Association of podocyte ultrastructural changes with proteinuria and pathological classification in type 2 diabetic nephropathy.

AIMS: Podocyte injury plays an essential role in the progression of diabetic nephropathy (DN). The associations between the ultrastructural changes of podocyte with proteinuria and the pathological classification of DN proposed by Renal Pathology Society (RPS) have not been clarified in patients with type 2 diabetic nephropathy (T2DN). METHODS: We collected 110 patients with kidney biopsy-confirmed T2DN at Peking University First Hospital from 2017 to 2022. The morphometric analysis on the podocyte foot process width (FPW) and podocyte detachment (PD) as markers of podocyte injury was performed, and the correlations between the ultrastructural changes of podocytes with severity of proteinuria and the RPS pathological classification of DN were analyzed. RESULTS: Mean FPW was significantly broader in the group of T2DN patients with nephrotic proteinuria (565.1 nm) than those with microalbuminuria (437.4 nm) or overt proteinuria (494.6 nm). The cut-off value of FPW (> 506 nm) could differentiate nephrotic proteinuria from non-nephrotic proteinuria with a sensitivity of 75.3% and a specificity of 75.8%. Percentage of PD was significantly higher in group of nephrotic proteinuria (3.2%) than that in microalbuminuria (0%) or overt proteinuria (0.2%). FPW and PD significantly correlated with proteinuria in T2DN (r = 0.473, p < 0.001 and r = 0.656, P < 0.001). FPW and PD correlated with RPS pathological classification of T2DN (r = 0.179, P = 0.014 and r = 0.250, P = 0.001). FPW value was increased significantly with more severe DN classification (P for trend =0.007). The percentage of PD tended to increase with more severe DN classification (P for trend = 0.017). CONCLUSIONS: Podocyte injury, characterized by FPW broadening and PD, was associated with the severity of proteinuria and the pathological classification of DN.

Glomerulopatía por invaginación podocítica; reporte del primer caso en Latinoamérica y revisión de la literatura / Podocyte infolding glomerulopathy; report of the first case in Latin America and review of the literatura

ANTECEDENTES: La glomerulopatía por invaginación podocítica (GIP) es una enfermedad de origen incierto, frecuentemente asociada a enfermedades autoinmunes, de la que se desconoce el tratamiento específico y su evolución. Caracterizada por engrosamiento de paredes capilares por la presencia de burbujas no argirofílicas intramembanosas similares a las encontradas en la glomerulopatía membranosa, pero sin depósitos de inmunocomplejos electrodensos en la ultraestructura, donde se observan microesferas traslúcidas generadas por invaginación del citoplasma podocítico dentro de las membranas basales. OBJETIVOS: Generalmente descrito en pacientes jóvenes de sexo femenino. Hasta la fecha, han sido reportados escasos casos en pacientes de origen asiático. Nuestro caso constituiría el primer reporte en paciente latinoamericano de raza blanca. MÉTODOS: Mujer de 38 años con LES. En el año 2014 presentó síndrome nefrótico tratado empíricamente con corticoides (CO) y ciclofosfamida intravenosa (CF) con buena respuesta. Presenta recaída en abril del 2015 con función renal normal y sin actividad lúpica extrarrenal, por lo que es derivada a nuestro hospital para ser biopsiada. RESULTADOS: La biopsia informó esclerosis glomerular focal y segmentaria sin depósitos de inmunocomplejos en la inmunofluorescencia, pero con técnica de metenamina plata se detectaron en las paredes capilares, espacios claros acompañados de marcadas alteraciones podocíticas. Al microscopio electrónico, se observaron agregados de ultraestructuras microvesiculares y cilíndricas unidas a las membranas sin evidencia de depósitos densos y borramiento difuso de pies pedicelares, confirmando el diagnóstico sospechado. CONCLUSIONES: Reportamos el primer caso de lo que puede ser considerada, una nueva entidad patológica glomerular, en una paciente de raza blanca latinoamericana, cuya evolución y terapéutica aún se desconocen

BACKGROUND: Podocyte infolding glomerulopathy (PIG) is a condition of uncertain origin, frequently associated with autoimmune diseases. Its specific treatment and clinical course are unknown. It is characterised by thickening of the capillary walls due to the presence of non-argyrophilic intramembranous bubbles similar to those found in membranous glomerulopathy, but without electron-dense deposits of immune complexes in the ultrastructure, where translucent microspheres generated by invagination of the podocyte cytoplasm into the basement membranes are observed. OBJECTIVES: Generally reported in young females patients. To date, few cases in Asian patients have been reported. Our case is the first to be reported in a Latin American Caucasian patient. METHODS: A 38-year-old woman with SLE. In 2014 she presented with nephrotic syndrome empirically treated with corticosteroids (CO) and intravenous cyclophosphamide with good response. She had a relapse in April 2015 with normal renal function and no extrarenal lupus activity, so she was referred to our hospital to be biopsied. RESULTS: The biopsy reported focal segmental glomerular sclerosis without deposits of immune complexes in the immunofluorescence. However, methenamine silver staining revealed clear spaces in the capillary walls accompanied by marked podocyte alterations. On electron microscope study, numerous aggregates of microvesicular and cylindrical ultrastructures bound to the membranes were observed, without evidence of dense deposits, and diffuse effacement of pedicel foot processes, confirming the suspected diagnosis. CONCLUSIONS: This is the first reported case of what can be considered a new pathological glomerular entity in a Latin American Caucasian patient, whose clinical course and therapy are still unknown

High prevalence of methicillin resistance and PVL genes among Staphylococcus aureus isolates from the nares and skin lesions of pediatric patients with atopic dermatitis

Staphylococcus aureus is highly prevalent among patients with atopic dermatitis (AD), and this pathogen may trigger and aggravate AD lesions. The aim of this study was to determine the prevalence of S. aureus in the nares of pediatric subjects and verify the phenotypic and molecular characteristics of the isolates in pediatric patients with AD. Isolates were tested for antimicrobial susceptibility, SCCmec typing, and Panton-Valentine Leukocidin (PVL) genes. Lineages were determined by pulsed-field gel electrophoresis and multilocus sequence typing (MLST). AD severity was assessed with the Scoring Atopic Dermatitis (SCORAD) index. Among 106 patients, 90 (85%) presented S. aureus isolates in their nares, and 8 also presented the pathogen in their skin infections. Two patients had two positive lesions, making a total of 10 S. aureus isolates from skin infections. Methicillin-resistant S. aureus (MRSA) was detected in 24 (26.6%) patients, and PVL genes were identified in 21 (23.3%), including 6 (75%) of the 8 patients with skin lesions but mainly in patients with severe and moderate SCORAD values (P=0.0095). All 24 MRSA isolates were susceptible to trimethoprim/sulfamethoxazole, while 8 isolates had a minimum inhibitory concentration (MIC) to mupirocin >1024 μg/mL. High lineage diversity was found among the isolates including USA1100/ST30, USA400/ST1, USA800/ST5, ST83, ST188, ST718, ST1635, and ST2791. There was a high prevalence of MRSA and PVL genes among the isolates recovered in this study. PVL genes were found mostly among patients with severe and moderate SCORAD values. These findings can help clinicians improve the therapies and strategies for the management of pediatric patients with AD.

Lupus-related podocytopathy. Could it be a new entity within the spectrum of lupus nephritis?

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Reduction of podocytes number in late diabetic alloxan nephropathy: prevention by glycemic control

PURPOSE: To determine podocyte number and GBM thickness in diabetic rats either under glycemic control or without glycemic control at 6 and 12 months after diabetes induction. METHODS: 100 wistar rats weighing 200-300g were divided into 6 groups: Normal group (N6 and N12- 25 rats); Diabetic group (D6 and D12- 25 rats), diabetic treated group ( DT 6 and DT 12- 25 rats) on insulin 1,8- 3,0 IU/Kg associated with acarbose (50mg to 100g of food) daily mixed in chow. Alloxan was injected intravenously in a dose of 42 mg/Kg of weight. Body weight, waterintake, 24-h diuresis, glycemia and glucosuria were determined before induction, 7 and 14 days after induction and monthly thereafter. Treatment started at day 14. Three groups were sacrificed at 6 months (N6,D6, DT6) and 3 groups at 12 months (N12, D12, DT12) with the renal tissue being prepared for electron microscopy. RESULTS: Glycemia in DT6¨and in DT12 was significantly different from that in D6 and D12 rats and similar to that in N6 and N12 animals. The number of podocytes in DT6 was not different from that in N6 and D6 (median = 11); the number of podocytes in DT12 (median = 11) differed from that in D12 (median = 8), but not from that in N12 (median = 11). GBM thickness in D6 (0.18 micrometers) was lower than in D12 (0.29 micrometers); while in DT6 (0.16 micrometers) it was lower than in D6 (0.18 micrometers). In DT12 (0.26 micrometers), it was lower than in D12 (0.29 micrometers). CONCLUSION: The control of hyperglycemia prevented GBM thickening in early and late (12 mo) alloxan diabetic nephropathy and podocyte number reduction.

OBJETIVO: Avaliar o número de podócitos e espessamento da membrana basal glomerular (MBG) em ratos diabéticos com e sem controle glicêmico com 6 e 12 meses da indução. MÉTODOS: 100 ratos Wistar com 200-300g compuseram 6 grupos: Normal (N6, N12 - 25 animais) Diabético (D6,D12 - 25 animais) e diabético tratado com insulina 1,8 a 3,0 U/Kg e acarbose misturada a ração (50g para cada 100g de ração) (DT6 e DT12 - 25 animais). Aloxana foi ministrada via endovenosa na dose de 42mg/Kg. Peso, ingestão hídrica e diurese de 24 horas e glicemia e glicosúria foram determinados antes da inoculação, 7 e 14 dias após e mensalmente. No 14ª dia foi iniciado o tratamento. Três grupos de animais (N6, D6 e DT6) foram sacrificados no 6° mês e três grupos (N12, D12 e DT12), no 12ª mês sendo o tecido renal processado para estudo à microscopia eletrônica. RESULTADOS: A glicemia dos animais DT6 e DT12 diferiram significativamente, dos ratos D6 e D12, e não diferiram dos grupos N6 e N12. O número de podócitos do grupo DT6 não diferiu de N6 e D6 (mediana=11); o número de podócitos de DT12 (mediana=11) diferiu de D12 (mediana=8) e não diferiu de N12 (mediana=11). O espessamento da MBG de D6 (0,18 micrômetros) foi menor que D12 (0,29 micrômetros); de DT6 (0,16 micrômetros) foi menor que D6 (0,18 micrômetros) e de DT12 (0,26 micrômetros) foi menor que D12 (0,29 micrômetros). CONCLUSÃO: O controle da hiperglicemia preveniu o espessamento da MBG na nefropatia diabética aloxânica precoce (6 meses) e tardia (12 meses), e a diminuição do número de podócitos.