Objective: to characterize the clinical, laboratory, and histopathological features of patients with lupus nephritis (LN) and identify factors associated with renal response after 12 months of treatment. Materials and methods : This single-center retrospective cohort study included adult patients with systemic lupus erythematosus (SLE) and biopsy-proven LN. Renal response was assessed according to the KDIGO 2024 guidelines. Ordinal logistic regression was used to identify factors associated with the level of renal response (no response, partial response, complete response) at 12 months. Results: A total of 54 patients with biopsy-proven LN and sufficient follow-up after kidney biopsy were included in the 12-month renal response analysis. Most patients were women (85%). The median age at the onset of kidney involvement was 29 [22-39] years. Proliferative LN (classes III to IV-V) was identified in 72% of patients. Median baseline proteinuria was 3.4 (1.6-4.0) g/day. A complete renal response was achieved in 38% of patients at 6 months and in 48% at 12 months. At 12 months, an additional 30% of patients had achieved a partial renal response, whereas 22% had no response. Mycophenolate mofetil–based regimens were associated with greater odds of achieving a better renal response (OR 3.08; 95% CI 1.10-8.96; p=0.03). Hydroxychloroquine use was also associated with a greater likelihood of renal response (OR 3.60; 95% CI 1.08-12.70; p=0.04). In the multivariable model, combined class III+V LN was independently associated with a better of renal response (OR 16.69; 95% CI 2.17-381.19; p=0.02), whereas a low baseline eGFR (<30 mL/min/1.73 m 2 ) was associated with a lower likelihood of response (OR 0.09; 95% CI 0.01-0.42; p<0.01) Conclusions: Baseline kidney function and the histopathological class of LN are key factors associated with treatment response.
Objective . The present study aimed to compare key demographic and clinical parameters with morphological features defined by the Oxford MEST-C classification, supplemented by additional quantitative assessment, in order to identify the principal clinico-morphological phenotypes of IgA nephropathy (IgAN). Materials and Methods . This retrospective study included 2,679 patients with biopsy-proven IgAN. The mean age was 35.3±13 years. Clinical and laboratory variables (degree of hematuria, 24-hour proteinuria, and serum creatinine) were assessed at the time of biopsy. Morphological evaluation comprised Oxford MESTC scoring, quantitative assessment of of interstitial fibrosis/tubular atrophy (IFTA), global and segmental glomerulosclerosis, cellular/fibrocellular and fibrous crescents. Results . At the time of biopsy, median proteinuria was 2.1 g/day (IQR: 0.75-3.0), estimated glomerular filtration rate (eGFR) was 60.4 mL/min (IQR: 33.3-84.16). Hematuria was detected in 88% of patients. The distribution of Oxford MEST-C lesions was as follows: M1, 37%; E1, 21%; S, 73%; T1, 37%; T2, 16%; C1, 16.5%; C2, 2.5%. The severity of proteinuria correlated with E and C lesions, as well as the extent of IFTA and both global and segmental glomerulosclerosis. Correlation coefficients were higher when lesions C and S were quantified (% involvement): 0.17 vs 0.24 and 0.07 vs 0.23, respectively. Decline in eGFR were associated with the degree of IFTA and the presence of crescents. Based on clinicopathological correlations and morphological profiling, three distinct phenotypes of IgAN, likely reflecting different dominant mechanisms of disease progression, were identified: Phenotype 1: (Typical): Defined by mesangial proliferation and segmental glomerulosclerosis. Clinically characterized by persistent microhematuria, gradually increasing proteinuria, and arterial hypertension. Phenotype 2: (Aggressive): Defined by endocapillary hypercellularity with or without crescents. Clinically associated with acute nephritic syndrome, marked proteinuria – often at nephrotic range – and hematuria. Phenotype 3: (Macrohematuric): Defined by focal necrosis of capillary loops and crescent formation in the absence of endocapillary hypercellularity. Clinically manifests with episodes of macroscopic hematuria; during remission, urinary abnormalities are typically absent and renal function remains preserved. Conclusion . Identification of clinicopathological phenotypes in IgAN represents a promising strategy for personalizing therapy and refining prognostic assessment, thereby improving risk stratification for disease progression.
Background : the catabolism of aromatic amino acids is closely linked to the immune response. Their metabolites act as molecular messengers, facilitating communication between the microbiome and the immune system. Selected studies suggested that the pathogenesis of immunoglobulin A nephropathy (IgAN) may be associated with alterations in tryptophan (Trp) metabolic pathways. Aim : to test the hypothesis about probable changes in Trp metabolism in IgAN using untargeted and targeted metabolomics analyses. Materials and methods : the cohort study included 113 patients with a clinical and morphological diagnosis of primary IgAN, comprised two subgroups: with an active/progressive process who did not receive treatment (IgAN-A, n=85); with inactive IgAN/remission (IgAN-R, n=28). Control groups included healthy volunteers without kidney disease (K1, n=31) and patients with non-inflammatory glomerulopathies (K2, n=33). Untargeted and targeted metabolomics studies of serum were performed using high-resolution high-performance liquid chromatography with mass spectrometric detection (HPLC-MS) in positive and negative ionisation mode. Intergroup differences in Trp metabolites were assessed, and their associations with clinical parameters were analysed. Results : untargeted analysis of mass spectrometric data revealed that tryptophan synthesis and metabolism were enriched among other metabolic pathways in patients with IgAN. Significant differences were found in kynurenic acid (KynA), kynurenine (Kyn), 5-hydroxytryptophan (HTrp), 3-hydroxyanthranilic acid, tryptamine, and indole-3-lactic acid (ILA), suggesting alterations in the serotonin, kynurenine, and indole metabolic pathways. Targeted analyses showed that Trp and its metabolites’ levels differed significantly in patients with IgAN (overall group, n=113) compared to healthy controls. Compared with the IgA-R subgroup, subjects with IgAN-A had higher levels of KynA:Kyn, Kyn:Trp, KynA:Trp, and HTrp:Trp ratios, alongside decreased tryptophan and indoxyacetic acid (IAA). In the IgAN-A group, diverse associations of Trp and its metabolites with clinical parameters were revealed. Except for Trp and indole acetate, metabolites of the Trp pathway were negatively correlated with estimated glomerular filtration rate (eGFR), blood pressure, and age. Tryptophan and indole acetate had negative associations with proteinuria and positive associations with serum albumin levels. Tryptophan and IAA concentrations were inversely associated with proteinuria and directly with serum albumin levels; the associations of these clinical indicators and the ratios of HTrp, Kyn, KynA, NA and ILA to tryptophan were opposite. Conclusions : In IgAN patients, apparent alterations in tryptophan metabolic pathways are associated with clinical parameters and may contribute to the pathogenesis of the disease.
