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

Background Lupus 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. Methodology A 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). Results Eighty-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. Conclusions LP is a spectrum of p-SLE, not an association as it is related to disease activity and its initial presentation.

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.

Clinical and pathological features of idiopathic membranous nephropathy with focal segmental sclerosis

Background The goal of this study was to investigate the clinical and pathological features and prognosis of idiopathic membranous nephropathy (IMN) with focal segmental lesions. Methods In our hospital, 305 patients with nephrotic syndrome confirmed as IMN by renal biopsy were divided into a non-focal segmental lesion group (FSGS- group) and a focal segmental glomerulosclerosis (FSGS) group (FSGS+ group) and retrospectively analyzed. In all, 180 patients were followed for periods ranging from six months to two years. The general clinicopathological data of both groups were compared, and the effects of different treatment schemes on the prognosis of both groups were observed. Results The FSGS+ group had a longer disease course, higher blood pressure levels, and higher serum creatinine and β2-microglobulin levels than did the FSGS- group (all P < 0.05). Pathologically, the FSGS+ group had increased glomerular sclerosis, glomerular mesangial hyperplasia, and acute and chronic tubular lesion rates (all P< 0.05). The remission rate was lower in the FSGS+ group than in the FSGS- group (64.7% vs 82.2%) and, among patients in the FSGS+ group, was lower in patients treated with calmodulin inhibitors than in those treated with cyclophosphamide (P < 0.01). Survival analysis showed that the FSGS+ group had a poor prognosis (χ2=4.377, P=0.036), and risk factor analysis suggested that age at renal biopsy (P=0.006), 24-hour urinary protein quantity (P=0.01), chronic tubulointerstitial lesions (P=0.055), and FSGS lesions (P= 0.062) were risk factors for worsening renal condition; furthermore, 24-hour urinary protein quantity was an independent risk factor for worsening renal condition. Conclusions Membranous nephropathy with FSGS is a risk factor, but not an independent risk factor, for IMN. Patients with membranous nephropathy with FSGS often present hypertension and tubule injury. The nonselective drug cyclophosphamide is preferred, and calcineurin inhibitors should be used with caution. Key words Idiopathic membranous nephropathy; focal segmental sclerosis; cyclophosphamide; calmodulin inhibitor; prognosis;

Clinical and pathological features of idiopathic membranous nephropathy with focal segmental sclerosis

Background Our goal was to investigate the clinical and pathological features and prognosis of idiopathic membranous nephropathy (IMN) with focal segmental lesions. Methods In our hospital, 305 patients with nephrotic syndrome confirmed by renal biopsy as IMN were divided into a non-focal segmental lesion group (FSGS- group) and a focal segmental glomerulosclerosis (FSGS) group (FSGS+ group) and retrospectively analyzed. A total of 180 patients were followed for periods ranging from six months to two years. The general clinical and pathological data of both groups were compared, and the effects of different treatment schemes on the prognosis of both groups were observed. Results The FSGS+ group had a longer disease course, higher blood pressure levels, and higher serum creatinine and β 2 -microglobulin levels than the FSGS- group (all P < 0.05). Pathologically, the FSGS+ group had increased glomerular sclerosis, glomerular mesangial hyperplasia, acute tubular lesion and chronic tubular lesion rates (all P< 0.05). The remission rate was lower in the FSGS+ group than in the FSGS- group (64.7% vs 82.2%) and was lower in patients treated with calmodulin inhibitors than in those treated with cyclophosphamide in the FSGS+ group (P < 0.01). Survival analysis showed that the FSGS+ group had a poor prognosis (χ 2 =4.377，P=0.036). Risk factor analysis suggested that age at renal biopsy (P=0.006), 24-hour urinary protein quantity (P=0.01), chronic tubulointerstitial lesions (P=0.055), and FSGS lesions (P= 0.062) were risk factors for worsening renal condition; 24-hour urinary protein quantity was an independent risk factor for worsening renal condition. Conclusions Membranous nephropathy with FSGS is a risk factor, but not an independent risk factor, for IMN. Patients with membranous nephropathy with FSGS often present hypertension and tubule injury. The nonselective drug cyclophosphamide is preferred, and calcineurin inhibitors should be used with caution. Key words Idiopathic membranous nephropathy; focal segmental sclerosis; cyclophosphamide; calmodulin inhibitor; prognosis;

Clinical and pathological features of idiopathic membranous nephropathy with focal segmental sclerosis

Abstract Background To investigate clinical and pathological features and prognosis of idiopathic membranous nephropathy (IMN) with focal segmental lesions. Methods In our hospital, 305 patients with biopsy-proven IMN were divided into a non-focal segmental lesion group (FSGS- group) and focal segmental glomerulosclerosis (FSGS) group (FSGS+ group) and retrospectively analyzed. The general clinical and pathological data of both groups were compared, and the effects of different treatment schemes on the prognosis of both groups were observed. Results The FSGS+ group had longer disease course; higher blood pressure levels; and higher serum creatinine andβ2-microglobulin levels than the FSGS- group (all P < 0.05). Pathologically, the FSGS+ group had increased glomerular sclerosis, glomerular mesangial hyperplasia, acute tubular lesion and chronic tubular lesion rates (all P< 0.05). The remission rate was lower in the FSGS+ group than in the FSGS- group（64.7% vs 82.2%) and was lower in association with calmodulin inhibitors than with cyclophosphamide in the FSGS+ group (P < 0.01). Survival analysis showed that the FSGS+ group had a poor prognosis（χ2=4.377，P=0.036). Risk factor analysis suggested that age at renal biopsy (P=0.006), 24-hour urinary protein quantity (P=0.01), chronic tubulointerstitial lesions (P=0.055), and FSGS lesions (P= 0.062) were risk factors for renal death; 24-hour urinary protein quantity was an independent risk factor for renal death. Conclusions Membranous nephropathy with FSGS is a risk factor for IMN but not an independent risk factor. Patients with membranous nephropathy with FSGS often present hypertension and tubule injury. Nonselective cyclophosphamide is preferred, and calcineurin inhibitors should be used with caution. Key words Idiopathic membranous nephropathy; focal segmental sclerosis; cyclophosphamide; calmodulin inhibitor; prognosis;

Schistosomiasis

The urinary system is the primary target of Schistosoma haematobium infection, which leads to granuloma formation in the lower urinary tract that heals with fibrosis and calcification. While the early lesions may be associated with distressing acute or subacute symptoms, it is the late lesions that constitute the main clinical impact of schistosomiasis. The latter include chronic cystitis, ureteric fibrosis, ureterovesical obstruction or reflux which may lead to chronic pyelonephritis. Secondary bacterial infection and bladder cancer are the main secondary sequelae of urinary schistosomiasis.The kidneys are also a secondary target of S. mansoni infection, attributed to the systemic immune response to the parasite. Specific immune complexes are responsible for early, often asymptomatic, possibly reversible, mesangioproliferative lesions which are categorized as ‘class I’. Subsequent classes (II–VI) display different histopathology, more serious clinical disease, and confounding pathogenic factors. Class II lesions are encountered in patients with concomitant salmonellosis; they are typically exudative and associated with acute-onset nephrotic syndrome. Classes III (mesangiocapillary glomerulonephritis) and IV (focal segmental sclerosis) are progressive forms of glomerular disease associated with significant hepatic pathology. They are usually associated with immunoglobulin A deposits which seem to have a significant pathogenic role. Class V (amyloidosis) occurs with long-standing active infection with either S. haematobium or S. mansoni. Class VI is seen in patients with concomitant HCV infection, where the pathology is a mix of schistosomal and cryoglobulinaemic lesions, as well as amyloidosis which seems to be accelerated by the confounded pathogenesis.Early schistosomal lesions, particularly those of the lower urinary tract, respond to antiparasitic treatment. Late urological lesions may need surgery or endoscopic interventions. As a rule, glomerular lesions do not respond to treatment with the exception of class II where dual antiparasitic and antibiotic therapy is usually curative. Patients with end-stage kidney disease may constitute specific, yet not insurmountable technical and logistic problems in dialysis or transplantation. Recurrence after transplantation is rare.

Primary focal segmental glomerulosclerosis

Primary focal segmental glomerulosclerosis (FSGS) causes nephrotic syndrome and by definition is not caused by any of the known causes of podocyte toxicity or focal segmental sclerosis such as viral infections or toxins. A number of genetic causes of FSGS are commonly diagnosed in early childhood. Other causes of segmental scarring need to be distinguished. Genotypes in APOL1 of African origin are associated with higher incidence of FSGS and poorer responses to treatment. Cellular and collapsing FSGS are variants of FSGS in which there is overt acute podocytopathy and they have a relatively poor prognosis. A glomerular tip lesion is thought to have a slightly better prognosis than other types. Some cases of primary FSGS respond to high-dose corticosteroids, sometimes only after prolonged therapy. Response to steroids is a good prognostic sign, and without a response, progressive loss of renal function is likely. A circulating factor is implicated by the observation that proteinuria can recur in a donor kidney within hours of transplant. Plasma exchange appears to remove this factor but it is not conclusively identified.