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BACKGROUND: The role of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in the management glomerular/systemic autoimmune diseases with proteinuria in real-world clinical settings is unclear. METHODS: This is a retrospective, observational, international cohort study. Adult patients with biopsy-proven glomerular diseases were included. The main outcome was the percentage reduction in 24-h proteinuria from SGLT2i initiation to 3, 6, 9 and 12 months. Secondary outcomes included percentage change in estimated glomerular filtration rate (eGFR), proteinuria reduction by type of disease and reduction of proteinuria ≥30% from SGLT2i initiation. RESULTS: Four-hundred and ninety-three patients with a median age of 55 years and background therapy with renin-angiotensin system blockers were included. Proteinuria from baseline changed by -35%, -41%, -45% and -48% at 3, 6, 9 and 12 months after SGLT2i initiation, while eGFR changed by -6%, -3%, -8% and -10.5% at 3, 6, 9 and 12 months, respectively. Results were similar irrespective of the underlying disease. A correlation was found between body mass index (BMI) and percentage proteinuria reduction at last follow-up. By mixed-effects logistic regression model, serum albumin at SGLT2i initiation emerged as a predictor of ≥30% proteinuria reduction (odds ratio for albumin <3.5 g/dL, 0.53; 95% CI 0.30-0.91; P = .02). A slower eGFR decline was observed in patients achieving a ≥30% proteinuria reduction: -3.7 versus -5.3 mL/min/1.73 m2/year (P = .001). The overall tolerance to SGLT2i was good. CONCLUSIONS: The use of SGLT2i was associated with a significant reduction of proteinuria. This percentage change is greater in patients with higher BMI. Higher serum albumin at SGLT2i onset is associated with higher probability of achieving a ≥30% proteinuria reduction.
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Diabetes Mellitus Tipo 2 , Glomerulonefrite , Nefropatias , Adulto , Humanos , Pessoa de Meia-Idade , Estudos de Coortes , Nefropatias/complicações , Glomerulonefrite/tratamento farmacológico , Glomerulonefrite/complicações , Proteinúria/etiologia , Proteinúria/complicações , Albumina Sérica , Sódio , Glucose , Diabetes Mellitus Tipo 2/complicaçõesRESUMO
Background: Genetic causes are increasingly recognized in patients with focal segmental glomerulosclerosis (FSGS), but it remains unclear which patients should undergo genetic study. Our objective was to determine the frequency and distribution of genetic variants in steroid-resistant nephrotic syndrome FSGS (SRNS-FSGS) and in FSGS of undetermined cause (FSGS-UC). Methods: We performed targeted exome sequencing of 84 genes associated with glomerulopathy in patients with adult-onset SRNS-FSGS or FSGS-UC after ruling out secondary causes. Results: Seventy-six patients met the study criteria; 24 presented with SRNS-FSGS and 52 with FSGS-UC. We detected FSGS-related disease-causing variants in 27/76 patients (35.5%). There were no differences between genetic and non-genetic causes in age, proteinuria, glomerular filtration rate, serum albumin, body mass index, hypertension, diabetes or family history. Hematuria was more prevalent among patients with genetic causes. We found 19 pathogenic variants in COL4A3-5 genes in 16 (29.3%) patients. NPHS2 mutations were identified in 6 (16.2%) patients. The remaining cases had variants affecting INF2, OCRL, ACTN4 genes or APOL1 high-risk alleles. FSGS-related genetic variants were more common in SRNS-FSGS than in FSGS-UC (41.7% vs 32.7%). Four SRNS-FSGS patients presented with NPHS2 disease-causing variants. COL4A variants were the most prevalent finding in FSGS-UC patients, with 12 patients carrying disease-causing variants in these genes. Conclusions: FSGS-related variants were detected in a substantial number of patients with SRNS-FSGS or FSGS-UC, regardless of age of onset of disease or the patient's family history. In our experience, genetic testing should be performed in routine clinical practice for the diagnosis of this group of patients.
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A cyclical corticosteroid-cyclophosphamide regimen is recommended for patients with primary membranous nephropathy at high risk of progression. We hypothesized that sequential therapy with tacrolimus and rituximab is superior to cyclical alternating treatment with corticosteroids and cyclophosphamide in inducing persistent remission in these patients. This was tested in a randomized, open-label controlled trial of 86 patients with primary membranous nephropathy and persistent nephrotic syndrome after six-months observation and assigned 43 each to receive six-month cyclical treatment with corticosteroid and cyclophosphamide or sequential treatment with tacrolimus (full-dose for six months and tapering for another three months) and rituximab (one gram at month six). The primary outcome was complete or partial remission of nephrotic syndrome at 24 months. This composite outcome occurred in 36 patients (83.7%) in the corticosteroid-cyclophosphamide group and in 25 patients (58.1%) in the tacrolimus-rituximab group (relative risk 1.44; 95% confidence interval 1.08 to 1.92). Complete remission at 24 months occurred in 26 patients (60%) in the corticosteroid-cyclophosphamide group and in 11 patients (26%) in the tacrolimus-rituximab group (2.36; 1.34 to 4.16). Anti-PLA2R titers showed a significant decrease in both groups but the proportion of anti-PLA2R-positive patients who achieved immunological response (depletion of anti-PLA2R antibodies) was significantly higher at three and six months in the corticosteroid-cyclophosphamide group (77% and 92%, respectively), as compared to the tacrolimus-rituximab group (45% and 70%, respectively). Relapses occurred in one patient in the corticosteroid-cyclophosphamide group, and three patients in the tacrolimus-rituximab group. Serious adverse events were similar in both groups. Thus, treatment with corticosteroid-cyclophosphamide induced remission in a significantly greater number of patients with primary membranous nephropathy than tacrolimus-rituximab.
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Glomerulonefrite Membranosa , Tacrolimo , Corticosteroides/efeitos adversos , Ciclofosfamida/efeitos adversos , Glomerulonefrite Membranosa/tratamento farmacológico , Humanos , Imunossupressores/efeitos adversos , Rituximab/efeitos adversos , Tacrolimo/efeitos adversos , Resultado do TratamentoRESUMO
OBJECTIVES: We investigated the impact of acute kidney failure after a heart valve procedure among patients with or without chronic kidney disease (CKD). METHODS: All patients who had undergone a surgical valve procedure between 2005 and 2017 at our institution were divided into 2 groups depending on whether they had previous history of CKD (estimated glomerular filtration rate <60 ml/min/1.73 m2) or not. Homogeneous groups were obtained by propensity score matching. Long-term mortality was compared between the 2 groups and according to the occurrence of postoperative acute kidney failure. Level of significance was set at P-value <0.008 for multiple comparison tests. RESULTS: From the 3907 patients included to this study, 1476 (37.78%) had previous history of CKD. After adjusting for propensity score 1:1, patients with preoperative impaired renal function were at a higher risk of acute kidney failure (26.83% vs 10.16%, P < 0.001) and postoperative mortality (8.48% vs 5.17%, P = 0.001). In the follow-up, they had a poorer survival at 1, 5 and 10 years as compared to patients with normal renal function (88% vs 91.95%, 78.29% vs 81.11% and 56.13% vs 66.29%, respectively; P < 0.001). Patients without postoperative kidney failure had similar survival whether they had preoperative CKD or not [hazard ratio (HR) 1.16, 99.2% confidence interval (CI) 0.87-2.52; P = 0.142]. As compared to patients with postoperative preserved renal function, those with postoperative kidney failure had a higher long-term mortality either if they had previous kidney disease or not [(HR 2.18, 99.2% CI 1.75-2.72; P < 0.001) and (HR 1.48, 99.2% CI 1.33-1.65; P < 0.001), respectively]. Preoperative CKD was the strongest predictor of acute kidney failure (odds ratio 4.45; 95% CI 3.59-5.53; P < 0.001). CONCLUSIONS: Patients with CKD are at higher risk of postoperative adverse events and have poorer long-term outcomes. Postoperative acute kidney failure increases long-term mortality.