<b><i>Introduction:</i></b> To date, almost 7 billion doses of the different types of vaccine against SARS-CoV-2 have been administered worldwide. Although the severity of new cases of SARS-CoV-2 has progressively decreased, and the pressure on national health systems has declined, the development of de novo glomerular injuries has been suggested. <b><i>Methods:</i></b> This study aimed to examine the patients who were hospitalized in our Unit between April and November 2021 and underwent renal biopsy for new-onset urinary abnormalities (UA) and/or renal impairment within 3 months of SARS-CoV-2 vaccination. <b><i>Results:</i></b> We identified 17 patients who developed UA and/or renal insufficiency within 3 months of vaccination. Minimal change disease was the most common disease in our cohort (5 patients, 29.4%) followed by acute tubulointerstitial nephritis (TIN; 3 patients, 17.6%), membranous nephropathy (3 patients, 17.6%), and rapidly progressive IgA nephropathy (2 patients, 11.8%). The other 4 patients had a diagnosis of membranoproliferative glomerulonephritis (1 patient), systemic lupus erythematosus (1 patient), ANCA-associated vasculitis (1 patient), and tip-variant focal segmental glomerulosclerosis (1 patient), respectively. Eight out of the 17 patients (47.1%) developed acute kidney injury. Two patients with acute TIN had to start hemodialysis that was discontinued after 1 and 2 months, respectively, due to the recovery of renal function. All patients underwent treatment with corticosteroids and/or immunosuppressants. <b><i>Discussion:</i></b> Although it is not possible to conclusively determine whether there is a causal relationship between SARS-CoV-2 vaccination and new-onset nephropathies, based on the appearance of UA and/or renal insufficiency shortly after vaccination, we hypothesize that the immune response to the COVID-19 vaccine may be a trigger of nephropathies. Therefore, our results highlight the need for pharmacovigilance. However, this report should not lead to vaccine hesitation during this pandemic as the benefits of vaccination strongly outweigh the potential risks.
Background and Aims Daratumumab is an anti-CD38 monoclonal antibody recently approved as a first-line therapy on top of standard therapy for the treatment of multiple myeloma and AL amyloidosis. The mechanism of action of Daratumumab is based on its ability to bind CD38, a transmembrane receptor expressed in particular by pathogenic plasma cells, inducing their death through multiple intra and extracellular signaling mechanisms and thus interrupting the production of monoclonal light chains and consequently the deposition of new amyloid substance. The following data describe the good results reported by our group and the long-term experience achieved in recent years on the efficacy of daratumumab used in monotherapy. Methods This paper describes 17 patients affected by AL amyloidosis who were treated with Daratumumab alone, 24 iv administration at a dose of 16 mg/kg. All of them had an histological confirmation and staging of renal involvement before treatment was started and were ineligible for ASCT A bone marrow biopsy excluded overt multiple myeloma and the patient could either be naïve or refractory. Haematological and organ response was evaluated every 4 infusions by checking NTproBNP, dFLC and FLC ratio, serum creatinine, Upt (24h), serum and urine IF; responses were defined by using the International Society of Amyloidosis extended criteria. When feasable, the patient who underwent the whole cycle of therapy underwent a second kidney biopsy at the end of the treatment. Results | mean age at diagnosis was 73 years. 16 out of 17 patients had proteinuria (in the nephrotic range in 11) that was associated with renal function impairment in 11. Two patients were on dialysis at the time of therapy initiation. 9 patient completed the treatment; 13 over 17 underwent at least 12 infusions. At this time, At the 12 th administrations 11 out of 13 pts (84,6%) had an overall hematological response. 6 pts (46,5%) achieved a complete hematological response, 5 pts had a very good partial response (38%), and 2 were non responders (15,5%). As regard to renal response 5/13 had already achieved an organ response; 6 didn't meet renal response criteria yet; the 2 patients who were in dialysis at the time of therapy initiation, remained on dialysis. 1 of them had a complete hematological and cardiac responses, the remaining pt didn't have any response. 7/9 achieved a renal response; the 2 remaining patients who were in dialysis at the time of therapy initiation, remained on dialysis. A significant decrease in 24-hour proteinuria from 6,02 g/24 hours (range 0,8 – 16,8) to 1,28 g/die (range 0,9 – 3,6 gr/die, p < 0.005) with stabilization or improvement of sCr (from 1,66 mg/dl to 1,1 mg/dl, p = 0.17) were observed. 8/9 patients with cardiac involvement obtained at least amelioration. At the end of follow-up (mean 30 months, range 19-46) 5 patients have persistent hematological and renal response. One patient with initial partial response had a relapse and initiated a treatment with Bortezomib plus cyclophosphamide and dexamethasone. Two patients died to COVID infection and cardiovascular disease respectively. The last patient is still alive and is currently being treated with a second line of therapy, because no hematologic or organ response was achieved with Daratumumab. 7 patients underwent a second kidney biopsy at the end of the treatment. Histological findings showed stable deposits in 6 over 7 cases, while the last one showed a reduction in the extention and amount of amyliod deposits. Conclusion The optimal management of patients with AL amyloidosis remains to be defined. In particular patients who are ineligible for transplant continue to have a poor outcome. In recent years daratumumab has emerged as an appealing therapeutic alternative as shown by several reports. However, in clinical trials daratumumab was always added to bortezomib, cyclophosphamide and dexamethasone. Our data, based on the real life experience of our center, suggest that daratumumab monotherapy may represent an effective therapeutic option, capable not only of inducing a substantial improvement in the renal status in pretreated or naïve patients, but also of limiting progression of amyloid deposition.
Background and Aims Rituximab (RTX) has shown to be an effective induction treatment for small-vessel vasculitides associated with antineutrophil cytoplasm antibodies (AAV) in both newly diagnosed and relapsing patients. However, the role of RTX in the management of the most severe cases of AAV remains to be fully elucidated. The aim of this study was to assess both safety and efficacy of an intensified B-cell depletion therapy (IBCDT) protocol, including RTX, cyclophosphamide (CYC), and methylprednisolone pulses without additional maintenance immunosuppressive therapy in a cohort of 15 AAV patients with the most severe features of AVV renal involvement (as <15 ml/min GFR and histological findings of paucimmune necrotizing glomerulonephritis with more than 50% crescents of non-sclerotic glomeruli at the renal biopsy). Method Results of the IBCDT regimen have been compared to those obtained in a control cohort of 10 patients with AAV treated with a conventional therapy regimen based on oral CYC and steroids followed by a prolonged maintenance therapy with azathioprine (AZA). Plasma exchange was equally employed in the study and the control group. Results Complete clinical remission (BVAS 0) was observed at 6 months in 14 of 15 patients treated with IBCDT (93%). All cases who achieved a complete clinical remission experienced a depletion of peripheral blood B cells at the end of therapy. Of the 10 dialysis dependent patients at onset, 6 subjects (60%) experienced a functional recovery allowing the suspension of dialysis treatment. When compared to the control group, no statistically significant difference was observed in patients treated with IBCDT in terms of overall survival, 6-month therapeutic response rate, and 6-, and 12-month functional renal recovery. The cumulative total dose of CYC in the case group was on average 1 g/patient while in the control group on average 8.5 g/patient (p = 0.00008). Conclusion Despite the retrospective design and relative limited sample size, IBCDT appeared to be safe and had the same efficacy profile when compared to the conventional therapy with CYC plus AZA in the management of the most severe patients with AAV. Additionally, this avoided the need of prolonged maintenance therapy for long, and limited the exposure to CYC with consequent reduced toxicity and drug-related side effect rates.
Introduction To date, almost 7 billion doses of the different types of vaccine against SARS-CoV-2 have been administered worldwide. Although the severity of new cases of SARS-CoV-2 has progressively decreased, and the pressure on national health systems has declined, the development of de novo glomerular injuries has been suggested. Methods This study aimed to examine the patients who were hospitalized in our Unit between April 2021 and January 2023 and underwent renal biopsy for new-onset urinary abnormalities (UA) and/or renal impairment within 3 months of SARS-CoV-2 vaccination. Results We identified 22 patients who developed UA and/or renal insufficiency within 3 months of vaccination. Minimal change disease was the most common disease in our cohort (6 patients, 27.3%) followed by membranous nephropathy (MN; 5 patients, 22.7%), acute tubulointerstitial nephritis (TIN; 3 patients, 13.6%) and rapidly progressive IgA nephropathy (3 patients, 13.6%). The other 5 patients had a diagnosis of ANCA-associated vasculitis (2 patient), membranoproliferative glomerulonephritis (1 patient), systemic lupus erythematosus (1 patient) and tip-variant focal segmental glomerulosclerosis (1 patient), respectively. Nine out of the 22 patients (40.9%) developed acute kidney injury. Two patients with acute TIN had to start hemodialysis that was discontinued after 1 and 2 months, respectively, due to the recovery of renal function. Two of the 5 patients who had a diagnosis of MN were positive for anti-PLA2r, while all patients were negative for anti-thrombospondin. All patients underwent treatment with corticosteroids and/or immunosuppressants. Conclusion Although it is not possible to conclusively determine whether there is a causal relationship between SARS-CoV-2 vaccination and new-onset nephropathies, based on the appearance of UA and/or renal insufficiency shortly after vaccination, we hypothesize that the immune response to the COVID-19 vaccine may be a trigger of nephropathies. Therefore, our results highlight the need for pharmacovigilance. However, this report should not lead to vaccine hesitation during this pandemic as the benefits of vaccination strongly outweigh the potential risks.
Background and Aims Systemic amyloidosis is a cluster of disorders characterized by tissue deposition of amyloid (highly ordered fibrils composed of low molecular weight subunits of a variety of proteins). Transthyretin (TTR) amyloidosis (ATTR) is either an autosomal dominant inherited condition (ATTRv, where v stands for “variant”) or a non hereditary disease due to misfolding of wild-type TTR (ATTRwt). ATTR is likely underdiagnosed due to its clinical variability and lack of specific symptoms or biomarkers. The first aim of the study is to emphasise the importance of suspecting ATTR when facing certain clinical manifestations in association with renal impairment and urinary abnormalities. Furthermore, renal biopsy provides crucial information for a correct diagnosis and treatment approach. Method We report 5 cases of biopsy-proven renal ATTR deposition in patients presenting with mild to moderate renal impairment and mild urinary abnormalities. The TTR precursor has been confirmed in kidney specimens by immunohistochemistry. Genotyping was carried out in every patient. Results The presence of amyloid was found in all patients, with different distribution (#1-3 pericapsular and vascular; #2 vascular; #4 mesangial, vascular, in tubular basement membrane and in the interstitium of cortex and medulla; #5 pericapsular, vascular and interstitial). On genetic analysis three patients were wild-type (#1-2-5), one carried the c.424G>A (p.(Val142Ile)) mutation (#3) and the last one the Val30Met mutation (#4). Conclusion Suspicion of ATTR should be considered in patients with increase in serum creatinine, mild proteinuria and cardiac and peripheral nerve symptoms. This can be of utmost importance in elderly patients in whom a monoclonal gammopathy of undetermined significance can co-exist and drive a wrong diagnosis of primary light chain amyloidosis (AL), that could lead the clinician to undertake inappropriate treatments. Renal biopsy and genetic sequencing are both critical in diagnosing ATTR. Finally, we suggest distinguishing in the context of the ATTR deposition disease an ATTR nephropathy characterized by mesangial accumulation of amyloid, that impacts functional and urinary assessment, from isolated deposition in small vessels without specific clinical consequences, albeit critical for ATTR diagnosis.
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