The impact of SARS-CoV-2 infection on renal function in patients with biopsy-proven kidney diseases.

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 (ß 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.

An open-label study evaluating the safety and efficacy of budesonide in patients with IgA nephropathy at high risk of progression.

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/1.73m2 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.

Oral Furosemide and Hydrochlorothiazide/Amiloride versus Intravenous Furosemide for the Treatment of Resistant Nephrotic Syndrome.

BACKGROUND: Data on diuretic treatment in nephrotic syndrome (NS) are scarce. Our goal was to assess the non-inferiority of the combined oral diuretics (furosemide/hydrochlorothiazide/amiloride) compared to intravenous (i.v.) furosemide in patients with NS and resistant edema. METHODS: We conducted a prospective randomized trial on 22 patients with resistant nephrotic edema (RNE), defined as hypervolemia and a FENa < 0.2%. Based on a computer-generated 1:1 randomization, we assigned patients to receive either intravenous furosemide (40 mg bolus and then continuous administration of 5 mg/h) or oral furosemide (40 mg/day) and hydrochlorothiazide/amiloride (50/5 mg/day) for a period of 5 days. Clinical and laboratory measurements were performed daily. Hydration status was assessed by bioimpedance on day 1 and at the end of day 5 after treatment initiation. The primary endpoint was weight change from baseline to day 5. Secondary endpoints were hydration status change measured by bioimpedance and safety outcomes (low blood pressure, severe electrolyte disturbances, acute kidney injury and worsening hypervolemia). RESULTS: Primary endpoint analysis showed that after 5 days of treatment, there was a significant difference in weight change from baseline between groups [adjusted mean difference: -3.33 kg (95% CI: -6.34 to -0.31), p = 0.03], with a higher mean weight change in the oral diuretic treatment group [-7.10 kg (95% CI: -18.30 to -4.30) vs. -4.55 kg (95%CI: -6.73 to -2.36)]. Secondary endpoint analysis showed that there was no significant difference between groups regarding hydration status change [adjusted mean difference: -0.05 L (95% CI: -2.6 to 2.6), p = 0.96], with a mean hydration status change in the oral diuretic treatment group of -4.71 L (95% CI: -6.87 to -2.54) and -3.91 L (95% CI: -5.69 to -2.13) in the i.v. diuretic treatment group. We observed a significant decrease in adjusted mean serum sodium of -2.15 mmol/L [(95% CI: -4.25 to -0.05), p = 0.04]), favored by the combined oral diuretic treatment [-2.70 mmol/L (95% CI: -4.89 to -0.50) vs. -0.10 mmol/L (95%CI: -1.30 to 1.10)]. No statistically significant difference was observed between the two groups in terms of adverse events. CONCLUSIONS: A combination of oral diuretics based on furosemide, amiloride and hydrochlorothiazide is non-inferior to i.v. furosemide in weight control of patients with RNE and a similar safety profile.

Characteristics of SARS-CoV-2 Infection in an Actively Monitored Cohort of Patients with Lupus Nephritis.

(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.

Anti-phospholipase A2 receptor antibody screening in nephrotic syndrome may identify a distinct subset of patients with primary membranous nephropathy.

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.

Corticosteroids are the major contributors to the risk for serious infections in autoimmune disorders with severe renal involvement.

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.

Clinical outcome of HCV-associated cryoglobulinemic glomerulonephritis following treatment with direct acting antiviral agents: a case-based review.

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.

Predictive Factors for Coronary Artery Disease among Peritoneal Dialysis Patients without Diabetic Nephropathy.

OBJECTIVES: Scientific literature indicates that the risk of coronary heart disease morbidity and death among peritoneal dialysis patients exceeds risk observed in non-renal patients. The aims of this study were to establish the independent predictors associated with increased risk of coronary heart disease in peritoneal dialysis patients without diabetic nephropathy. MATERIALS AND METHODS: A number of 116 end-stage renal disease patients without diabetic nephropathy undergoing peritoneal dialysis were evaluated for coronary heart disease and predictive risk factors were investigated and identified. Also intima-media thickness measurements, as an early sign of atherosclerosis, were analyzed in a subset of patients in correlation with a number of traditional and non-traditional cardiovascular risk factors. RESULTS: The study sample was found to be characterized by a high prevalence of traditional risk factors: hypertension (95.7%), dyslipidemia (93.1%) and metabolic syndrome (58.6%), but also of dialysis-related risk factors: inflammation (82.8%) and anemia (55.2%). Independent variables found to be associated in regression analysis with coronary heart disease were: age, smoking status, nephroangiosclerosis, albumin, C-reactive protein and iPTH levels. Intima-media thickness was significantly higher in patients with coronary heart disease, values greater than 0.89 mm being associated with increased risks for coronary heart disease, acute coronary syndrome and cardiovascular death. CONCLUSIONS: The prevalence of traditional cardiovascular risk factors in these peritoneal dialysis patients is extremely high, but there are also some other factors involved, especially malnutrition and inflammation. Age higher than 55 years, smoking, albumin less than 3.5 g/dl, iPTH less than 150 pg/ml and nephroangiosclerosis were associated with highest odds ratio for coronary heart disease. An increasing CRP levels was associated with an increasing gradient for coronary heart disease risk.