Hepatitis C virus (HCV) can cause a range of kidney diseases. HCV is the primary cause of mixed cryoglobulinaemia, which leads to cryoglobulinaemic vasculitis and cryoglobulinaemic glomerulonephritis (GN). Patients with acute cryoglobulinaemic vasculitis often exhibit acute kidney disease due to HCV infection, which typically progresses to acute kidney injury (AKI). HCV also increases the risk of chronic kidney disease (CKD) and the likelihood of developing end-stage renal disease (ESRD). Currently, direct-acting antiviral agents (DAAs) can be used to treat kidney disease at different stages. This review focuses on key findings regarding HCV and kidney disease, discusses the impact of DAAs, and highlights the need for further research and treatment.

Primary Sjögren\'s syndrome (pSS) is an autoimmune systemic disease characterized by the destruction of exocrine glands, mainly salivary and lacrimal glands. The diagnosis is generally made upon objective tests aimed at assessing salivary and lacrimal glandular function, autoantibody assays, and the results of labial salivary gland biopsies. A major salivary gland biopsy is usually reserved to assess lymphoproliferative complications. Recently, the sonographic evaluation of the major salivary glands has gained a crucial role in assessing the glandular parenchyma and early detecting abnormalities, while the role of ultrasonography in the assessment of lacrimal glands is still secondary. Our case report is about a male patient who presented parotid gland swelling and purpuric lesions, with preserved salivary and lacrimal glandular function. Considering the presence of risk factors associated with lymphoproliferative development and the peculiar characteristics detected by salivary and lacrimal gland ultrasonography, we performed a parotid gland biopsy, confirming Sjögren\'s syndrome. Our case demonstrates that lacrimal gland ultrasonography could be implemented, along with major salivary gland ultrasonography, as a routine procedure in evaluating patients with suspected or definite diagnoses of pSS.

Cryoglobulinaemia vasculitis can present with a variety of symptoms and there is limited data on the incidence and presentation of cryoglobulinaemia vasculitis in haemodialysis patients. We report a case of a 63-year-old male who had a series of presentations with rash, visual changes, abdominal pain, weight loss, fevers and digital ischaemia. This is on a background of a congenital single kidney with end-stage renal failure secondary to diabetes and hypertension, receiving haemodialysis for nearly 5 years. He initially experienced a leukocytoclastic vasculitis rash confirmed on skin biopsy, followed by multiple hospital presentations for undifferentiated abdominal pain and fever of unknown source. Jejunal biopsy revealed intestinal vasculitis. His peripheral blood flow cytometry and bone marrow biopsy were consistent with marginal zone lymphoma (indolent subtype, IgM kappa clone). Further testing revealed a type II cryoglobulinaemia consisting of an IgM kappa monoclonal band with polyclonal IgG (cryocrit 5%). A diagnosis of cryoglobulinaemia vasculitis was established and he was treated with pulsed methylprednisolone and rituximab therapy. However, after receiving three doses of rituximab the patient developed a presumed vasculitis-associated pulmonary haemorrhage for which he received treatment with five sessions of plasma exchange. His symptoms resolved and cryocrit reduced to < 1% after his final dose of rituximab. The clinical features of cryoglobulinaemia may be difficult to detect in chronic haemodialysis patients and vigilance is required.

Monoclonal immunoglobulin M-associated type I cryoglobulinaemia is poorly characterised. We screened 534 patients with monoclonal IgM disorders over a 9-year period and identified 134 patients with IgM type I cryoglobulins. Of these, 76% had Waldenström macroglobulinaemia (WM), 5% had other non-Hodgkin lymphoma (NHL) and 19% had IgM monoclonal gammopathy of undetermined significance (MGUS). Clinically relevant IgM-associated disorders (including cold agglutinin disease [CAD], anti-MAG antibodies, amyloidosis and Schnitzler syndrome) coexisted in 31%, more frequently in MGUS versus WM/NHL (72% vs. 22%/29%, p < 0.001). The majority of those with cryoglobulins and coexistent CAD/syndrome had the molecular characteristics of a CAD clone (wild-type MYD88 in 80%). A half of all patients had active manifestations at cryoglobulin detection: vasomotor (22%), cutaneous (16%), peripheral neuropathy (22%) and hyperviscosity (9%). 16/134 required treatment for cryoglobulin-related symptoms alone at a median of 38 days (range: 6-239) from cryoglobulin detection. At a median follow-up of 3 years (range: 0-10), 3-year cryoglobulinaemia-treatment-free survival was 77% (95% CI: 68%-84%). Age was the only predictor of overall survival. Predictors of cryoglobulinaemia-related treatment/death were hyperviscosity (HR: 73.01; 95% CI: 15.62-341.36, p < 0.0001) and cutaneous involvement (HR: 2.95; 95% CI: 1.13-7.71, p = 0.028). Type I IgM cryoglobulinaemia is more prevalent than previously described in IgM gammopathy and should be actively sought.

Serum autoantibodies targeting the SSA/Ro proteins are a key component of the classification criteria for the diagnosis of Sjögren\'s syndrome (SS). Most patients\' serum reacts with both Ro60 and Ro52 proteins. Here we compare the molecular and clinical characteristics of patients diagnosed with SS with anti-Ro52 in the presence or absence of anti-Ro60/La autoantibodies.
A cross-sectional study was performed. Patients in the SS biobank at Westmead Hospital (Sydney, Australia) that were positive for anti-Ro52 were included and stratified based on the absence (isolated) or presence (combined) of anti-Ro60/La, measured by line immunoassay. We examined clinical associations and the serological and molecular characteristics of anti-Ro52 using ELISA and mass spectrometry in serological groups.
A total of 123 SS patients were included for study. SS patients with isolated anti-Ro52 (12%) identified a severe serological subset characterised by higher disease activity, vasculitis, pulmonary involvement, rheumatoid factor (RhF) and cryoglobulinaemia. Serum antibodies reacting with Ro52 in the isolated anti-Ro52 subset displayed less isotype switching, less immunoglobulin variable region subfamily usage and a lower degree of somatic hypermutation than the combined anti-Ro52 subset.
In our cohort of SS patients, isolated anti-Ro52 represents a severe subset of SS, and is associated with the presence of cryoglobulinaemia. We therefore provide clinical relevance to the stratification of SS patients by their sero-reactivities. It is possible that the autoantibody patterns may be immunological epiphenomena of the underlying disease process, and further work is required to unearth the mechanisms of the differential clinical phenotypes.

To describe the clinical and pathological features of biopsy-proven cutaneous vasculitis (CV) associated with SLE, focusing on diagnosis classification and impact on overall SLE activity.
Retrospective multicentric cohort study including SLE patients with biopsy-proven CV identified by (i) data from pathology departments of three university hospitals and (ii) a national call for cases. SLE was defined according to 1997 revised ACR and/or 2019 ACR/EULAR criteria. CV diagnosis was confirmed histologically and classified by using the dermatological addendum of the Chapel Hill classification. SLE activity and flare severity at the time of CV diagnosis were assessed independently of vasculitis items with the SELENA-SLEDAI and SELENA-SLEDAI Flare Index.
Overall, 39 patients were included; 35 (90%) were female. Cutaneous manifestations included mostly palpable purpura (n = 21; 54%) and urticarial lesions (n = 18; 46%); lower limbs were the most common location (n = 33; 85%). Eleven (28%) patients exhibited extracutaneous vasculitis. A higher prevalence of Sjögren\'s syndrome (51%) was found compared with SLE patients without CV from the French referral centre group (12%, P < 0.0001) and the Swiss SLE Cohort (11%, P < 0.0001). CV was mostly classified as urticarial vasculitis (n = 14, 36%) and cryoglobulinaemia (n = 13, 33%). Only 2 (5%) patients had no other cause than SLE to explain the CV. Sixty-one percent of patients had inactive SLE.
SLE-related vasculitis seems very rare and other causes of vasculitis should be ruled out before considering this diagnosis. Moreover, in more than half of patients, CV was not associated with another sign of active SLE.

We report a 53-year-old man who presented with acute renal failure. His medical history revealed a spondyloarthropathy, for which secukinumab was started recently, and a monoclonal gammopathy of unknown significance. Kidney function deteriorated despite the withdrawal of secukinumab and dialysis was started. In the serum, type 1 cryoglobulins were present and a kidney biopsy showed ischaemic glomeruli, with thrombosis of the larger interlobular arteries. Other causes of thrombotic microangiopathy were excluded. Bone marrow immunophenotyping showed 1% monoclonal plasma cells. A diagnosis of monoclonal gammopathy of renal significance was made. Haematological treatment resulted in haematological and renal response.

UNASSIGNED: Direct-acting antiviral agents (DAAs) have shown high rates of sustained virological response in chronic hepatitis C virus (HCV) infection. However, the influence of DAAs on the course of kidney involvement in HCV-associated mixed cryoglobulinaemia (HCV-MC) has been little studied. The aim of this study was to analyse the effects of antiviral treatment on kidney prognosis and evolution in patients diagnosed with HCV-MC.
UNASSIGNED: The RENALCRYOGLOBULINEMIC study is an observational multicentre cohort study of 139 patients with HCV-MC from 14 Spanish centres. Clinical and laboratory parameters were measured before and after antiviral treatment. Primary endpoints were kidney survival and mortality after HCV-MC diagnosis. Secondary endpoints were clinical, immunological and virological responses after antiviral treatment.
UNASSIGNED: Patients were divided into three groups based on the treatment received: treatment with DAAs (n = 100) treatment with interferon (IFN) and ribavirin (RBV) (n = 24) and no treatment (n = 15). Patients were followed up for a median duration of 138 months (interquartile range 70-251. DAA treatment reduced overall mortality {hazard ratio [HR] 0.12 [95% confidence interval (CI) 0.04-0.40]; P < 0.001} and improved kidney survival [HR 0.10 ( 95% CI 0.04-0.33); P < 0.001].
UNASSIGNED: Results from the RENALCRYOGLOBULINEMIC study indicated that DAA treatment in patients with HCV-MC improves kidney survival and reduces mortality.

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Cryoglobulins are immunoglobulins that undergo reversible precipitation at cold temperatures. Monoclonal type-I cryoglobulinaemia is the least frequent and is associated to hematological diseases such as multiple myeloma, Waldenström\'s macroglobulinaemia, chronic lymphocytic leukaemia and lymphoma. We describe the case of a 60-year-old female patient, who suffered from burning pain in her feet for ten months before her admission. The patient presented intermittent distal cyanosis that progressed to digital ischaemia. She also reported paresthesia in her hands, difficulty in writing, and a 26-kg-weight loss. At the physical examination, it was identified livedo reticularis, palpable purpura, and painful ecchymotic lesions in her calves and feet. Moreover, peripheral pulses were palpable and symmetrical. It was observed an atrophy of the right first dorsal interosseous and both extensor digitorum brevis, as well as a distal bilateral apalesthesia and allodynia. Both Achilles reflexes were absent. Laboratory tests revealed anemia, high erythrosedimentation rate and C-reactive protein. Serum protein electrophoresis showed a monoclonal IgG-Kappa gammopathy. The results also evidenced the presence of Bence-Jones proteinuria. The bone marrow biopsy revealed less than 10% of plasma cells, and skin biopsy informed leukocytoclastic vasculitis. The patient was treated with high-dose intravenous steroids and cyclophosphamide. The treatment showed that the skin lesions had improved, pain disappeared and motor deficit stopped its progression.