Increase In Mesangial Matrix Research Articles

Integrated miRNA-mRNA Analysis Reveals Critical miRNAs and Targets in Diet-Induced Obesity-Related Glomerulopathy.

This study aimed to investigate obesity-related glomerulopathy (ORG) at cellular, structural, and transcriptomic levels. Thirty Wistar rats were randomized into two groups: 15 rats were fed with a standard diet (SD-rats), and 15 rats were fed with a high-fat diet (HFD-rats). After 10 weeks, the weight, kidney function, histological features, and transcriptomic changes were assessed. HFD-rats gained significantly more weight (55.8% vs. 29.2%; p < 0.001) and albuminuria (10,384.04 ng/mL vs. 5845.45 ng/mL; p < 0.001) compared to SD-rats. HFD-rats exhibited early stages of ORG, with predominant mesangial matrix increase and podocyte hypertrophy (PH). These lesions correlated with differentially expressed (DE) genes and miRNAs. Functional analysis showed that miR-205, which was DE in both the kidneys and urine of HFD-rats, negatively regulated the PTEN gene, promoting lipid endocytosis in podocytes. The downregulation of PTEN was proved through a higher PTEN/nephrin ratio in the SD-rats and the presence of lipid vacuoles in HFD-podocytes. This study has found a specific targetome of miRNAs and gene expression in early stages of ORG. Also, it emphasizes the potential value of miR-205 as a urinary biomarker for detecting podocyte injury in ORG, offering a tool for early diagnosis, and opening new avenues for future therapeutic research of obesity-related glomerulopathy.

Monosodium glutamate altered renal architecture and modulated expression of NMDA-R, eNOS, and nNOS in normotensive and hypertensive rats

Monosodium glutamate (MSG) administration has been shown to pronounce hypertension and oxidative status with increased renal blood flow (RBF), however, the precise mechanisms of action have never been demonstrated. This study aimed to investigate the MSG action by studying the alteration in renal architecture and specific protein expression in 2-kidney-1-clip hypertensive comparing to sham operative normotensive rats. The administered doses of MSG were 80, 160, or 320 mg/kg BW daily for 8 weeks. Using routine chemical staining, the congestion of glomerular capillaries, a lesser renal corpuscles and glomeruli size, a widen Bowman capsule's space, an increase in mesangial cell proliferation and mesangial matrix, renal interstitial fibrosis, focal cloudy swelling of renal tubular epithelial cells were observed. Immunological study revealed an increase in the expression of N-methyl-D-aspartate receptor (NMDA-R) and endothelial nitric oxide synthase (eNOS) but a decrease in neuronal NOS (nNOS). It is suggested that MSG may upregulate the NMDA-R levels which responsible for the oxidative stress, glomerular injury, and renal interstitial fibrosis. The NMDA-R may also stimulate eNOS overexpression which resulted in renal microvascular dilatation, a raise in RBF and GFR, and natriuresis and diuresis promotion. Long-term exposure of MSG may trigger adaptation of tubuloglomerular feedback through nNOS downregulation.

#1493 Upregulated miR-205 as a biomarker of diet-induced obesity-related glomerulopathy

Abstract Background and Aims Obesity is a modifiable risk factor for the development and progression of chronic kidney disease (CKD). Pathways through which obesity might cause renal disease are not completely understood, as not all obese subjects develop CKD. In terms of deepening the knowledge of the preliminary steps of obesity-related renal damage, our group has developed a diet-induced obese murine model with obesity related glomerulopathy (ORG). The objective of this study was to investigate ORG at a cellular, structural and transcriptomic level as a way to discover the triggering pathogenic phenomena of ORG and evaluate potential biomarkers. Method Thirty Wistar rats were randomized into two groups: control rats (n = 15), which were fed with standard diet (SD) and study rats (n = 15), which were fed with high-fat diet (HFD). After 10 weeks, weight, parameters of kidney function, renal histological features, transcriptomic changes, miRNA and mRNA isolation were compared. Results HFD gained significantly more weight (55.8%) than SD(29.2%), p = 0.001. Albuminuria was also significantly higher in HFD (10,384.04) compared with SD (5,845.45), p = 0.001. HFD rats showed typical lesions of early-stages of ORG, with a predominance of mesangial matrix increase (MMI) and podocyte hypertrophy (PH). All histologic lesions correlated with genes differentially expressed (DE) in kidneys of HFD group and, both MMI and PH, also correlated with specific miRNAs DE in the urine of HFD group. The functional analysis showed 4 miRNAs DE in the kidneys of HFD group that negatively regulates PTEN gene, which promotes podocyte endocytosis of lipids in ORG. The electronic microscope confirmed the spaces of lipid vacuoles in the podocytes of HFD rats. Between those 4 miRNAs DE, miR-205 was also found to be upregulated in the urine of HFD group. Conclusion Wistar rats fed with HFD for 10 weeks developed early-stages of ORG, with a specific targetome of miRNAs and gene expression. The upregulation of miR-205 in kidney and its isolation in urine is associated with lipid endocytosis of podocytes, which takes place in the early-stages of ORG and could become a plausible biomarker of early-stages of ORG and open new avenues for future therapeutics research.

#3051 Light chain only variant of proliferative glomerulonephritis with monoclonal immunoglobulin deposits: a case report

Abstract Background and Aims Proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID) is an entity characterized by glomerular deposition of monoclonal immunoglobulins, typically IgG. Recently, a cohort of 17 patients presenting with light chain only variant of PGNMID was published. Strikingly, in this cohort, glomerular deposition of C3 was detected in all cases. We herein report a case of PGNMID with a rare presentation on the kidney biopsy. Case presentation We present the case of a 73-year-old female with a past medical history of rheumatoid arthritis and hypertension, under methotrexate 10 mg per week, prednisone 2.5 mg per day, amlodipine, nebivolol, azilsartan, and a recurrent naproxen intake. She presented with fatigue, anorexia, weight loss of about 12% of her body weight, epistaxis, oral bleeding ulcers, and lower extremities oedema. Pancytopenia, acute kidney injury (urea 150 mg/dL, creatinine 2.92 mg/dL), and nephrotic syndrome (serum albumin of 2.7 mg/dL and proteinuria of 12 g/day) were noted. Further evaluation showed an imbalance of the free light chains’ ratio with kappa light chain's level of 1250 mg/dL. Serum protein electrophoresis and immunofixation were normal. A CT scan showed numerous cervical, mediastinal, and iliac enlarged lymph nodes. Kidney biopsy showed an increase in mesangial cells and matrix and capillary walls’ thickening without nodular lesions under a light microscope. Immunofluorescence microscopy showed granular deposits of kappa light chains and no deposition IgA, IgG, IgM, C1q, C3, fibrin and lambda. Considering the previous literature, C3 was reanalyzed, with a consistent negative staining. Based on the above findings, a diagnosis of Light chain only variant of PGNMID was made. Concomitantly, evaluation of the bone marrow sample showed Small lymphocytic lymphoma. The patient was started on Bortezomib, cyclophosphamide and dexamethasone. Three months after proteinuria was 0.47 g/g and creatinine 1.7 mg/dL. Conclusion This case highlights the rare occurrence of a PGNMID with light chains only deposition (without C3 co-deposition) as a complication of small lymphocytic lymphoma. This contributes to the growing body of evidence surrounding this entity, with the particularity being that C3 was not detected. The authors hypothesized some pathophysiologic mechanisms to justify the absence of C3 co-deposition.

Renal biopsy pattern in diabetes mellitus patients and their correlation with clinical parameters

Background. Diabetic nephropathy is a condition marked by persistent proteinuria, hypertension, and a progressive loss of renal function. End-stage kidney disease needing continuous renal replacement treatment is now primarily caused by diabetes. According to Kimmelstiel and Wilson, the hallmark lesion of diabetic nephropathy is nodular glomerulosclerosis. Diabetic nephropathy or Nondiabetic renal disease, or the coexistence of both can be seen in renal histopathology and in differentiating between these diagnostic groups can have an impact on patient care and prognosis.Patients and Methods. Total of 21 cases of Diabetic nephropathy were included in the study. Clinical details and laboratory parameters like diastolic blood pressure, creatinine level, 24 hrs urinary protein level and HbA1C% were recorded in pretested performa in all cases. The biopsy specimens were stained with hematoxylin &amp; eosin and special stains.Results. Among the total DM cases only 21 patients have done renal biopsy, 11 cases (52.3 %) showed KW lesion (Class III) while 06 cases (28.5 %) showed diffuse diabetic glomerulosclerosis (Class IV). The remaining 04 cases (19 %) showed a mild increase in mesangial matrix and slight thickening of glomerular basement membrane (Class II). When compared with clinical parameters, they were more raised in Nodular diabetic glomerulosclerosis type (Class III) lesion as compared to diffuse diabetic glomerulosclerosis.Conclusion. Nodular diabetic glomerulosclerosis was the most common lesion in renal biopsy of type II diabetes mellitus patients. This KW lesion is responsible for more severe clinical and biochemical renal abnormality in most patients with type II diabetes mellitus.

Discordance of light chain isotypes between serum and glomerular deposits in proliferative glomerulonephritis with monoclonal IgG deposits: a case report and review of the literature

BackgroundProliferative glomerulonephritis with monoclonal immunoglobulin G (IgG) deposits (PGNMID) is a disease entity with nonorganized granular glomerular deposition with monoclonal proteins of both heavy and light chains. Dysproteinemia was observed in only 30% of the patients with PGNMID. We herein report a case of PGNMID with discrepancy between serum and glomerular deposits.Case presentationThe patient was a 50-year-old man who had been followed at a local clinic due to hypertension, type 2 diabetes, hyperlipidemia, hyperuricemia, fatty liver, and obesity. Proteinuria had been noted five years previously, and he had been referred to a hematology department due to hyperproteinemia, high gamma globulin, and κ Bence-Jones protein (BJP) positivity one year previously. Bone marrow aspiration showed 5% plasma cells, and he was referred to the nephrology department to evaluate persistent proteinuria. He was hypertensive, and his estimated glomerular filtration rate was 54.2 ml/min/1.73 m2. His urinary protein level was 0.84 g/g⋅Cr. Urine and serum immunofixation showed BJP-κ type and IgG-κ type, respectively. Kidney biopsy showed an increase in mesangial cells and matrix without nodular lesions under a light microscope. Immunofluorescence microscopy showed granular deposits of IgG and C3 on the capillary wall and weak positivity for C1q. IgG3 was predominant among the IgG subclasses, and intraglomerular κ and λ staining was negative for κ and positive for λ. Direct fast scarlet staining was negative. Electron microscopy showed lumpy deposits without a fibrillar structure in the subepithelial area. Based on the above findings, a diagnosis of membranous nephropathy-type PGNMID was made. Since proteinuria increased gradually after three years of treatment with valsartan (40 mg, daily), oral prednisolone (30 mg, daily) was initiated, which led to decreased proteinuria. The dose of oral prednisolone was gradually tapered to 10 mg per day. At that time, proteinuria was 0.88 g/g⋅Cr. We found 204 cases in 81 articles in the PubMed database, among which 8 showed discrepancy in the heavy and/or light chains between serum and kidney.ConclusionsWe experienced a case of membranous nephropathy-type PGNMID with discrepancy in light chains between serum and kidney that was successfully treated with oral prednisolone.

Association between Kidney Donor Risk Index, kidney graft function and histological changes in early post-transplant graft biopsy.

Proper assessment of donor organ quality is crucial for optimal kidney allocation and best long-term outcomes. The aim of this study was to analyze the association between the Kidney Donor Risk Index (KDRI) and histological parameters in early post-transplant graft biopsy in a Polish cohort of kidney transplant recipients. In 418 consecutive kidney transplant recipients, a histological evaluation of very early [at median 11 (9-13) post-transplant day] protocol core needle biopsy was performed and analyzed according to the Banff classification. Subjects were divided into quartiles of the KDRI value. Kidney graft function, patient and graft survival were also analyzed over a median follow-up period of 44 (26-56) months. There was a significant trend toward greater intensity of chronic histology changes along the KDRI quartiles (χ2=20.8; P<.001), including interstitial fibrosis, tubular atrophy, mesangial matrix increase and arteriolar hyalinosis. Stepwise multivariate regression analysis revealed that only higher KDRI value independently increased the severity of chronic graft injury (rpartial=0.340, P<.001). KDRI values were valuable in the determination of both early and long-term graft function. The KDRI values correlate with chronic histological changes found in early post-implantation kidney biopsies and can also be helpful in the prediction of graft outcome.

#4488 OLD BIOPSY IS ALWAYS GOLD, REVISING MEMBRANOPROLIFERATIVE GN DIAGNOSIS IN A RENAL TRANSPLANT PATIENT

Abstract Background and Aims MPGN resulting from hepatitis C virus (HCV) infection typically shows granular deposition of immunoglobulin M (IgM), C3, and both kappa and lambda light chains. Immunoglobulin G (IgG) may or may not be present, and C1q is typically negative, the same pathology can be found in other viral infections. The recurrence rate post-transplantation is high, with 33% of immune-complex MPGN. Graft loss is even higher 65%, especially among patients with idiopathic MPGN. Treatment of a patient with significant proteinuria can be tricky, as no proven treatment is described yet, but plasmapheresis and induction with cyclophosphamide were described for heavy proteinuria &amp;gt;3.5 g/day. Method 79 year old female patient, known case of live unrelated renal transplantation in December 2013, primary renal disease is unknown. She had a history of equivocal hepatitis C virus antibodies, but Hepatitis C virus RNA was not detected. She is also known to have Type II Diabetes Mellitus and hypertension. The patient had baseline creatinine of 100-120 micromol/L. 24 hr urine protein was 0.8 g/Day but started rising quickly to reach a peak of 9.2 g/g seven months post-transplantation to nephrotic range proteinuria but her serum albumin level was always above 35 g/L. Serum protein electrophoresis showed no M band, a kappa/ Lambda ratio 1.21 within a normal range (0.260-1.65). Anti- nuclear antibody (ANA), P-ANCA, C-ANCA, and Double-stranded DNA all were negative. Complements were within normal range C3 1.39 g/L (0.79 -1.52), C4 0.44 g/L(0.17-0.57)m rheumatoid factor and Anti- citrullinated peptide antibodies were negative. Hepatitis b Virus surface antigen and core antibodies were not reactive, HIV screening was negative. Urine analysis showed RBCs but no RBC casts. Renal biopsy showed mild mesangial expansion and mild l increase in mesangial cells and matrix. Some glomeruli show increased lobulation with increase in mesangial cells and matrix with segmental endocapillary proliferation There is double contour of the glomerular basement membrane with scattered spikes and holes within the basement membrane seen best with silver stain. There is mild increase in the thickness of glomerular basement membrane. There is focal mild lymphocytic infiltration. Tubulitis is not seen in the examined material. One Focal area of mild interstitial fibrosis. Sampled blood vessels are unremarkable. The stain for C4d is negative. Immunofluorescence showed granular capillary wall immunoreactivity to IgM (+2), C4 (+1), C1q (+1), and Lambda light chain (+2). The glomeruli show no immunoreactivity to IgG, IgA, C3, Kappa and fibrin. The glomeruli show (+) staining for albumin. Tubular protein reabsorption droplets showed immunoreactivity for albumin, IgG, IgM, C3, kappa and lambda light chains. Electron microscopy showed many subendothelial, and mesangial electron-dense deposits. The patient was on maintenance immunosuppression medications inform of mycophenolic acid 720 mg, cyclosporine; 250mg BID, and Prednisolone 5 mg daily.Revisiting the new classification of membranoproliferative glomerulonephritis is challenging in this patient, since there is the dominance of IgM deposition by immunofluorescence and C4 but not C3 makes it challenging, the negative monoclonal band in serum electrophoresis and negative autoimmune workup excludes immune complex mediate MPGN, leave idiopathic MPGN a possibility, keeping in mind that hepatitis C virus infection was never confirmed. On the other hand, IF showed IgM with C4 subendothelial and mesangial dense deposits that excludes away the C4 glomerulopathy. Results Whether this is a recurrence of glomerular disease early on post-transplantation or denovo membranoproliferative disease, she responded well to the addition of losartan 100 mg daily, with a reduction of her urinary protein to less than 1 g/g. the patient never received treatment for the hepatitis C virus. Conclusion In our patient, it is difficult to conclude if the cause of MPGN is recurrence or denovo GN, especially with severe proteinuria that responded well to ACEi treatment. The pathological findings can be tricky.

#3741 A CASE OF PODOCYTIC INFOLDING GLOMERULOPATHY WITH DIABETES MELLITUS, NEPHROTIC RANGE PROTEINURIA AND POSITIVE ANTI-PLA2R IN SERUM

Abstract Background and Aims Podocytic infolding glomerulopathy (PIG) is a rare glomerular abnormality which was first proposed as a new disease entity in 2008. It is characterized by glomerular basement membrane (GBM) bubbling viewable by light microscopy, due to extensive trapping of podocytic cytoplasm fragments and cell membrane projections within the GBM. Electron microscopy reveals podocyte infolding and invagination into the glomerular basement membranes (GBMs). Most of the cases reported worldwide, indicate that PIG usually co-exists with autoimmune diseases. In this case we present a diabetic patient with no other autoimmune disease in his medical history, whose biopsy was characterized as PIG. Method A 60-year-old Caucasian man with a 5-year history of type II diabetes mellitus, hyperlipidemia, hypertension, hyperuricemia and benign colon polyps, was noted by his family physician to have proteinuria. He had been treated with an angiotensin II receptor blocker, statin, and allopurinol for 5 years and he was well regulated. At the point of admission, his 24-h urine collection showed 4,5gr of urine protein. His creatinine at the time was normal (0,89mg/dl), no hypoalbuminemia, no edema or deregulation of hyperlipidemia was noted. His fundoscopy at this point had no diabetic lesions. In the immunological work up, we found normal values of autoantibodies ANA, anti-dsDNA, anti-ENA, complement screening C3, C4, serum and urine protein electrophoresis - immunofixation. Everything was within normal limits except from serum autoantibodies to Phospholipase A2 Receptor of podocytes which was tested with ELISA and valued 35 RU/mL (&amp;lt;20RU/mL). In the following 9 months his proteinuria remained at the same levels. Due to the persistent nephrotic range proteinuria (&amp;gt;3.5gr/24h) a kidney biopsy was performed. Biopsy was evaluated under light microscope (histochemistry for Congo-Red and immunohistochemistry for C4d, PLA2R and DNAJB9 included), immunofluorescence and electron microscope. Results The renal biopsy included 8 glomeruli, 3 of them globally sclerosed (37.5%), the rest enlarged with mild to moderate mesangial matrix increase and thickening of the GBMs, without spikes, pin holes or reduplications. Immunohistochemistry for C4d, PLA2R and DNAJB9 was negative. Immunofluorescence revealed nothing noticeable (no staining of IgG, IgA, IgM, C3, C1q, C4, κ-λ chains) apart from a moderate linear albumin staining. Without electron microscopy the whole picture was rather reminiscent of mild to moderate lesions of diabetic nephropathy. On electron microscopy, no classical electron-dense deposits were found. Effacement of podocytes’ foot processes was multi-segmental. More importantly, podocytic cytoplasmic processes invaginating into the GBMs were observed, accompanied by scattered endomembranous, partially microspherular microstructures, sometimes with adjacent unclear small pyknotic areas. The biopsy report concluded that although light microscopy and immunofluorescence findings could indicate diabetic nephropathy, the electron microscopy lesions suggest the diagnosis of PIG. Conclusion To our knowledge, this is the first reported case with PIG and anti-PLA2R antibodies detected in the serum, without clear histological evidence of membranous nephropathy. Our patient was diabetic for five years with no diabetic lesions in fundoscopy. Although PIG has been reported mainly in the context of autoimmune diseases, the coexistence with diabetes or its possible role in PIG's pathogenesis has not been addressed. The treatment of this peculiar morphologically disease, still remains an open query for physicians.

Prognostic value of the 7-year protocol biopsy of adult kidney allografts: impact of mesangiosclerosis and proteinuria

Aim The aim of the present study was to clarify the relationship between the Banff score of the 7-year protocol biopsy and the allograft outcome. Methods One-hundred-and-eighty-four patients received kidney transplantation from 2002 to 2008. We excluded patients aged <20 years at transplantation (n = 24), those who did not undergo a 7-year protocol biopsy (n = 66), and those who underwent for-cause biopsy (n = 5). Consequently, 89 patients who underwent a 7-year protocol biopsy were enrolled. We analyzed the relationship between the clinicopathological findings 7 years after transplantation and the estimated glomerular filtration rate (eGFR) change per year and allograft survival. Histological evaluation was performed using the Banff 2015 classification. Results Among the clinicopathological findings, each Banff mesangial matrix increase (mm) score ≥1 and proteinuria ≥1+ was independently associated with the eGFR decline per year during a median follow-up of 73 months. Furthermore, in the model of the clinicopathological findings including the presence of mm with proteinuria, mm ≥1 alone and mm ≥1 with proteinuria were each independently associated with the eGFR decline. The graft survival was significantly worse for those with mm ≥1 with proteinuria than those with mm ≥1 without proteinuria. Conclusion Among the 7-year protocol biopsy findings, the presence of mm alone and mm with proteinuria were each significant predictors of eGFR decline. The presence of both proteinuria and mm had a negative impact on graft survival. These results underscore the significance of the Banff mm score and proteinuria at the time of the 7-year protocol biopsy to predict the allograft outcome.

Recurrent Podocytopathy after Kidney Transplantation.

A 61-year-old unsensitized White man with a history of FSGS and rheumatoid arthritis underwent a deceased donor kidney transplant. FSGS was diagnosed on native kidney biopsy 1.5 years prior, which was notable for segmental sclerosis, mild to moderate increase in mesangial cellularity and matrix,

A case report of relapse of minimal change disease after the first dose of Pfizer-BioNTech Covid-19 vaccine in King Abdul-Aziz Specialist Hospital, Taif, Saudi Arabia

Background: Documented cases of de novo glomerular disease or relapse of pre-existing glomerular disease was acquired shortly after administration of COVID-19 messenger RNA (mRNA) vaccinations. Objectives: to present a case of a 64-year-old female who received the Pfizer-BioNTech COVID-19 vaccination as a first dose and then experienced a relapse of minimal change disease (MCD) presenting with nephrotic syndrome. Case presentation: The presenting symptom was ankle swelling and frothy urine which started 9 days after the first dose of vaccine. Albumin level was 24 g/L, urine albumin/creatinine ratio was 668 mg/mmol, Creatinine had risen to 1.3 mg/dl, urine analysis showed 3+ protein. light microscopy showed 17 patent glomeruli, one of which was globally sclerosed. There was mild focal increase in mesangial matrix with occasional atrophic tubules with minor interstitial scarring affecting less than 5% of cortical area. There was moderate fibrointimal thickening. In electron microscopy, 100% of podocyte foot process were effaced with microvillation and marked cytoplasmic vacuolation. The findings were consistent with minimal change disease (MCD) with mild chronic renal parenchymal damage. The patient started furosemide 80 mg daily for 21 days after the onset of complaints. prednisolone 1 mg/kg was initiated 1 week and patient`s symptoms improved. The patient achieved a complete remission 4 weeks after initiation of prednisolone. Conclusion: For the best management of MCD as a potential side effect following COVID-19 vaccination, more knowledge is required. Keywords: case, relapse, MCD, Pfizer-BioNTech, Covid-19, Taif

SUN-422 MONOCLONAL IGA NEPHROPATHY WITH LATTICE LIKE PARA-CRYSTALLINE DEPOSITS IN AN ELECTRON MICROSCOPY: A RARE FINDING

Abnormal plasma cells frequently cause the secretion of monoclonal immunoglobulins or immunoglobulin fragments into the serum which leads to various diseases including renal diseases. When patients do not meet the criteria for overt multiple myeloma/B-cell proliferation, and the hematologic disorder is generally consistent with monoclonal gammopathy of undetermined significance (MGUS) but renal abnormalities are consistent, it is called monoclonal gammopathy of renal significance (MGRS). It is associated with high morbidity so early recognition is important, as chemotherapy invariably improves outcomes. Proliferative glomerulonephritis secondary to monoclonal IgA has been previously described on single occasional only and electron microscopy finding is quite unique, with mesangial and subendothelial deposition of lattice-like para crystalline arrays. This is a case report. Case details: A 46-year-old male patient with proteinuria and hematuria for 20 months presented to the nephrology outpatient department. His protein was 3+ and hemoglobin was 2+ in urine. All of the serologies were negative. Renal biopsy was done, which showed mild increase in mesangial matrix with slight accentuation of lobulation, double contours on silver and PAS stains. There were no glomeruli in the original frozen material for immunofluorescence studies; therefore, immunofluorescence was carried out on paraffin sections which showed moderate mesangial IgA staining and mild mesangial lambda staining. Rest of the stains were negative in glomeruli. IgG, IgA, IgM, C3, C1q, kappa, lambda and albumin were used as a panel for immunofluorescence. Electron microscopy showed numerous electron-dense para crystalline deposits in mesangial and subendothelial locations with highly distinctive organized substructure forming lattice-like para crystalline arrays with a periodicity of 18 nm which were slightly curved in some areas. Proliferative glomerulonephritis with monoclonal gammopathy has been reported few times but most of these deposits were granular and rarely fibrillary deposits were present. Among of the cases of renal disease due to monoclonal gammopathy, IgG was the most common immunoglobulin that was deposited, followed by IgM. Renal disorder secondary to a monoclonal IgA lambda is very rare. Deposition of lattice like paracrystalline substructure with parallel arrays in a “blocky” pattern is a unique finding in proliferative glomerulonephritis due to monoclonal lambda restricted IgA nephropathy, which was only reported by Soares et al before this case. Such electron microscopy picture is very rare and unique, and diagnostic for the disease.

Effect of electroacupuncture on renal fibrosis in spontaneously hypertension rats and its related mechanisms

To observe the effect of electroacupuncture (EA) on blood pressure, renal fibrosis and expression of tissue inhibitors of metalloproteinase-1 (TIMP-1), plasminogen activator inhibitor 1 (PAI-1), and alpha smooth muscle actin (α-SMA) in spontaneous hypertension rats (SHR), so as to explore its mechanisms underlying improving hypertensive renal damage. Forty male SHR (15 weeks in age) were randomly divided into 5 groups: model, medication (Losartan), Shenshu, Geshu, and Shenshu＋Geshu groups(n=8 rats in each group), and the same age-old male 8 Wistar-Kyoto (WKY) rats were used as the normal control group. Rats of the medication group were treated by gavage of Losartan potassium solution (3 mg/mL, 30 mg·kg-1·d-1, once a day for 12 weeks), and those of the 3 EA groups treated by EA stimulation of bilateral "Shenshu" (BL23), "Geshu"(BL17) or both BL23 and BL17 (2 Hz/100 Hz, 1 mA, 15 min each time, once every other day for 12 weeks). The systolic blood pressure of the tail artery was measured before, and 4, 8 and 12 weeks after the intervention. The expression of TIMP-1, PAI-1 and α-SMA proteins of the right kidney tissue was measured by immunohistochemistry. Histopathological changes of the right renal tissue were observed under light microscope after H.E. stain. The blood pressure was significantly higher in the mo-del group than those in the normal control group (P<0.01), and considerably decreased at the 4th , 8th, and 12th week of the interventions in the medication and 3 EA groups (P<0.01). The expression levels of renal TIMP-1, PAI-1 and α-SMA proteins were notably higher in the model group than those in the normal control group and considerably decreased at the 12th week of the interventions in the medication and 3 EA groups than in the model group (P<0.01). H.E. staining of the renal tissue showed disordered arrangement of the renal cells, congestion and dilation of capillaries with thickened vascular wall, renal tubule atrophy and lumen stenosis with some necrosis of renal tubules, protein tubule and cell tubules, increase of some glomerular mesangial matrix and hyperplasia of fibrous tissue in the model group, which was re-latively milder in the medication and 3 EA groups. EA of BL23 and BL17 can reduce the blood pressure in SHR, which may be related to its function in down-regulating expression of TIMP-1, PAI-1 and α-SMA proteins.

Association of c4d deposition in renal allograft biopsy with morphologic features in Banff diagnosis

Association of c4d deposition in renal allograft biopsy with morphologic features in Banff diagnosis - IJPO- Print ISSN No: - 2394-6784 Online ISSN No:- 2394-6792 Article DOI No:- 10.18231/j.ijpo.2019.033, Indian Journal of Pathology and Oncology-Indian J Pathol Oncol

512-P: Sexual Differences in Progression of Diabetic Nephropathy in over 26 Type 1 Diabetic Mice

As a transgenic type 1 diabetic model, OVE26 mice develop diabetic nephropathy (DN) with the feature close to advanced DN in human, which makes it a valuable rodent model to study DN. Nevertheless, sexual differences in renal lesions, especially dynamic progression with different ages, remain undefined in OVE26 mice. To explore these issues, male and female OVE26 and wild type nondiabetic FVB mice at 4-, 12-, 24 - and 36-weeks old were used (N=6). Urine albumin-to-creatinine ratio (UACR) was detected to evaluate renal function. Renal histopathology and immunochemical and Western blotting protein expression of inflammation, tubular epithelial-myofibroblast transdifferentiation and fibrosis markers were examined. In FVB mice, blood glucose, triglyceride, UACR and podocytes numbers were constant during aging and comparable in male and female. Age-dependent slightly increase of glomerular mesangial matrix, inflammatory cells infiltration and renal fibrosis were observed in FVB mice. Compared with the age- and sex- matched FVB mice, male OVE26 mice developed hyperglycemia, mesangial matrix accumulation and increased trend of triglyceride at 4-week-old and albuminuria, glomerular enlargement, and upregulations of TGF-β1, α-SMA at 12 weeks old. Significant loss of podocytes, tubular dilation, collagen accumulation, increased trend of macrophage and T lymphocytes infiltrations, and increased protein levels of TNF-α, ICAM and fibronectin in kidney were observed in 24-week old male OVE26 mice. Compared with age-matched male OVE26 mice, female OVE26 mice had significant hypertriglyceridemia, worse renal function and kidney lesions at older age, including higher UACR and sustained loss of podocytes at age of 24 weeks; more inflammatory cells infiltration and renal fibrosis at age of 36 weeks. Our findings suggest the sexual difference in the progression of DN in OVE26 mice to provide evidence for researchers to properly select the age and sex of OVE26 mice in the future type 1 DN study. Disclosure W. Wang: None. L. Cai: None.

IL17A and IL17F genes polymorphisms are associated with histopathological changes in transplanted kidney

BackgroundInterleukin 17 is a proinflammatory cytokine involved in immune response after allograft transplantation. IL-17 family of proinflammatory cytokines includes IL-17A and IL-17F. Previous studies have demonstrated that the rs2275913 IL17A and the rs11465553 IL17F gene polymorphism are associated with kidney allograft function. Because of the association between these polymorphisms and post-transplant immune response, we assume that these single nucleotide polymorphisms may affect morphological structure of transplanted kidney.The aim of this study was to examine the association of rs2275913 IL17A and rs2397084, rs11465553 and rs763780 IL17F gene polymorphisms with histopathological changes in transplanted kidney biopsies such as: glomerulitis, tubulitis, arteritis, cell infilitration and fibrosis.MethodsThe study enrolled 82 patients after renal graft transplantation in whom a kidney biopsy was performed because of impaired graft function. The rs2397084 T > C (Glu126Gly), rs11465553 G > A (Val155Ile) and rs763780 T > C (His167Arg) polymorphisms within the IL17F gene and the rs2275913 A > G (− 197 A > G) polymorphism within the IL17A gene promoter were genotyped using TaqMan genotyping assays on a 7500 FAST Real-Time PCR System (Applied Biosystems, USA).ResultsThere was a significant association between the rs2275913 IL17A gene polymorphism and the grade of tubulitis, which was more severe among patients with the A allele, compared to recipients with the GG genotype (GG vs. AG + AA, P = 0.02), and with the grade of arteriolar hyaline thickening and mesangial matrix increase, which were more severe among patients with the G allele compared to recipients with the AA genotype (AA vs. AG + GG, P = 0.01 and P = 0.04, respectively). Tubular atrophy and interstitial fibrosis were more severe among individuals with the C allele at the rs763780 IL17F gene polymorphism (TT vs. TC, P = 0.09 and P = 0.017, respectively). However, it should be taken into account that the statistical significance was achieved without correction for multiple testing, and no significant association would remain significant after such correction.ConclusionsThe results of this study may suggest a possible association between the rs2275913 IL17A and rs2275913 IL17A gene polymorphisms and some histopathological changes in transplanted kidney biopsies.

In glomerular cells of puromycin aminonucleoside nephrosis rats both phosphorylated and total STAT3 levels increased during proteinuria

Recent studies showed that JAK/STAT pathway plays role in glomerular damages. The fact that STAT3 could be activated also by oxidative stress make Puromycin Aminonucleoside (PAN) Nephrosis model very appropriate for examination of STAT3 expression changes in glomerular pathology. Along with a control group, three PAN groups sacrificed on different days were formed by the i.p. injection of PAN for 5 consecutive days. Throughout the experiment, 24-hour-urines were collected on specific days and proteinuria levels were monitored. At the end of the experiments, tissue specimens were stained immunohistochemically for both total and phosphorylated STAT3 and evaluated subjectively. They were also examined ultrastructurally in transmission electron microscope. The proteinuria levels did not increase significantly on 5th day but showed a dramatic increase on 10th and 15th days. On 20th and 25th days, urinary protein levels gradually decreased. Ultrastructural examinations showed glomerular damages such as significant decrease in slit pore number, a significant gradual increase in glomerular basement membrane thickness and podocyte hypertrophy on 5th and 15th days; besides significant increase in mesangial matrix. The first significant increases in phosphorylated and total STAT3 levels occurred in 5th day and 15th day groups respectively. These increases diminished in 25th day group. Regarding all the findings, it was deduced that STAT3 is one of the active factors in glomerular pathologies.

A case of glomerulonephritis showing remarkable segmental extracapillary proliferation; Is this a new category disease or not?

Background: Significant capillary proliferation is common in post-streptococcal acute glomerulonephritis (PSAGN) after streptococci and is a prognostic disease. Focal segmental glomerulosclerosis is a disease characterized by segmental sclerosis although it may have a poor prognosis Case Presentation: A 50-year-old man with nephrotic syndrome underwent renal biopsy, which showed marked endocapillary proliferation due to enlarged vascular endothelial cells and infiltration of lymphocytes. However, there was no mesangial cell proliferation, mesangial matrix increase, or crescent formation. Electron microscopy showed fusion of podocytes without any electron-dense deposits. Immunostaining for CD68 and CD3 was positive, and the presence of macrophages and T-cells was suggested. Steroid therapy, including pulse therapy, was performed, and then cyclosporine was added to steroid therapy. Although urinary protein decreased, his renal function did not respond well to steroid therapy, and the patient initiated dialysis 2 years later. Conclusions: We report this case considering that it was nephritis of unknown origin showing segmental endocapillary proliferation that had not been recognized previously.

Effects Of Ginger Extract On Glomerular Mesangial Matrix Of Kidneys In Alloxan Induced Diabetic Nephropathy Of Albino Rats

Background: For a long time, Diabetes mellitus has been treated with medicines derived from plants. Objective: To evaluate the effect of Ginger aqueous extract on Glomerular mesangial matrix in Alloxan induced diabetic nephropathy of albino rats. Materials and Methods: In this study we induced diabetes mellitus with Alloxan intraperitoneally (150 mg/kg body weight) in Experimental groups B &amp; C. Then the rats of Experimental group C received 200mg/kg body weight of ginger aqueous extract by gavage daily for five weeks starting from 8th day after Alloxan injection. Results: We observed that on histopathological examination, Experimental group B kidneys revealed highly increased mesangial matrix while the animals of experimental group C treated with ginger aqueous extract showed less increase in mesangial matrix as compared to experimental group B but it was more than control group A. Three groups had significant difference among them having p-values &lt;0.001. Conclusion: The results of the present study indicated that the co-treatment of Ginger aqueous extract prevented alloxan induced diabetic nephropathy in albino rats. The aqueous extract of Ginger showed amazing results regarding renal histopathology of diabetic rats. The overall nephroprotective effect of Ginger is probably due to a counteraction of free radicals by its antioxidant components