Histological reappraisal of IgA nephropathy: the role of glomerular pattern of injury and mesangial complement deposition.

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/1.73m2 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.

Sodium citrate versus sodium bicarbonate for metabolic acidosis in patients with chronic kidney disease: A randomized controlled trial.

BACKGROUND: Metabolic acidosis (MA) is frequently associated with chronic kidney disease (CKD) progression. Our aim was to compare the effect of oral sodium citrate (SC) with that of oral sodium bicarbonate (SB) on renal function and serum bicarbonate correction, as well as to evaluate their safety profile in patients with MA of CKD. METHODS: We conducted a prospective, single-center, randomized 1:1, parallel, controlled, unblinded clinical trial of 124 patients with MA and CKD stages 3b and 4. The primary outcome was the mean change in estimated glomerular filtration rate (eGFR). The secondary outcomes were mean change in serum bicarbonate level, eGFR decrease by 30%, eGFR decrease by 50%, dialysis, death or prolonged hospitalization, and a combined endpoint. RESULTS: No significant difference was found between the groups in terms of mean eGFR change [adjusted mean difference = -0.99 mL/min/1.73 m2 (95% CI: -2.51 to 0.93, P = .20)]. We observed a mean serum bicarbonate change of 6.15 mmol/L [(95% CI: 5.55-6.74), P < .001] in the SC group and of 6.19 mmol/L [(95% CI: 5.54-6.83), P < .001] in the SB group, but no significant difference between the 2 groups [adjusted mean difference = 0.31 mmol/L (-0.22 to 0.85), P = .25]. Cox proportional hazard analysis showed similar risks regarding eGFR decrease by 30% (P = .77), eGFR decrease by 50% (P = .50), dialysis (P = .85), death or prolonged hospitalization (P = .29), and combined endpoint (P = .57). Study drug discontinuation due to adverse events was significantly more common in the SB group (17.7% vs 4.8%, P = .02). CONCLUSIONS: SC and SB have a similar effect on kidney function decline, both improve serum bicarbonate level, but SB is associated with higher rates of medication discontinuation due to adverse events.

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.

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.

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.

Neurological and Dermatological Manifestations of Tuberous Sclerosis Complex: Report from a Romanian Tertiary Hospital Cohort.

Tuberous sclerosis complex is a rare multisystem genetic disorder characterized by multiorgan involvement, frequently associated with intellectual impairment and epilepsy. The aim of our study was to describe the neurological and dermatological manifestations of TSC in 32 adult patients (of whom 19 were females) who attended the Neurology and Nephrology Clinics of Fundeni Clinical Institute in Romania from 2015 to 2020. Seventeen patients were diagnosed with epilepsy, nine patients had intellectual impairment, and complete neuroimaging was available for twenty-two patients. As expected, the most frequent dermatological lesions were cutaneous angiofibromas in 20 patients, but with a lower frequency than described in the current literature. Statistical analysis was performed considering the small number of patients. Cortical tubers in neuroimaging seemed to be associated with the diagnosis of epilepsy, while subependymal nodules represented a risk factor for intellectual impairment. Males showed a larger number of dermatological types of lesions, especially café -au-lait patches. Interestingly, we found a statistically significant positive association between epilepsy and the presence of cutaneous angiofibromas, as well as total dermatological involvement. Females had significantly higher Charlson comorbidity index scores, indicating a higher burden of disease. Everolimus seemed to be a well-tolerated treatment and showed promising results in controlling epileptic seizures alone in two patients. More studies, with the inclusion of a larger number of patients, are needed to confirm these results.

Hantavirus infections in the South­Eastern European countries: A study of two cases and literature review.

Hantavirus infection is a rare zoonosis in South-Eastern Europe. Depending on the serotype involved, the virus can cause hemorrhagic fever with renal syndrome which is also known as endemic nephropathy, and cardiopulmonary syndrome. Prompt diagnosis of the disease is essential for reducing the risk of severe manifestations and complications like chronic kidney disease, secondary hypertension or even death because there is no specific treatment or vaccine approved. The present study reported two cases of hemorrhagic fever with renal syndrome diagnosed in the Department of Nephrology of The Fundeni Clinical Institute (Romania). In both patients, kidney needle biopsy played a major role in establishing the diagnosis. The difficulties encountered in diagnosing this disease were also emphasized, taking into consideration the rarity of this infection in South-Eastern Europe. The key literature data on the epidemiology, pathogenesis and management of this infection were further reviewed.

Importance of Tissue Doppler Evaluation in Dilated Cardiomyopathy: The Value of Diastolic Filling Pattern as a Prognostic Predictor.

(1) Background: The presence of restrictive left ventricular diastolic filling pattern (LVDFP) is associated with an unfavorable prognosis in many cardiac diseases, but few data are available on the prognostic implications of this pattern in patients with dilated cardiomyopathy (DCM). We aimed to establish the main prognostic predictors at the 1- and 5-year follow-ups in DCM patients and the value of restrictive LVDFP in increasing morbidity and mortality. (2) Methods: A prospective study of 143 patients with DCM divided in non-restrictive LVDFP group (95 patients) and restrictive group (47 patients). The patients were evaluated at a 5-year follow-up through an in-patient visit during the pre-pandemic period and hybrid methods (face-to-face, teleconsultation and home monitoring with a telemedicine application) during the pandemic period. Statistical analysis compared the two groups in terms of NYHA class, quality of life, hospitalizations/emergency department (ED) visits due to HF exacerbation and total mortality. (3) Results: The mortality rate in the restrictive group was markedly higher than that in the non-restrictive group at 1 year (17.02% vs. 10.59%, respectively, p < 0.05) and at 5 years (68.08% vs. 50.53%, p < 0.05). In the restrictive group, hospitalizations/ED visits due to HF decompensations at 1 year were significantly higher (85.11% vs. 57.89%, p < 0.05), with hospitalizations for ventricular arrhythmia being almost three times higher (21.28% vs. 7.37%, respectively, p < 0.05). The percentage of patients with a favorable evolution (in terms of NYHA class and quality of life) at the 1- and 5-year follow-ups were higher in the non-restrictive LVDFP group. The main prognostic predictors in patients with DCM at the 1-year follow-up were: restrictive LVDFP, age > 75 years, markedly dilated LV, comorbidities (DM, COPD), 2nd-degree mitral regurgitation and severe pulmonary hypertension (p < 0.05). (4) Conclusions: At the 1- and 5-year follow-ups, the presence of the restrictive LVDFP in DCM patients was independently associated with a poor prognosis, being the best clinical predictor for unfavorable evolution, after adjustment for other well-established predictive parameters in DCM patients.

Challenges in Caring for People with Cardiovascular Disease through and beyond the COVID-19 Pandemic: The Advantages of Universal Access to Home Telemonitoring.

(1) Background: Cardiovascular prevention was left in second place during the COVID-19 pandemic and the use of telemedicine turned out to be very useful. We aimed to evaluate the effectiveness of a telemedicine application for remote monitoring and treatment adjustments in terms of improving cardiovascular prevention. (2) Methods: A prospective study of 3439 patients evaluated between the 1st of March 2019 and the 1st of March 2022, in the pre-pandemic period by face-to-face visits and during the pandemic by teleconsultations or hybrid follow-up. We compared four periods: pre-pandemic-Pre-P (1 March 2019-1 March 2020), lockdown-Lock (1 March-1 September 2020), restrictive-pandemic-Restr-P (1 September 2020-1 March 2021), and relaxed-pandemic-Rel-P (1 March 2021-1 March 2022). (3) Results: The average values of total cholesterol (TC), LDL cholesterol, triglycerides, uric acid, and glucose had an increasing trend during Lock and Restr-P, and they decreased close to the baseline level during the Rel-P, with the exception of glucose which remained elevated in Rel-P. The number of patients with newly discovered DM increased significantly in the Rel-P, and 79.5% of them had mild/moderate forms of COVID-19. During Lock and Res-P, the percentage of obese, smoking, or hypertensive patients increased, but probably through the use of telemedicine, we managed to reduce it, although it remained slightly higher than the pre-pandemic level. Physical activity decreased in the first year of the pandemic, but in Rel-P people became more active than before the pandemic. (4) Conclusions: The use of telemedicine for cardiovascular prevention seems to yield favorable results, especially for secondary prevention in the very high-risk group and during the second year.

Telemedicine for Optimizing Secondary Prevention in Coronary Artery Bypass Grafting Patients during COVID-19 Pandemic.

(1) Background: The COVID-19 pandemic has introduced a major disruption to the delivery of secondary prevention measures in patients with established atherosclerotic cardiovascular disease (CVD). It required a rapid and widespread adoption of new medical services, including the use of telemedicine. This study aimed to examine the impact of COVID-19 on secondary prevention in patients with coronary artery bypass grafting (CABG) and to evaluate the effectiveness of the telemedicine application for the implementation of lifestyle change measures, remote monitoring, and treatment regimen adjustment; (2) Methods: This prospective study on 194 CABG patients evaluated three consecutive years between 2019 and 2022 in the pre-pandemic period by face-to-face visits and during the pandemic by teleconsultations or hybrid follow-up. Variables of interest were compared between four periods: pre-pandemic-pre-P (1 March 2019-29 February 2020), lockdown-Lock (1 March-31 August 2020), restrictive-pandemic-Restr-P (1 September 2020-28 February 2021), and relaxed-pandemic-Rel-P (1 March 2021-1 March 2022). (3) Results: The average values of the lipidogram, blood sugar, and uric acid increased during Lock and Restr-P, but, through the use of teleprevention, they returned to the pre-pandemic level or even below this level. The exception was blood sugar, which remained high in Rel-P. The number of newly diagnosed patients with diabetes also increased, with most of them having moderate forms of COVID. During Lock and Res-P, the percentage of obese, smoking, or hypertensive patients increased, but, through the use of teleprevention, we managed to reduce it, although it remained slightly higher than the pre-pandemic level. Physical activity decreased in the first year of the pandemic, but, in Rel-P, CABG patients became more active than before the pandemic (4) Conclusions: The use of telemedicine for cardiovascular secondary prevention allowed us to not only continue seeing CABG patients but, also, to adjust their medication and to expand cardiovascular preventive counseling and testing with favorable results, especially during the second year of the pandemic.

Incidence and Risk Factors for Long-Term Persistence of Diastolic Dysfunction after Aortic Valve Replacement for Aortic Stenosis Compared with Aortic Regurgitation.

(1) Background: Severe left ventricular (LV) diastolic dysfunction with a restrictive diastolic pattern (LVDFP) is generally associated with a worse prognosis. Its evolution and reversibility in the short- and medium-term after aortic valve replacement (AVR) has been little-studied. We aimed to evaluate the evolution of LV remodeling and LV systolic and diastolic function after AVR in aortic stenosis (AS) patients compared to aortic regurgitation (AR). Moreover, we tried to identify the main predictive parameters for postoperative evolution (cardiovascular hospitalization or death and quality of life) and the independent predictors for the persistence of restrictive LVDFP after AVR. (2) Methods: A five-year prospective study on 397 patients undergoing AVR for AS (226 pts) or AR (171 pts), evaluated clinically and by echocardiography preoperatively and until 5 years postoperatively. (3) Results: 1. In patients with AS, early post AVR, LV dimensions decreased and diastolic filling and LV ejection fraction (LVEF) improved more rapidly compared to patients with AR. At 1 year postoperatively, persistent restrictive LVDFP was found especially in the AR group compared to the AS group (36.84% vs. 14.16%). 2. Cardiovascular event-free survival at the 5-year follow-up was lower in the AR group (64.91% vs. 87.17% in the AS group). The main independent predictors of short- and medium-term prognosis after AVR were: restrictive LVDFP, severe LV systolic dysfunction, severe pulmonary hypertension (PHT), advanced age, severe AR, and comorbidities. 3. The persistence of restrictive LVDFP after AVR was independently predicted by: preoperative AR, the E/Ea ratio > 12, the LA dimension index > 30 mm/m2, an LV endsystolic diameter (LVESD) > 55 mm, severe PHT, and associated second-degree MR (p < 0.05). (4) Conclusions: AS patients had an immediate postoperative evolution in terms of LV remodeling, and LV systolic and diastolic function were more favorable compared to those with AR. The restrictive LVDFP was reversible, especially after the AVR for AS. The main prognostic predictors were the presence of restrictive LVDFP, advanced age, preoperative AR, severe LV systolic dysfunction, and severe PHT.

Challenges for Management of Dilated Cardiomyopathy during COVID-19 Pandemic-A Telemedicine Application.

BACKGROUND AND OBJECTIVES: The 2019 coronavirus pandemic (COVID-19) represented a significant challenge for the medical community. The first aim of this study was to examine the COVID-19 impact on the follow-up of patients with dilated cardiomyopathy (DCM) and to establish the advantages of multiparametric home monitoring. Also, we tried to establish the main prognostic predictors at 2-years follow-up and the value of LV diastolic filling pattern (LVDFP) in increasing mortality and morbidity. MATERIALS AND METHODS: We conducted a prospective study of 142 patients with DCM assessed by in-patient visit in the pre-pandemic period and hybrid (face-to-face, online consultation and telemedicine home monitoring with a dedicated application) during the pandemic period. The statistical analysis compared the strategy used in the pre-pandemic with management during the pandemic, in terms of clinical assessment, hospitalizations/emergency room visits due to HF exacerbation and total mortality. RESULTS: We did not observe significant changes in blood pressure (BP), heart rate (FC), weight and symptoms or an increased rate of adverse drug events between the two periods. We successfully titrated HF medications with close monitoring of HF decompensations, which were similar in number, but were mostly managed at home during the pandemic. There was also no statistically significant difference in emergency room visits due to severe decompensated HF. Mortality in the first and second year of follow-up was between 12.0 and 13%, similar in the pre-pandemic and pandemic periods, but significantly higher in patients with restrictive LVDFP. Clinical improvement or stability after 2 years was more frequent in patients with nonrestrictive LVDFP. The main prognostic predictors at 1 and 2-years follow-up were: the restrictive LVDFP, significantly dilated LV, comorbidities (DM, COPD), older age, associated severe mitral regurgitation and pulmonary hypertension. CONCLUSIONS: The pandemic restrictions determined a marked decrease of the healthcare use, but no significant change in the clinical status of DCM patients under multiparametric home monitoring. At 2-years follow-up, the presence of the restrictive LVDFP was associated with an increased risk of death and with a worse clinical status in DCM patients.

Diastolic versus Systolic Left Ventricular Dysfunction as Independent Predictors for Unfavorable Postoperative Evolution in Patients with Aortic Regurgitation Undergoing Aortic Valve Replacement.

Background and Objectives: Chronic severe aortic valve disease is associated with important changes in left ventricle (LV) performance associated with eccentric or concentric LV hypertrophy. We aimed to assess the immediate prognostic implications of the type of the LV diastolic filling pattern (LVDFP) compared with LV systolic performance in patients with severe aortic regurgitation (AR) undergoing aortic valve replacement (AVR) and to define the independent echographic predictors for the immediate and long-term prognoses. Materials and Methods: We performed a prospective study enrolling 332 AR patients undergoing AVR, divided into two groups: Group A­201 pts with normal LV systolic function, divided into two subgroups (A1: 129 pts with a nonrestrictive LVDFP and A2: 72 pts with restrictive LVDFP), and Group B­131 pts with LV systolic dysfunction (LV ejection fraction LVEF < 50%), divided into two subgroups (B1: 83 pts with a nonrestrictive LVDFP and B2: 48 pts with restrictive LVDFP). Results: The early postoperative mortality rate was higher in patients with a restrictive LVDFP (11.12% in A2 and 12.5% in B2) compared with normal LV filling (2.32% in A1 and 7.63% in B1, p < 0.0001), regardless of the LVEF. The restrictive LVDFP­defined by at least one of the following echographic parameters: an E/A > 2 with an E wave deceleration time (EDt) < 100 ms; an isovolumetric relaxation time (IVRT) < 60 ms; or an S/D ratio < 1 in the pulmonary vein flow­was an independent predictor for early postoperative mortality, increasing the relative risk by 8.2-fold. Other independent factors associated with early poor prognosis were an LV end-systolic diameter (LVESD) > 58 mm, an age > 75 years, and the presence of comorbidities (chronic obstructive pulmonary disease-COPD or diabetes mellitus). On a medium-term, an unfavorable evolution was associated with: an age > 75 years (RR = 8.1), an LV end-systolic volume (LVESV) > 95 cm3 (RR = 6.7), a restrictive LVDFP (RR = 9.8, p < 0.0002), and pulmonary hypertension (RR = 8.2). Conclusions: The presence of a restrictive LVDFP in patients with AR undergoing AVR is associated with both increased early and medium-term mortality rates. The LV diastolic function is a more reliable parameter for prognosis than LV systolic performance (RR 9.2 versus 2.1). Other independent predictors for increased early postoperative mortality rate were: an age > 75 years, an LVESD > 58 mm, and comorbidities (diabetes mellitus, COPD), and for unfavorable evolution at 2 years postoperatively: an age > 75 years, an LVESV > 95 cm3, and severe pulmonary hypertension.

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.

Additional Prognostic Value of Tissue Doppler Evaluation in Patients with Aortic Stenosis and Left-Ventricular Systolic Dysfunction Undergoing Aortic Valve Replacement.

Background and Objectives: Patients with surgical aortic stenosis (AS) show impaired diastolic filling, which is a risk factor for early and late mortality after aortic valve replacement (AVR). There is a paucity of information concerning the impact of restrictive diastolic filling and the evolution of diastolic dysfunction in the early and medium terms post-AVR. We aimed to determine the prognostic value of the presence of a restrictive left-ventricular (LV) diastolic filling pattern (LVDFP) and dilated left atrium (LA) in patients with AS and LV systolic dysfunction (LVEF < 40%) who underwent AVR, and to define the independent predictors for immediate and long-term prognosis and their value for preoperative risk estimation. Materials and Methods: The study was prospective and included 197 patients with surgical AS and LVEF <40% who underwent AVR. Preoperative echocardiographic examinations were repeated at day 10, at 1, 3 and 6 months, and at 1 and 2 years after surgery, with evaluation of LVEF, diastolic function and LA dimension index (mm/m2). Depending on LV systolic performance, patients were classified as Group A (LVEF: 30−40%) or Group B (LVEF < 30%). Results: The main echographic independent parameters for early and late postoperative death were: restrictive LVDFP, significant pulmonary hypertension, LV end-systolic diameter (LVESD) >55 mm and the presence of second-degree mitral regurgitation. Restrictive LVDFP and LA dimension >30 mm/m2 were independent predictors for fatal outcome (p = 0.0017). Conclusions: Assessment of diastolic function and LA dimension are reliable parameters in predicting fatal outcome and hospitalization for heart failure, having an independent and incremental prognostic value in patients with surgical AS. Complete evaluation of LVDFP with all the echographic measurements (including TDI) should routinely be part of the preoperative assessment of patients with LV systolic dysfunction undergoing AVR.

Impact of Pulmonary Hypertension on Mortality after Surgery for Aortic Stenosis.

Background and Objectives: The prognosis of patients with aortic stenosis (AS) adding pulmonary hypertension (PHT) is worse than in those with normal pulmonary artery pressure (PAP), and there are few results reported for the association between PHT and adverse outcomes of AS. We aimed to determine the predictive factors for the development of PHT in patients with surgical AS and to identify those factors that may predict the surgical prognosis. We aimed to identify the independent predictors for PHT regression at 2 years after surgery. Additionally, we tried to evaluate the involvement of PHT as an additional perioperative risk factor in patients with AS undergoing surgical aortic valve replacement (AVR). Materials and Methods: We carried out a two-year prospective study on 340 patients with AS undergoing surgical AVR. Results: The independent predictors for the occurrence of PHT in patients with surgical AS were: age > 75 years (RR = 6, p = 0.001), a restrictive left ventricle diastolic filling pattern (LVDFP) (RR = 9, p = 0.001) and associated moderate mitral regurgitation (MR) (RR = 9, p = 0.0001). The presence of severe PHT increased by 7.6 times the early postoperative risk of death, regardless of the presence of other parameters. The independent predictors for early postoperative mortality were: severe PHT, restrictive left ventricle diastolic pattern, age > 75 years, interventricular septum (IVS) thickness >18 mm and the presence of comorbidities. Conclusions: The presence of a severe PHT in patients with AS undergoing surgical AVR is associated with an early postoperative increased mortality rate. The mean PAP is a more reliable parameter for prognosis appreciation than the LV systolic function.

Enoxaparin versus Unfractionated Heparin for the Perioperative Anticoagulant Therapy in Patients with Mechanical Prosthetic Heart Valve Undergoing Non-Cardiac Surgery.

Background and Objectives: Immediate postoperative anticoagulation regimens in patients with mechanical prosthetic valves undergoing non-cardiac surgery are clear only for unfractionated heparin (UH), whereas the few low-molecular-weight heparin (LMWH) trials available to date concern the use of Enoxaparin in general/orthopedic surgery. We performed a single-center real-world data study comparing the efficacy and safety of LMWH­Enoxaparin (E)­ and UH during the perioperative period in non-cardiac surgical procedures in patients with mechanical prosthetic valve replacement in the mitral, aortic, or tricuspid positions. Materials and Methods: We enrolled 380 patients, who received E or UH together with oral anticoagulation with antivitamin K (acenocoumarol) until they achieved an optimal International Normalized Ratio (INR). Objective assessment of E efficacy included the following: normal value for all the parameters of ultrasound prosthetic functioning, no early thrombosis of the prosthesis, and rapid achievement of target INR with a decreased period of subcutaneous anticoagulation. Subjective assessment included the following: clinical improvement with decreased immobilization and in-hospital stay, fewer gluteal ulcerations, and fewer postoperative depression and anxiety episodes. Results: Comparing with UH, anticoagulation with E was more effective (p < 0.0001 and p = 0.02). The probability of death was smaller in the E group compared with the UH group. No major hemorrhagic event was reported. Mild bleeding episodes and thrombocytopenia were more common in the UH group. Patient's compliance and quality of life were better with E due to shortened hospitalization, decreased need for testing of coagulation (every 6 h for UH), better dosing (SC every 12 h for E versus continuous infusion for UH), shortened immobilization during the immediate postoperative period with subsequent improvement in the psychological status, as well as due to lack of significant side effects. Conclusions: Taking into consideration the improved efficiency and safety, as well as all the supplementary advantages, such as no need for anticoagulation monitoring, the ease of administration, and reduced duration of hospitalization, E should be seen as an attractive alternative for anticoagulation which deserves further investigation.

Tumor Lysis Syndrome: An Endless Challenge in Onco-Nephrology.

Tumor lysis syndrome (TLS) is a common cause of acute kidney injury in patients with malignancies, and it is a frequent condition for which the nephrologist is consulted in the case of the hospitalized oncological patient. Recognizing the patients at risk of developing TLS is essential, and so is the prophylactic treatment. The initiation of treatment for TLS is a medical emergency that must be addressed in a multidisciplinary team (oncologist, nephrologist, critical care physician) in order to reduce the risk of death and that of chronic renal impairment. TLS can occur spontaneously in the case of high tumor burden or may be caused by the initiation of highly efficient anti-tumor therapies, such as chemotherapy, radiation therapy, dexamethasone, monoclonal antibodies, CAR-T therapy, or hematopoietic stem cell transplantation. It is caused by lysis of tumor cells and the release of cellular components in the circulation, resulting in electrolytes and metabolic disturbances that can lead to organ dysfunction and even death. The aim of this paper is to review the scientific data on the updated definition of TLS, epidemiology, pathogenesis, and recognition of patients at risk of developing TLS, as well as to point out the recent advances in TLS treatment.

Incidence and Risk Factors for Acute Kidney Injury after Allogeneic Stem Cell Transplantation: A Prospective Study.

(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.

Serum soluble urokinase plasminogen activator receptor as a potential biomarker of renal impairment severity in diabetic nephropathy.

AIMS: To investigate serum soluble form of urokinase-type plasminogen activator receptor (suPAR) in patients with diabetic kidney disease (DKD) and biopsy-proven diabetic nephropathy (DN), its correlation with histological parameters and its capacity as a biomarker for renal impairment severity. METHODS: We conducted a cross-sectional study on 75 patients with diabetes mellitus (DM) and DKD, among whom 28 had biopsy-proven DN. RESULTS: Among the 75 patients, 9 (12%) had type 1 and 66 (88%) type 2 DM. The median value of the serum suPAR level was 2857.2 pg/mL (1916.4-3700) in the entire cohort and 2472.1 pg/mL (1782.6-3745.8) in the biopsy-proven DN subgroup, respectively. suPAR was significantly correlated with diabetes duration, diabetic retinopathy, anti-proteinuric treatment, albuminuria, kidney function, DN class, interstitial fibrosis and tubular atrophy (IFTA) score and with interstitial inflammation score. suPAR had a good accuracy for the association with chronic kidney disease (CKD) stages G3b-5, macroalbuminuria, DN class IV, IFTA score 3 and interstitial inflammation score 2. CONCLUSIONS: Serum suPAR was increased in DN patients and was associated with DM duration, diabetic retinopathy, renoprotective treatment, kidney function, proteinuria, DN class, IFTA and interstitial inflammation scores. Also, suPAR had a good capacity as a biomarker for advanced renal impairment and severe histological lesions of DN.