UNASSIGNED: Patients with lupus podocytopathy show a high incidence of acute kidney injury (AKI) and relapse, but the risk factors and mechanisms were unclear. This study analysed the clinicopathological features and risk factors for AKI and relapse in lupus podocytopathy patients.
UNASSIGNED: The cohort of lupus podocytopathy was generated by screening the biopsies of patients with lupus nephritis (LN) from 2002 to 2022 and was divided into the mild glomerular lesion (MGL) and focal segmental glomerulosclerosis (FSGS) groups based on glomerular morphological characteristics. The acute (ATI) and chronic (CTI) tubulointerstitial lesions were semi-quantitatively scored. Logistic and Cox regressions were employed to identify the risk factors for AKI and relapse, respectively.
UNASSIGNED: Among 6052 LN cases, 98 (1.6%) were diagnosed as lupus podocytopathy, with 71 in the MGL group and 27 in the FSGS group. All patients presented with nephrotic syndrome and 33 (34.7%) of them had AKI. Seventy-seven (78.6%) patients achieved complete renal response (CRR) within 12 weeks of induction treatment, in which there was no difference in the CRR rate between glucocorticoid monotherapy and combination therapy with glucocorticoids plus immunosuppressants. Compared with the MGL group, patients in the FSGS group had significantly higher incidences of hypertension and haematuria; in addition, they had higher Systemic Lupus Erythematosus Disease Activity Index 2000, ATI and CTI scores but a significantly lower CRR rate. Urinary protein ≥7.0 g/24 h and serum C3 ≤0.750 g/l were independent risk factors for AKI. During a median follow-up of 78 months, 57 cases (60.0%) had relapse and none reached the kidney endpoint. Failure to achieve CRR within 12 weeks, maintenance with glucocorticoid monotherapy and AKI at onset were independent risk factors for kidney relapse.
UNASSIGNED: In this study, histological subtypes of lupus podocytopathy were found to be associated with clinical features and treatment response. In addition, several risk factors associated with AKI occurrence and kidney relapse were identified.

Lupus podocytopathy, a unique form of lupus nephritis, mimics minimal change disease (MCD) or primary focal segmental glomerulosclerosis (FSGS) and represents approximately 1% of lupus nephritis biopsies. Lupus podocytopathy is characterized by diffuse epithelial cell foot process effacement without immune complex deposition or with only mesangial immune complex deposition. We present the case of a young woman with systemic lupus erythematosus (SLE) who presented with nephrotic syndrome and acute kidney injury (AKI) and was subsequently diagnosed with lupus podocytopathy.

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UNASSIGNED: Systemic lupus erythematosus (SLE) represents a principal prototype of a multisystemic autoimmune disease with the participation of both cell- and antibody-mediated mechanisms causing significant renal impairment. A renal biopsy diagnosis is the gold standard for clinical renal disease in SLE, which includes a broad range of indications.
UNASSIGNED: Renal disease in SLE can involve glomerular, tubulointerstitial, and/or vascular compartments, none of which are mutually exclusive. In most instances, the basic pathogenetic mechanism involves tissue deposition of immune complexes and/or cell-mediated mechanisms, identified by light microscopy, immunohistochemical methods, and electron microscopy (EM), evoking intraglomerular proliferative, inflammatory, and other tissue responses. These produce a spectrum of histologic lesions, depending on the participation of a wide range of clinical triggers, namely, genetic, serological, and immunological factors, correlating with their underlying pathogenetic potential. In addition to light and immunofluorescence microscopy, EM in this setting facilitates an accurate diagnosis, assesses disease activity, delineates subclasses, differentiates from primary forms of non-lupus renal lesions, identifies organized deposits, and rarely, identifies other forms of nonimmune complex lesions such as podocytopathies, amyloidosis, and thrombotic microangiopathy.
UNASSIGNED: EM findings that are distinctive for most of the renal lesions in SLE include immune complex and nonimmune complex diseases as well as overlapping entities. Routine ultrastructural examination not only provides significant diagnostic and prognostic information from both initial and repeat renal biopsies from lupus patients but also contributes toward the understanding of the underlying pathophysiology of the disease process.

Lupus podocytopathy is a glomerular lesion in systemic lupus erythematosus (SLE) characterized by diffuse podocyte foot process effacement (FPE) without immune complex (IC) deposition or with only mesangial IC deposition. It is rarely seen in children with SLE. A 13-year-old girl met the 2019 European League Against Rheumatism (EULAR)/ American College of Rheumatology (ACR) Classification Criteria for SLE based on positive ANA; facial rash; thrombocytopenia; proteinuria; and positive antiphospholipid (aPL) antibodies, including lupus anticoagulant (LAC), anti-β2 glycoprotein-I antibody (anti-β2GPI), and anti-cardiolipin antibody (aCL). The renal lesion was characterized by 3+ proteinuria, a 4.2 mg/mg spot (random) urine protein to creatinine ratio, and hypoalbuminemia (26.2 g/l) at the beginning of the disease. Kidney biopsy findings displayed negative immunofluorescence (IF) for immunoglobulin A (IgA), IgM, fibrinogen (Fb), C3, and C1q, except faint IgG; a normal glomerular appearance under a light microscope; and diffuse podocyte foot process effacement (FPE) in the absence of subepithelial or subendothelial deposition by electron microscopy (EM). Histopathology of the epidermis and dermis of the pinna revealed a hyaline thrombus in small vessels. The patient met the APS classification criteria based on microvascular thrombogenesis and persistently positive aPL antibodies. She responded to a combination of glucocorticoids and immunosuppressive agents. Our study reinforces the need to consider the potential cooccurrence of LP and APS. Clinicians should be aware of the potential presence of APS in patients with a diagnosis of LP presenting with NS and positivity for aPL antibodies, especially triple aPL antibodies (LCA, anti-β2GPI, and aCL).

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In systemic lupus erythematosus, nephrotic-range proteinuria typically signals the presence of a proliferative lupus nephritis (class III/IV) and/or membranous lupus nephritis (class V, with or without concomitant class III or IV lesions). However, in rare instances, systemic lupus erythematosus patients with nephrotic syndrome have kidney biopsy findings of normal glomeruli or focal segmental glomerulosclerosis lesions, with or without mesangial proliferation, on light microscopy; the absence of subepithelial or subendothelial deposits on immunofluorescence and electron microscopy; and diffuse foot process effacement on electron microscopy. This pattern, termed lupus podocytopathy, is a unique form of lupus nephritis that mimics minimal change disease or primary focal segmental glomerulosclerosis and represents approximately 1% of lupus nephritis biopsies. Here we review the clinical features, histological manifestations, diagnostic criteria and classification, pathogenesis, treatment, and prognosis of lupus podocytopathy.

Systemic lupus erythematosus (SLE) is characterized by a broad spectrum of renal lesions. In lupus glomerulonephritis, histological classifications are based on immune-complex (IC) deposits and hypercellularity lesions (mesangial and/or endocapillary) in the glomeruli. However, there is compelling evidence to suggest that glomerular epithelial cells, and podocytes in particular, are also involved in glomerular injury in patients with SLE. Podocytes now appear to be not only subject to collateral damage due to glomerular capillary lesions secondary to IC and inflammatory processes, but they are also a potential direct target in lupus nephritis. Improvements in our understanding of podocyte injury could improve the classification of lupus glomerulonephritis. Indeed, podocyte injury may be prominent in two major presentations: lupus podocytopathy and glomerular crescent formation, in which glomerular parietal epithelial cells play also a key role. We review here the contribution of podocyte impairment to different presentations of lupus nephritis, focusing on the podocyte signaling pathways involved in these lesions.

Systemic lupus erythematosus (SLE) patients clinically presenting with nephrotic syndrome demonstrating minimal change disease (MCD), mesangial proliferation (MsP) or focal segmental glomerulosclerosis (FSGS), while on electronic microscopy, diffuse podocyte foot process effacement in absence of sub-epithelial or sub-endothelial deposition is the only morphological feature and now diagnosed as lupus podocytopathy. Lupus podocytopathy with glomerular morphology of MCD or MsP usually presents with typical nephrotic syndrome and sensitive to glucocorticoid treatment, but the relapse rate could reach up to 90% on maintenance treatment with glucocorticoid alone. Glucocorticoid plus other immunosuppressive agents could significantly decrease the relapse rate. Lupus podocytopathy with FSGS presents with a higher rate of acute kidney injury and less sensitivity to glucocorticoid treatment. The long-term outcomes of lupus podocytopathy are optimistic, but pathological transition could occur after renal relapses. The unique clinical and morphological features of lupus podocytopathy indicate that this special SLE-associated glomerulopathy should be included in the upcoming revised pathological classification of lupus nephritis.

Lupus nephritis (LN) is usually associated with immune deposition in the glomerular capillary wall. On the other hand, focal segmental glomerulosclerosis (FSGS) is not typically associated with immune deposition, and its pathogenesis includes podocyte damage and loss. The definition of lupus podocytopathy (LP) excludes patients with electron-dense glomerular basement membrane deposits. Here, we report the case of an LN patient with nephrotic proteinuria. Renal pathology demonstrated focal endocapillary hypercellularity superimposed on foam cells. Immunofluorescence revealed diffuse global subepithelial immune deposits, and electron microscopy showed electron-dense glomerular basement membrane deposits and diffuse foot process effacement. Treatment with steroid and cyclosporine improved her proteinuria. Post-treatment renal re-biopsy revealed focal segmental sclerotic lesions closely resembling FSGS. These results indicate that the pathogenesis of this case may involve an FSGS-like condition or podocytopathic change. It is possible that careful examination would reveal podocytopathic changes other than LP in patients previously diagnosed as LN class III + V. Further investigations are needed to understand FSGS-like pathological changes accompanied with capillary immune deposits in LN.