Cryoglobulinemia is a rare entity which frequently occurs in the setting of an underlying disease, with chronic hepatitis C virus infections and primary Sjogren syndrome being the most common ...underlying conditions. Cryoglobulinemic vasculitis (CV) is an immune-mediated type of small-vessel vasculitis with a broad spectrum of specific organ involvement, including renal, pulmonary, peripheral nerve, and cutaneous involvement and variable manifestations that can be life threatening. Moreover, a strong relationship between cryoglobulinemia and CV, with the future development of lymphoma, is well established. We present the case of a 72-year-old Caucasian male referred for nephrotic syndrome and acute renal injury. A diagnosis of Sjogren syndrome-associated CV was made, and he was successfully treated with rituximab and plasma exchange sessions.
Fibrillary glomerulonephritis (FGN) is a rare form of glomerulonephritis, and the incidence in native renal biopsies is less than 1%. The diagnosis of FGN is defined by the ultrastructural finding of ...organized, randomly oriented, nonbranching fibrils with a diameter of 10-30 nm. FGN is immune-mediated glomerulonephritis with predominant immunoglobulin (Ig) G deposits. Hypocomplementemia is very rare. We report the case of a 68-year-old Caucasian man with renal impairment, hematuria, subnephrotic proteinuria, hypocomplementemia (low C4, normal C3), and hypergammaglobulinemia. The kidney biopsy revealed a mesangial proliferative pattern with IgM deposits, and the electron microscopy demonstrated FGN. Upon further investigation, secondary causes, such as malignancy, monoclonal gammopathy, or autoimmune disease were excluded, and human immunodeficiency virus (HIV) infection was revealed. Only three cases with FGN associated with HIV infection without concurrent hepatitis C virus have been reported and all of them in already known medical records. Our patient received treatment with corticosteroids and highly active antiretroviral therapy, and the renal function improved.
Peripheral nervous system is early involved in Fabry disease (FD) and preferentially the small nerve fibers, causing the characteristic neuropathic pain crises usually beginning in childhood. Early ...detection of this likely underdiagnosed disease is an important approach because causal therapies are available.
We conducted a case-series study to investigate the small nerve fiber involvement in FD and its contribution to the diagnosis of the disease but also to the timely effective therapy administration. We used specific structured scales of symptoms and signs to detect peripheral neuropathy, as well as suitable functional and structural tests to diagnose the small fiber neuropathy (SFN).
Twenty-seven consecutive patients (14 men, mean age 44.62 ± 10.70 years) with suspected FD were included in this study. Most of the patients presented symptoms of small nerve fiber involvement, which were accompanied by abnormal test results, fulfilling the criteria for SFN. The detection of SFN in our patients allowed the completion of the FD diagnostic criteria and thus the initiation of therapy. In five patients the SFN diagnosis determined the administration of therapy, whereas in two others it might be considered.
Our results further suggest the importance of early diagnosis of peripheral neuropathy, especially of small nerve fiber involvement, in patients with suspected FD as it contributes crucially not only to the diagnosis but also to the timely effective initiation of FD therapy.
•Neuropathic pain crises and/or acroparesthesia are usually the first symptoms of Fabry disease starting early in childhood•The diagnosis of small nerve fibers involvement requires specific functional and structural tests.•The early detection of small nerve fibers involvement is crucial to establish the diagnosis the Fabry disease.•The early diagnosis of Fabry disease is necessary for timely effective initiation of therapy.•Early initiation of enzyme replacement therapy is crucial for reducing the morbidity and mortality.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Abstract
BACKGROUND AND AIMS
Transforming growth factor-β1 (TGF-β1) has long been considered as a potent, multifunctional cytokine that is involved in the pathogenesis of fibrosis and inflammation, ...which acts through Smad signaling in renal pathology. We intended to investigate the expression of TGF-β1/Smad3 signaling in glomerulonephritis (GN) and to assess its role as risk factor for progression to chronic kidney disease (CKD).
METHOD
We evaluated the immunohistochemical expression of TGF-β1, phosphorylated Smad3 (pSmad3) and Smad7 semiquantitatively and quantitatively using computerized image analysis program in different compartments of 50 renal biopsies with GN and the results were statistically analyzed with clinicopathological parameters. We also examined the associations among their expressions, the impact of their co-expression and their role in progression to CKD.
RESULTS
TGF-β1 expression correlated positively with segmental glomerulosclerosis (P = .025) and creatinine level at diagnosis (p = .002), while pSmad3 expression with interstitial inflammation (P = .024). In glomerulus, we recorded different expression patterns of pSmad3 in crescents, while concomitant expressions of strong Smad7 and moderate pSmad3 were observed to be correlated with renal inflammation, such as cellular crescent (P = .011), intense interstitial inflammation (P = .029) and lower serum complement 3 (P = .028) and complement 4 (P = .029). We also reported a significant preferable expression between pSmad3 and glomerular endothelial cells of proliferative GN (P = .045) and podocytes of non-proliferative GN (P = .005). Finally, on multivariate Cox-regression analysis, TGF-β1 expression (HR = 5.08; 95% CI 1.133–22.78; P = .034) was emerged as independent predictor for CKD.
CONCLUSION
TGF-β1/Smad3 dependent signaling is upregulated, especially in proliferative GN, with specific characteristics in different forms of GN. TGF-β1 expression is indicated as independent risk factor for progression to CKD, while specific co-expression pattern of pSmad3 and Smad7 in glomerulus is correlated with renal inflammation.
Abstract
BACKGROUND AND AIMS
Although vaccination against COVID-19 infection in dialysis patients is an urgent issue of worldwide concern, literature data regarding the antibody level and their ...kinetics over time and the efficacy towards complete COVID-19 vaccination and booster dose in these patients is inconclusive.
METHOD
We retrospectively assessed the response to COVID-19 vaccination, after the completion of vaccine series and after a booster dose in haemodialysis (HD) patients. IgG antibodies to the spike protein S1 subunit of SARS-CoV-2 were measured using ELISA at least 15 days after completion of a vaccination series, 1 month and finally 15–30 days after the booster dose.
RESULTS
Among the 28 vaccinated HD patients (mean age = 59.8 years, 100% male) with two doses of mRNA vaccine, a seroconversion was documented in all the patients (100%) with a median antibody titre of 3270.6 U/mL (IQR: 94–40.000). We recorded 9 out of 28 early responders (peak level at 2 weeks) and 19/28 late responders (peak level at 1 month). The early responders were younger (56.25 years versus 61.63; P = 0.07), without cardiovascular history (88% versus 44%; P = 0.042) or diabetes (100% versus 63%; P = 0.042), compared with late responders. On multivariate analysis, combined haemoperfusion and haemodialysis (HR = 0.167, 95% confidence interval: 0.034–0.826; P = 0.028) was an independent prognostic factor for early responders. After 6 months, all the patients received a booster mRNA dose. The patients presented median antibody levels of 33.939 U/mL (IQR: 1112–181.223), much higher titre than the first peak. Finally, four patients, all from the late responders group, presented COVID-19 infection during the vaccination period (two patients in the early period <1 month and two patients in the late period >5 months).
CONCLUSION
HD patients develop a substantial humoral response against SARS-CoV2 and the booster dose much higher response. The early responders presented more rapidly and more efficacious antibody levels, while the combined haemoperfusion and haemodialysis emerged as a positive predictor factor.
Abstract
Background and Aims
There is limited guidance and evidence for the ideal duration of maintenance treatment in ANCA-associated vasculitis (AAV) with rituximab (RTX). This study aimed to ...describe the efficacy and safety of long-term maintenance treatment with RTX, in a cohort of patients with AAV.
Method
Retrospective, descriptive study of 62 patients with AAV. We included 42 patients, who received RTX maintenance treatment in a newly diagnosed or a relapsed disease. We recorded the duration, dosage, and adverse events (infections, infusion-related events, relapses, late onset leukopenia, malignancy and hypogammaglobulinemia).
Results
43 patients (average age 60.33 years, 49% women) received fixed interval dosing with RTX maintenance 1000 mg every 6 months. The most frequent organ involvement (74%) was lung and/or kidney. 33% (14/43) of the patients received RTX maintenance in a relapsed disease. The RTX regimen was followed after induction treatment with rituximab (47%), cyclophosphamide (33%), combination cyclophosphamide and rituximab (14%) or methotrexate/MMF (6%). Median total duration of maintenance treatment was 24 months (range 6-72 months). The most frequent adverse event was serious infections in 23% of the patients, including SARS-CoV-2 in two patients, while four of these patients died. We also recorded: hypogammaglobulinemia in 14%, malignancy in 5% and infusion-related events in 2%. The rate of the major relapses in our cohort during RTX maintenance was quite low at 7% (3/43), the time between 24-60 months, and the rate of the major relapses dependent on the induction treatment was quite the same: cyclophosphamide group vs rituximab group (7 vs 10%, p=0.786).
Conclusion
In our cohort long-term maintenance treatment in AAV with rituximab maintains remission for longer time, with a quiet safety profile. This could suggest that in selected patients, extended periods of rituximab treatment might be safe.
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