The Role of Rituximab in Primary Focal Segmental Glomerular Sclerosis of the Adult.

Introduction: Primary focal segmental glomerular sclerosis (FSGS) is a rare, likely immune-mediated disease. Rituximab (RTX) may play a role in management, although data in adults are scanty. Methods: We collected cases of RTX-treated primary FSGS within the Italian Society of Nephrology Immunopathology Working Group and explored response rate (24-hour proteinuria <3.5 g and <50% compared with baseline, stable estimated glomerular filtration rate). Results: A total of 31 patients were followed for at least 12 months; further follow-up (median 17 months, interquartile range [IQR] 15-33.5) was available for 11. At first RTX administration, median creatinine and 24-hour proteinuria were 1.17 mg/dl (IQR 0.83-1.62) and 5.2 g (IQR 3.3-8.81), respectively. Response rate at 3, 6, and 12 months was 39%, 52%, and 42%, respectively. In the first 12 months, creatinine level remained stable whereas proteinuria and serum albumin level improved, with an increase in the proportion of patients tapering other immunosuppressants. There were 6 patients who were retreated with RTX within 12 months, either for proteinuria increase or refractory disease; only the 2 responders to the first RTX course experienced a further response. At univariate analysis, 6-month response was more frequent in steroid-dependent patients (odds ratio [OR] 7.7 [95% CI 1.16-52.17]) and those with proteinuria <5 g/24 h (OR 8.25 [1.45-46.86]). During long-term follow-up, 4 of 5 responders at 12 months maintained a sustained response, either without further immunosuppression (2 of 4) or with pre-emptive RTX (2 of 4); 1 relapsed and responded to RTX retreatment. Conclusion: RTX may be an option in primary FSGS, especially in steroid-dependent patients, with 24-hour proteinuria <5 g and previously responders to RTX. Optimal long-term management for responders is unclear, with some patients experiencing sustained remission and others requiring RTX retreatment, either preemptive or after rising proteinuria.

Lung ultrasound may help in the differential diagnosis of suspected oligosymptomatic COVID-19 patients on hemodialysis: A case report.

INTRODUCTION: Considering that patients on dialysis showed a poor outcome during COVID-19 pandemic, and that COVID-19 symptoms in dialysis patients are often mild or absent, each dialysis unit should implement local strategies to early recognize patients affected by COVID-19. However, many available SARS-CoV-2 diagnostic tests demonstrated a moderate sensitivity, 70%-80% is probably a reasonable estimate. Consequently, having useful tools for differential diagnosis becomes essential. In this scenario, lung ultrasound (LUS) may have an important role in the evaluation of lung involvement in hemodialysis patients during COVID-19 pandemic. METHODS: We present two cases of hemodialysis patients with COVID-19 pneumonia in whom LUS had a central role in the diagnostic process. Ultrasound images of COVID-19 pneumonia show a typical bilateral pattern characterized by multiple or confluent B-lines with spared areas, thickened and irregular pleural line, and rare subpleural consolidations. LUS showed high accuracy in diagnosing COVID-19 pneumonia. FINDINGS: Despite both patients appeared clinically euvolemic and afebrile, they presented with acute diarrhea and oxygen saturation level of 92%-93%. Although clinical manifestations were mild and not specific in both patients, LUS raised suspicion on the possible COVID-19 diagnosis which was confirmed by a positive nasopharyngeal RT-PCR. DISCUSSION: There are many reasons for a patient on dialysis to present shortness of breath, fever, and multiple B-lines at LUS assessment (such as heart failure, fluid overload, vascular access infection, interstitial pneumonia) but the recognition of typical ultrasound patterns of the COVID-19 pneumonia is helpful for differential diagnosis. LUS may have an important role in the screening process of hemodialysis patients during the COVID-19 pandemic, especially in oligosymptomatic patients before the SARS-CoV-2 diagnostic tests, and in those with suspected symptoms and/or known exposure with unexpected negative SARS-CoV-2 diagnostic tests.

Optical Coherence Tomography Angiography for the Evaluation of Retinal Vasculature in Fabry Disease: Our Experience and Review of Current Knowledge.

Purpose: Optical coherence tomography angiography (OCTA) is a non-invasive and objective tool for the evaluation of the retinal microvascular changes in Fabry disease (FD). We investigated changes in retinal vasculature in FD patients, and the possible correlation with systemic parameters, by using OCTA, and reviewed the current status of literature. Methods: Thirteen FD patients (eight females, five males, mean age 49.85 ± 14.7 years) were compared with 13 age- and sex-matched healthy controls. OCTA 3 × 3 mm macular scans were performed in all subjects. We evaluated the vessel density and vessel perfusion in distinct macular areas (whole, inner, and outer) of both the superficial capillary plexus (SCP VD and SCP VP) and of the deep capillary plexus (DCP VD and DCP VP). We also evaluated the foveal avascular zone (FAZ) metrics (area, perimeter, and circularity), and correlation between systemic and OCTA parameters. A literature review on the current understanding of OCTA in FD is then presented. Results: FD patients showed significantly lower SCP VD values in the whole area (17.37 ± 2.08 mm-1 vs. 18.54 ± 1.21 mm-1; p-value 0.022), as well as in the outer area (17.46 ± 2.10 mm-1 vs. 19.08 ± 1.14 mm-1; p-value 0.002), but not in the inner. Even the DCP VD was significantly lower in all the imaged areas: whole (17.75 ± 3.93 mm-1 vs. 19.71 ± 1.20 mm-1; p-value 0.024), outer (18.25 ± 4.17 mm-1 vs. 20.33 ± 1.20 mm-1; p-value 0.023), and inner (19.54 ± 4.17 mm-1 vs. 21.96 ± 1.55 mm-1; p-value 0.011). There were no significant differences in vessel perfusion parameters (both SCP VP and DCP VP ones) and FAZ. No significant correlations were found between the OCTA parameters and systemic parameters (maximal left ventricular wall thickness and glomerular filtration rate) in FD patients. Conclusions: OCTA can be considered as a promising non-invasive tool, which enables a quantitative evaluation of retinal vascular involvement in FD, despite the varying data reported in literature. Our results support the use of OCTA as an objective tool to evaluate retinal vascular abnormalities in FD. The utility of OCTA in FD needs to be validated by longitudinal studies taking into account the overall progression of the disease.

Delayed graft function and perfusion parameters of kidneys from uncontrolled donors after circulatory death.

Better preservation and evaluation of kidneys from donors after circulatory death serve to increase the number of kidneys available for transplantation and hypothermic machine perfusion has been shown to decrease ischemia reperfusion injury and delayed graft function. Data on relation between hemodynamic parameters during hypothermic machine perfusion and delayed graft function in kidneys from donors after circulatory death are so far scarce and not univocal. We aimed at assessing whether hemodynamic parameters measured during hypothermic machine perfusion (flow, mean perfusion pressure, and renal resistance) are associated with delayed graft function in 26 kidneys retrieved from uncontrolled donors after circulatory death. In our series, the incidence of delayed graft function was 57.7% (15/26). Recipients who developed delayed graft function had a longer warm ischemic time (p = 0.04). All hemodynamic parameters measured during hypothermic machine perfusion were comparable between recipients with delayed graft function and those without. According to our data, in kidneys from uncontrolled donors after circulatory death, a longer warm ischemic time (that is the overall time of no flow, as the sum of the no-flow and the no-touch period) is associated with delayed graft function. This finding underscores the pivotal role of ischemic injury in terms of absence of flow in affecting graft function. No association was detectable between hemodynamic parameters during hypothermic machine perfusion and the development of delayed graft function in our series.

Exercise Prescription in Renal Transplant Recipients: From Sports Medicine Toward Multidisciplinary Aspects: A Pilot Study.

Renal transplantation is the choice treatment for end-stage renal disease. In spite of transplantation, cardiovascular morbidity and mortality remains high, possibly due to a prolonged sedentary lifestyle prior to transplantation. This study aimed to evaluate the impact of unsupervised intervention in a tailored home-based aerobic resistance exercise program, based on the anthropometric and cardiovascular parameters in a group of renal transplant recipients (RTRs) followed for 12 months. METHODS: a group of 21 RTRs (mean age: 46.8 ± 12 years) were enrolled in a combined aerobic and step count unsupervised prescription program. Body composition (BMI, waist circumferences, skin-folds); water distribution (TBW: Total body water; ECW: Extra cellular water; and ICW: Intracellular water) and myocardial function were measured every 6 months for 1 year. The MEDI-LITE score was used to estimate adherence to the Mediterranean diet. RESULTS: Significant reductions in waist circumference (Waist Cir: 89.12 ± 12.8 cm T0; 89.1 ± 12.5 cm T6 (95% CI: 6.3, 5.7); 88.6 ± 11.4 cm T12; (95% CI: 6.7, 4.7) p < 0.01), weight:71.8 ± 14.8 kg T0; 70.6 ± 14.7 kg T6(95% CI:-8, 6); 70.6 ± 14.7 kg T12(95% CI: 6.6, 7) p < 0.05), as well as an improvement of myocardial function, as shown by the significant increase of contractility and change in the GLS % value (-18.3 ± 3.8% at T0 (95% CI:-16.57, 20.0.2)-20.4 ± 3.0% at T6(95% CI:-4, 0.2);-22.9 ± 3.1%T12(95% CI:-3, 4, -1, 6) p < 0.02), were observed. Adherence to the Mediterranean diet was in the normal range. CONCLUSIONS: Despite unsupervised intervention, combined moderate physical exercise appears to have a positive effect on the main parameters related to cardiovascular risk factors. The long-term efficacy of this program requires further investigation, particularly for evaluating constant adherence to the home-based physical exercise program.

Broad spectrum of interferon-related nephropathies-glomerulonephritis, systemic lupus erythematosus-like syndrome and thrombotic microangiopathy: A case report and review of literature.

BACKGROUND: Interferons (IFNs) are characterized by a wide range of biological effects, which justifies their potential therapeutic use in several pathologies, but also elicit a wide array of adverse effects in almost every organ system. Among them, renal involvement is probably one of the most complex to identify. CASE SUMMARY: We describe four cases of kidney damage caused by different IFN formulations: IFN-ß-related thrombotic microangiopathy, IFN-ß-induced systemic lupus erythematosus, and two cases of membranous nephropathy secondary to pegylated-IFN-α 2B. In each case, we carefully excluded any other possible cause of renal involvement. Once suspected as the casual relationship between drug and kidney damage, IFN treatment was immediately discontinued. In three cases, we observed a complete and persistent remission of clinical and laboratory abnormalities after IFN withdrawal, while the patient who developed thrombotic microangiopathy, despite IFN withdrawal and complement-inhibitor therapy with eculizumab, showed persistent severe renal failure requiring dialysis. CONCLUSION: This case series highlights the causal relationship between IFN treatment and different types of renal involvement and enables us to delineate several peculiarities of this association.

Addition of azathioprine to corticosteroids does not benefit patients with IgA nephropathy.

The optimal treatment for IgA nephropathy (IgAN) remains unknown. Some patients respond to corticosteroids, suggesting that more aggressive treatment may provide additional benefit. We performed a randomized, multicenter, controlled trial to determine whether adding azathioprine to steroids improves renal outcome. We randomly assigned 207 IgAN patients with creatinine ≤2.0 mg/dl and proteinuria ≥1.0 g/d to either (1) a 3-day pulse of methylprednisolone in months 1, 3, and 5 in addition to both oral prednisone 0.5 mg/kg every other day and azathioprine 1.5 mg/kg per day for 6 months (n = 101, group 1) or (2) steroids alone on the same schedule (n = 106, group 2). The primary outcome was renal survival (time to 50% increase in plasma creatinine from baseline); secondary outcomes were changes in proteinuria over time and safety. After a median follow-up of 4.9 years, the primary endpoint occurred in 13 patients in group 1 (12.9%, 95% CI 7.5 to 20.9%) and 12 patients in group 2 (11.3%, CI 6.5 to 18.9%) (P = 0.83). Five-year cumulative renal survival was similar between groups (88 versus 89%; P = 0.83). Multivariate Cox regression analysis revealed that female gender, systolic BP, number of antihypertensive drugs, ACE inhibitor use, and proteinuria during follow-up predicted the risk of reaching the primary endpoint. Treatment significantly decreased proteinuria from 2.00 to 1.07 g/d during follow-up (P < 0.001) on average, with no difference between groups. Treatment-related adverse events were more frequent among those receiving azathioprine. In summary, adding low-dose azathioprine to corticosteroids for 6 months does not provide additional benefit to patients with IgAN and may increase the risk for adverse events.

Multiple immune disorders in unrecognized celiac disease: a case report.

We reported a female patient with unrecognized celiac disease and multiple extra intestinal manifestations, mainly related to a deranged immune function, including macroamilasemia, macrolipasemia, IgA nephropathy, thyroiditis, and anti-b2-glicoprotein-1 antibodies, that disappeared or improved after the implementation of a gluten-free diet.