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Background Autosomal recessive Alport syndrome (ARAS) is caused by pathogenic variants in both alleles of either COL4A3 or COL4A4 genes. Reports on ARAS are rare due to small patient numbers and there are no reports on renin-angiotensin-aldosterone system (RAAS) inhibition therapy in ARAS. Methods Retrospective study in 101 patients with ARAS from Chinese Registry Database of Hereditary Kidney Diseases and European Alport Registry. Genotype-phenotype correlations and nephroprotective effects of RAAS inhibition in ARAS were evaluated. Results Median age was 15 years (range 1.5-46 years). Twelve patients progressed to stage 5 chronic kidney disease (CKD5) at median age 20.5 years. Patients without missense variants had both higher prevalence and earlier onset age of hearing loss, nephrotic-range proteinuria, more rapid decline of eGFR, and earlier onset age of CKD5 compared to patients with 1 or 2 missense variants. Most patients (79/101, 78%) currently are treated with RAAS inhibitors; median age at therapy initiation was 10 years and mean duration 6.5 ± 6.0 years. Median age at CKD5 for untreated patients was 24 years. RAAS inhibition therapy delayed CKD5 onset in those with impaired kidney function (T-III) to median age 35 years, but is undefined in treated patients with proteinuria (T-II) due to low number of events. No treated patients with microalbuminuria (T-I) progressed to CKD5. ARAS patients with 1 or 2 missense variants showed better response to treatment than patients with non-missense-variants. Conclusions Our study provides the first evidence for early use of RAAS inhibition therapy in patients with ARAS. Furthermore, genotype in ARAS correlates with response to therapy in favor of missense variants., Author(s): Yanqin Zhang [sup.1] [sup.2] , Jan Böckhaus [sup.2] , Fang Wang [sup.1] , Suxia Wang [sup.3] , Diana Rubel [sup.2] , Oliver Gross [sup.2] , Jie Ding [sup.1] Author [...]

Calcium oxalate (CaOx) crystal deposition in acute kidney injury (AKI) patients is under recognized but impacts renal outcomes. This study investigates its determinants and effects. We studied 814 AKI patients with native kidney biopsies from 2011 to 2020, identifying CaOx crystal deposition severity (mild: <5, moderate: 5–10, severe: >10 crystals per section). We assessed factors like urinary oxalate, citrate, urate, electrolytes, pH, tubular calcification index, and SLC26A6 expression, comparing them with creatinine-matched AKI controls without oxalosis. We analyzed how these factors relate to CaOx severity and their impact on renal recovery (eGFR < 15 mL/min/1.73 m2 at 3-month follow-up). CaOx crystal deposition was found in 3.9% of the AKI cohort (32 cases), with 72% due to nephrotoxic medication-induced tubulointerstitial nephritis. Diuretic use, higher urinary oxalate-to-citrate ratio induced by hypocitraturia, and tubular calcification index were significant contributors to moderate and/or severe CaOx deposition. Poor baseline renal function, low urinary chloride, high uric acid and urea nitrogen, tubular SLC26A6 overexpression, and glomerular sclerosis were also associated with moderate-to-severe CaOx deposition. Kidney recovery was delayed, with 43.8%, 31.2%, and 18.8% of patients having eGFR < 15 mL/min/1.73 m2 at 4, 12, and 24-week post-injury. Poor outcomes were linked to high urinary α1-microglobulin-to-creatinine (α1-MG/C) ratios and active tubular injury scores. Univariate analysis showed a strong link between this ratio and poor renal outcomes, independent of oxalosis severity. In AKI, CaOx deposition is common despite declining GFR. Factors worsening tubular injury, not just oxalate-to-citrate ratios, are key to understanding impaired renal recovery. [ABSTRACT FROM AUTHOR]

Objective To analyze the correlation between thrombus composition and the prognosis of patients with acute cerebral infarction after mechanical thrombectomy. Methods This retrospective analysis was conducted among 48 patients with the diagnosis of acute ischemic stroke, who were eligible for mechanical thrombectomy as assessed by the first aid group and successfully underwent the surgery between June, 2015 and February, 2019. The clinical data were collected from the patients including TOAST(trail of org 10172 in acute stroke treatment) classification, thrombus position, number of stents placed, recanalization time, thrombolysis in cerebral infarction (TICI) grading and the use of recombinant tissue plasminogen activator (rt-PA) for intravenous thrombolysis. The patients were followed up and the modified Rankin scale (mRS) score at 3 months after the surgery was recorded. The composition of the retrieved thrombus was examined using HE staining, and the correlation between thrombus composition and the patients' outcomes was analyzed. Results Of the 48 patients included, 24 were diagnosed to have cardioembolic stroke, 16 had large artery atherosclerotic stroke, and 8 had stroke with unknown etiology. A significant difference was found in fibrin and platelet contents between the cardiogenic thrombi and atherosclerotic thrombi. Fibrin-rich thrombi were found in 35 patients, and erythrocyte-rich thrombi were found in 13 patients; the percentage of favorable mRS scores at the end of the third month after the surgery was significantly lower in the former patients than in the latter patients (26% vs 62%, P < 0.05). During mechanical thrombectomy, the recanalization time was significantly shorter in patients receiving intravenous thrombolysis with rt-PA than in those without the use of rt-PA (90±47.6 vs 131.6 ± 57.5 min, P < 0.05). Conclusion In patients with acute ischemic stroke undergoing mechanical thrombectomy, high fibrin and platelet contents in the thrombus are associated with a poor prognosis, and intravenous thrombolysis with rt-PA is associated with a shortened recanalization time during mechanical thrombectomy.

Background The prognostic value and response to immunosuppressive therapy (IST) of patients with crescents in the different backgrounds of pathological presentations in immunoglobulin A nephropathy (IgAN) is unclear. Methods A total of 1262 IgAN patients were enrolled. Crescents (C, 0/1/2), fibrinoid necrosis (FN, 0/1) and endocapillary hypercellularity (E, 0/1) were integrated into different degrees of glomerular activity (0–4 points): mild (0), moderate (1–2) and severe (≥3). The effect of IST on patients with different glomerular activity scores and chronic tubular and interstitial lesions (T, 0/1/2) were analysed using Cox regression analysis. The kidney outcome was defined as an estimated glomerular filtration rate decrease ≥30% or end-stage kidney disease. Results C2 was an independent risk factor for kidney outcomes {overall cohort: hazard ratio [HR] 1.85 [95% confidence interval (CI) 1.03–3.31], P  = .040; T0 patients: HR 6.52 [95% CI 2.92–14.54], P  < .001; reference to C0} in those without IST, while the HR decreased to 0.83 (95% CI 0.54–1.27; P  = .396) in the overall cohort and 2.39 (95% CI 1.00–5.67; P  = .049) in T0 patients with IST. For patients with severe glomerular activity, IST decreased the risk of kidney outcomes by 70% in the overall cohort [HR 0.30 (95% CI 0.12–0.74), P  = .009; reference to those without IST] and 86% in T0 patients [HR 0.14 (95% CI 0.04–0.54), P  = 0.005; reference to those without IST]. Conclusions IST could reduce the risk for kidney outcomes in IgAN patients with C2 and T0 lesions together, as well as in those with crescents and at least one other active lesion, including FN and E1 lesions. [ABSTRACT FROM AUTHOR]