SAT-366 RITUXIMAB IN IMMUNE-MEDIATED GLOMERULAR DISEASE

Background and Aims Glomerulonephritis is an autoimmune glomerular inflammation that can lead to severe morbidity and mortality if left untreated. Conventional treatment for this condition involves the use of glucocorticoids and immunosuppressive drugs. In recent years, Rituximab has gained popularity as a treatment for several types of glomerular diseases. Rituximab is a monoclonal antibody that targets the CD20 protein expressed on the surface of B cells. Rituximab has shown promising results in the treatment of a variety of glomerular diseases, including minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy, ANCA vasculitis, and lupus nephritis. This work was performed to study the efficacy and safety of Rituximab in patients with different glomerular diseases managed with the drug in our renal unit. Method This work was conducted in 2022–2023, retrospectively collecting data of adult patients with different glomerular disease treated with Rituximab between January 2019 and October 2022 in a large teaching hospital in the United Kingdom. Data of patients were collected from the electronic patient records system and patient notes. Results A total of 83 patients were included in the analysis 40 Females and 43 Males. The mean age of all the patients was 56 years with range being 20–89 years. Patients had a range of glomerular diseases for which they were treated. The cohort of patients included patients with different glomerular diseases presenting with nephritic (28 patients) and nephrotic presentations (55 patients). Number of patients according to the disease : ANCA Glomerulonephritis (25), Membranous Nephropathy (18), Minimal Change Disease (15), Lupus Nephritis (10) , Focal Segmental Glomerulosclerosis (9), Immune Complex GN(3), and C1q Nephropathy (2) and mesangial proliferative glomerulonephritis (1). Patients with nephrotic presentations had significant improvement in their Urinary Protein Creatinine Ratio (UPCR) (P = <0.001). There was also significant suppression of B cell load (P = <0.001). We analysed patients presented with both nephritic and nephrotic presentations (81 patients) looking at kidney survival (2 patients excluded as they were on dialysis and had Rituximab for relapse with pulmonary haemorrhage). Only 7 patients (9%) progressed to end stage renal disease (ESRD) and dialysis suggesting Rituximab had (91%) success rate in preserving renal survival and preventing progression to ESRD and dialysis treatment. The length of time B cells stayed suppressed (<1%) was analysed. B cells stayed suppressed for a significant amount of time longer than the six-month dosing schedule of Rituximab (P = <0.001). This suppression was significantly longer in males than females (P < 0.01). The safety of Rituximab was also assessed. Patients received 263 doses during the study period. Fifteen adverse effects were recorded. Five patients sadly died during the study period. Of significance, one patient died due to COVID-19 infection and another one due to septic colonic perforation. Conclusion Rituximab was effective in preserving renal survival and stopping progression to ESRD in patients with the different studied glomerular diseases. It was highly effective in treating proteinuria and suppressing B cells for a significantly longer time than the known six-month period. This point at the possible use of longer dosing interval regimens for patients may be appropriate. Rituximab is a safe drug to use in the patients with glomerulonephritis with clear efficacy in managing renal disease and a good safety profile.

The challenge in diagnosing de novo minimal change disease after transplantation.

Objective To analyze the common clinical and pathological types of elderly patients after renal biopsy in Guangxi. Methods By means of enrolling 373 elderly patients (aged ≥ 60 years) who had undergone renal biopsy in the First Affiliated Hospital of Guangxi Medical University from August 2012 to August 2015, and collecting the data of gender, age, nationality, clinical diagnosis, kidney pathological diagnosis, etc, the renal disease spectrum of elderly patients were retrospectively analyzed with the SPSS13.0 software. And statistical descriptions were made for the categorical variables with frequency and percentage. Results The most common clinical syndrome in elderly patients after renal biopsy was nephrotic syndrome (NS, 50.1%), followed by acute kidney injury (AKI, 28.7%) and chronic nephritis syndrome (15.5%). In the elderly patients after renal biopsy, primary glomerular diseases accounted for 67.8%, and secondary glomerular diseases accounted for 26.8%. In primary glomerular diseases, idiopathic membranous nephropathy (IMN, 71.9%) was the leading renal histopathological type, followed by minimal change disease (MCD, 9.9%) and focal segmental glomerulosclerosis (FSGS, 7.9%). In the secondary glomerular diseases, the most common type was ANCA-associated vasculitis (AAV, 31.0%), followed by lupus nephritis (20.0%) and diabetic nephropathy (12%). In the NS of elderly patients, the most common cause was IMN (75.4%), followed by MCD (5.3%) and FSGS (5.3%). In the AKI of elderly patients after renal biopsy, the most common pathological type was IMN (26.2%), followed by AAV (24.3%). Conclusion NS was the most common clinical syndrome of elderly patients after renal biopsy in Guangxi. IMN was the most common pathological type in the elderly NS and primary glomerular diseases; AAV was the most common cause of secondary glomerular diseases; and IMN and AAV were the main causes of AKI. Key words: Elderly; Renal pathology; Nephrotic syndrome; Idiopathic membranous nephropathy; Acute kidney injury; ANCA-associated vasculitis

B-cell oligoclonal expansions in renal tissue of patients with immune-mediated glomerular disease

Objective To detect serum level of anti-M-type phospholipase A2 receptor (PLA2R) antibody in elderly patients with idiopathic membranous nephropathy (IMN) and to explore its clinical significance in IMN disease. Methods A total of 134 patients with renal biopsy-proved glomerular diseases were enrolled in this study, including 42 elderly cases with IMN, 45 non-elderly cases with IMN, 19 elderly cases with minimal change nephropathy (MCN), 12 elderly cases with IgA nephropathy (IgAN), 8 elderly cases with hepatitis B-associated membranous nephropathy (HBV-MN) and 8 elderly cases with focal segmental glomerulosclerosis (FSGS). Western blotting was used to detect serum anti-PLA2R antibody and the correlation of anti-PLA2R antibody with laboratory parameters in elderly IMN patients was analyzed. Results The elderly and non-elderly patients with IMN showed that the positive rate of anti-PLA2R antibody was 71.4% and 73.3%, respectively (P>0.05). The positive rate of anti-PLA2R antibody in elderly IgA nephropathy, HBV-MN and MCN patients was 16.7%, 12.5% and 5.3% respectively. Anti-PLA2R antibody was not detected in serum from elderly FSGS patients. The positive rates of serum anti-PLA2R antibody were significantly higher in both elderly and non-elderly IMN patients than in elderly patients with secondary MN and other types of glomerlonephritis (P<0.01). Furthermore, anti-PLA2R autoantibody level was positively correlated with 24-hour urine protein level and negatively correlated with the concentration of serum albumin in elderly patients with IMN (P<0.01). Conclusions Anti-PLA2R antibody is a sensitive serological marker of IMN. Detection for anti-PLA2R antibody might be helpful for the diagnosis of both elderly and non-elderly IMN and for the monitor of IMN disease severity. Key words: Glomerulonephritis, membranous; Phospholipase A2; Antibodies, antiphospholipid

BackgroundPodocytes can be the primary site of injury or secondarily involved in various protienuric states. Cross talk between adjacent foot processes and with basement membrane is important for slit diaphragm function. Does expression of podocyte associated proteins in kidney biopsies alter with site/type of primary injury? Genetic mutations of podocin result in steroid resistant FSGS. Can protein expression of podocin predict resistant cases to initiate further genetic evaluation?MethodsAdult patients (n-88) with protienuria- minimal change disease(MCD)-22, focal segmental glomerulosclerosis(FSGS)-21,membranous glomerulonephritis(MGN)-25 and IgA nephropathy(IgAN)-20 were selected for immunohistochemistry with podocin and beta dystroglycan . Results were graded (0 - 3+scale )and compared with control biopsies and internal control. Treatment and follow up (6 months -2 ½ years) of FSGS and MCD cases were collected.ResultsThere was intense to moderate staining of the podocytes with podocin and β dystroglycan in the glomeruli in all cases (MCD, FSGS, IgAN and MGN) except for weak staining with β dystroglycan in 3 cases of MCD. There was loss of immunostains in areas of segmental/global sclerosis. There was no significant difference in the staining pattern between the groups. In primary podocytopathies, staining pattern did not differ between steroid resistant, sensitive or dependent cases.ConclusionsImmunohistochemical expression of podocin and β dystroglycan does not differ in nephropathies which have different site of injury depending on absence (MCD and FSGS) or presence of immune deposits and their localization (MGN and IgAN). Podocin and β dystroglycan staining did not differentiate steroid sensitive and resistant cases, hence, does not give clue to initiate genetic studies. However, analysis of bigger cohort may be required.SummaryPodocin and β dystroglycan immunohistochemistry was done to analyze podocyte - podocyte and podocyte -basement membrane matrix connections in adult protienuric states. Primary podocytopathies i.e. MCD and FSGS and secondary podocytopathy due to immune complex deposition i.e. MGN (subepithelial) and IgAN (mesangial) were analyzed. There was no difference in staining patterns between primary and secondary podocytopathies or between steroid sensitive, resistant and dependent cases of FSGS and MCD.Virtual slidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2258608781052786

The management of steroid-resistant glomerulopathies remains a clinical problem. In this trial, we report a clinical observation of 43 patients treated with mycophenolate mofetil (MMF) for steroid-resistant glomerulopathies. All patients underwent renal biopsies, and immunofluorescence and light microscopy examinations were conducted in all cases. All patients had been treated with prednisone at a dose of 1 mg/kg per day for at least 8 weeks. Of the 43 patients, 16 were treated with cyclophosphamide and five were treated with cyclosporine A before MMF started. The primary study outcomes were the change in the urinary protein excretion, serum creatinine, comparing the levels at the start of MMF treatment with those at the end of the MMF treatment period. Changes in renal function were also estimated with Modification of Diet in Renal Failure calculation. Wilcoxon signed-ranks test was used as appropriate to compare data from the start with data at the end of the treatment period. The primary glomerular diseases represented included membranoproliferative glomerulonephritis in 23.2%, membranous glomerulonephritis in 18.6%, IgA nephropathy in 13.9%, focal segmental glomerulosclerosis in 9.3%, lupus nephritis (systemic lupus erythematosus) in 25.6% and pauci-immune glomerulopathy in 9.3% of patients. The mean follow-up time was 28.9+/-12 months. Before MMF treatment, 16 patients (37%) had nephrotic range proteinuria and 11 (26%) had renal insufficiency. The urinary protein before MMF treatment was 3.3+/-2.6 g/dL (0.6-9.6) and decreased significantly to 0.87+/-1.1 g/dL (0-5.5) at the end of the MMF treatment period (P=0.02). During treatment, complete remission was seen in 27 patients, partial remission in 10 patients and MMF failure in six patients. The serum creatinine level decreased significantly from 1.29+/-0.55 mg/dL (0.6-3.0) to 1.14+/-0.38 mg/dL (0.5-2.4) post MMF therapy (P=0.046). Using the four-variable Modification of Diet in Renal Failure formula, the glomerular filtration rate increased from 71.5+/-28 mL/min per 1.73 m2 to 78.1+/-27 mL/min per 1.73 m2 (P=0.021). Renal insufficiency resolved in seven of the 11 (63.6%) patients with renal insufficiency initially, two with membranoproliferative glomerulonephritis, two with membranous glomerulonephritis, one with focal segmental glomerulosclerosis, four with pauci-immune glomerulopathy, two with systemic lupus erythematosus nephritis, and in two patients de novo renal insufficiency developed. In general, MMF was well tolerated, and most of the patients achieved remission and improvement of renal functions. MMF treatment appeared to offer benefits to problematic patients refractory to conventional therapies for glomerulopathies.

The nationwide clinical features of Japanese patients with primary nephrotic syndrome (NS), including minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), or membranous nephropathy (MN), have not yet been reported. We collected the clinical personal records of patients with primary NS between 2015 and 2018 from the national registry organized by the Japanese Ministry of Health, Labour, and Welfare. Overall, the demographics, chronic kidney disease classification based on glomerular filtration rate and albuminuria, and treatment of 6036 patients were collected: 3394 (56.2%) with MCD, 677 (11.2%) with FSGS, 1455 (24.1%) with MN, and 510 (8.5%) with others. MN patients were older than MCD and FSGS patients (67 vs. 42 and 47 years, respectively). Steroid-dependent NS or frequently relapsing NS was found in 70.2%, 40.5%, and 24.6%, whereas steroid-resistant NS was found in 6.4%, 36.0%, and 37.9% of patients in the MCD, FSGS, and MN, respectively. The present oral prednisolone use (mean dose, mg/day) was 87.2% (21.2), 80.9% (20.0), and 77.5% (18.8) of patients in the MCD, FSGS, and MN, respectively. The national registry of clinical personal records of primary NS could provide an informative insight into the characteristics, clinical features, and treatment approaches for patients with primary NS in Japan.

The prevalence of glomerular diseases differs according to geographic area, race, age and indications for a renal biopsy. This study was conducted to evaluate the distribution and changing patterns of renal diseases during the past 20 years in a large patient population in Korea. Patients aged 16 years or older who underwent a renal biopsy at Severance Hospital in the Yonsei University Health System from 1987 to 2006 were enrolled. All medical records were reviewed retrospectively. In total, 1818 patients (M:F = 1.02:1) were reviewed. Glomerulonephritis (GN) comprised 85.9% of the total biopsied cases. The most common primary GN was IgA nephropathy (IgAN) (28.3%), which was followed by minimal change disease (MCD) (15.5%), membranous nephropathy (MN) (12.3%), focal segmental glomerulosclerosis (FSGS) (5.6%) and membranoproliferative GN (MPGN) (4.0%). The most common secondary GN was lupus nephritis (8.7%). The most common idiopathic nephrotic syndrome was MCD (38.5%), which was followed by MN and IgAN. Among 128 (7.4%) patients who were HBsAg-positive, MN (30.5%) and MPGN (21.1%) were the most common GN. When the incidence rates between 1987-91 and 2002-06 were compared, IgAN increased from 25.6 to 34.5%, while MCD (from 23.2 to 7.0%) and MPGN (from 6.7 to 1.7%) decreased significantly (P < 0.01). IgAN was the most common primary GN, and MCD was the most common cause of nephrotic syndrome. In the 5-year quartile comparison, the relative frequency of IgAN increased, while the relative frequency of MCD and MPGN decreased significantly during the past 20 years.

Diagnostic value of soluble urokinase-type plasminogen activator receptor serum levels in adults with idiopathic nephrotic syndrome

C4d is a well-known biomarker of the complement cascade. It is derived from cleavage of the labile thioester bond of C4b. This was a retrospective and prospective cross-sectional study, done at our tertiary care hospital. Methods: We evaluated 50 cases and 10 controls to adjudge the significance of C4d deposits in native renal diseases. Majority of the patients (44%) were in the age group of 10-20 years followed by 20% in the age group of 31-40 years. 62% of study population were male. Results: Majority of patients were diagnosed with FSGS (16%), followed by membranous nephropathy (14%), Lupus nephropathy (14%) and IgA nephropathy (12%). All patients diagnosed with Membranous nephropathy, IgA nephropathy and hypertensive nephropathy showed glomerular C4d deposits. All patients diagnosed with IgA Nephropathy, post infectious glomerulonephritis, Lupus Nephritis, minimal change disease, acute/ chronic tubulointerstitial nephritis, diabetic nephropathy, hypertensive nephropathy showed tubular C4d deposits. All patients diagnosed with Diabetic nephropathy and hypertensive nephropathy showed arterial C4d deposits. There was correlation of intensity expression of glomerular C4d deposits with presenting 24 hours urinary protein level at the time of biopsy ( p value=0.027) but no correlation with urea/creatinine. There was significant association (p value 0.019) of tubular C4d positivity with 24 hour protein at the time of biopsy. Tubular C4d deposits showed no significant presenting serum urea and creatinine at the time of biopsy. Conclusion: There was also no correlation noted between presenting 24 hours urinary protein and serum urea and creatinine levels with arterial C4d deposit in diabetic and hypertensive nephropathy patients.

This is a retrospective study of all native kidney biopsies performed at our center between October 1, 2012 and March 31, 2015. Relevant clinical and laboratory variables were recorded. Biopsy samples were processed for light microscopy and immunofluorescence in all cases. Histological classification was adapted from the World Health Organization recommendations. The indications for kidney biopsy were nephrotic syndrome in adults in 190 cases, rapidly progressive renal failure in 43, unexplained renal failure in 25, and steroid-resistant nephrotic syndrome in children in 12. The mean age of the patients was 31.48 ± 13.46 years. Male-to-female ratio was 1.87:1. Mean serum creatinine (SCr) of the patients was 2.36 ± 2.07 mg/dL. Primary glomerulonephritis accounted for 88.89% of cases (240) while secondary glomerulonephritis accounted for 7.40% of total cases (20). Interstitial disease accounted for 1.5% and vascular disease for 2.2%. The most common lesion among primary glomerulonephritis was focal segmental glomerulosclerosis (FSGS) (31.11%) followed by diffuse proliferative glomerulonephritis (DPGN) (13.33%) and membranous glomerulonephritis (MGN) (12.59%). Among secondary glomerulonephritis, lupus nephritis was the most common (5.56%). In patients with SCr 1.4 mg/dL or less (n = 131), FSGS was the most common histology (17.26%) followed by MGN (23.66%) and minimal change disease (7.63%). Whereas, in patients with SCr more than 1.4 mg/dL (n = 139), DPGN was the most common diagnosis (23.74%) followed by FSGS (17.26%) and IgAN (12.23%). Fourteen patients (5.2%) had one or more episode of gross hematuria, three of whom required blood transfusion. The overall FSGS was the most common lesion seen. When we consider only patients with deranged renal function, DPGN was the most common histopathological lesion. The reason for disproportionate high incidence for DPGN is not clear and requires further research.

Glomerular diseases are an important cause of chronic renal failure in developing countries. The spectrum of diseases causing nephrotic syndrome is changing globally in the last few decades. The aim of this prospective study was to look at this spectrum at a tertiary care center in North India and to analyze the changing trends over the last five decades. Patients in the age group 18-60 years with nephrotic syndrome were consecutively included in the study. Renal biopsies were performed in all patients and were subjected to light microscopy, immunofluorescence (IF) and electron microscopy (EM). While the IF was performed in 78% of cases, EM was available in one-fourth of cases. During 2002-2007, 364 patients (60.2% males) were included in the study. The mean age was 31.5 years. Primary glomerular diseases accounted for 89% of cases while lupus nephritis was the most common secondary glomerular disease. Focal segmental glomerulosclerosis (FSGS) accounted for 30.6% of primary glomerular diseases making it the most common cause of nephrotic syndrome. It was followed by membranous glomerulonephritis (MGN) in 24.4%, mesangiocapillary glomerulonephritis in 17.9% and minimal change disease in 14.8%. In the age group >40 years, MGN was the most common lesion (32.5%) followed by FSGS (27.7%). Over the last five decades, there was a nearly five-fold increase in the incidence of FSGS, 3-fold increase in MGN and a 10-fold reduction in diffuse proliferative glomerulonephritis while there was no major change in incidence of other diseases. The biopsy diagnosis of FSGS has increased considerably in last few decades and it is now the most common cause of nephrotic syndrome in adults in North India. MGN is the most common lesion in patients over 40 years of age.

Glomerular diseases vary with age, and it is important to investigate the spectrum of glomerular diseases in pediatric patients to help in a more precise clinical diagnosis and optimize the management of patients. We aimed to study the clinicopathologic pattern of pediatric glomerular diseases in North India. This is a 5-year retrospective, single-center cohort study. The database was searched to identify all pediatric patients with glomerular diseases in their native kidney biopsies. About 2890 native renal biopsies were studied, of which 409 were pediatric glomerular diseases. The median age was 15 years with a male preponderance. Nephrotic syndrome was the most common presentation (60.8%), followed by non-nephrotic proteinuria with hematuria (18.5%), rapidly proliferative glomerulonephritis (7%), isolated hematuria (5.3%), acute nephritic syndrome (3.4%), non-nephrotic proteinuria (1.9%), and advanced renal failure (0.7%). Minimal change disease (MCD) was the most common histological diagnosis, followed by focal segmental glomerulosclerosis (17.4%), IgA nephropathy (IgAN; 10%), membranous nephropathy (6.6%), lupus nephritis (5.9%), crescentic glomerulonephritis (2.9%), and C3 glomerulopathy (2.9%). Diffuse proliferative glomerulonephritis (DPGN) was the most common histological diagnosis in patients with hematuria and non-nephrotic as well as nephrotic range proteinuria. The most common histological diagnoses for isolated hematuria and acute nephritic syndrome were IgAN and postinfectious glomerulonephritis (PIGN), respectively. MCD and lupus nephritis are the most common pediatric primary and secondary histopathologic diagnoses, respectively. The adolescent-onset glomerular diseases have a higher frequency of IgAN, membranous nephropathy, and DPGN. PIGN is still an important differential in our pediatric patients presenting with acute nephritic syndrome.

The current treatment regimes for patients with nephrotic syndrome due to idiopathic membranous nephropathy (MN) and focal segmental glomerulosclerosis (FSGS) are based on steroids and/or cytotoxic agents. Data on the effect of mycophenolate mofetil (MMF) for these conditions are scarce and confounding. We compared the efficacy of an MMF-based therapy with standard therapies in inducing remission in adult nephrotics with MN and FSGS in a randomized pilot study. MMF was given at 2 g/day for 6 months along with prednisolone at 0.5 mg/kg/day for 2-3 months. Conventional therapy was prednisolone 1 mg/kg/day for 3-6 months for FSGS and alternating monthly cycles of steroids and cyclophosphamide for 6 months for MN. The primary end point was change in urinary protein/creatinine ratio. A total of 54 patients (21 MN and 33 FSGS) were recruited; 28 were randomized to receive MMF (group A) and 26 were on conventional treatment (group B). There was no difference in the proportion of patients achieving remission in two groups (64 and 80% in MN and 70 and 69% in FSGS). The frequency of relapses and incidence of infections was also similar. FSGS patients in group A achieved remission faster and received a lower cumulative steroid dose. A 6-month treatment with MMF is as effective as the conventional treatment for primary treatment of MN and FSGS in the short term. It induces remission faster and reduces steroid exposure in FSGS patients. Studies with more cases and longer follow-up are required to evaluate its impact on preservation of kidney function.