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 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. Results: 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. Discussion: 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.

Fibrosis can be defined as a pathological process in which deposition of connective tissue replaces normal parenchyma. The kidney, like any organ or tissue, can be impacted by this maladaptive reaction, resulting in persistent inflammation or long-lasting injury. While glomerular injury has traditionally been regarded as the primary focus for classification and prognosis of lupus nephritis (LN), increasing attention has been placed on interstitial fibrosis and tubular atrophy as markers of injury severity, predictors of therapeutic response, and prognostic factors of renal outcome in recent years. This review will discuss the fibrogenesis in LN and known mechanisms of renal fibrosis. The importance of the chronicity index, which was recently added to the histological categorization of LN, and its role in predicting treatment response and renal prognosis for patients with LN, will be explored. A better understanding of cellular and molecular pathways involved in fibrosis in LN could enable the identification of individuals at higher risk of progression to chronic kidney disease and end-stage renal disease, and the development of new therapeutic strategies for lupus patients.

The hepatitis B virus (HBV) infection leads to chronic hepatitis, cirrhosis, and hepatocarcinoma. However, about 20% of patients experience extrahepatic manifestations such as polyarteritis nodosa, non-rheumatoid arthritis, non-Hodgkin lymphoma, cryoglobulinemic vasculitis, and glomerulonephritis. These influence the patient’s morbidity, quality of life and mortality. The treatment of an HBV infection is based on nucleotide analogues (NAs) which are safe and effective for the suppression of HBV-DNA in almost 100% of cases. A few studies have shown that NAs induce a viral response and an improvement of extrahepatic diseases. There is a lack of a thorough analysis of the available treatments for extrahepatic HBV manifestations. In 90% to 100% of cases, the NAs stop the HBV replication, and they produce a clinical response in the majority of patients with mild to moderate extrahepatic signs/symptoms. Arthritis can definitely disappear after the HBV elimination and, in some cases, the HBV eradication following NAs therapy appears to improve the renal function in HBV-related nephropathies. Plasma exchange can be used in subjects who are suffering from the most aggressive forms of cryoglobulinemic vasculitis and glomerulonephritis, progressive peripheral neuropathy, and life-threatening cases, and this can be combined with glucocorticosteroids and antiviral agents. In selected refractory patients, the use of rituximab in conjunction with NAs therapy can be considered. The review provides an update on extrahepatic conditions that are linked to HBV and the impact of treating HBV with NAs.

Immunoglobulin light chain amyloidosis (AL amyloidosis) is a rare systemic disease characterized by monoclonal light chains (LCs) depositing in tissue as insoluble fibrils, causing irreversible tissue damage. The mechanisms involved in aggregation and deposition of LCs are not fully understood, but CD138/38 plasma cells (PCs) are undoubtedly involved in monoclonal LC production.CD38 is a pleiotropic molecule detectable on the surface of PCs and maintained during the neoplastic transformation in multiple myeloma (MM). CD38 is expressed on T, B and NK cell populations as well, though at a lower cell surface density. CD38 is an ideal target in the management of PC dyscrasia, including AL amyloidosis, and indeed anti-CD38 monoclonal antibodies (MoAbs) have promising therapeutic potential. Anti-CD38 MoAbs act both as PC-depleting agents and as modulators of the balance of the immune cells. These aspects, together with their interaction with Fc receptors (FcRs) and neonatal FcRs, are specifically addressed in this paper. Moreover, the initiallyavailable experiences with the anti-CD38 MoAb DARA in AL amyloidosis are reviewed.

In the countries where HCV infection is still endemic, about 90% of subjects with mixed cryoglobulinemia had previously been infected with HCV and about 80% are RNA positive. Remarkable results in severe HCV-related cryoglobulinemic vasculitis have been obtained with Rituximab. Details of the clinical characteristics and effective treatment of non HCV-related cryogloulinemic syndromes are presently lacking. This paper reports on a prospective single-Center open study aimed at evaluating the clinical presentation and effects of Rituximab administered alone in patients with severe non HCV-related cryoglobulinemic syndrome. The study group included 11 patients followed for at least 6 months. Three patients had type I cryoglobulinemia, 6 had type II and the remaining 2 patients had type III. Mean cryocrit was 2.5%. Four out of 11 patients had symptomatic sicca complex with anti-SSA (Ro)/anti SSB (La) antibodies. All 11 patients presented with biopsy-proven renal involvement, 4 out of 11 with leukocytoclastic vasculitis, and 8 with involvement of the peripheral nervous system. Renal biopsy revealed diffuse membranoproliferative glomerulonephritis (MPGN) in 9 out of 11 patients. Extracapillary proliferation and necrosis of the glomerular tuft was observed in 1 of these 9 cases. Interstitial nephritis together with mesangial expansion and capillary immune deposits were observed in 1 patient. Prevalent interstitial fibrosis and glomerular sclerosis were detected in the remaining case. Patients underwent treatment with rituximab alone. After 6 months we observed a remarkable improvement in the necrotizing skin ulcers and a substantial amelioration of the electrophysiological parameters of motor and sensory peripheral neuropathy. Improvement in both renal function (from 2.8 to 1.4 mg/dl, p < 0.001) and proteinuria (from 4.2 g/24 to 0.4 g/24 h, p < 0.001) was found in 10 out of 11 patients, while 1 could not be fully treated because of a severe infusion reaction and sudden development of anti-Rituximab antibodies. Good renal response was confirmed at the end of follow-up (38.4 months). Three patients had a relapse at 6, 12, and 48 months, respectively. In our cohort the administration of 4 once-weekly infusions of Rituximab followed by 2 more infusions after 1 and 2 months proved to be effective in the management of these rare patients.

Transthyretin (TTR) amyloidosis (ATTR) is either an inherited condition or a non hereditary disease due to misfolding of wild-type (WT) TTR. Amyloid deposits can be mainly detected in nerves in the inherited form and in myocardium in the acquired variant. Renal involvement has been described only in the Val30Met mutation of the familial form and is thought to be extremely rare in the WT TTR. However, ATTR is multi-organ disease, and even in the WT forms, apparently limited to the heart, carpal tunnel syndrome and lumbar or cervical spine amyloid deposition have been described. A series of 4 cases of biopsy-proven renal TTR amyloid deposition is reported in the present paper. We describe 2 WT ATTR patients, 1 patient with c.424G>A (p.(Val142Ile)) mutation of the TTR gene, and 1 patient with Val30Met mutation of the TTR gene. In all patients, the biopsy showed the presence of amyloid deposits with different distribution (#1 pericapsular, #2–3 vessels, #4 vessels, interstitium of medulla and cortex, and tubular basement membrane). The use of immunohistochemistry has enabled the identification of TTR, and identify the precursor protein. The possibility of kidney involvement in TTR amyloidosis should be taken into account in patients with renal impairment and unexplained cardiomyopathy and/or neuropathy. This is even of greater interest to the elderly for the possible confounding co-existence of plasma cell dyscrasia that could lead the clinician, in the presence of renal amyloid deposits, to misdiagnose AL amyloidosis and undertake inappropriate treatments.