فهرست مطالب
Journal of nephropathology
Volume:8 Issue: 3, Jul 2019
- تاریخ انتشار: 1398/04/03
- تعداد عناوین: 12
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Page 2BackgroundTransplant nephrectomy (TN) is not commonly performed but it may be essential for several indications.
ObjectivesThis study details an in-depth evaluation of the histological changes present in TN specimens.We identified 124 consecutive TN cases between 2004 and 2014. The indication for TN was divided into four groups: acute graft loss without significant blood flow (AGL group- 47 cases); suspected ongoing rejection or graft intolerance syndrome (Rej/GIS group44 cases); infection (INF group- 24 cases); and miscellaneous reasons (MIS group- 9 cases). We examined the histological changes, including the main renal artery (MRA), intrarenal arteries, the renal vein and the ureter.
Patients and Methods
ResultsIn AGL group, most cases showed no tubulointerstitial inflammation, interstitial fibrosis and tubular atrophy, but 74.5% had necrosis. All cases in Rej/GIS group showed severe interstitial fibrosis
and tubular atrophy, since 40.9% showed severe tubulointerstitial inflammation. Glomerulitis was observed in 52.3% and transplant glomerulopathy (TG) was detected in 75.0%. Arteritis of
intrarenal arteries and the MRA were detected in 70.5% and 59.1%. In INF group, 66.7% had tubulitis and 79.2% had interstitial inflammation with lymphocytes, and severe interstitial fibrosis
while, tubular atrophy were detected in 66.7%. TG was detected in 62.5%. In MIS group, the
histological changes were minor.
ConclusionsThis study provides a detailed description of the morphological characteristics associated with various indications for TN. TN will occasionally reveal unexpected and significantfindingsthat may require specific forms of treatment to manage the patient appropriately.Keywords: Renal transplantation, Transplant nephrectomy, Graft failure, Renal pathology -
Page 3BackgroundFocal segmental glomerulosclerosis (FSGS) and Minimal change disease (MCD) are two disease entities presented mainly by nephrotic syndrome. While 95% of MCD cases showed
complete remission on steroid therapy, 50% of FSGS cases progress to end stage renal disease. Early sclerotic lesions in FSGS can be missed in routine H&E examination.ObjectiveTo differentiate early FSGS from MCD by detection of activated parietal epithelial cells (PECs) in early glomerular sclerotic lesions using Claudin-1 immunohistochemical (IHC) staining and by examining podocyte ultrastructural changes.Materials and MethodsThis retrospective study included 28 cases diagnosed as MCD and 20 cases diagnosed as early FSGS. Clinicopathologic data collection, claudin-1 IHC staining and reviewing ultrastructural changes were performed and the results were statistically analyzed.ResultsA statistically significant correlation was detected between claudin-1 expression and the initial diagnosis of the studied groups (P=0.005). Claudin-1 was expressed in a visceral location in (39.28%) of the biopsies initially diagnosed as MCD thus were reevaluated as early FSGS lesions. 63.64% of these positive cases were presented by steroid resistant nephrotic syndrome and 63.6% of which showed some ultrastructural changes of FSGS in podocytes including abnormalities in mitochondrial shapes, endoplasmic reticulum changes and a decreased number of autophagic vacuoles.ConclusionClaudin-1 is a novel diagnostic marker that can differentiate between confusing cases of early FSGS versus MCD. Defective autophagy plays a role in the pathogenesis of FSGS.Keywords: Claudin-1 immunohistochemistry, Focal segmental glomerulosclerosis, Minimal change disease, Parietal epithelial cells, ultrastructural changes, defective autophagy -
Page 4BackgroundModified Ponticelli regimen (mPR), consisting of cyclical steroids and cyclophosphamide, is the most established therapy for primary membranous nephropathy (MN). Yet, the potential
toxicity of this treatment regimen poses a significant concern.
ObjectivesThe aim of this study was to assess the efficacy and safety of a modified version of the conventional mPR for primary MN using lower-than-standard dose pulse steroids.This was a retrospective single-center analysis of patients admitted between January 2008 to December 2017. All treatment-naive patients with biopsy-proven primary MN treated with a lower-than-standard dose pulse steroid-based modification of the conventional mPR (intravenous pulse of 500 mg methyl-prednisolone, instead of 1000 mg) were included. We report the remission rates at the end of 6 months (both complete and partial), relapses and adverse effects of treatment at the end of follow-up.
Patients and Methods
ResultsA total of 41 individuals were included. Of 31 individuals who completed six months of treatment (six were lost to follow-up, while four discontinued immunosuppression due to infections),71% (n=22) responded to treatment [complete remission in 25.8% (n=8), partial remission in 45.2% (n=14)]. Most common complications detected throughout the treatment were steroid induced diabetes mellitus in 40% (n=14/35), infections in 25.7% (of which immunosuppression was discontinued for four participants), and leucopenia in 8.5% (n=3/35). Relapses were seen in 29% (n=9) during follow-up (mean follow-up period: 36 months).
ConclusionsThe modified- ‘modified Ponticelli’ regimen with lower-than-standard dose intravenous steroids and cyclophosphamide was efficient in attaining remission in primary MN.Keywords: Nephrotic syndrome, Steroids, Alkylating agents, Glomerular disease, Membranous nephropathy, Immunosuppression -
Page 5BackgroundAlbuminuria showed to be a deteriorating condition in diabetic kidney disease (DKD) associated with high morbidity and mortality. A need for a novel marker for early detection of DKD development and progression becomes mandating.
ObjectiveTo study the clinical value of urinary podocin as an early marker of diabetic kidney disease and its association with severity of the disease.
Patients andMethodsThis study included 45 individuals with type 2 DM whose GFR >60 mL/min/1.73 m2 , recruited from Ain Shams University Hospital, Cairo, Egypt. Patients were further divided into three groups according to urinary albumin/creatinine ratio (ACR). In addition to, ten healthy volunteers serving as the control group was enrolled in the study. Routine chemistry including serum creatinine, fasting blood glucose (FBG), HbA1c, albumin, lipid profile, urine analysis, ACR and urinary podocin quantification were conducted for all participants (by ELISA method).
ResultsPodocin was higher in patients with ACR <30 mg/g, ACR 30-299 mg/g and ACR ≥ 300 mg/g versus healthy controls, respectively (P<0.001). Both GFR and serum albumin showed highly significant negative correlations with urinary podocin. Significant positive correlations were detected between urinary podocin with blood urea nitrogen (BUN), serum creatinine, FBG, HbA1c, cholesterol, and triglyceride levels.
ConclusionsUrinary podocin is assumed to be a promising marker for early DKD detection in type 2 DM patients.Keywords: Podocin, Diabetic kidney disease, Podocyturia, Glomerular filtration rate, Diabetes mellitus -
Page 6BackgroundThrombotic microangiopathy (TMA) is a morphologic lesion characterized by thrombi occluding microvasculature related to endothelial injury.
ObjectivesThis study aimed to assess the association between histopathological findings and etiology of TMA.
Patients and MethodsThis cross-sectional study comprised a sample of 34 patients who underwent renal biopsy and received an initial TMA diagnoses resulting in 29 definitive TMA cases. We evaluated the TMA features and clinical histopathological correlation.
ResultsThe most frequent etiologies were atypical hemolytic uremic syndrome (aHUS) (n= 10; 34.5%), hemolytic uremic syndrome caused by Shiga toxin-producing Escherichia coli (STECHUS) (n=6; 24.1%) and secondary causes of TMA (n= 12; 41.4%). We found the following histological features; patients with aHUS had thrombi in 60% of biopsies, membranoproliferative glomerulonephritis (MPGN)-like pattern in 20% and ischemia in 20%; patients with STEC-HUS had thrombi (14.3%), MPGN-like pattern (14.3%), endothelial swelling (14.3%) and ischemia (57.1%); patients with secondary etiologies had thrombi (58.3%), endothelial swelling (16.7%), ischemia (16.7%) and MPGN-like pattern (8.3%).
ConclusionsThe distribution of classic TMA findings was not related to etiology in spite of microthrombi having been found mostly in aHUS and secondary etiologies, whereas ischemia was found
mainly in STEC-HUS. We did not find a histopathological pattern to each etiology of TMA.Keywords: Thrombotic microangiopathy, Hemolytic uremic syndrome, Microthrombi, Endothelium, Shiga toxin -
Page 7BackgroundFocal segmental glomerular sclerosis (FSGS) and necrotizing crescentic glomerulonephritis is a rare combination of diagnoses in the same patient. We report on a patient with FSGS who 10 years later developed anti-neutrophil cytoplasmic antibody (ANCA) associated glomerulonephritis.
Case PresentationPatient is a 60-year-old female with chronic kidney disease stage 3, osteopenia and anemia. In 2007, she was positive for ANCA proteinase-3 antibody, but kidney biopsy revealed FSGS. She was treated with high-dose oral steroids with tapered dose and went into remission. In 2017, she developed acute renal failure with increased proteinuria. Despite prior FSGS diagnosis, her
new kidney biopsy revealed pauci-immune necrotizing glomerulonephritis. Patient was treated with methylprednisolone 250 mg IV for three days and high dose oral steroids with tapered dose. She was also started on rituximab 375 mg/m2 IV once weekly for 4 doses. Given the extent of kidney damage, the patient decided to start peritoneal dialysis and she is also on the kidney transplant list.
ConclusionsThe rare concurrence of FSGS and ANCA associated glomerulonephritis has not yet been reported. The case also emphasizes the significance of screening for ANCA or obtaining kidney
biopsy when indicated not only as the gold standard for diagnosis but also as prognostic value.Keywords: Chronic kidney disease, End stage renal disease, Rapidly progressive glomerulonephritis, Pauci-immune crescentic glomerulonephritisclerosis, Focal segmental glomerular sclerosis, Gloerulonephritis -
Page 8BackgroundVenous and arterial thromboembolism are frequently seen in nephrotic syndrome. They generally occur during periods of sustained proteinuria in patients who are not responding to treatment and more commonly seen in minimal change disease and membranous nephropathy.
Case PresentationA 28-year-old male presented to cardiology department of our hospital with worsening breathlessness for 1 week. We found pulmonary embolism and an infarct in the lower pole of the right kidney by CT pulmonary angiogram. He had no previous history or features of nephrotic syndrome. Urine analysis showed numerous red blood cells, 3+ proteinuria and granular casts. Urine protein creatinine ratio was 5.2 g/g of creatinine. Serum creatinine was 2.61 mg/dL. Renal biopsy was suggestive of IgA nephropathy and patient was started on steroids and warfarin and responded to treatment.
ConclusionsPatients with nephrotic syndrome can rarely present initially with venous and arterial thromboembolism. Rarely even IgA nephropathy can present with such thromboembolic episodes.Keywords: IgA nephropathy, Nephrotic syndrome, Arterial thromboembolism, Proteinuria -
Page 9BackgroundC3 glomerulopathy is a recently described entity classified as complementassociated glomerular disease.
Case PresentationWe report a case of a 48-year-old man referred to the nephrology department for nephrotic syndrome with rapidly progressive kidney failure, acquired partial lipodystrophy and drusen in Bruch’s membrane of the retina. Blood tests showed low C3 and no evidence for autoimmune diseases, monoclonal gammopathy or infection. The renal biopsy revealed a proliferative endocapillary and crescentic glomerulonephritis with glomerular deposits exclusively of C3 and significant interstitial fibrosis. The electronic microscopy was consistent with dense deposit disease. The complement analysis revealed a pathogenic mutation of the complement factor B (CFB) gene not previously described in literature.
ConclusionsThe authors report a new mutation of CFB, in a dense deposit disease patient; this finding brings a new insight to the pathogenic pathway of C3 glomerulopathy and possibly to other complement dysregulation associated glomerular diseases. More clinical trials are needed to clarify both the pathogenicity and the optimal treatment for these entities.Keywords: C3 glomerulopathy, Complement factor B, Dense deposit disease, Genetic mutation, Nephrotic syndrome -
Page 10Henoch-Schönlein purpura (HSP) is an immune-complex mediated vasculitis affecting small vessels with dominant IgA deposits. It is seen mostly in children, with a self-limiting disease, but can present with more severe clinical features in older patients, such as gastrointestinal (GI) involvement, with a propensity for rapid progression. In this report, we describe our experience with a male HSP patient who presented with pneumonia, palpable purpuric rash, severe GI involvement with hemodynamic compromise and acute kidney injury. Even though we escalated therapy over time given the lack of response with each previous strategy, with corticosteroids and cyclophosphamide, he developed massive lower gastrointestinal hemorrhage that was not responsive to any supportive measure and died as a result of hemorrhagic shock. There was no established protocol that guided this treatment due to lack of rigorous data, which emphasizes the need for more studies on adult HSP in order to establish the optimal management for HSP patients with severe gastrointestinal manifestations.Keywords: Henoch-schönlein purpura, Gastrointestinal bleeding, Acute kidney failure, Treatment, Immunosuppression, Hemorrhagic shock
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Page 11BackgroundIgG4-related disease (IgG4-RD) is a systemic immune-mediated disease that typically manifests as fibro-inflammatory masses that can affect nearly any organ system.We present here a case of a 49-year old man with forgotten old disease (Mikulicz disease) with membranous nephropathy (MN).
Case Report
ConclusionsThis entity is currently included within the spectrum of IgG4-related disease. The development of renal disease shortly after the suspension of rituximab suggests another probable
pathway involved. To our knowledge the transforming growth factor may be responsible for existing pattern of fibrosis in this disease. The lack of response or at least partial response to rituximab can be explained by greater involvement of regulatory T lymphocyte in the pathophysiology of this entityKeywords: IgG4 related disease_membranous nephropathy_Mikulicz disease_rituximab_regulatory T lymphocyte -
Page 12ContextMatrix metalloproteinases (MMPs) are involved in the remodelling of the glomerularbasement membrane (GBM) by tightly regulating the metabolism of extracellular matrix (ECM)
of the GBM.Evidence AcquisitionsDirectory of Open Access Journals (DOAJ), Google Scholar, PubMed,EBSCO, Scopus and Web of Science have been searched.ResultsGelatinases (MMP-2 and MMP-9) are mainly found involved in the remodelling of GBM and therefore this review focuses on these two MMPs and their action in nephrotic syndrome (NS),
which is a protein losing enteropathy occurring due to the loss of integrity of GBM. In addition to the blood corpuscles, glomerular epithelial cells and mesangium are also expressing MMPs, and various cytokines and growth factors are involved in addition to tissue inhibitors of metalloproteinases (TIMPs) in regulating the metabolism of ECM via MMPs. While examining the results of
MMP activity and expression in NS, except diabetic nephropathy (DN), membranoproliferative glomerulonephritis (MPGN) and hereditary NS where there was a clear down-regulation of MMP,
all the other types of NS showed conflicting results. Both suppression and induction of MMPs are finally leading to GBM thickening, loss of integrity and proteinuria. Enhanced MMP activity leads
to increase in matrix turnover and accumulation of ECM remnants and apoptotic cells leading to fibrosis. On the other hand, diminished expression of MMPs prevents the normal ECM turnover
and matrix accumulation. The review compiled the mechanisms of action of both downregulation and upregulation of MMPs.
ConclusionsImbalance of ECM metabolism due to varied expression levels and activities of MMPs in different types of primary NS might contribute to the progression of nephropathies. Further studies are required to identify the potential and usage of MMPs as a diagnostic/prognostic/ therapeutic tool.Keywords: Matrix metalloproteinases, Nephrotic Syndrome, Glomerular Basement Membrane, Extra cellular Matrix