Focal Segmental Sclerosis Research Articles

Idiopathic membranous nephropathy with focal segmental sclerosis

To evaluate the clinical and pathological features and prognosis of idiopathic membranous nephropathy (IMN) with focal segmental sclerosis (FSGS) in a group of Russian patients. 101 patients with morphologically verified IMN were enrolled in our single-center cohort retrospective study. The patients were divided into IMN group and IMN+FSGS group. The primary and secondary outcomes were analyzed in 59 patients, which had follow-up data for period more than 6 months. At the time of renal biopsy the median age was 46.0 (33.0; 55.0) years and the median follow-up was 6.8 (4.0; 15.6) months. Secondary FSGS was revealed in 15 (14.9%) patients with IMN. The IMN and IMN+FSGS groups did not differ in gender, age of onset IMN and age of renal biopsy. In the IMN+FSGS group proteinuria was higher and estimated glomerular filtration rate was lower than that in the IMN group (p<0.05). The systolic arterial pressure and creatinine levels in the IMN+FSGS group were slightly higher than in the IMN group, but the difference was not significant. Anti-PLA2R positivity was similar in both groups. Chronic kidney disease (CKD) progression was observed in 10/52 (19.2%) and 5/7 (71.4%) patients in IMN and IMN+FSGS groups, respectively. In a multivariate Cox regression model, age of renal biopsy (odds ratio - OR 1.12, 95% confidence interval - CI 1.03-1.22; р=0.07), FSGS (OR 0.05, 95% CI 0.01-0.34; р=0.002) и response to initial course of immunosuppression (OR 0.33, 95% CI 0.12-0.95; р=0.039) were associated with the CKD progression. In patients with IMN secondary FSGS is associated with a greater severity of proteinuria and a decrease in estimated glomerular filtration rate, and is also an independent factor of the CKD progression.

Abstract 14188: Myopericarditis as the Initial Presentation of Systemic Lupus Erythematosus

Introduction: Systemic lupus erythematosus (SLE) is an autoimmune disorder that can affect any organ. However, myocardial involvement is uncommon and rarely presents as the initial manifestation of SLE. Case: We present a case involving a 31-year-old male with no past medical history who presented to the emergency department with chest pain, fatigue, and intermittent swelling in his hands and feet. Initial workup was remarkable for high sensitivity troponin of 11, 821 and respiratory viral panel positive for parainfluenza. Results: Evaluation with left heart catheterization showed no obstructive coronary artery disease thus a cardiac MRI was obtained for further investigation. It showed late gadolinium enhancement involving the lateral apical wall extending to the apex as well as the lateral wall at the base (figure 1). The initial diagnosis was suspected to be viral-induced myopericarditis. However, he started developing accelerated acute kidney injury out of proportion to the current clinical presentation leading us to pursue rheumatological workup as it could explain the cardiac and renal pathologies. He was found to have ANA &gt;= 1:2560, positive dsDNA, and positive anti-smith antibody. Kidney biopsy revealed diffuse spike formation on the glomerular basement membrane and focal endocapillary proliferation and segmental sclerosis consistent with lupus nephritis. He was started on prednisone and mycophenolate mofetil resulting in symptom and disease control. Conclusion: Myocardial involvement of SLE is uncommon and can be a life-threatening condition in the acute phase; however, the disease has an overall good prognosis with early treatment.

Anti-Nephrin Antibody as a Potential Etiology in Primary Focal Segmental Sclerosis (FSGS)

Anti-Nephrin Antibody as a Potential Etiology in Primary Focal Segmental Sclerosis (FSGS)

Histomorphological Patterns of Focal Segmental Glomerulosclerosis and Their Clinical Correlation in Tertiary Care Hospitals in Bangladesh

Background: Being one of the commonest glomerular diseases in adults and a major etiology of the nephrotic syndrome, Focal Segmental Glomerulosclerosis (FSGS) gradually progresses towards end-stage renal disease (ESRD). According to pathogenesis, FSGS can be classified into primary or secondary ones and in both instances, histomorphological findings are nearly indistinguishable. Five histomorphological variants of primary as well as secondary focal segmental sclerosis have already been accepted, for instance, NOS (not otherwise specified), tip, cellular, perihilar, and collapsing variants. Nonetheless, primary FSGS is a diagnosis of exclusion and all the time, primary and secondary FSGS can not be distinguished discernibly. For this reason, correlation with clinical and biochemical parameters are extremely important. The present study was undertaken to identify various histomorphological patterns of FSGS by light microscopy and immunofluorescence study at tertiary care hospitals in Bangladesh as well as to correlate those patterns with clinical, biochemical parameters and additional histologic findings. Methods: This is an observational &amp; cross sectional study which was conducted among 57 paraffin blocks of renal biopsy specimens of histologically confirmed FSGS cases including all age groups and both sexes, which were collected from department of Pathology, BSMMU &amp; Kidney foundation hospital &amp; research institute, Mirpur, Dhaka. Renal biopsies received for light microscopy only and biopsies that contained less than eight glomeruli were exluded from the study . Routine Haematoxylin &amp; Eosin (H&amp;E), Periodic Acid Schiff (PAS), Jones silver &amp; Masson’s trichrome stains were used to evaluate renal biopsy specimens &amp; histomorphological patterns of FSGS were identified. Data regarding clinical &amp; biochemical parameters were collected from patient’s medical records. Statistical analyses were performed by SPSS-22. Result: In our study, it was observed that, among 57 biopsies, 35(61.4%) biopsies were diagnosed as NOS, 12(21.1%) biopsies as perihilar, 4(7.0%) biopsies as tip, 3(5.3%) biopsies as collapsing and 3(5.3%) biopsies as cellular variant. No clinical and biochemical parameters were significantly associated with these histomorphological patterns of FSGS. Regarding additional histologic features, thick walled blood vessels was significantly associated with histomorphological patterns. Conclusion: This study was conducted on only two tertiary level hospitals in Bangladesh, therefore, the result may not reflect the exact scenario of Bangladesh. It is the need of the moment to mention the histomorphological patterns of FSGS in renal histopathology reports. Moreover, logistic support is a necessity to institute nephro-pathology section in the pathology department of all the tertiary care hospitals in order to identify renal glomerular disease precisely. Sir Salimullah Med Coll J 2023; 31: 26-33

Focal Segmental Sclerosis Associated with the Novel Multi-tyrosine Kinase Inhibitor Ponatinib: A Case Report.

Ponatinib is a novel multi-tyrosine kinase inhibitor (TKI) with potent inhibitory activity against refractory chronic myeloid leukemia (CML). Despite its high clinical efficacy, ponatinib induces various adverse events due to its multi-target characteristic. However, renal complications associated with ponatinib are rare. A 76-year-old woman had a history of chronic myeloid leukemia (CML) resistant to imatinib and nilotinib. Our patient developed proteinuria and renal function deterioration during treatment with ponatinib but not with imatinib or nilotinib. We herein report the first case of a patient with secondary focal segmental glomerulosclerosis (FSGS) with partial glomerular collapse induced by ponatinib treatment.

#2776 KIDNEY INVOLVEMENT IN PATIENTS WITH RHEUMATOID ARTHRITIS

Abstract Background and Aims In rheumatoid arthritis (RA) kidney is commonly affected organ with clinical presentation characterized by proteinuria and microalbuminuria, followed by chronic renal failure. RA is associated with reduced kidney function, possibly due to chronic inflammation or the use of nephrotoxic therapies. Renal diseases occurring in patients with RA may have a variable clinicopathological picture. Little is known about the effects of using the novel biological agents on the risk of kidney diseases. The aim of this study was to determine the relationship between effect of therapy and kidney involvement in patients with RA and evaluated the histopathological findings and associated clinical manifestation. Method In this retrospective study 275 patients with diagnosis of RA were included. In 48 patients renal biopsy was performed. The patients were divided in three groups according to changes in management of RA: 1991-2001, 2002-2011 and 2012-2022 year. Data of demographic characteristics, clinical symptoms and pathological diagnosis were extracted from medical records and pathological reports. Results In our study amyloidosis was the most common histologic pattern, followed by chronic glomerulonephritis (GN) and tubulointerstitial nephritis. Renal amyloidosis was diagnosed in 13 patients, membranous GN – in 9, mesangioproliferative GN – in 7 patients, focal segmental necrotizing GN – in 5, focal segmental sclerosis – in 4, minimal change disease – in 3, tubulointerstitial nephritis – in 7 patients. Between 1991 and 2001 year the most common clinical manifestation was nephrotic syndrome and the most common histopathological findings – renal amyloidosis, followed by membranous GN and focal segmental necrotizing GN. The membranous GN was related to the use of gold and its frequency decreased after 2001. The mesangioproliferative GN was the leading cause of kidney disease between 2002–2011 years and focal segmental sclerosis – between 2012–2022. In our study 68 patients had a decrease of glomerular filtration rate (GFR) &amp;lt; 60 mL/min/m2. No kidney biopsies were performed in these cases because no urine abnormalities were detected. We found that age, duration of the disease, arterial hypertension, C-reactive protein were significant risk factors for GFR decline in patients with RA. Patients with RA who are treated with biologic agents are less likely to experience progressive decline in kidney function than those not receiving biologic treatment (hazard ratios {HRs] [95% CI], 0,84 [0,68-1,02]}. Conclusion In all patients with RA, renal function should be monitored and in the case of pathologic results, renal biopsy should be performed. In RA patients with renal disorder, suspected causal drug should be removed from the treatment and specific immunosuppressive therapy initiated. Improved pain management associated with biologic treatment may help to reduce the need for potentially nephrotoxic anti-inflammatory agents such as NSAIDs and certain types of non-biologic DMARDs, which could consequently reduce the risk of drug-induced nephrotoxicity and thereby contribute to the lower risk of renal diseases.

The hereditary nephrotic syndrome in children: features of clinical phenotype and genotype, pathogenesis, renal prognosis of isolated and syndromic forms

The review of the literature presents the clinical phenotype and genotype pathogenesis, renal prognosis of isolated and extra-renal manifestation form of hereditary nephrotic syndrome in children. The clinical and genetic features of hereditary steroid-sensitive and steroid-resistant nephrotic syndrome in children caused by mutations of genes encoding the main components of the slit diaphragm, glomerular basement membrane, structural and functional proteins of the podocyte are highlighted. Literature data demonstrate an unfavorable renal prognosis in children with hereditary steroid-resistant nephrotic syndrome with focal segmental glomerulosclerosis and diffuse mesangial sclerosis with clinical manifestation at the age of 0–17 years with progression to terminal renal failure at the age of 0.4–18 years. Renal replacement therapy with dialysis and kidney transplantation improves the prognosis, survival, and quality of life of children with hereditary nephrotic syndrome.

Glomerular capillary C3 deposition as a risk factor for unfavorable renal outcome in pediatric primary focal segmental glomerular sclerosis.

Some patients with primary focal segmental sclerosis (FSGS) demonstrate complement 3 (C3) deposition in glomerular capillary loops (Cap-C3) and/or mesangial area (Mes-C3). The clinicopathological and prognostic significance of C3 deposition remains incompletely investigated, especially in the pediatric cohort. We retrospectively analyzed 264 children of biopsy-proven primary FSGS between January 2003 and December 2020. The correlation between Cap-C3 and renal outcome was evaluated by the Kaplan-Meier method and Cox multivariate regression analysis. Renal end-point event was defined as the development of end-stage renal disease, death for renal disease, or an estimated glomerular filtration rate reduction by at least 50% from baseline. Among the 264 patients, 30 (11.4%) had Cap-C3. Kaplan-Meier analysis showed that patients with Cap-C3 had significantly lower renal survival rates than patients without Cap-C3 (60.17% vs. 84.71% at 5 years, 39.49% vs. 65.55% at 10 years, P < 0.01). Cox multivariate regression analysis showed that Cap-C3 was an independent risk factor for poor renal outcome (HR 3.53, 95% CI 1.22-10.19, P = 0.02). Glomerular capillary C3 deposition was an independent risk factor for unfavorable renal outcome in children with primary FSGS.

PS-R05-3: SEVERE GLOMERULAR MICROANGIOPATHY IN A PATIENT WITH NEPHROTIC SYNDROME FOLLOWING TAKAYASU ARTERITIS

Introduction: Takayasu arteritis (TA) is a large vessel inflammation that predominantly involves aorta and its main arteries. TA-caused kidney injury is known to be mainly due to renal artery stenosis. However, glomerulonephritis including membranous proliferative glomerulonephritis, focal segmental sclerosis, or crescentic nephritis has been histologically identified in some TA cases. Case description: A 69-year-old female presented with leg edema and refractory hypertension with nephrotic range proteinuria (17.0 g/gCr). She exhibited &gt; 10 mmHg blood pressure discrepancy between left and right upper limbs and severe aortic regurgitation. Lab test showed high level of C-reactive protein and high erythrocyte sedimentation rate. Contrast-enhanced computed tomography identified wall thickening of the left subclavian artery, which led to the diagnosis of TA. Renal biopsy demonstrated that double basement membrane, enlarged subendothelial space, and mesangiolysis with no immunoglobulin deposition. Although azilsartan 40 mg QD and nifedipine 30 mg BID had been prescribed, systolic blood pressure (sBP) was still &gt; 160 mmHg. Thus, while oral prednisolone was started to suppress TA-induced inflammation, azilsartan was replaced with sacubitril valsartan, an angiotensin receptor-neprilysin inhibitor (ARNI), for treating refractory hypertension. After a few weeks, sBP was decreased to 130 mmHg with sacubitril valsartan 200 mg QD and proteinuria was dramatically improved to 0.5 g/gCr. Discussion: TA commonly involves the renal artery, leading to stenosis and subsequent ischemic nephropathy. However, no stenosis and occlusion were observed in renal artery of this case. In addition, small vessel inflammation in the kidney such as vessel wall necrosis and immune cells infiltration around arterioles was not found. Serum levels of pro-inflammatory cytokines including vascular endothelial growth factor and interleukin-6, a well-known contributors for progression of TA-related inflammation, were within the normal range. The results indicate that TA-caused hypertension, but not vessel inflammation induced by TA, seems to play a pathological role for development of glomerular microangiopathy in this case. A previous study showed that 70% of TA patients presenting with glomerular lesion has severe hypertension and intimal thickening in renal arterioles was observed more frequently in TA patients presenting with glomerular lesion when compared to those without glomerulonephritis, which supports our hypothesis. In the present case, ARNI significantly reduced sBP which might directly contribute to the improvement of proteinuria. ARNI can be potent to control hypertension more effectively than conventional hypertensive agents in TA patients.

Clinicopathological significance of tubulointerstitial CD68 macrophages in proliferative lupus nephritis.

Tubulointerstitial macrophage plays a pathogenic role in renal damage of lupus nephritis (LN). However, the clinical and pathological role of these CD68 macrophages has not been fully described. The aim of the present study is to decipher the correlation between clinicopathological features and tubulointerstitial CD68 macrophages in 76 proliferative LN patients and further evaluate the prognostic significance of tubulointerstitial CD68 macrophages. Tubulointerstitial CD68 macrophages were quantitated by standard histochemical staining. The correlation between the number of tubulointerstitial CD68 macrophages and clinicopathological features was analyzed by Spearman's correlation analysis. Factors potentially affecting renal prognosis were further evaluated by Cox regression analysis. Among the 76 proliferative LN cases, the number of CD68 macrophage infiltrates was positively correlated with serum creatinine (SCr) level, the proportion of glomeruli sclerosis and focal segmental sclerosis, tubulointerstitial inflammation, and chronicity indices, while negatively correlated with the glomerular filtration rate. During a mean follow-up period of 45months, 5 patients (6.6%) progressed to dialysis, and 3 patents (3.9%) had a twofold increase in SCr. Multivariate Cox regression analysis showed that the number of tubulointerstitial CD68 macrophages was an independent variable associated with poor renal outcomes (HR = 1.002, P = 0.012). The optimal cutoff value of tubulointerstitial CD68 macrophages was 340/mm2 in our study with 87.5% sensitivity and 61.8% specificity to predict end-stage renal disease within 4years. The number of tubulointerstitial CD68 macrophages was positively linked to poor prognosis of LN. Urgent immunosuppression should be considered in LN patients with abundant tubulointerstitial CD68 macrophages. Key Points • Tubulointerstitial CD68 macrophage infiltrates are positively correlated with clinicohistologic impairment in proliferative lupus nephritis. • The positive association between the number of tubulointerstitial CD68 macrophages and poor renal outcome of lupus nephritis patients were observed. • Urgent immunosuppression and monitor are required when abundant tubulointerstitial CD68 macrophage infiltrates are detected.

Dual Glomerular Lesion in Hiv Patient

HIV-associated nephropathy (HIVAN), the classic kidney disease associated with HIV infection, was first described in 1984 as a complication of AIDS although HIVAN may also occur in patients with less advanced HIV infection or following acute seroconversion Histologically, HIVAN is a collapsing form of focal segmental glomerulosclerosis (FSGS) accompanied by microcystic tubular dilatation and interstitial inflammation. HIV-immune complex kidney disease (HIVICK). Other immune complex diseases may also occur in HIV-infected patients, including IgA nephropathy and postinfectious glomerulonephritis, and are best diagnosed as those specific entities The pathophysiological mechanism of HIVAN injury is mediated by direct infection of renal epithelial cells by HIV, expression of intrarenal viral genes, and dysregulation of host genes by modulating cell differentiation and the cell cycle. In contrast, kidney disease by HIV immune complexes (HIVICK) involves a different immune mechanism with antibody deposits within glomerular structures. Both entities progressively present different degrees of proteinuria and progressive decrease in the glomerular filtration rate, depending on the commitment or histology suffered by the patient. In this case reports patient with clinical picture of 3 months of evolution of temporo-spatial disorientation and alteration of the state of consciousness associated with hyperthermia. We perform neuroimaging without alterations, a lumbar puncture performed with evidence of an infectious process by coconuts + in the GRAM of the cerebrospinal fluid, normochromic normocytic anemia and renal failure, sub nephrotic proteinuria, glomerular hematuria, HIV positive, recount of normal CD4, renal biopsy with diagnosis of immune-mediated glomerulonephritis (IgG and C3), in the immunofluorescence (HIVICK) and with membrano pattern proliferative and in two glomeruli focal segmental sclerosis collapsing variant (HIVAN)is observed.

A Case of Covaxin-Induced Focal Sclerosing Glomerulonephritis (Collapsing Variety)

We report on the development of focal glomerular segmental sclerosis FSGS (collapsing variety) with nephritic symptoms immediately after receiving the first injection of the Covaxin COVID-19 vaccination and acute kidney damage (AKI) (Bharat-Biotech). A 45-year-old lady who had previously been healthy was taken to a hospital outside of the city after developing a headache and pedal edoema. She had gotten the first shot of the immunisation 10 days ago. She experienced bilateral lower limb edoema 4 days following the injection, which turned into anasarca over time. At her admission, UPCR was 7.2 and serum creatinine was 0.9 mg/dl. Over the following days, kidney function continued to deteriorate, and serum creatinine rose to 3.2 mg/dl. The patient was sent to our institution for a kidney biopsy after an abdominal ultrasound revealed normal-sized bilateral kidneys. After doing a kidney biopsy, the results were consistent with FSGS. MCD, IgA nephropathy, and anti-GBM are only a few examples of the diverse glomerulonephritis. Several m-RNA vaccinations have been associated with nephritis in the past, but not the Covaxin COVID-19 vaccine. At this point, the correlation between the immunisation and FSGS is temporal, by exclusion, and in no way clearly established. To assess the actual prevalence of this potential vaccination adverse effect, we must wait for more reports of instances that are comparable to those already reported.

A case of covaxin-induced focal sclerosingglomerulonephritis (collapsing variety)

We report on the development of focal glomerular segmental sclerosis FSGS (collapsing variety) with nephriticsymptoms immediately after receiving the first injection of the Covaxin COVID-19 vaccination and acute kidneydamage (AKI) (Bharat-Biotech). A 45-year-old lady who had previously been healthy was taken to a hospital outsideof the city after developing a headache and pedal edema. She had gotten the first shot of the immunisation 10 daysago. She experienced bilateral lower limb edema 4 days following the injection, which turned into anasarca overtime. At her admission, UPCR was 7.2 and serum creatinine was 0.9 mg/dl. Over the following days, kidneyfunction continued to deteriorate, and serum creatinine rose to 3.2 mg/dl. The patient was sent to our institutionfor a kidney biopsy after an abdominal ultrasound revealed normal-sized bilateral kidneys. After doing a kidneybiopsy, the results were consistent with FSGS. MCD, IgA nephropathy, and anti-GBM are only a few examples ofthe diverse glomerulonephritis. Several m-RNA vaccinations have been associated with nephritis in the past, butnot the Covaxin COVID-19 vaccine. At this point, the correlation between the immunisation and FSGS is temporal,by exclusion, and in no way clearly established. To assess the actual prevalence of this potential vaccinationadverse effect, we must wait for more reports of instances that are comparable to those already reported.

Clinical and Pathological Features of Renal Presentations in Polycythemia Vera

BackgroundPolycythemia vera (PV) is a common type of Philadelphia chromosome-negative chronic myeloproliferative disorder. PV-associated kidney disease is rarely reported and remains poorly understood. It has been observed that chronic kidney disease could be a risk factor for poor prognosis in PV. MethodsWe retrospectively analyzed the clinicopathological features of renal presentations in eight patients with confirmed PV-associated kidney disease. ResultsThe eight patients were 6 males and 2 females, with a mean age of 46.4 ± 16.8 years. Six patients had a history of PV, with a duration range 0.5–16 years. The other two patients were newly diagnosed with PV simultaneously with glomerular disease. Seven patients conducted a JAK2 V617F mutation test, with a positive result in five. Proteinuria and renal dysfunction were the patients' main complaints, with only one having nephrotic syndrome and three having microscopic hematuria. The level of proteinuria ranged from 0.52–10.96 g/day. Three patients had advanced chronic kidney disease (CKD), two in stage 3b and one in stage 4, but only one patient had anemia. Three patients had monoclonal immunoglobulinemia, one patient with immunoglobulin (Ig) G kappa plus light chain lambda, one patient with IgG kappa, and one patient with IgG lambda. Five patients underwent a renal biopsy. The pathological diagnosis was IgA nephropathy in three, non-IgA mesangial proliferative glomerulopathy in one, and glomerular hypertrophy with ischemic renal injury in one patient. Glomerular ischemia, ischemic shrinkage, focal segmental sclerosis, and glomerulomegaly were common pathological features. Glomerular crescents and endocapillary proliferation were also observed. All patients were administered hydroxyurea, and seven were administered renin-angiotensin system inhibitors. During follow-up, one patient with uncontrolled PV developed secondary myelofibrosis and died, three patients were lost to follow-up, and four patients remained alive with CKD. ConclusionsPatients with untreated or uncontrolled PV could have massive proteinuria and advanced CKD, pathologically showing ischemic, sclerosing glomerular lesions with hypercellurity, glomerular crescents and endocapillary proliferation. IgA nephropathy was most commonly diagnosed. These findings deserve attention because early screening and effective control of PV may benefit the long-term kidney prognosis.

Stromal Cell-Derived Factor (SDF)-1-Pretreated Bone Marrow Mesenchymal Stem Cells (BMSCs) Ameliorates Acute Kidney Injury in Mice

To explore the effects of stromal cell-derived factor (SDF-1) pretreatment of bone marrow mesenchymal stem cells (BMSCs) on acute kidney injury (AKI) in mice. BMSCs were cultured and treated with SDF-1 to detect osteogenic and adipogenic ability. Cisplatin (20 mg/kg) was used to establish AKI model and then divided into blank group, control group 2 (BMSCs injection), and experimental group (intraperitoneal injection of BMSCs treated with SDF-1 (80 ng/ml)) followed by analysis of serum cytokines (Toll like receptor 4 (TLR4), tumor necrosis factor-α (TNF-α), and interleukine-6 (IL-6)) by enzyme linked immunosorbent assay (ELISA). In cultured BMSCs, positive rates of CD29, CD44, CD45, and CD11b were 98.2%, 97.6%, 2.5% and 2.1%, respectively. When the concentration of SDF-1 was within 80 ng/mL, the chemotaxis and proliferation ability was dose-dependent (p &lt; 0.05). SDF-1 pretreatment did not affect BMSCs adipogenic and osteogenic abilities. The creatinine and serum cytokines (TLR4, TNF-α, and IL-6) level in experimental group showed statistical significance (p &lt; 0.05). At 24 h, thrombosis and tubular dilatation in the mesangial region of control group 2 and experimental group under light microscope were similar without difference of inflammatory cell infiltration and fibrosis. At 72 h, the glomerular mesangium widened in control group 2 with focal segmental sclerosis, renal tubules dilated, and protein casts and inflammatory cell infiltration and fibrosis. Experimental group showed a small amount of cell proliferation in the glomerular mesangium with few inflammatory cell infiltration and fibrosis. SDF-1 can enhance the migration and proliferation activity of BMSCs, reduce extracellular matrix precipitation, improve renal fibrosis, and alleviate AKI.

Alternative Complement Pathway Is Activated and Associated with Galactose-Deficient IgA1 Antibody in IgA Nephropathy Patients.

BackgroundGalactose-deficient IgA1 (Gd-IgA1) and alternative complement pathway activation are considered to be involved in the pathogenesis of IgA nephropathy (IgAN). Nevertheless, the relationships between alternative pathway activation and disease activity or Gd-IgA1 level remains unclear.MethodsNinety-eight biopsy-diagnosed IgAN, twenty-five primary focal segmental sclerosis (FSGS) patients and forty-two healthy individuals were recruited in this study. Among them, fifty IgAN patients received immunosuppression. Follow-up blood samples at 1 and 3~6 months after immunosuppression were collected. Plasma levels of complement C5a, factor Ba and Gd-IgA1 were measured and analyzed. Immunostaining for complement was performed in twenty-five IgAN and FSGS patients.ResultsAt baseline, IgAN patients had higher levels of plasma C5a, factor Ba and Gd-IgA1 than control subjects. Gd-IgA1 levels positively correlated with plasma C5a and factor Ba. In addition, levels of factor Ba and Gd-IgA1 were positively associated with proteinuria and negatively associated with renal function. Immunostaining revealed positive staining for factor Bb and C3c in glomeruli in IgAN patients, but not in FSGS patients. At baseline, patients receiving immunosuppression had more severe proteinuria and higher factor Ba. After 6 months, eGFR declined and proteinuria persisted in patients without immunosuppression. In contrast, patients who received immunosuppression exhibited decreased plasma levels of C5a, factor Ba, and Gd-IgA1 as early as 1 month after treatment. Proteinuria decreased and renal function also remained stable 6 months after immunosuppression.ConclusionsOur results indicate a close relationship between alternative complement pathway activation, Gd-IgA1 concentration and clinical severity of IgAN. Level of complement factor B may be a potential marker for disease activity and therapeutic target in IgAN patients.

Is podocytopathy another image of renal affection in p-SLE?

BackgroundLupus podocytopathy (LP) is a renal affection described in systemic lupus erythematosus (SLE) patients with nephrotic range proteinuria, characterized by diffuse foot process effacement without immune deposits and glomerular proliferation. This study describes LP, its pathological features and outcomes of pediatric (p-SLE) patients in comparison to the usual lupus nephritis (LN) cases.MethodologyA retrospective cohort study conducted on a 10-year registration (2010–2019) of 140 p-SLE patients at the Pediatric Department, Tanta University. Histopathological analysis with light microscopy (LM) and immunofluorescence (IF) of all renal biopsies were evaluated according to the International Society of Nephrology Renal Pathology Society (ISN/RPS) grading system. In addition, some biopsies were examined with electron microscopy (EM).ResultsEighty-six p-SLE cases (61.4%) had renal involvement; seventy-nine biopsies (91.86%) of them met the classification criteria of LN as defined by ISN/RPS system. Five biopsies were normal (MCD) and two showed focal segmental sclerosis (FSGN) that did not meet any known classification of LN. Hence, they were reevaluated using EM that revealed diffuse effaced podocytes without glomerular sub-epithelial, endocapillary or basement membrane immune deposits, and were classified as having lupus podocytopathy, representing (8.14%) of all LN biopsies. Those seven cases showed good response to steroids with a complete remission duration of 3.40 ± 1.95 weeks. However, some case had 1–3 relapses during the duration of follow up.ConclusionsLP is a spectrum of p-SLE, not an association as it is related to disease activity and its initial presentation.

POS-088 PREDICTORS OF CHRONIC RENAL FAILURE IN ADULT-ONSET MINIMAL CHANGE DISEASE.

Most patients with minimal change disease (MCD) have a good response to treatment and keep a preserved renal function. Therefore progression to end-stage renal disease (ESRD) is uncommon, seen in less than 5% of patients. This study aimed to Identify the predictor factors of progressing to chronic renal failure (CRF) in adult patients with MCD. This is a retrospective study including adults having NS with biopsy proven MCD from January 2006 to December 2019 in a medical nephrology department. Were compared patients having CRF with those keeping a normal renal function. Statistical analysis included Cox-regression analysis to examine which factors were associated with risk of CRF. 48 adults with biopsy proven MCD were analyzed. 7 (14.58%) patients evolved to CRF. Mean age was higher in patients with CRF, 50.71±23.54 years against 33.21±13.59 years in the other group (p=0,099). They also had higher albumin and protein serum levels, 21.4±5.02 g/l against 16.51±5.01 g/l (p=0.048, r=1.122) and 53.40±6.14g/l against 46.39±7.33g/l (p=0.048, r=1.077). Steroid resistance was also higher in patients with CRF found in 42.9% while no steroid resistance was found among the second group (p=0,003). 50% of patients having focal segmental sclerosis in their second biopsy had evolved to CRF. This study demonstrated that MCD patients who are older and those who have poor response to treatment are more likely to develop CRF. However, low serum albumin and protein levels seem to be protective factors.

KM55 Monoclonal Antibody Staining in IgA-Dominant Infection-Related Glomerulonephritis

Introduction: IgA-dominant infection-related glomerulonephritis (IgA-IRGN) is a unique form of IRGN, which needs to be distinguished from IgA nephropathy (IgAN), due to overlapping clinical and pathological features. The key factor in the pathogenesis of IgAN is galactose-deficient IgA1 (Gd-IgA1). However, the mechanism of glomerular IgA deposition in patients with IgA-IRGN is unclear. Therefore, we evaluated whether Gd-IgA1 could be a useful biomarker to distinguish between these 2 diseases. Methods: A case-control study was conducted to analyze the clinical and pathological characteristics of 12 patients with IgA-IRGN. The intensity and distribution of glomerular Gd-IgA1 (KM55) staining in renal biopsies were assessed. The control group consisted of 15 patients diagnosed with IgAN and an additional 17 patients with glomerulopathy involving IgA deposition. Results: The main clinical manifestations of patients with IgA-IRGN were nephrotic-range proteinuria, hematuria, acute renal injury, and hypocomplementemia. Active lesions were the leading pathological feature, while focal segmental sclerosis was rare. Half of the patients exhibited hump-shaped subepithelial deposits. Glomerular KM55 staining was negative in 7 patients, trace in 4 patients, and 2+ in 1 patient. The median intensity of KM55 staining in IgA-IRGN patients was 0 (range 0∼2+), which was significantly lower than that of primary IgAN patients (median 2+, range 1+∼3+). The receiver operating characteristic analysis demonstrated that the optimal cutoff level to identify these 2 diseases was 0.5+. Conclusions: Glomerular KM55 staining intensity might be helpful to distinguish IgA-IRGN from primary IgAN. Weak or negative staining may favor IgA-IRGN. In addition, integrated analysis including clinical data, pathological findings, and prognostic information would further improve the differential diagnosis.

Clinicopathologic characteristic and prognosis in idiopathic membranous nephropathy patients with focal segmental sclerosis lesion: A retrospective observational study.

To explore the clinicopathological characteristics and prognosis of idiopathic membranous nephropathy (IMN) with focal segmental sclerosis lesions (FSL).A total of 70 IMN patients with FSL (FSL+group) were enrolled in this study, and 140 patients were randomly selected by age and sex matching as disease controls (FSL-group). The clinical and renal histopathological data on renal biopsy and clinical data of patients regularly followed were collected. Serum anti-phospholipase A2 receptor (PLA2R) autoantibody, thrombospondin type-1 domain-containing 7A (7A) autoantibody, glomerular PLA2R and 7A expression, and IgG4 deposition were detected. First, the clinical and pathological significance of IMN combined with the FSL group was analyzed. Whether FSL is a risk factor for renal outcomes was further analyzed. 1.Compared with the FSL- group, patients in the FSL+ group had a significantly higher incidence of hypertension and a longer duration of hypertension as well as higher levels of systolic blood pressure, serum creatinine, serum triglycerides, serum cholesterol, 24-hour urinary protein excretion, and lower eGFR and urine osmotic pressure. Patients in the FSL+ group had an increased frequency of Churg stage III and more severe glomerulosclerosis and interstitial fibrosis. The remission rate was significantly lower in the FSL+ group than in the FSL- group (50.0% vs 75.9%, P = .027).2.Multivariate Cox regression analysis showed that FSL (HR = 3.01, 95%CI = 1.07–8.52, P = .038) was an independent risk factor for progression of renal function deterioration, and FSL (HR = 3.25, 95%CI = 1.43–7.38, P = .005) and high levels of serum anti-PLA2R antibody (HR = 1.89, 95%CI = 1.27–2.82, P = .002) were independent risk factors for nonremission of IMN.IMN patients who developed FSL had more severe clinical and pathological characteristics than those without FSL. FSL was an independent risk factor for poorer prognosis. When the appearance of FSL in IMN patients with a high level of serum anti-PLA2R antibody, the treatment needs to be more aggressive to promote remission and to delay the progression of renal function.