Systemic lupus erythematosus (SLE) is a chronic, systemic autoimmune disease with a wide range of clinical expressions. The kidney is often affected, usually within 5 years of the onset of SLE, and lupus nephropathy (LN) carries a high risk for increased morbidity. The clinical heterogeneity of the disease is accompanied by complex disturbances affecting the immune system with inflammation and tissue damage due to loss of tolerance to nuclear antigens and the deposition of immune complexes in tissues. Several studies have reported that in human SLE, there is an important role of the Type-I-interferons (INF) system suggested by the upregulation of INF-inducible genes observed in serial gene expression microarray studies. This review aims to describe the transduction pathways of Type-I-interferons, in particular INFα, and its immune-regulatory function in the pathogenesis of SLE and, in particular, in LN. In addition, recent novelties concerning biologic therapy in LN will be discussed.

Glomerulonephritis (GN) continues to be one of the main causes of end-stage kidney disease (ESKD) with an incidence rating from 10.5% to 38.2%. Therefore, recurrent GN, previously considered to be a minor contributor to graft loss, is the third most common cause of graft failure 10 years after renal transplantation. However, the incidence, pathogenesis, and natural course of recurrences are still not completely understood. This review focuses on the most frequent diseases that recur after renal transplantation, analyzing rate of recurrence, epidemiology and risk factors, pathogenesis and bimolecular mechanisms, clinical presentation, diagnosis, and therapy, taking into consideration the limited data available in the literature. First of all, the risk for recurrence depends on the type of glomerulonephritis. For example, recipient patients with anti-glomerular basement membrane (GBM) disease present recurrence rarely, but often exhibit rapid graft loss. On the other hand, recipient patients with C3 glomerulonephritis present recurrence in more than 50% of cases, although the disease is generally slowly progressive. It should not be forgotten that every condition that can lead to chronic graft dysfunction should be considered in the differential diagnosis of recurrence. Therefore, a complete workup of renal biopsy, including light, immunofluorescence and electron microscopy study, is essential to provide the diagnosis, excluding alternative diagnosis that may require different treatment. We will examine in detail the biomolecular mechanisms of both native and transplanted kidney diseases, monitoring the risk of recurrence and optimizing the available treatment options.

Hypoxia activates hypoxia-related signaling pathways controlled by hypoxia-inducible factors (HIFs). HIFs represent a quick and effective detection system involved in the cellular response to insufficient oxygen concentration. Activation of HIF signaling pathways is involved in improving the oxygen supply, promoting cell survival through anaerobic ATP generation, and adapting energy metabolism to meet cell demands. Hypoxia can also contribute to the development of the aging process, leading to aging-related degenerative diseases; among these, the aging of the immune system under hypoxic conditions can play a role in many different immune-mediated diseases. Thus, in this review we aim to discuss the role of HIF signaling pathways following cellular hypoxia and their effects on the mechanisms driving immune system senescence.

Aging is characterized by a chronic, low-grade inflammatory state known as inflammaging, which closely interacts with immunosenescence—the gradual deterioration of immune function. Together, these processes contribute to tissue dysfunction and the development of age-related diseases. This review explores the cellular and molecular mechanisms underlying inflammaging, including mitochondrial dysfunction, telomere attrition, impaired autophagy, and gut microbiota dysbiosis. A particular emphasis is given to the senescence-associated secretory phenotype (SASP), which sustains a pro-inflammatory microenvironment and exacerbates tissue damage. We further discuss the impact of inflammaging on major age-related pathologies, with a focus on the kidney as a paradigmatic model of age-related decline, where inflammaging and cellular senescence contribute to chronic kidney disease (CKD) and impaired regeneration. Finally, we summarize emerging therapeutic strategies such as senolytics, senomorphics, immunomodulation, and lifestyle interventions, aimed at reducing the burden of senescent cells, mitigating inflammaging and extending healthspan.

Access to renal transplantation guarantees a substantial improvement in the clinical condition and quality of life (QoL) for end-stage renal disease (ESRD) patients. In recent years, a greater number of older patients starting renal replacement therapies (RRT) have shown the long-term impact of conservative therapies for advanced CKD and the consequences of the uremic milieu, with a frail clinical condition that impacts not only their survival but also limits their access to transplantation. This process, referred to as “inflammaging,” might be reversible with a tailored approach, such as RRT accompanied by specific nutritional support. In this review, we summarize the evidence demonstrating the presence of several proinflammatory substances in the Western diet (WD) and the positive effect of unprocessed food consumption and increased fruit and vegetable intake, suggesting a new approach to reduce inflammaging with the improvement of ESRD clinical status. We conclude that the Mediterranean diet (MD), because of its modulative effects on microbiota and its anti-inflammaging properties, may be a cornerstone in a more precise nutritional support for patients on the waiting list for kidney transplantation.

Renal cell carcinoma (RCC) presents a significant diagnostic challenge, particularly in small renal masses. The search for non-invasive screening methods and biomarkers has directed research toward liquid biopsy, which focuses on microRNAs (miRNAs), exosomes, and circulating tumor cells (CTCs). miRNAs are small non-coding RNA molecules that show considerable dysregulation in RCC, and they have potential for both diagnostic and prognostic applications. Research has highlighted their utility on biofluids, such as plasma, serum, and urine, in detecting RCC and characterizing its subtypes. Promising miRNA signatures have been associated with overall survival, suggesting their potential importance in the management of RCC. Exosomes, which carry a variety of molecular components, including miRNAs, are emerging as valuable biomarkers, whereas CTCs, released from primary tumors into the bloodstream, provide critical information on cancer progression. However, translation of these findings into clinical practice requires additional validation and standardization through large-scale studies and robust evidence. Although there are currently no approved diagnostic tests for RCC, the future potential of liquid biopsy in monitoring, treatment decision-making, and outcome prediction in patients with this disease is significant. This review examined and discussed recent developments in liquid biopsy for RCC, assessing both the strengths and limitations of these approaches for managing this disease.