INTRODUCTION: AL amy loidosis is caused by a plasma cell clone. Due to the impact of the disease on patient survival, careful evaluation of organ involvement is essential. Treat ment of A L amy loidosis should be adapted to the patient's degree of risk. AIM : We analy zed the clinical, laboratory and histological characteristics of 21 elderly patients (pts) (mean age 74.7 ± 7.97 yrs, range 55-81) with AL amylo idosis, including 17 patients (81%) with biopsy-proven renal involvement, who were ineligib le for bone marro w transplantation, and evaluated the impact of renal impairment on survival. RESULTS: Card iac and renal involvement was found in 67% of cases. Among the 17 patients with renal involvement, 12 had renal failure with proteinuria, and 1 showed isolated renal failu re and vascular amylo id deposition. Hematological response was 57.1 % at first line therapy (75% after three cycles). With regard to renal outcome, 6 of the 17 patients with renal involvement responded: proteinuria decreased fro m 4.2 to 1.1 gr/24 h (range 0.2-3 gr/ 24 h) with stabilization or improvement of serum Creatinine (sCr) levels. Applying the Staging System for Renal Outcome in AL A mylo idosis to our pts with biopsy-proven renal amylo idosis proved to be unreliable. Only severe renal failu re at d iagnosis was found to directly influence patient survival. CONCLUSIONS: To our knowledge this is the only case series in which the whole cohort of patients with urinary or functional abnormalit ies underwent a histological evaluation. None of the patients were elegible for bone marro w transplantation. Hematologic response was 57.1%, wh ile renal response was much lower (35%).Of note, the Staging System d id not comp letely apply to this peculiar setting of patients in who m renal involvement was not presumptive but actually biopsy-proven. More aggressive approaches are needed in these patients to avoid the inexorable progression of the disease.
Background: AL amyloidosis is a systemic disorder characterized by extracellular deposition of characteristic fibrils that results in progressive multi-organ failure and premature death. Recently daratumumab has been demonstrating higher hematological and organ response rates when compared to the standard of care. We hereby report our long-term experience on the effects of daratumumab given alone on the deposition of amyloid as evaluated in repeat renal biopsy. Results: Six patients were enrolled. All patients had proteinuria that was associated with renal function impairment in four. After therapy with daratumumab, four patients achieved complete hematological response and two had partial hematological response at the end of treatment. With regard to renal response, four out of six patients achieved an organ response; one patient had fluctuating proteinuria levels and did not meet the needed criteria at the end of the treatment and the last patient, who was already in dialysis at the time of therapy initiation, remained on dialysis despite complete hematological and cardiac responses. A significant decrease in 24-h proteinuria from 7.9 g/24 h to 1.1 (p < 0.005) with stabilization or improvement of sCr (from 1.5 mg/dL to 1.2 mg/dL; p = 0.34) were observed. All patients underwent a repeat biopsy after 24 administrations of daratumumab. In five patients, the repeat biopsy showed unchanged features; while in one it showed an improvement. Conclusions: Our data, based on real life experience, show that daratumumab monotherapy can be an effective therapeutic option. It is capable not only of achieving a substantial rate of renal improvement in pre-treated and naïve patients, but also of limiting renal deposition
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.
Background and Aims The introduction of innovative therapies, resulting from revisiting cancer as a disease of the immune system, has changed the scenario of complications. These new classes of drugs, such as targeted therapies and immune checkpoint inhibitors, assure substantial advantages in cancer therapy, despite some side affecting various organs, including the kidney. Histological evaluations of kidney disorders induced by targeted/immunotherapy are limited. Method In this study we examined the histological features of patients treated with new cancer agents who underwent kidney biopsy for new onset kidney failure and/or urinary abnormalities. Results The cohort included 30 adult patients. The most frequently administered therapies were immunotherapy (30%), targeted therapy (26.7%), immunotherapy plus targeted therapy (13.3%), immunotherapy plus chemotherapy (13.3%), targeted therapy plus chemotherapy (16.7%). The most common histological finding was tubular interstitial nephritis (30%) that was associated with acute tubular necrosis in 4 cases, and thrombotic microangiopathy (23.3%). After kidney biopsy, 16 of the 30 patients were treated according to the histological diagnosis. Fourteen patients were treated with steroids. One patient with membranous nephropathy was treated with a single dose of rituximab. A patient with severe thrombotic microangiopathy requiring dialysis received a treatment with eculizumab for 3 months. Overall some renal response was obtained in all patients treated with glucocorticoids, while complete kidney response was achieved in the patient treated with rituximab. Cancer treatment was resumed without change in 21 out of 30 patients. Conclusion Kidney biopsy is critical for the management of kidney toxicities and should be strongly encouraged for patients showing adverse kidney effects of novel cancer agents.
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