IgA Nephropathy (IgAN) is the most prevalent glomerular disease worldwide. Complement system activation is crucial in its pathogenesis. Few studies correlated serum C3 and C4 with disease activity and prognosis. This retrospective study investigated the prognostic value of serum complement at the time of diagnosis in patients with IgAN. Specifically we evaluated whether adding serum C3 and C4 levels to established predictive models-one based on variables related to chronic kidney disease (CKD) progression and another incorporating variables from the International IgA Prediction Tool (IntIgAPT)-enhances the accuracy of outcome prediction. A composite renal outcome was defined as 50% decline in eGFR or onset of kidney failure. 101 patients were stratified according to baseline C3 levels in three groups (Low, Medium and High). During a median follow-up of 54 months, the Low group exhibited higher incidence of primary outcome (16.3 events vs 2.9 and 1.7 events × 100 pts/year, p = 0.0026). Model-1 (M1), consisting of CKD progression variables, and Model-3 (M3), comprising IntIgANPT variables, were implemented with baseline C3 and C4 to create Model-2 (M2) and Model-4 (M4), respectively. M2 demonstrated better predictive performance over M1, showing higher discrimination (lower AIC and BIC, higher C-index and NR2). Similarly, M4 outperformed M3, showing enhanced outcome prediction when C3 and C4 levels were added. Implementation of serum C3 and C4 can enhance prediction accuracy of already-validated prognostic models in IgAN. Lower C3 and higher C4 levels were associated with poorer prognosis, highlighting a more 'Complement-Pathic' subset of patients.

This real-world analysis evaluated the clinical and economic burden of non-dialysis-dependent CKD patients with and without secondary hyperparathyroidism (sHPT) in Italy. An observational retrospective study was conducted using administrative databases containing a pool of healthcare entities covering 2.45 million health-assisted individuals. Adult patients with hospitalization discharge diagnoses for CKD stages 3, 4, and 5 were included from 1 January 2012 to 31 March 2015 and stratified using the presence/absence of sHPT. Of the 5710 patients, 3119 were CKD-only (62%) and 1915 were CKD + sHPT (38%). The groups were balanced using Propensity Score Matching (PSM). Kaplan-Meier curves revealed that progression to dialysis and cumulative mortality had a higher incidence in the CKD + sHPT versus CKD-only group in CKD stage 3 patients and the overall population. The total direct healthcare costs/patient at one-year follow-up were significantly higher in CKD + sHPT versus CKD-only patients (EUR 8593 vs. EUR 5671, p < 0.001), mostly burdened by expenses for drugs (EUR 2250 vs. EUR 1537, p < 0.001), hospitalizations (EUR 4628 vs. EUR 3479, p < 0.001), and outpatient services (EUR 1715 vs. EUR 654, p < 0.001). These findings suggest that sHPT, even at an early CKD stage, results in faster progression to dialysis, increased mortality, and higher healthcare expenditures, thus indicating that timely intervention can ameliorate the management of CKD patients affected by sHPT.

Introduction: Kidney transplantation is the preferred treatment for end-stage kidney disease (ESKD), enhancing survival and quality of life. However, kidney transplant recipients (KTRs) are at high risk for bone disorders, particularly low bone turnover disease, which increases fracture risk. Teriparatide, an anabolic agent, may provide a beneficial treatment option for these patients. Materials and methods: This single-center, retrospective observational study involved 18 KTRs with osteoporosis, low bone turnover, and a history of vertebral or non-vertebral fractures. Patients received teriparatide (20 μg/day) for up to 2 years. Areal bone mineral density (aBMD) at the lumbar spine (LS), total hip (TH), femoral neck (FN), and trabecular bone score (TBS) were measured at baseline, 1 year, and 2 years. In addition, bone turnover markers (BTMs), serum calcium, phosphorus, parathyroid hormone (PTH), and kidney function were monitored. Results: Significant increases in LS aBMD were observed after 1 year (0.941 ± 0.152 vs 1.043 ± 0.165, p = 0.04) and maintained after 2 years compared to baseline (0.941 ± 0.152 vs 1.074 ± 0.154, p = 0.03). TH aBMD significantly increased after 2 years (0.753 ± 0.145 vs 0.864 ± 0.141, p = 0.04), while FN and TBS showed non-significant improvement. Teriparatide was well-tolerated, with mild and transient hypercalcemia and hypophosphatemia. Conclusion: Teriparatide significantly improved BMD at the LS and TH in KTRs with osteoporosis and low bone turnover, showing a favorable safety profile.

Introduction: Proteinuria is a major risk factor for the progression of chronic kidney disease (CKD). Sodium-glucose cotransporter 2 inhibitors (SGLT2i) demonstrated a nephroprotective and antiproteinuric effect in people with type 2 diabetes (T2DM) and proteinuric CKD. We conducted a retrospective study to evaluate clinical and laboratory variables that can help predict proteinuria reduction with SGLT2i therapy. Materials and methods: Patients affected by T2DM and CKD who started any SGLT2i were included in the study. Patients were stratified into two subgroups, Responder (R) and non-Responder (nR), based upon the response to the therapy with SGLT2i, namely the reduction in a 24 h urine proteins test (uProt) of ≥30% from baseline levels. The aim of the study is to analyse differences in baseline characteristics between the two groups and to investigate the relationship between them and the proteinuria reduction. A Kruskal–Wallis test, unpaired t-test and Chi² test were used to test the difference in means and the percentage (%) between the two groups. Linear and logistic regressions were utilized to analyse the relationship between proteinuria reduction and basal characteristics. Results: A total of 58 patients were enrolled in the study: 32 patients (55.1%) were in the R group and 26 patients (44.9%) in the nR group. R’s patients had a significant higher uProt at baseline (1393 vs. 449 mg/24 h, p = 0.010). There was a significant correlation between baseline uProt and proteinuria reduction with SGLT2i in both univariate (β = −0.43, CI −0.55 to −031; p < 0.001) and multivariate analyses (β = −0.46, CI −0.57 to −0.35, p < 0.001). In the multivariate analysis, there was a significant positive correlation between the estimated glomerular filtration rate (eGFR) and proteinuria reduction (β = −17, CI −31 to −3.3, p = 0.016) and a significant negative correlation with body mass index (BMI) (β = 81, CI 13 to 50, p = 0.021). The multivariate logistic regressions show a positive correlation of being in the R group with diabetic retinopathy at baseline (Odds Ratio (OR) 3.65, CI 0.97 to 13.58, p = 0.054), while the presence of cardiovascular disease (CVD) at baseline is associated with being in the nR group (OR 0.34, CI 0.09 to 1.22, p = 0.1), even if these statements did not reach statistical significance. Conclusions: In this real-life experience, following the administration of SGLT2i, a reduction of more than 30% in proteinuria was observed in more than half of the patients, and these patients had a significantly higher baseline proteinuria value. Variables such as eGFR and BMI are variables that, considered in conjunction with proteinuria, can help predict treatment response before therapy initiation. Different phenotypes of diabetic kidney disease may have an impact on the antiproteinuric response.

Chronic-active antibody mediated rejection (caAMR) is the leading causes of long-term kidney graft failure. Tocilizumab (TCZ), an anti-IL-6 receptor antibody, has been suggested as a treatment, but data are conflicting. We retrospectively studied consecutive adult kidney transplant recipients with caAMR or microvascular inflammation (MVI) without Donor-Specific Antibodies (DSA) and without C4d deposition (MVI + DSA-C4d-), who received TCZ as first-line therapy in two European centers. Estimated glomerular filtration rate (eGFR) and DSA were assessed one-year before and after TCZ initiation. The study included 64 patients who received TCZ between July 2018 and September 2023. The eGFR trajectory significantly decreased after TCZ treatment (−1.2 ± 0.2 vs. 0.03 ± 0.2 mL/min/1.73 m²/month pre- vs. post-TCZ, respectively; p = 0.001). The percentage of patients with DSA decreased from 63.9% to 38.9% (p < 0.001), and the average MFI decreased from 9,537 to 7,250 (p = 0.001). In multivariate analysis, younger age (OR = 0.95, p = 0.02), MVI + DSA-C4d- phenotype (OR = 5.2, p = 0.01), and lower chronic glomerulopathy score (OR = 4.5, p = 0.02) were associated with TCZ response (trajectory ≥0 after TCZ). Patient survival was 98.4%, and graft survival was 93.7% at one-year. First-line TCZ therapy for caAMR or MVI + DSA-C4d- is associated with an improvement of eGFR trajectories, reduced DSA numbers and MFI and histological inflammation in glomeruli. These data suggest a potential benefit of TCZ in these settings.

Diabetic kidney disease (DKD) is a major cause of morbidity and mortality in individuals with type 2 diabetes mellitus (T2DM). The aim of this study was to investigate whether albumin structural alterations correlate with DKD severity and evaluate whether native and reduced albumin concentrations could complement the diagnosis of DKD. To this end, one hundred and seventeen T2DM patients without (n = 42) and with (n = 75) DKD (DKD I-III upon KDIGO classification) were evaluated; the total albumin concentration (tHA) was quantified by a bromocresol green assay, while structural alterations were profiled via liquid chromatography–high-resolution mass spectrometry (LC-HRMS). The concentrations of native albumin (eHA, effective albumin) and reduced albumin (rHA) were subsequently assessed. The HRMS analyses revealed a reduced relative amount of native albumin in DKD patients along with an increased abundance of altered forms, especially those bearing oxidative modifications. Accordingly, both eHA and rHA values varied during the stages of progressive renal failure, and these alterations were dose-dependently correlated with renal dysfunction. A ROC curve analysis revealed a significantly greater sensitivity and specificity of eHA and rHA than of tHA for diagnosing DKD. Importantly, according to the multivariate logistic regression analysis, the eHA was identified as an independent predictor of DKD.