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BACKGROUND: Granulomatous interstitial nephritis in sarcoidosis (sGIN) is generally clinically silent, but in <1% causes acute kidney injury (AKI). METHODS: This Italian multicentric retrospective study included 39 sarcoidosis-patients with renal involvement at renal biopsy: 31 sGIN-AKI, 5 with other patterns (No-sGIN-AKI), 3 with nephrotic proteinuria. We investigate the predictive value of clinical features, laboratory, radiological parameters and histological patterns regarding steroid response. Primary endpoint: incident chronic kidney disease (CKD) beyond the 1°follow-up (FU) year; secondary endpoint: response at 1°line steroid therapy; combined endpoint: the association of initial steroid response and outcome at the end of FU. RESULTS: Complete recovery in all 5 No-sGIN-AKI-patients, only in 45% (13/29) sGIN-AKI-patients (p=0.046) (one lost in follow-up, for another not available renal function after steroids). Nobody had not response. Primary endpoint of 22 sGIN-AKI subjects: 65% (13/20) starting with normal renal function developed CKD (2/22 had basal CKD; median FU 77 months, 15-300). Combined endpoint: 29% (6/21) had complete recovery and final normal renal function (one with renal relapse), 48% (10/21) had partial recovery and final CKD (3 with renal relapse, of whom one with basal CKD) (p=0.024). Acute onset and hypercalcaemia were associated to milder AKI and better recovery than subacute onset and patients without hypercalcaemia, women had better endpoints than men. Giant cells, severe interstitial infiltrate and interstitial fibrosis seemed negative predictors in terms of endpoints. CONCLUSIONS: sGIN-AKI-patients with no complete recovery at 1°line steroid should be treated with other immunosuppressive to avoid CKD, in particular if males with subacute onset and III stage-not hypercalcaemic AKI.
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BACKGROUND: A considerable minority of patients on waiting lists for kidney transplantation either have no diagnosis (and fall into the subset of undiagnosed cases) because kidney biopsy was not performed or histological findings were non-specific, or do not fall into any well-defined clinical category. Some of these patients might be affected by a previously unrecognised monogenic disease. METHODS: Through a multidisciplinary cooperative effort, we built an analytical pipeline to identify patients with chronic kidney disease (CKD) with a clinical suspicion of a monogenic condition or without a well-defined diagnosis. Following the stringent phenotypical and clinical characterization required by the flowchart, candidates meeting these criteria were further investigated by clinical exome sequencing followed by in silico analysis of 225 kidney-disease-related genes. RESULTS: By using an ad hoc web-based platform, we enrolled 160 patients from 13 different Nephrology and Genetics Units located across the Piedmont region over 15 months. A preliminary "remote" evaluation based on well-defined inclusion criteria allowed us to define eligibility for NGS analysis. Among the 138 recruited patients, 52 (37.7%) were children and 86 (62.3%) were adults. Up to 48% of them had a positive family history for kidney disease. Overall, applying this workflow led to the identification of genetic variants potentially explaining the phenotype in 78 (56.5%) cases. CONCLUSIONS: These results underline the importance of clinical exome sequencing as a versatile and highly useful, non-invasive tool for genetic diagnosis of kidney diseases. Identifying patients who can benefit from targeted therapies, and improving the management of organ transplantation are further expected applications.
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Exoma , Insuficiencia Renal Crónica , Pruebas Genéticas , Humanos , Italia , Secuenciación del ExomaRESUMEN
IgG4-related disease (IgG4-RD) is an immune-mediated disorder often showing elevated serum IgG4 concentrations, dense T and B lymphocyte infiltration, and IgG4-positive plasma cells and storiform fibrosis. We prospectively evaluated for 4 years 5 patients with histologically proven IgG4-RD of whom 3 had tubulointerstitial nephritis (TIN) and 2 had retroperitoneal fibrosis (RPF). They received an intensive B depletion therapy with rituximab. The estimated glomerular filtration rate of TIN patients after 1 year increased from 9 to 24 ml/min per 1.73 m2. IgG/IgG4 dropped from 3236/665 to 706/51 mg/dl, C3/C4 went up from 49/6 to 99/27 mg/dl, and the IgG4-RD responder index fell from 10 to 1. CD20+ B cells decreased from 8.7 to 0.5%. A striking drop in interstitial plasma cell infiltrate as well as normalization of IgG4/IgG-positive plasma cells was observed at repeat biopsy. Both clinical and immunological improvement persisted over a 4-year follow-up. Treating these patients who were affected by aggressive IgG4-RD with renal involvement in an effort to induce a prolonged B cells depletion with IgG4 and cytokine production decrease resulted in a considerable rise in eGFR, with IgG4-RD RI normalization and a noteworthy improvement in clinical and histological features. Furthermore, the TIN subgroup was shown not to need for any maintenance therapy.
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Enfermedad Relacionada con Inmunoglobulina G4/complicaciones , Enfermedad Relacionada con Inmunoglobulina G4/terapia , Enfermedades Renales/etiología , Enfermedades Renales/terapia , Depleción Linfocítica , Biomarcadores , Biopsia , Manejo de la Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Enfermedad Relacionada con Inmunoglobulina G4/sangre , Enfermedad Relacionada con Inmunoglobulina G4/diagnóstico , Inmunohistoquímica , Inmunofenotipificación , Enfermedades Renales/diagnóstico , Pruebas de Función Renal , Recuento de Linfocitos , Depleción Linfocítica/efectos adversos , Depleción Linfocítica/métodos , Subgrupos Linfocitarios/inmunología , Subgrupos Linfocitarios/metabolismo , Masculino , Tomografía Computarizada por Tomografía de Emisión de Positrones , Índice de Severidad de la Enfermedad , Tomografía Computarizada por Rayos X , Resultado del TratamientoRESUMEN
BACKGROUND: It is unknown whether renal pathology lesions in immunoglobulin A nephropathy (IgAN) correlate with renal outcomes over decades of follow-up. METHODS: In 1130 patients of the original Validation Study of the Oxford Classification for IgA Nephropathy (VALIGA) cohort, we studied the relationship between the MEST score (mesangial hypercellularity, M; endocapillary hypercellularity, E; segmental glomerulosclerosis, S; tubular atrophy/interstitial fibrosis, T), crescents (C) and other histological lesions with both a combined renal endpoint [50% estimated glomerular filtration rate (eGFR) loss or kidney failure] and the rate of eGFR decline over a follow-up period extending to 35 years [median 7 years (interquartile range 4.1-10.8)]. RESULTS: In this extended analysis, M1, S1 and T1-T2 lesions as well as the whole MEST score were independently related with the combined endpoint (P < 0.01), and there was no effect modification by age for these associations, suggesting that they may be valid in children and in adults as well. Only T lesions were associated with the rate of eGFR loss in the whole cohort, whereas C showed this association only in patients not treated with immunosuppression. In separate prognostic analyses, the whole set of pathology lesions provided a gain in discrimination power over the clinical variables alone, which was similar at 5 years (+2.0%) and for the whole follow-up (+1.8%). A similar benefit was observed for risk reclassification analyses (+2.7% and +2.4%). CONCLUSION: Long-term follow-up analyses of the VALIGA cohort showed that the independent relationship between kidney biopsy findings and the risk of progression towards kidney failure in IgAN remains unchanged across all age groups and decades after the renal biopsy.
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Glomerulonefritis por IGA/clasificación , Glomerulonefritis por IGA/patología , Riñón/fisiopatología , Adolescente , Adulto , Niño , Estudios de Cohortes , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Tasa de Filtración Glomerular , Humanos , Masculino , PronósticoRESUMEN
IgG4-related disease (IgG4-RD) is a recently recognized disorder, characterized by elevated serum IgG4 concentrations, dense tissue infiltration of IgG4-positive plasma cells and storiform fibrosis. Treatment is usually based on steroids, however, relapses and long-term adverse effects are frequent. We prospectively studied 5 consecutive patients with histologically-proven IgG4-RD and renal involvement, treated with an extended Rituximab protocol combined with steroids. Two doses of intravenous cyclophosphamide were added in 4 patients. Five patients with IgG-RD were investigated: three had tubulointerstitial nephritis (TIN), while two had retroperitoneal fibrosis (RPF). In the patients with TIN, renal biospy was repeated after 1 year. In the patients with TIN, estimated glomerular filtration rate (eGFR) at 12 months increased from 9 to 24 ml/min per 1.73 m2; IgG/IgG4 decreased from 3,236/665 to 706/51 mg/dl; C3/C4 increased from 49/6 to 99/27 mg/dl; CD20+ B-cells decreased from 8.7% to 0.5%; Regulatory T-cells decreased from 7.2% to 2.5%. These functional and immunologic changes persisted at 24 months and in two patients at 36 months. A repeat renal biopsy in the patients with TIN showed a dramatic decrease in interstitial plasma cell infiltrate with normalization of IgG4/IgG positive plasma cells. The patients with RPF showed a huge regression of retroperitoneal tissue. In this sample of patients with aggressive IgG4-RD and renal involvement, treatment aimed at depleting B cells and decreasing antibody and cytokine production was associated with a substantial, persistent increase in eGFR, and a definite improvement in immunologic, radiologic and histological parameters.
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Chronic kidney disease (CKD) is increasingly recognized in pregnant patients. Three characteristics are associated with a risk of preterm delivery or small for gestational age babies; kidney function reduction, hypertension, and proteinuria. In pregnancy, the anti-proteinuric agents (ACE-angiotensin converting enzyme-inhibitors or ARBS -angiotensin receptor blockers) have to be discontinued for their potential teratogenicity, and there is no validated approach to control proteinuria. Furthermore, proteinuria usually increases as an effect of therapeutic changes and pregnancy-induced hyperfiltration. Based on a favourable effect of low-protein diets on proteinuria and advanced CKD, our group developed a moderately protein-restricted vegan-vegetarian diet tsupplemented with ketoacids and aminoacids for pregnant patients. This report describes the results obtained in three pregnant patients with normal renal function, nephrotic or sub-nephrotic proteinuria, and biopsy proven diagnosis of focal segmental glomerulosclerosis, a renal lesion in which hyperfiltration is considered of pivotal importance (case 1: GFR (glomerular filtration rate): 103 mL/min; proteinuria 2.1 g/day; albumin 3.2 g/dL; case 2: GFR 86 mL/min, proteinuria 3.03 g/day, albumin 3.4 g/dL; case 3: GFR 142 mL/min, proteinuria 6.3 g/day, albumin 3.23 g/dL). The moderately restricted diet allowed a stabilisation of proteinuria in two cases and a decrease in one. No significant changes in serum creatinine and serum albumin were observed. The three babies were born at term (38 weeks + 3 days, female, weight 3180 g-62th centile; 38 weeks + 2 days, female, weight 3300 g-75th centile; male, 38 weeks + 1 day; 2770 g-8th centile), thus reassuring us of the safety of the diet. In summary, based on these three cases studies and a review of the literature, we suggest that a moderately protein-restricted, supplemented, plant-based diet might contribute to controlling proteinuria in pregnant CKD women with focal segmental glomerulosclerosis. However further studies are warranted to confirm the potential value of such a treatment strategy.
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Dieta con Restricción de Proteínas , Dieta Vegana , Dieta Vegetariana , Glomeruloesclerosis Focal y Segmentaria/dietoterapia , Proteinuria/dietoterapia , Adulto , Aminoácidos/administración & dosificación , Biomarcadores/sangre , Biomarcadores/orina , Biopsia , Población Negra , Ciclofosfamida/uso terapéutico , Ciclosporina/uso terapéutico , Femenino , Tasa de Filtración Glomerular , Glomeruloesclerosis Focal y Segmentaria/complicaciones , Glomeruloesclerosis Focal y Segmentaria/tratamiento farmacológico , Humanos , Inmunosupresores/uso terapéutico , Cetoácidos/administración & dosificación , Riñón/diagnóstico por imagen , Masculino , Ácido Micofenólico/uso terapéutico , Embarazo , Proteinuria/complicaciones , Proteinuria/tratamiento farmacológico , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/dietoterapia , Insuficiencia Renal Crónica/tratamiento farmacológico , Población BlancaRESUMEN
BACKGROUND: Acute renal infarction is a rare condition whose diagnosis is often delayed. Major risk factors include atrial fibrillation, valvular or ischemic heart disease, renal artery thrombosis/dissection and coagulopathy. METHODS: We reviewed the medical records of 18 patients admitted to our Nephrology Department between 1999 and 2015 for acute renal infarction diagnosed by computed tomography. Tc-99m dimercaptosuccinic acid (DMSA) scintigraphy was performed in some patients during follow-up to assess parenchymal lesions and estimate differential kidney function. RESULTS: Mean age was 59.8 years. Major associated risk factors included hypertension (44 %), obesity (33 %), atrial fibrillation (28 %), peripheral vascular disease (17 %), smoking (17 %), prior thromboembolic event (11 %), diabetes (11 %), estroprogestinic therapy (11 %). Seventy-two percent of patients presented with flank pain. Mean serum creatinine was 1.2 ± 0.6 mg/dl. Acute kidney injury occurred as the initial manifestation in two patients. Patients were managed conservatively, with low molecular weight heparin (83 %) or aspirin (11 %). At the end of follow-up serum creatinine was 1.1 ± 0.3 mg/dl; one patient remained on chronic hemodialysis. 58 % of patients who underwent renal scintigraphy after a median of 8 months had a reduced contribution of the previously affected kidney to total renal function. CONCLUSION: Risk factors associated with the development of chronic kidney disease following renal infarction are unknown. In our subjects, renal function remained stable in all but one patient who developed end stage renal disease. Further studies should focus on etiology and evolution of kidney function in patients with acute renal infarction.
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Infarto/complicaciones , Riñón/irrigación sanguínea , Enfermedad Aguda , Adulto , Anciano , Anciano de 80 o más Años , Creatinina/sangre , Femenino , Heparina de Bajo-Peso-Molecular/uso terapéutico , Humanos , Infarto/diagnóstico por imagen , Infarto/fisiopatología , Infarto/terapia , Riñón/diagnóstico por imagen , Riñón/fisiopatología , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Tomografía Computarizada por Rayos XRESUMEN
BACKGROUND: There is a need for early identification of children with immunoglobulin A nephropathy (IgAN) at risk of progression of kidney disease. METHODS: Data on 261 young patients [age <23 years; mean follow-up of 4.9 (range 2.5-8.1) years] enrolled in VALIGA, a study designed to validate the Oxford Classification of IgAN, were assessed. Renal biopsies were scored for the presence of mesangial hypercellularity (M1), endocapillary hypercellularity (E1), segmental glomerulosclerosis (S1), tubular atrophy/interstitial fibrosis (T1-2) (MEST score) and crescents (C1). Progression was assessed as end stage renal disease and/or a 50 % loss of estimated glomerular filtration rate (eGFR) (combined endpoint) as well as the rate of renal function decline (slope of eGFR). Cox regression and tree classification binary models were used and compared. RESULTS: In this cohort of 261 subjects aged <23 years, Cox analysis validated the MEST M, S and T scores for predicting survival to the combined endpoint but failed to prove that these scores had predictive value in the sub-group of 174 children aged <18 years. The regression tree classification indicated that patients with M1 were at risk of developing higher time-averaged proteinuria (p < 0.0001) and the combined endpoint (p < 0.001). An initial proteinuria of ≥0.4 g/day/1.73 m2 and an eGFR of <90 ml/min/1.73 m2 were determined to be risk factors in subjects with M0. Children aged <16 years with M0 and well-preserved eGFR (>90 ml/min/1.73 m2) at presentation had a significantly high probability of proteinuria remission during follow-up and a higher remission rate following treatment with corticosteroid and/or immunosuppressive therapy. CONCLUSION: This new statistical approach has identified clinical and histological risk factors associated with outcome in children and young adults with IgAN.
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Glomerulonefritis por IGA/epidemiología , Corticoesteroides/uso terapéutico , Factores de Edad , Biopsia , Niño , Preescolar , Estudios de Cohortes , Progresión de la Enfermedad , Determinación de Punto Final , Europa (Continente)/epidemiología , Femenino , Tasa de Filtración Glomerular , Glomerulonefritis por IGA/tratamiento farmacológico , Glomerulonefritis por IGA/patología , Humanos , Inmunosupresores , Lactante , Riñón/patología , Fallo Renal Crónico/epidemiología , Fallo Renal Crónico/patología , Masculino , Proteinuria/epidemiología , Proteinuria/patología , Estudios Retrospectivos , Factores de Riesgo , Factores Sexuales , Análisis de SupervivenciaRESUMEN
This paper reports a description of the characteristics of the Nephrology and Dialysis department of the Yangzhou Northern Peoples Hospital (Jiangsu province - China) observed by the Author in a two weeks stay. The most outstanding remark is that, in spite of the modern and highly developed structure and information technology of the hospital, the Chinese Health System, an insurance based system, doesnt cover all the care expenses, leaving the remaining cost to be payed by the patients (about 30%). This often induces an empirical method of treatment of nephropathy, because of the lack of a histologic diagnosis and a minimalistic approach for choosing drugs. Another important point is the discontinuity in the follow-up of the disease and the frequent development of uremic complications, especially hyperparathyroidism.
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Unidades de Hemodiálisis en Hospital , Nefrólogos , Nefrología , China , Unidades de Hemodiálisis en Hospital/organización & administración , Unidades de Hemodiálisis en Hospital/estadística & datos numéricos , Unidades Hospitalarias/organización & administración , Unidades Hospitalarias/estadística & datos numéricos , Humanos , Italia , Nefrología/estadística & datos numéricosRESUMEN
In this paper we concentrate on the role of infections in IgA nephropathy both from a pathogenetic and clinic point of view. The current hypotheses as regards the role of infections in the pathogenesis of IgA nephropathy are: (a) role of particular pathogens, (b) chronic exposure to mucosal infections, (c) abnormal handling of commensal microbes (gut microbiota). We also focus on particular infections reported in association with classic IgA nephropathy (HIV, malaria, Chlamydia, Lyme disease), as well as on IgA dominant-infection-associated glomerulonephritis. This is a unique form of glomerulonephritis, where IgA deposition is dominant. It is mostly recognized in old, diabetic patients and in association with staphylococcal infection.
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Glomerulonefritis por IGA/microbiología , Diagnóstico Diferencial , Glomerulonefritis por IGA/diagnóstico , Glomerulonefritis por IGA/fisiopatología , HumanosRESUMEN
BACKGROUND: Tonsillectomy has been considered a treatment for IgA nephropathy (IgAN). It is aimed at removing a source of pathogens, reducing mucosa-associated lymphoid tissue and decreasing polymeric IgA synthesis. However, its beneficial effect is still controversial. In Asia, favorable outcomes have been claimed mostly in association with corticosteroids. In Europe, small, single-center uncontrolled studies have failed to show benefits. METHODS: The European validation study of the Oxford classification of IgAN (VALIGA) collected data from 1,147 patients with IgAN over a follow-up of 4.7 years. We investigated the outcome of progression to end-stage renal disease (ESRD) and/or 50% loss of estimated glomerular filtration rate (eGFR) and the annual loss of eGFR in 61 patients who had had tonsillectomy. RESULTS: Using the propensity score, which is a logistic regression model, we paired 41 patients with tonsillectomy and 41 without tonsillectomy with similar risk of progression (gender, age, race, mean blood pressure, proteinuria, eGFR at renal biopsy, previous treatments and Oxford MEST scores). No significant difference was found in the outcome. Moreover, we performed an additional propensity score pairing 17 patients who underwent tonsillectomy after the diagnosis of IgAN and 51 without tonsillectomy with similar risk of progression at renal biopsy and subsequent treatments. No significant difference was found in changes in proteinuria, or in the renal end point of 50% reduction in GFR and/or ESRD, or in the annual loss of eGFR. CONCLUSION: In the large VALIGA cohort of European subjects with IgAN, no significant correlation was found between tonsillectomy and renal function decline.
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Glomerulonefritis por IGA/cirugía , Tonsilectomía/estadística & datos numéricos , Adulto , Factores de Edad , Estudios de Cohortes , Progresión de la Enfermedad , Etnicidad , Europa (Continente)/epidemiología , Femenino , Estudios de Seguimiento , Tasa de Filtración Glomerular , Humanos , Fallo Renal Crónico/epidemiología , Fallo Renal Crónico/fisiopatología , Masculino , Persona de Mediana Edad , Puntaje de Propensión , Estudios Retrospectivos , Factores Sexuales , Resultado del TratamientoRESUMEN
The Piedmont Group of Clinical Nephrology compared the activity of 15 nephrology centers in Piedmont and Aosta Valley as regards bone protection in patients on corticosteroids therapy. Fracture prevalence shows great variability: in 4/15 centers (27%) no fractures were found, in 6/15 centers (40%) fractures were present in 1-4% of cases, in 1 center in 18% of patients. Clinical risk of fracture was based on sex, age and postmenopausal status in 11/14 of the centers (79%), history of fractures and bone disease in 4/14 centers (27%), smoking and alcohol consumption in 3 and 2 centers respectively, glucocorticoid dose and duration in 4, in children bone age and calcium phosphorus status. Dual energy X-ray absorptiometry was performed in 12 centers based on risk factors, in 8 (57%) DXA was performed during the follow-up, in 4 it was performed after 12 months and in 2 after 2-3 years. DXA is not prescribed in children. Only in one center, risk assessment is based on FRAX. Most of the patients are treated with vitamin D supplementation at a dose of steroids of 5 mg/d (80%). Calcium carbonate is used in 9 centers (60%), in two it is used only in the presence of low ionized calcium or bone mineral density. Bisphosphonates are used following AIFA prescription, in particular alendronate in all centers, risedronate in seven and denosumab in one. The analysis shows the great variability of the clinical and therapeutic approach regarding bone protection in patients on corticosteroids therapy, in Piedmont and Aosta Valley.
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Corticoesteroides/efectos adversos , Fracturas Óseas/inducido químicamente , Fracturas Óseas/prevención & control , Humanos , Encuestas y CuestionariosRESUMEN
Frequency of autoimmune diseases secondary to biologic drugs used in rheumatic disorders (bio-DMARDS) is increasing. Reports of renal diseases is also increasing. The literature reports small series and many case reports of association between the use of a biologic drug and glomerular, vascular or interstitial nephropathies elapsing several months to more than 3 years from the beginning of treatment. Some of the reported glomerular diseases are already known to be possibly associated to the rheumatic disease. Prevention consists in careful clinical, immunologic and renal evaluation before giving bioDMARDS and in careful monitoring. These nephropathies and autoimmune diseases may go into remission just by drug discontinuation, which is mandatory in case of renal, nervous and pulmonary involvement. Corticosteroids or immunsuppressive drugs may be necessary.
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Antirreumáticos/efectos adversos , Productos Biológicos/efectos adversos , Enfermedades Renales/inducido químicamente , HumanosRESUMEN
The benefits of tonsillectomy in IgA nephropathy (IgAN) are still debated. Tonsillectomy may remove pathogen sources and reduce the mucosal associated lymphoid tissue (MALT), limiting degalactosylated IgA1 (deGal-IgA1) production, which is considered to be the initiating pathogenetic event leading to IgA glomerular deposition. In the European network VALIGA, 62/1147 IgAN patients underwent tonsillectomy (TxIgAN). In a cross-sectional study 15 of these patients were tested and compared to 45 non-tonsillectomized IgAN (no-TxIgAN) and healthy controls (HC) regarding levels of deGal-IgA1, and markers of innate immunity and oxidative stress, including toll-like receptors (TLR)2, 3, 4 and 9 mRNAs, proteasome (PS) and immunoproteasome (iPS) mRNAs in peripheral blood mononuclear cells (PBMC), and advanced oxidation protein products (AOPP). Levels of deGal-IgA1 were lower in TxIgAN than in no-TxIgAN (p = 0.015), but higher than in HC (p = 0.003). TLR mRNAs were more expressed in TxIgAN than in HC (TLR4, p = 0.021; TLR9, p = 0.027), and higher in TxIgAN than in no-TxIgAN (p ≤ 0.001 for TLR2, 4, 9). A switch from PS to iPS was detected in PBMC of TxIgAN in comparison to HC and it was higher than in no-TxIgAN [large multifunctional peptidase (LMP)2/ß1, p = 0.039; LPM7/ß5, p < 0.0001]. The levels of AOPP were significantly higher in TxIgAN than HC (p < 0.001) and no-TxIgAN (p = 0.033). In conclusion, the activation of innate immunity via TLRs and ubiquitin-proteasome pathways and the pro-oxidative milieu were not affected by tonsillectomy, even though the levels of aberrantly galactosylated IgA1 were lower in patients with IgAN who had tonsillectomy. The residual hyperactivation of innate immunity in tonsillectomized patients may result from extra-tonsillar MALT.