A Pattern of Glomerular Diseases in Egyptian Children: A Single-center Experience

BACKGROUND: Findings indicative of the glomerular disease are proteinuria, hematuria, nephrotic syndrome (NS), hypertension, and renal insufficiency. These presentations can be used to define different clinical patterns that resemble different underlying etiologies. METHODS: This study is a cross-sectional study enrolled in Children Hospital Cairo University. The study participants were recruited on two stages, retrospective and prospective stages. In the retrospective stage, all eligible patients across 5 years (between 2011 and 2015) with any glomerular disease were included in the study. In addition, prospectively, the new cases a long 6 months (from February 2016 till July 2016) with glomerular diseases were included in the study. RESULTS: A total of 594 cases with different glomerular diseases were identified. Cases were two groups: The retrospective group that involved 543 cases and the prospective group that included 51 cases. In the retrospective part of the study, the most common presentations were NS (68%), nephritis (16.4%), gross hematuria (10.5%), and nephrotic/nephritic syndrome (3.5%). The most common biopsies in the retrospective study were NS: MCNS (27.3%), NS: focal segmental glomerulosclerosis (FSGS) (23.4%), NS: Mesangioproliferative GN (9.4%), NS: Membranous GN (2.3%), Crescentric GN (3.9%), Membranous GN (0.8%), MPGN (0.8%), congenital nephrotic syndrome (CNS):Diffuse Mesangial Sclerosis (3.9%), CNS: Finnish type (2.3%), Alport (4.7%), IgA nephropathy (3.9%), IgM nephropathy (1.6%), lupus nephritis (LN) (3.1%), Thin basement membrane disease (3.1%), and others (9.4%) In the prospective study, the most common presentations were NS (76.5%), nephritis (11.8%), nephrotic/nephritic syndrome (7.8%), and gross hematuria (3.9%). The biopsies results were mainly NS: FSGS (33.3%) and NS: MCNS (33.3%). Other biopsies results in the prospective part were NS: Mesangioproliferative GN (16.7%), LN (8.3%), and IgA nephropathy (8.3%). CONCLUSION: The most common glomerular disease in childhood is NS. The most common pathology of glomerular diseases is minimal change NS.

P0431TRENDS OF PRIMARY GLOMERULAR DISEASE IN TURKEY FROM 2009 TO 2017: A REGIONAL REGISTRY REPORT FROM TSN-GOLD WORKING GROUP

Background and Aims Several glomerular disease registries in Europe, and they shared their data; however, there was a lack of current data on trends of primary glomerulopathy in Turkey. Glomerular disease patterns can change geographical areas and populations decade by decade. Our aim is to present Turkey's primary glomerular disease pattern from 2009 to 2017. Method 3878 native kidney biopsy records were assessed in the Turkish Society of Nephrology Glomerulopathy (TSN-GOLD) Working Group Registry. Secondary disease (lupus, etc.) and transplant biopsies do not enroll in the registry. These records divided into four periods, before 2009, 2009 to 2013, 2013 to 2017, and 2017 to current. Results A total of 3858 patients (M = 2173, K = 1685) were examined. There was no difference in the distribution of number of patients according to periods (Q1 = 968, Q2 = 960, Q3 = 968, Q4 = 962). Nephrotic syndrome was the most common biopsy indication in all quarters (58.6%, 53%, 44.1%, 51.6%, respectively). Glomerulopathy types; Membranous GN (29.9%, n = 290) was the first in Q1 and IgA nephropathy (17.7%, n = 172) was the second. IgA nephropathy (28.5%, n = 274) was the most common glomerulopathy in Q2, while Membranous GN (25.5%, n = 245) was the second most common. IgA nephropathy (29.9%, n = 285) was the most common glomerulopathy in Q3, followed by FSGS (22.9%, n = 222) and Membranous GN. In Q4, FSGS (26.8, n = 258) was the most common glomerulopathy, followed by IgA nephropathy (26.7%, n = 257) and Membranous GN (24.5%, n = 236) (Figure 1). Conclusion While biopsy indications did not change over the years, the incidence of FSGS and IgA nephropathy gradually increased.

Nephrotic Syndrome After Allogeneic Hematopoietic Cell Transplantation: Incidence and Outcomes.

Abstract 3324 Poster Board III-212 The NIH Consensus recognizes nephrotic syndrome (NS) as part of the chronic GVHD symptomatology, but this manifestation is rare and the incidence and outcomes have not been well-defined. To characterize this complication, we conducted an IRB-approved retrospective review of 626 consecutive patients (age > 16 yrs: related donor [RD], n=352; unrelated donor [URD], n=274) who underwent allogeneic hematopoietic cell transplantation (HCT) between October 2000 and December 2007 at the University of Michigan. Data abstraction was facilitated by the use of an electronic medical record search engine (EMERSE) that allowed for efficient identification of key concepts based on a specified set of key words and phrases (e.g. “GVHD,” “proteinuria,” and “nephrotic syndrome”). Conditioning regimens included full intensity (FIC) in 470 patients and reduced intensity (RIC) in 156 patients. Nephrotic range proteinuria was identified in 17 of the patients, which is the largest cohort reported to date following allogeneic HCT. Renal biopsy confirmed the diagnosis in seven of these patients. The median time to onset of NS was 7.3 months (range 1.4 – 40.6 months) following allogeneic HCT. Clinical manifestations included hypoalbuminemia (100%), hypercholesterolemia (82%), edema (76%), renal impairment (65%), and thrombosis (29%). The overall cumulative incidence of NS was 2.9%: 2.4% in FIC and 4.6% in RIC HCT recipients; and 2.3% in RD and 3.7% URD HCT recipients. Of note, in patients who received irradiation-based conditioning regimens, there was an increased cumulative incidence of NS compared to those who did not, 4.8% versus 2.1%, respectively. Diagnostic symptoms of chronic GVHD based upon the NIH Consensus was seen in 65% (n=11) of the patients, all of whom were on immunosuppressive therapy at the time of diagnosis of NS. Prior history of acute GVHD was seen in 65% (n=11) of the patients. Interestingly, history of symptomatic cystitis was seen in 53% (n=9) of the patients, eight of whom had BK virus detected in the urine. The management and treatment for NS was variable. All of the patients received systemic steroids (0.25 mg/kg – 2 mg/kg), with or without mycophenolate mofetil and a calcineurin inhibitor. Additional therapy with rituximab was administered in nine patients. Durable remission with no further recurrence of proteinuria was observed in 47% of the patients (n=8). The median time to response was 4.8 months (range 0.3 – 13.5 months). Recurrence of proteinuria was seen in 29% of the patients (n=5), and primary refractory proteinuria was observed in 23% of the patients (n=4). Overall survival for the cohort was 49.5% at 4 years (confidence interval 24% - 75%) with median follow up of 5.1 years. The median survival from diagnosis of NS was 2.5 years. As of May 2009, eight patients are alive and nine have died. The causes of death include GVHD (n=6), relapse (n=2) and unknown (n=1). NS is a rare but important complication following allogeneic HCT. Early recognition of the clinical presentations and identification of high-risk groups may limit the potential morbidity and mortality associated with NS. Patient MUD/MRD PB vs BM Age at TP Conditioning Regimen DX Proteinuria estimate (g/24h) Gender GVHD Regimen Kidney Biopsy 1 MUD PB 53 FluBuTLI MPD 5.5 F Tacro/MTX Minimal change GN 2 MUD PB 56 FluBuTLI MM 14 M Tacro/MTX Membranous GN 3 MRD PB 57 BuCy MDS 14 M Tacro/MTX Membranous GN 4 MUD PB 55 BAC AML 3.4 M Tacro/MTX N/A 5 MRD PB 30 CVB NHL 3.74 M Tacro/MTX Membranous GN 6 MRD PB 47 BAC AML 10 M Tacro/MTX Membranous GN 7 MUD PB 49 FluBuTLI NHL 6.9 M Tacro/MMF N/A 8 MUD PB 38 BuCy AML 8.7 F Tacro/MMF N/A 9 MUD BM 18 CyATG Aplastic Anemia 4.22 F Tacro/MTX N/A 10 MRD PB 34 BAC AML 5.96 F Tacro/MTX N/A 11 MUD PB 61 FluBuTLI MDS 13.27 M Tacro/MTX N/A 12 MRD PB 26 BuCy CMML 3.58 F Tacro/MMF N/A 13 MRD PB 63 FluBuTLI NHL 4.54 F Tacro/MMF/MTX N/A 14 MUD PB 55 BuCy AML 22.57 M Tacro/MTX/Etanercept Minimal change GN 15 MRD PB 59 CVB-R NHL 3.37 M Tacro/MMF N/A 16 MRD PB 62 FluBuTLI AML 5.47 F Tacro/MMF/MTX Membranous GN 17 MUD PB 46 CyTBI AML 7.96 F Tacro/MTX/Etanercept N/A MUD = matched unrelated donor; MRD = matched related donor; PB = peripheral blood; BM = bone marrow; GN = glomerulonephritis; N/A = non applicable; MTX = methotrexate; MMF = mycophenolate mofetil; FluBuTLI = Fludarabine, Busulfan, Total Lymphoid Irradiation; BuCy = Busulfan, Cytoxan; BAC = Busulfan, Ara-C, Cytoxan; CVB = Cytoxan, Etoposide, BCNU; CyATG = Cytoxan, ATG Disclosures Hanauer: UMERSE, LLC: Consultancy, Patents & Royalties.

MONOCLONAL ANTIBODY IDENTIFICATION OF FIBRIN DEPOSITS IN RENAL DISEASE

Glomerular and vascular "fibrin" deposition has frequently been reported in human and experimental renal diseases. The biochemical form of this "fibrin" has not been well defined. We studied 16 renal biopsies (Bouin's fixed paraffin embedded) with the ABC-immunoperoxidase technique using monoclonal antibodies (MAbs); MAb I8C6 (Bβ1-42) to fibrinogen and fibrin I; MAb T2G1 (β15-42) to fibrin II; and MAb GC4 to fragment D or D-D. Polyclonal antisera to fibrinogen, albumin and IgG were used as controls. Renal biopsy specimens included 9 cases of microangiopathy (Group I: 6 hemolytic uremic syndrome (HUS), 1 sclerodero-ma, 2 acute humoral rejection) and 7 miscellaneous cases of other renal disease (Group II: 2 IgA nephropathy, 2 minimal change disease, 2 membranous GN, 1 acute interstitial nephritis). Fibrinogen and fibrin I were present on the glomerular (glom) endothelial cells in 8/9 Group I and 7/7 Group II cases, but was present in glom capillary lumens in Group I only. Staining of the endothelial aspect of interstitial capillaries, arterioles and arteries was also observed in both groups. Fibrin II was present in most glom and interstitial capillaries in both groups. However, intense staining for fibrin II was observed in arterioles and arteries in Group I only. Staining for fragments D and D-D was observed in glom capillaries in 6 Group I cases (6 HUS) and 3 Group II cases (2 IgA nephropathy, 1 membranous GN) but was most diffuse and intense in Group I. Traditional histochemical stains for fibrin (Lendrum and PTAH) were positive in 4 Group I cases only, indicating that the ABC technique is far more sensitive. Controls (14 needle biopsies of non-renal tissue) showed no vascular ractivity for fibrinogen, fibrin I, II and fragments D and D-D, suggesting that the vascular staining observed in renal biopsy tissue is not caused by the biopsy procedure itself. These findings indicate that 1) Fibrin formation and lysis occur in many renal diseases of both vascular and non—vascular origin. 2) Fibrinolytic activity is higher in the glom capillaries than in the larger vessels. 3) Damaged renal endothelium may be an active participant in these processes.

Renal Pathology in Adult Onset Idiopathic Nephrotic Syndrome A Study of 100 Cases

This study was carried out in the nephrology unit to Rajshahi Medical College Hospital, Rajshahi during the period 2003-2005. Renal biopsy was done in one hundred adult patients with Nephrotic syndrome to evaluate the histopathological pattern. Mesangioproliferative GN was the commonest underlying cause which is found in 36 (40%) cases. MPGN is followed by minimal change disease in 22 (24.44%), membranous GN 16 (17.77%), membranoproliferative glomerulonephritis 12 (13.33%), Focal segmental glomerulosclerosis 3 (3.34%) and IgA nephropathy 1 (1.12%) cases. This is concordant with other studies. doi: 10.3329/taj.v20i2.3076 TAJ 2007; 20(2): 140-143