (500 mg/day) and oral prednisolone (60 mg/day) therapy. The pleural effusion and ascites disappeared, and renal function normalized. Cyclosporine was added to prevent relapse. She went home, with no relapse 8 months after hospitalization. MPGN-like lesions were found frequently in patients with TAFRO syndrome in recent reports. However, there are few reports of pathologically confirmed cases of progressive renal involvement in TAFRO syndrome. The relationship between VEGF expression in renal tissue and the pathogenesis of renal injury in TAFRO syndrome was investigated in the present case.
Topics: Abdominal Pain; Anti-Inflammatory Agents; Castleman Disease; Cyclosporine; Female; Fever; Glomerulonephritis, Membranoproliferative; Humans; Immunosuppressive Agents; Kidney; Kidney Glomerulus; Methylprednisolone; Middle Aged; Thrombocytopenia; Treatment Outcome; Vascular Endothelial Growth Factor A
PubMed: 31077056
DOI: 10.1007/s13730-019-00400-9