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Human immunodeficiency virus (HIV) is no longer considered a contraindication for kidney transplantation (KT). KT management in HIV patients is a complex process with challenges, such as drug interactions between immunosuppression and antiretroviral (ARV) therapy. In our country, no KT has been performed thus far in this category of patients.

Perioperative acid-base disturbance could be informative regarding the possible slow graft function (SGF) or delayed graft function (DGF) development. There is a lack of data regarding the relationship between perioperative acid-base parameters and graft dysfunction in kidney transplant (KT) recipients. We aim to determine the incidence of graft dysfunction types and the association between them and acid-base parameters.

The evidence regarding thrombotic microangiopathy (TMA) related to Coronavirus Infectious Disease 2019 (COVID-19) in patients with complement gene mutations as a cause of acute kidney injury (AKI) are limited. We presented the case of a 23-year-old male patient admitted with an asymptomatic form of COVID-19, but with uncontrolled hypertension and AKI. Kidney biopsy showed severe lesions of TMA. In evolution patient had persistent microangiopathic hemolytic anemia, decreased level of haptoglobin and increased LDH level. Decreased complement C3 level and the presence of schistocytes were found for the first time after biopsy. Kidney function progressively decreased and the patient remained hemodialysis dependent. Complement work-up showed a heterozygous variant with unknown significance in complement factor I (CFI) c.-13G>A, affecting the 5’ UTR region of the gene. In addition, the patient was found to be heterozygous for the complement factor H (CFH) H3 haplotype (involving the rare alleles of c.-331C>T, Q672Q and E936D polymorphisms) reported as a risk factor of atypical hemolytic uremic syndrome. This case of AKI associated with severe TMA and secondary hemolytic uremic syndrome highlights the importance of genetic risk modifiers in the alternative pathway dysregulation of the complement in the setting of COVID-19, even in asymptomatic forms.

Introduction and Objectives. In the era of increased need for kidney allografts, it is essential to identify predictors of graft dysfunction after kidney transplantation. Delayed graft function (DGF) is the most common form of acute kidney injury diagnosed in the first week following kidney transplantation that is frequently associated with a negative impact on short-term and long-term allograft function. This study aimed to determine the risk factors influencing DGF after deceased donor kidney transplantation in our center. Materials and Methods. In this prospective study we enrolled 116 recipients of kidney grafts transplanted from deceased donors between January and December 2014 in the Center of Uronephrology and Renal Transplantation, Fundeni Clinical Institute. Our kidney transplant center team consisted of experts in transplant surgery, nephrology and anesthesiology was involved in all steps of transplantation. The endpoint of our study was DGF which was defined as the need for dialysis within the first 7 days after kidney transplantation. Results. Incidence of DGF was 12.9%. Recipient cardiac heart failure (CHF) was the only independent risk factor for DGF. Moreover, by multivariate analysis, CHF significantly increased the risk of DGF by 7.4 times (OR=7.39; 95% CI 1.57- 34.63, p=0.01). Recipient weight and cold ischemia time > 12 h presented a statistical trend of association with DGF. Conclusions. In our study, recipient weight and recipient CHF were the most important risk factor associated with DGF, highlighting the importance of recipient characteristics for a successful kidney transplant. Moreover, prolonged CIT presented a trend association with DGF, underlining the importance of logistic period until reimplantation. [ABSTRACT FROM AUTHOR]

Introduction and Objectives. Tuberous sclerosis complex (TSC) is a rare autosomal dominant disease with multisystemic involvement. Renal angiomyolipomas (AMLs) affect up to 80% of TSC patients and AML hemorrhage risk increases with size. Everolimus (EVE) is a mTOR inhibitor and is the only approved drug for managing renal AMLs in the adult population. We studied a series of TSC patients who received EVE therapy to evaluate its renal efficiency and safety. Materials and Methods. 18 patients with TSC and renal AML were enrolled, and they received 10 mg Everolimus daily. AML measurements were performed yearly, by using either computed tomography (CT) or magnetic resonance imaging (MRI). The largest baseline diameter of the biggest renal tumor was compared with the subsequent measurements. Clinical examination was performed, and biological parameters were systematically evaluated. Results. Of the total of 17 patients who underwent efficiency assessment, 16 (94.1%) responded to EVE by renal tumor shrinkage. A significant AML reduction was observed after 12 months of treatment, from a mean of 74.5 mm to 57.3 mm (23% reduction). The primary endpoint (AML’s diameter shrinkage ≥ 25% from baseline) was attained by 8 (47%) patients. In the aspect of adverse events (AE), no treatment interruptions were necessary due to intolerance. The most frequent AE was dyslipidemia, affecting 14 patients (82.3%), followed by anemia in 10 patients (58.8%). Proteinuria was the most common renal AE, which was managed by temporarily lowering the EVE dose. There were no AML-related hemorrhage and no local interventions were necessary. Conclusions. In our experience, EVE is an efficient and well tolerated treatment for adult TSC patients and associated AML. The most important positive result observed was no new bleeding episodes, which improves both renal and general outcomes. [ABSTRACT FROM AUTHOR]

Introduction and Objectives. Cystatin C is a reliable, alternative marker to creatinine in estimating glomerular filtration rate in patients with chronic kidney disease (CKD), even in those with kidney transplant. Also, cystatin C tends to be superior to serum creatinine in evaluating early stages of CKD in kidney recipients, which is critical to early detection of acute rejection. The aim of our study was to evaluate the correlation of serum cystatin C measured after transplantation with demographical, biological parameters and organ preservation time. Materials and methods. We performed a prospective observational study on 44 consecutive kidney transplant recipients, followed for 3 months after transplantation. Graft kidney function was evaluated with both serum creatinine and cystatin C and was estimated with CKD-EPI and Cystatin C formula. Cystatin C was analyzed on a latex enhanced immunoturbidimetric assay. Results. We found that cystatin C levels measured first time post-transplant was correlated with recipient age (r=0.39, p=0.008), cold ischemia time (r=0.56, p< 0.001) and warm ischemia time (r=0.35, p= 0.01). Results evaluated at 3 months after transplantation showed that serum cystatin C was also correlated with recipient age (r=0.36, p=0.001) and cold ischemia time (r=0.32, p=0.003) and more than that, with pretransplant recipient weight (r=0.34, p=0.002), tryglicerides and haemoglobin levels (r=0.40, p= 0.008 and r= -0.36, p=0.01). Conclusions. We showed that serum cystatin C measured early after kidney transplantation is correlated with demographic, biological parameters and ischemia times, in kidney transplant recipients. [ABSTRACT FROM AUTHOR]

Introduction and Objectives. Despite refinements in the initial evaluation and management of patients with newly diagnosed localized high-risk prostate cancer, urologist have difficulties to counsel their patients based upon currently used pretreatment parameters. In this study, we investigate preoperative characteristics that can predict unfavorable pathological outcome in patients undergoing radical prostatectomy for clinically localized high-risk prostate cancer. Materials and Methods. We analyzed a database of 279 patients diagnosed with prostate cancer and treated with radical prostatectomy in our institute between 2014 and 2017 and identified 83 patients with high-risk characteristics because of PSA > 20 ng/ml or biopsy Gleason score ³ 8. The following postsurgical parameters were considered unfavorable pathological outcome: seminal vesicle invasion, surgical margins, perineural invasion and lymph node invasion. To identify the determinants associated with unfavorable pathologic outcomes, we performed univariate and multivariate logistic regression in two models. Results. 77.1% of patients (n=64) had unfavorable pathological outcome. In multivariate analysis, we pointed out that PSA > 20 ng/ml was an independent determinant associated with lymph node invasion ( OR: 3.7, 95 % CI: 1.02- 14.36, p=0.04), biopsy Gleason score ≥ 8 was independently associated with increased risk of perineural invasion ( OR: 6.04, 95% CI: 1.09-33.31, p=0.03) and PSA > 20 ng/ml and biopsy Gleason score ≥ 8 were independent high risk factors for seminal vesicle invasion (OR: 11.10, 95% CI: 1.30-98.44, p=0.02; OR: 11.45, 95% CI: 1.28-102, p=0.02, respectively). Moreover, in the second model, we showed that Gleason score pattern 5 increased the risk of lymph node invasion by 3.21 (OR: 3.21, 95% CI: 1.03-9.99, p=0.04). Conclusions. Newly diagnosed patients with PSA > 20 ng/ml or biopsy Gleason score≥ 8 are at increased risk of more extensive disease. Our data is important for urologist in the selection of patients with high risk characteristics proposed for radical prostatectomy and for patients to better understand their disease. [ABSTRACT FROM AUTHOR]

Introduction and Objectives. Cystatin C could be used as a reliable alternative marker to creatinine in estimating glomerular filtration rate (GFR), even in kidney transplant recipients. The aim of our study was to evaluate the clinical and biological determinants of glomerular filtration rate estimated with cystatin C (CysC) in kidney transplant recipients, at 3 months after kidney transplantation. Materials and Methods. We performed a prospective observational study on 44 consecutive kidney transplant patients, followed for 3 months after kidney transplantation. Cystatin C was measured by latex enhanced immunoturbidimetric assay (EuroLyser). Results. Thirty patients (68.2%) out of 44 had an estimated GFRCysC less than 60 ml/min/1.73m2. Patients with estimated GFRCysC < 60 ml/min/1.73m2 tended to be older (33.4 ± 11 vs 40.6 ± 12 years, p = 0.06), were more frequently males (35.7% vs 80%, p = 0.004) and presented significantly decreased levels of pretransplant total cholesterol (208± 32.7mg/dl vs 175.8 ± 54.6 mg/dl, p= 0.04). By multivariate binary logistic regression, recipient male gender (OR: 5.59; 95% CI: 1.06-29.53; p= 0.04) and pretransplant total cholesterol levels (OR: 0.97; 95% CI: 0.95-0.99; p= 0.02) were independently associated with estimated GFRCysC < 60 ml/min/1.73m2 at 3 months after transplantation and recipient age had a near-significant trend (OR: 1.08; 95% CI: 0.98-1.18; p= 0.07). Conclusions. In conclusion, we found that recipient male gender and pretransplant total cholesterol levels were independent determinants of glomerular filtration rate estimated with cystatin C in kidney transplant recipients, at 3 months after kidney transplantation [ABSTRACT FROM AUTHOR]

Introduction: Cold Ischemia time (CIT) could be informative regarding the possibility of slow graft function (SGF) or delayed graft function (DGF). We aim to determine the incidence of graft dysfunction types and the association with ischemia time. Material and Methods: We performed a prospective study on 54 adults KT recipients, transplanted between 1 of January 2019 and 31 of December 2019. Graft was defined and classified into three categories: immediate graft function (IGF), SGF, and DGF. Cox regression analysis has been used to identify risk factors for graft dysfunction. Results: According to multivariate Cox regression analysis, it was observed that CIT [HR = 1.004, 95%CI = 1.001-1.007, p = 0.007] was an independent risk factor for the occurrence of graft dysfunction, while the brain death donor [HR = 11.94, 95%CI = 0.73-194.94, p = 0.08] and diabetes [HR = 2.71, 95%CI = 0.083-8.80, p = 0.09] had a trend of association with the followed outcome. In two separate models of multivariate we found that CIT was an independent risk factor for DGF [HR = 1.003, 95%CI = 1.001-1.006, p = 0.01], but not for SGF. Conclusion: In conclusion we found that kidney graft dysfunction types are associated with high CIT and CIT was an important risk factor for DGF, but no SGF in KT recipients., (Celsius.)

Background: There is a clear need to refine the histological assessment in IgA Nephropathy (IgAN). We sought to investigate the clinical significance of the light microscopy (LM) pattern of glomerular injury and of the intensity of mesangial C3 staining in IgAN., Methods: We conducted a retrospective, observational study that included all patients with biopsy-proven primary IgAN that had at least 12 months of follow-up. The LM pattern of glomerular injury was reevaluated based on a modified HAAS classification. Mesangial C3 deposition by immunofluorescence (IF) staining was scored semi-quantitatively. The study primary composite endpoint was defined as doubling of serum creatinine or ESRD (dialysis, renal transplant or eGFR < 15 ml/min). The secondary study endpoint was eGFR decline per year., Results: This cohort included 214 patients with IgAN (mean age, 41.4 ± 12.6 years), with a mean eGFR and median 24-h proteinuria of 55.2 ± 31.5 ml/min/1.73m 2 and 1.5 g/day (IQR:0.8-3.25), respectively. The most frequent LM pattern was the mesangioproliferative (37.4%), followed by the sclerotic (22.5%) and proliferative/necrotizing patterns (21.4%). Regarding the IF findings, mild-moderate and intense mesangial C3 staining was present in 30.6% and 61.1% of patients, respectively. Those with sclerosing and crescentic patterns had the worst renal survival (5-year renal survival of 48.8% and 42.9%) and the highest rate of eGFR change/year (-2.32 ml/min/y and - 2.16 ml/min/y, respectively) compared to those with other glomerular patterns of injury. In addition, those with intense C3 staining reached the composite endpoint more frequently compared to those without intense C3 staining (35.5% vs. 21.4%, p = 0.04). After multivariate adjustment, patients with crescentic and sclerosing patterns had a 3.6-fold and 2.1-fold higher risk for the composite endpoint compared to those with mesangioproliferative pattern, while an intense mesangial C3 deposition being also associated with a worse renal outcome (HR, 3.33; 95%CI, 1.21-9.2)., Conclusions: We have shown that the LM pattern of glomerular injury and the intensity of mesangial C3 deposition might stratify more accurately the renal outcome in patients with IgAN., (© 2024. The Author(s).)

Background: We sought to evaluate the long-term effects of COVID-19 on renal function in patients with biopsy-proven kidney diseases., Methods: A total of 451 patients with biopsy-proven kidney disease and at least 12 months of follow-up subsequent to COVID-19 pandemic onset were included in the study. The primary study endpoint was a composite of a persistent decline of more than 30% in eGFR or ESRD., Results: 23.1% of patients had COVID-19 during a follow-up period of 2.5 y (0.8-2.6), while 17.6% of patients reached the composite endpoint. Those with COVID-19 were more likely to reach the composite endpoint [26.7% vs. 14.8%; OR, 2.1 (95%CI, 1.23-3.58), p = 0.006). There was a significant eGFR change in the first year of follow-up between the two study groups [-2.24 (95%CI,-4.86; 0.37) vs. +2.31 (95%CI, 0.78; 3.85) ml/min, p = 0.004], with an adjusted mean difference of -4.68 ml/min (95%CI,-7.7; -1.59)(p = 0.03). The trend for worse renal outcomes remained consistent in patients with IgAN, MN and FSGS, but not in those with LN. After multivariate adjustment, the independent predictors of the composite endpoint were baseline eGFR (HR, 0.94; 95%CI, 0.92-0.95), COVID-19 (HR, 1.91; 1.16-3.12) and male gender (HR, 1.64; 95%CI, 1.01-2.66). In multivariate linear regression analysis, COVID-19 independently determined a reduction of eGFR at 12 months by 4.62 ml/min/1.73m2 (β coefficient, -4.62; 95%CI, -7.74 to -1.5, p = 0.004)., Conclusions: There is a significant impact of COVID-19 on long-term renal function in patients with biopsy-proven kidney diseases, leading to a greater decline of eGFR and a worse renal survival., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Obrișcă et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

We sought to evaluate the efficacy and safety of budesonide (Budenofalk) in the treatment of patients with IgA Nephropathy. We conducted a prospective, interventional, open-label, single-arm, non-randomized study that enrolled 32 patients with IgAN at high risk of progression (BUDIGAN study, ISRCTN47722295, date of registration 14/02/2020). Patients were treated with Budesonide at a dose of 9 mg/day for 12 months, subsequently tapered to 3 mg/day for another 12 months. The primary endpoints were change of eGFR and proteinuria at 12, 24 and 36 months. The study cohort had a mean eGFR and 24-h proteinuria of 59 ± 24 ml/min/1.73m 2 and 1.89 ± 1.5 g/day, respectively. Treatment with budesonide determined a reduction in proteinuria at 12-, 24- and 36-months by -32.9% (95% CI - 53.6 to - 12.2), - 49.7% (95% CI - 70.1 to - 29.4) and - 68.1% (95% CI - 80.6 to - 55.7). Budesonide determined an eGFR preservation corresponding to a 12-, 24- and 36-months change of + 7.68% (95% CI - 4.7 to 20.1), + 7.42% (95% CI - 7.23 to 22.1) and + 4.74% (95%CI - 13.5 to 23), respectively. The overall eGFR change/year was + 0.83 ml/min/y (95% CI - 0.54 to 4.46). Budesonide was well-tolerated, and treatment emergent adverse events were mostly mild in severity and reversible. Budesonide was effective in the treatment of patients with IgAN at high-risk of progression in terms of reducing proteinuria and preserving renal function over 36 months of therapy., (© 2023. The Author(s).)

Background: The occurrence of autoantibodies in human immunodeficiency virus (HIV)-infected patients has been previously reported, with a prevalence ranging from 20 to 83%. There are also a few reports of clinically relevant autoantibody profiles in HIV-positive patients that lead to true systemic autoimmune disease; these possible life-threatening diseases have to be considered and treated accordingly., Case Presentation: Here, we present the case of a 29-year-old female patient with a history of well-controlled HIV infection in the last 6 years who was admitted to our department for the evaluation of acute kidney injury and nephrotic syndrome with active urinary sediment. A diagnosis of systemic antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) with renal and pulmonary involvement was established. The patient was treated with cyclophosphamide, rituximab and tapering glucocorticoids,and the diffuse alveolar hemorrhage resolved, but the evolution of kidney function was unfavorable, which led to the need to initiate hemodialysis. We highlight the importance of establishing the correct diagnosis, treating the disease accordingly and the possible clinical issues that can appear in a patient with HIV infection during immunosuppressant treatment as induction treatment. Additionally, we performed a thorough literature review of ANCA positivity in HIV-infected patients to properly understand the current evidence., Conclusions: Although it is not clear whether HIV infection and AAV are causally or coincidentally related, the possibility of this systemic autoimmune phenomenon should be acknowledged by physicians to establish the correct diagnosis and treat the disease accordingly by maintaining a balance between the risks and benefits of immunosuppression in this category of patients, with treatment decisions being made by the members of a multidisciplinary team in centers with experience in AAV., (© 2023. The Author(s).)

(1) Background: We sought to investigate the impact of the COVID-19 pandemic in patients with lupus nephritis (LN); (2) Methods: A total of 95 patients with LN actively monitored in our department between 26 February 2020, when the first case of COVID-19 was diagnosed in Romania, and 1 May 2021, were included in the study. Multivariate logistic regression analysis was performed to identify the independent risk factors for SARS-CoV-2 infection; (3) Results: A total of 15 patients (15.8%) had a confirmed SARS-CoV-2 infection during a total follow-up time of 105.9 patient-years (unadjusted incidence rate: 14.28 SARS-CoV-2 infections per 100 patient-years). Median time to SARS-CoV-2 infection was 9.3 months (IQR: 7.2-11.3). The majority of patients had a mild form of SARS-CoV-2 infection (73.3%), while the remaining had moderate forms. None of the patients had a severe infection or a SARS-CoV-2-related death. The most frequent symptom was fatigue (73.3%), followed by loss of taste/smell (53.3%) and fever (46.7%). Forty percent of those with SARS-CoV-2 infection were hospitalized for a median 11.5 days (IQR:3.75-14). In the multivariate logistic regression analysis, a current oral corticosteroid dose ≥ 15 mg/day was associated with a 7.69-fold higher risk (OR, 7.69; 95%, 1.3-45.46), while the use of hydroxychloroquine was associated with a 91% lower risk for a SARS-CoV-2 infection (OR, 0.09; 95%CI, 0.01-0.59). (4) Conclusions: Our study confirms that the SARS-CoV-2 infection-associated morbidity might only be moderately increased in patients with LN. The current oral corticosteroid dose was the only independent predictor of infection occurrence, while use of hydroxychloroquine was associated with a protective effect.

Purpose: We sought to investigate the utility of anti-PLA2R antibody as a non-invasive screening method for the diagnosis of primary MN in patients with nephrotic syndrome (NS)., Methods: All consecutive patients with NS admitted in our department, between 01.01.2015 and 31.12.2019 were screened for anti-PLA2R antibodies by an ELISA assay (EUROIMMUN, Lübeck, DE). A positive anti-PLA2R serology was defined as an ELISA value over 2 RU/ml. Subsequently, all patients underwent kidney biopsy to confirm the histological diagnosis., Results: Of the 203 patients with NS, we identified 67 patients with "high" titer of anti-PLA2R antibodies (> 20 RU/ml) and 47 patients with "intermediate" titer (2-20 RU/ml). In the entire cohort, the area under the curve (AUC) was 0.83 (95% CI 0.78-0.89; p < 0.001). With a cutoff of 20 RU/ml, the anti-PLA2R antibodies had a 64% sensitivity (95% CI 53-73%) and 94% specificity (95% CI 88-97%) to discriminate MN from other causes of NS. In addition, the PPV and NPV were 91% (95% CI 82-95%) and 75% (95% CI 69-79%). When analyzing the posttest effect, we identified a LR+ of 11.56 (95% CI 5.2-25.2) and LR- of 0.38 (95% CI 0.29-0.5). The overall accuracy of the test was 80.3% (95% CI 74-85%) and the diagnostic odds ratio was 30.42. When performing subgroup analysis, we identified that in younger patients, in those with preserved renal function or with negative workup for secondary causes, the diagnostic performance of anti-PLA2R antibodies was improved, the sensitivity increasing to 68-71%, the PPV to 93-95% and the LR+ to 12.23-15.4., Conclusion: Serum anti-PLA2R antibody screening in patients with NS is a useful method for the diagnosis of primary MN. In younger patients (less than 60 years old) who have a preserved renal function and a negative workup for secondary causes of NS, a positive anti-PLA2R test highly predicts a diagnosis of primary MN., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)

(1) Background: Acute kidney injury (AKI) is a serious complication of hematopoietic stem cell transplantation (HSCT). (2) Methods: The aim was to identify the incidence, severity, and risk factors for AKI during the first 100 days after allo-HSCT; we performed a prospective observational study on 135 consecutive patients. (3) Results: The mean age was 38.3 ± 11.9 years (50.6% females), AKI developed in 93 patients (68.9%), the median time of appearance was 28 days, and the mean serum creatinine at the time of AKI was 1.8 ± 0.8 mg/dL. A total of 36 (38.7%) patients developed stage 1 AKI, 33 (35.5%) patients developed stage 2, and 24 (25.8%) patients developed stage 3; eight (8.6%) patients required temporary hemodialysis, and the mortality rate in these patients was 87.5%. Death was twice as frequent in the AKI subgroup, without statistical significance. Cyclosporine overdose (HR = 2.36, 95% CI: 1.45-3.85, p = 0.001), tacrolimus overdose (HR = 4.72, 95% CI: 2.22-10.01, p < 0.001), acute graft-versus-host disease (aGVHD) (HR = 1.96, 95% CI: 1.13-3.40, p = 0.01), and CRP level (HR = 1.009, 95% CI: 1.007-1.10, p < 0.001) were independent risk factors for AKI. Sepsis (HR = 5.37, 95% CI: 1.75-16.48, p = 0.003) and sinusoidal obstruction syndrome (HR = 5.10, 95% CI: 2.02-12.85, p = 0.001) were found as independent risk factors for AKI stage 3. (4) Conclusions: AKI occurs with high incidence and increased severity after allo-HSCT. Careful monitoring of calcineurin inhibitors and proper management of sepsis may reduce this risk.

Introduction: We sought to investigate the infection profile and associated risk factors in a compiled cohort of patients with autoimmune disorders with severe renal involvement treated with aggressive immunosuppressive (IS) regimens., Methods: A total of 162 patients with aggressive glomerulonephritis [101 with lupus nephritis (LN), 24 with cryoglobulinemic vasculitis (CryoVasc), and 37 with ANCA-associated vasculitis (AAV)] were retrospectively reviewed for any infection occurrence. Infection incidence, type, site, and grade (1-5) were recorded. Multivariate Cox proportional hazard regression analysis was performed to identify independent risk factors for infections., Results: A total of 179 infection episodes occurred during a follow-up of 468 patient-years. Eighty-two patients (50.6%) had at least one infection. The incidence rates of infections and severe infections were 38.2 and 14.3 events per 100 patient-years. Patients with AAV had more infections than those with CryoVasc and LN (100.6, 47.5, and 26.6 infections per 100-patient-years, respectively; p = 0.002). Most patients developed infections early during the initial induction therapy (62.1% in the first 6 months of follow-up). In multivariate Cox regression analysis, high-dose oral corticosteroids (≥ 0.5 mg/kg/day in the first month of induction therapy) was an independent predictor of any infection (HR 2.66; 95% CI, 1.5-4.73), severe infections (HR 2.45; 95% CI, 1.03-5.82), and pulmonary infections (HR 2.91; 95% CI, 1.05-8.01). Pulmonary involvement increased the risk for pulmonary infections (HR 3.67; 95% CI, 1.32-10.1) and severe infections (HR 2.45; 95% CI, 1.01-5.92)., Conclusion: Infections occur frequently with current IS regimens in aggressive glomerulonephritis. Pulmonary involvement and high-dose corticosteroid regimen were the most significant risk factors for infections. Key Points • Infections occur frequently with current immunosuppressive regimens in autoimmune aggressive glomerulonephritis. • High-dose corticosteroids are the major contributors to the risk for serious infections., (© 2021. International League of Associations for Rheumatology (ILAR).)

(1) Background: We sought to investigate the clinical outcome and to identify the independent predictors of clinical remission in a prospectively followed cohort of patients with primary membranous nephropathy (pMN). (2) Methods: We conducted a prospective, observational, non-interventional study that included 65 consecutive patients diagnosed with pMN between January 2015 and December 2019 at our department and followed for at least 24 months. The primary outcomes evaluated during the follow-up period were the occurrence of immunological and clinical remission (either complete or partial remission). Univariate and multivariate Cox proportional hazard regression analyses were performed to identify independent predictors of clinical remission. (3) Results: In the study cohort, 13 patients had a PLA2R-negative pMN, while, of those with PLA2R-associated pMN, 27 patients had a low anti-PLA2R antibody titer (<200 RU/mL), and 25 patients had a high anti-PLA2R antibody titer at baseline (≥200 RU/mL). The clinical outcome was better in patients with PLA2R-negative pMN compared to patients with PLA2R-positive pMN. These patients had a higher percentage of complete remissions (46.2%, compared to 33.3% in those with low anti-PLA2R antibody titer or 24% in those with high anti-PLA2R antibody titer), a faster decline of 24 h proteinuria and lower time to complete remission. In multivariate Cox regression analysis, patients with PLA2R-negative pMN had a 3.1-fold and a 2.87-fold higher chance for achieving a complete or partial remission compared to patients with high anti-PLA2R antibody titer or to all PLA2R-positive patients, respectively. Additionally, patients with a baseline 24 h proteinuria of less than 8 g/day and with an immunological remission at 24 months had a 2.4-fold (HR, 2.4; 95%CI, 1.19-4.8) and a 2.2-fold (HR, 2.26; 95%CI, 1.05-4.87), respectively, higher chance of achieving a clinical response. By contrary, renal function at diagnosis, type of therapeutic intervention or anti-PLA2R antibody titer did not predict the occurrence of clinical remission. (4) Conclusions: We identified a different clinical phenotype between PLA2R-positive and PLA2R-negative pMN. Additionally, we have shown that baseline proteinuria seems to be a more important predictor of clinical outcome than anti-PLA2R-ab titer.

Systemic lupus erythematosus (SLE) is the prototype of autoimmune disorders caused by a loss of tolerance to endogenous nuclear antigens triggering an aberrant autoimmune response targeting various tissues. Lupus nephritis (LN), a major cause of morbidity and mortality in patients with SLE, affects up to 60% of patients. The recent insights into the genetic and molecular basis of SLE and LN paved the way for newer therapies to be developed for these patients. Apart from the traditional B-cell-centered view of this disease pathogenesis, acknowledging that multiple extrarenal and intrarenal pathways contribute to kidney-specific autoimmunity and injury may help refine the individual therapeutic and prognostic characterization of such patients. Accordingly, the formerly induction-maintenance treatment strategy was recently challenged with the exciting results obtained from the trials that evaluated add-on therapy with voclosporin, belimumab, or Obinutuzumab. The scope of this review is to provide an insight into the current knowledge of LN pathogenesis and future therapeutic strategies.

Hypocomplementemic urticarial vasculitis syndrome (HUVS), or McDuffie syndrome, is a rare small vessel vasculitis associated with urticaria, hypocomplementemia and positivity of anti-C1q antibodies. In rare cases, HUVS can manifest as an immune-complex mediated glomerulonephritis with a membranoproliferative pattern of injury. Due to the rarity of this disorder, little is known about the clinical manifestation, pathogenesis, treatment response and outcome of such patients. We describe here three cases of HUVS with severe renal involvement. These patients had a rapidly progressive form of glomerulonephritis with severe nephrotic syndrome against a background of a membranoproliferative pattern of glomerular injury with extensive crescent formation. Therefore, these patients required aggressive induction and maintenance immunosuppressive therapy, with a clinical and renal response in two patients, while the third patient progressed to end-stage renal disease. Because of the rarity of this condition, there are few data regarding the clinical presentation, pathology and outcome of such patients. Accordingly, we provide an extensive literature review of cases reported from 1976 until 2020 and place them in the context of the current knowledge of HUVS pathogenesis. We identified 60 patients with HUVS and renal involvement that had adequate clinical data reported, out of which 52 patients underwent a percutaneous kidney biopsy. The most frequent renal manifestation was hematuria associated with proteinuria (70% of patients), while one third had abnormal kidney function on presentation (estimated glomerular filtration (GFR) below 60 mL/min/1.73 m 2 ). The most frequent glomerular pattern of injury was membranoproliferative (35%), followed by mesangioproliferative (21%) and membranous (19%). Similar to other systemic vasculitis, renal involvement carries a poorer prognosis, but the outcome can be improved by aggressive immunosuppressive treatment.

IgA Nephropathy (IgAN) is characterized by mesangial deposition of dominant, polymeric, galactose-deficient IgA1 molecules of gut-associated lymphoid tissue origin. We sought to evaluate the efficacy of targeting the mucosal immune system dysregulation underlying IgAN pathogenesis with a pH-modified formulation of budesonide with a maximum release of active compound in the distal ileum and proximal colon.We did a retrospective study evaluating the efficacy of budesonide (Budenofalk) in the treatment of IgAN. From a retrospective cohort of 143 patients with IgAN followed in our department we identified 21 patients that received treatment with budesonide. These patients received budesonide at a dose of 9 mg/d in the first 12 months, followed by a dose reduction to 3 mg/d for the subsequent period. Only patients that received a 24-month treatment with budesonide were included in the analysis (n = 18). We matched the budesonide-treated cohort to 18 patients with IgAN treated with systemic steroids from the same retrospective cohort. Efficacy was measured as change in proteinuria, hematuria and estimated glomerular filtration rate over a 24-month period.Treatment with budesonide was associated with a 24-month renal function decline of -0.22 (95%CI, -8.2 to 7.8) ml/min/1.73m, compared to -5.89 (95%CI, -12.2 to 0.4) ml/min/1.73m in the corticosteroid treatment group (p = 0.44, for between group difference). The median reduction in proteinuria at 24-month was 45% (interquartile range [IQR]: -79%; -22%) in the budesonide group and 11% (IQR: -39%; 43%) in the corticosteroid group, respectively (P = .009, for between group difference). The median reduction in hematuria at 24-month was 72% (IQR: -90%; -45%) in the budesonide group and 73% (IQR: -85%; 18%) in the corticosteroid group, respectively (P = .22, for between group difference). Treatment with budesonide was well tolerated with minimal side effects.Budesonide (Budenofalk) was effective in the treatment of patients with IgAN at high-risk of progression in terms of reducing proteinuria, hematuria and preserving renal function over 24 months of therapy.

Background and objectives. Venous thromboembolic events (VTEs) are among the most important complications of nephrotic syndrome (NS). We conducted a study that aimed to determine the prevalence of inherited risk factors for VTE in NS and to identify which factors are independent predictors of VTE. Materials and Methods. Thirty-six consecutive patients with primary NS that underwent percutaneous kidney biopsy between January 2017 and December 2017 were enrolled in this retrospective, observational study. VTEs were the primary outcome. Baseline demographic and biochemical data were collected from medical records, and genetic testing was done for polymorphisms of Factor V, PAI, MTHFR, and prothrombin genes. Results. The incidence of VTE was 28%, and the median time to event was 3 months (IQR: 2-9). The prevalence of inherited risk factors was 14% for Factor V Leiden mutation, 5.6% for prothrombin G20210A, 44.5% for PAI, and 27.8% for each of the two polymorphisms of the MTHFR gene. On multivariate analysis, the presence of at least two mutations was independently associated with the risk of VTE (HR, 8.92; 95% confidence interval, CI: 1.001 to 79.58, p = 0,05). Conclusions. These findings suggest that genetic testing for inherited thrombophilia in NS could play an important role in detecting high-risk patients that warrant prophylactic anticoagulation ., Competing Interests: The authors declare no conflict of interest.

Newer treatment protocols involving direct-acting antiviral agents (DAAs) have been associated with high rates of sustained virologic response (SVR) and clinical remission in patients with hepatitis C virus (HCV) associated cryoglobulinemic vasculitis (HCV-CV), but clinical response in those with renal involvement is less clear. Our goal was to evaluate the clinical course following DAA therapy in one of the largest cohorts of patients with HCV-associated cryoglobulinemic glomerulonephritis (HCV-GN) reported to date. This is an observational study of patients with chronic HCV infection and circulating cryoglobulins (CC) treated with DAAs in our department from January 2015 to January 2019. We identified a total of 67 patients with HCV and CC out of which nine patients fulfilled the criteria of HCV-GN and had adequate clinical follow-up time. We describe a cohort of nine patients with a mean age of 57 years and known duration of HCV infection ranging 3-20 years (four with evidence of compensated cirrhosis). All patients received the ritonavir-boosted paritaprevir/ombitasvir/dasabuvir regimen for 12 weeks and achieved SVR without subsequent viral relapse. Following DAAs completion, one patient developed "new-onset" cryoglobulinemic glomerulonephritis, six showed either persistent or worsening glomerulonephritis, and only two patients had a complete clinical response (CCR). Of the six patients with either persistent or worsening CV, 67% received additional immunosuppressive (IS) therapy for uncontrolled CV. Of the two patients that had a CCR, one patient received prior IS therapy while the other one improved without any additional intervention. Newer HCV treatment protocols involving DAAs are highly successful in eradication of HCV infection; however, in our experience, DAA treatment alone is insufficient in improving the renal outcomes of patients with HCV-GN and additional IS therapies should be considered.

Thymic tumors are rare mediastinal tumors that can present with a wide variety of symptoms. They can cause distant manifestations and are frequently associated with paraneoplastic syndromes. In our case, we describe the evolution of a 68-year-old male whose first manifestation was thrombosis of the inferior vena cava and renal veins. Thrombosis of large abdominal veins is rare, especially without being associated with any other comorbidity or risk factors., Competing Interests: The authors declare that there is no conflict of interests regarding the publication of this paper.