Intravenous pulse methylprednisolone (MP) is commonly included in the management of severe ANCA associated vasculitis (AAV) despite limited evidence of benefit. We aimed to evaluate outcomes in patients who had, or had not received MP, along with standard therapy for remission induction in severe AAV. We retrospectively studied 114 consecutive patients from five centres in Europe and the United States with a new diagnosis of severe AAV (creatinine > 500 μmol/L or dialysis dependency) and that received standard therapy (plasma exchange, cyclophosphamide and high-dose oral corticosteroids) for remission induction with or without pulse MP between 2000 and 2013. We evaluated survival, renal recovery, relapses, and adverse events over the first 12 months. Fifty-two patients received pulse MP in addition to standard therapy compared to 62 patients that did not. There was no difference in survival, renal recovery or relapses. Treatment with MP associated with higher risk of infection during the first 3 months (hazard ratio (HR) 2.7, 95%CI [1.4–5.3], p = 0.004) and higher incidence of diabetes (HR 6.33 [1.94–20.63], p = 0.002), after adjustment for confounding factors. The results of this study suggest that addition of pulse intravenous MP to standard therapy for remission induction in severe AAV may not confer clinical benefit and may be associated with more episodes of infection and higher incidence of diabetes.

The relation that connects cancer and renal damage is bidirectional and this renal damage worsens quality of life and increases morbidity in high-complexity patients such as patients with cancer and kidney injury. Strikingly, in the last decade, the treatment of advanced cancer has clearly advanced in terms of new therapeutic strategies with the ability to transform the advanced metastatic cancer in a chronic condition. In this new era of cancer therapies, cancer treatment including conventional chemotherapy, targeted cancer agents and immunotherapies among others are significantly associated with kidney injury. Renal toxicity that is currently seen in onconephrology departments is in part related to the new therapies such as immunotherapy, and to the prolonged survival achieved at the expense of increasing therapy lines, and a combination of different drugs. In this review, we will discuss in a practical way, nephrotoxicity caused by the main oncospecific treatments such as classical chemotherapy agents, targeted therapies, and immunotherapy. In addition, strategies for prevention and management recommendations in patients with malignancies and kidney disease will also be addressed.

Objectives: ANCA-associated vasculitis (AAV) is a group of chronic diseases with relapses that associate organic damage because of the disease and its treatment. Avacopan is a new treatment indicated for AAV. We present the first experiences with avacopan in Spain as part of an Early Access program. Methods: Patients with AAV who started avacopan between June 2022 and September 2023 were included. For comparison, a historical cohort of patients diagnosed with AAV around the same time and treated without avacopan was also included. Results: Twenty-nine patients treated with avacopan were analysed. Twelve patients (41.4%) were male, and median age was 56 years. Most patients were ANCA MPO positive (21/29, 72.4%). The most frequently affected organ was the kidney (23/29, 79.31%), with a mean estimated glomerular filtration rate (eGFR) of 23.2 ml/min. Mean follow-up was 456.8 (±181.7) days with a remission rate of 86.2%. eGFR increased from 23.2 (11.2) to 38.38 (18.55) ml/min after 12 months of diagnosis. Two patients had adverse events related to avacopan (severe neutropenia and a gastrointestinal affectation), 13 infections were reported and one death. Patients treated with avacopan received a significantly lower cumulative dose of prednisone at 6 and 12 months (P-values of 0.02 and <0.01, respectively) compared with historical controls. The evolution of GFR at 1 year of follow-up and the incidence of relapse were similar in both groups. Conclusion: The combination of avacopan with standard immunosuppressive therapy presents a good safety profile and provides added value by contributing to the control of AAV activity, increase GFR and removal of steroids.

The closure of long-standing gaps in our knowledge of aetiological factors behind anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a major challenge. Descriptive and analytical epidemiological studies can improve our understanding of environmental influences. Reported seasonal variations in AAV, mainly related to Wegener's disease, have shown an increasing number of cases in the winter months, which could be related to an extrinsic factor underlying infection. The objective of this paper was to study seasonal variations in AAV with respect to renal affectation diagnosed in Catalonia, Spain. Two hundred and thirty-four patients diagnosed for renal AAV between 2001 and 2014 in eight hospitals in Catalonia were included in the study. We used medical records to retrospectively analyse the date of the first symptoms attributed to the AAV, ANCA subtypes, the degree of renal impairment and renal histology. Of the 234 patients studied, 49.2% were male and 50.8% female. For ANCA status, 8.5% were positive, 15.9% were proteinase-3-positive and 75.6% were myeloperoxidase-positive. In relation to histological classification, 17.8% were sclerotic, 11.7% focal, 38.8% crescentic and 31.7% mixed. Regarding seasonal distribution, we observed a clear seasonal periodicity with a significantly higher incidence of cases in the winter. Applying an Eigen decomposition, we observed a periodic fluctuation of frequencies around the annual cycle with peaks every 10–12 months, and higher incidence of AAV cases in February. Our results confirm, in Catalonia, the seasonal periodicity of AAV with a higher incidence in the winter, as formerly described in the literature for other regions. An environmental factor, likely one that is infectious, may explain this finding.

Background: The incidence of acute tubulointerstitial nephritis (ATIN) related to drugs has dramatically increased over recent years. A new subtype of ATIN, apparently different from classical drug-related ATIN, has emerged that has been related to the administration of immune checkpoint inhibitors (ICIs). We investigated these differences between ICI-related ATIN (ICI ATIN) and non-ICI-related ATIN in terms of clinical features, response to treatment with steroids and the evolution of kidney function. Methods: A total of 47 patients diagnosed with ATIN from two centres were recruited. Of these, 13 patients presented with ATIN during ICI treatment and 34 were diagnosed with ATIN attributed to other drugs. The main demographic, clinical and analytical variables such as gender, age and current medication were recorded. The type of malignancy, oncological treatment, ICI dose and presence of extrarenal immune-related adverse events were also reviewed. Renal biopsy diagnosis, time to drug withdrawal and ATIN-specific treatment, as well as laboratory data during follow-up, were also studied. Results: Patients diagnosed with ICI ATIN presented with lower creatinine (ICI ATIN 3.8 ± 1.03 versus classical ATIN 5.98 ± 4.15 mg/dL, P = 0.007) at diagnosis and higher urinary leucocyte counts (ICI ATIN 263.2 ± 418.04 versus classical ATIN 133.55 ± 284.62, P = 0.048) compared with patients with non-ICI-related ATIN. Time from initiation of the culprit drug to ATIN diagnosis was longer in patients with ICI ATIN than in those with classical ATIN (197.07 ± 184.99 versus 114.4 ± 352.16 days, P = 0.006). In addition, during follow-up, the slope of decreasing creatinine over time was lower for ICI ATIN compared with non-ICI-related ATIN. Conclusions: In this study, we analysed differences between ICI ATIN and classical ATIN. We found that patients with ICI ATIN presented with a larger latency period after culprit drug initiation, milder acute kidney injury and slower creatinine amelioration compared with those with classical ATIN. These results may, in part, be ascribed to potential differences in the pathological mechanisms involved in ATIN development, suggesting that ICI and classical ATIN may be different diseases with similar renal histologies.

The inflammasome is an immune multiprotein complex that activates pro-caspase 1 in response to inflammation-inducing stimuli and it leads to IL-1β and IL-18 proinflammatory cytokine production. NLRP1 and NLRP3 inflammasomes are the best characterized and they have been related to several autoimmune diseases. It is well known that the kidney expresses inflammasome genes, which can influence the development of some glomerulonephritis, such as lupus nephritis, ANCA glomerulonephritis, IgA nephropathy and anti-GBM nephropathy. Polymorphisms of these genes have also been described to play a role in autoimmune and kidney diseases. In this review, we describe the main characteristics, activation mechanisms, regulation and functions of the different inflammasomes. Moreover, we discuss the latest findings about the role of the inflammasome in several glomerulonephritis from three different points of view: in vitro, animal and human studies.