Chiara Casuscelli

In many immune-mediated kidney diseases, tissue injury is driven by dysregulated B-cell immunity, with autoantibodies and complement acting as key effectors at the glomerulus. Corticosteroids and conventional immunosuppressants control these diseases only in part, and they do so at the price of cumulative toxicity and frequent relapse. Anti-CD20 antibodies deplete circulating B cells but spare plasmablasts and CD19+ plasma cells that sustain autoantibody production, leaving a residual autoreactive compartment that may contribute to refractory disease and relapse. Anti-CD19 chimeric antigen receptor (CAR) T cells target a broader spectrum of B-cell populations, and early clinical studies suggest that this deeper depletion extends into secondary lymphoid tissues. The clinical evidence, however, is uneven. It is strongest in systemic lupus erythematosus and refractory lupus nephritis, where case series and early-phase trials report clinical and serological remission together with discontinuation of immunosuppression and treatment-free remission. In multiple myeloma and immunoglobulin light-chain (AL) amyloidosis with renal involvement, anti-B-cell maturation antigen (anti-BCMA) CAR-T products are increasingly used in real-world cohorts of patients with reduced estimated glomerular filtration rate (eGFR) or on dialysis, while bispecific T-cell engagers such as teclistamab offer an off-the-shelf alternative. The toxicity of these agents concerns the nephrologist directly. Cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, tumor lysis syndrome, and the immune effector cell-associated hemophagocytic lymphohistiocytosis-like syndrome (IEC-HS) (IEC-HS) can each involve the kidney, as can the newly defined local immune effector cell-associated toxicity syndrome (LICATS). This review explores the immunological basis of CAR-T constructs, the evidence by disease, the renal toxicity profile, and the criteria for candidate selection and nephrological monitoring.

Renal impairment affects up to half of patients with newly diagnosed multiple myeloma, and roughly 2–4% require dialysis at presentation, most often because of light-chain cast nephropathy. In these patients, renal recovery is associated with the speed and magnitude of serum free light-chain (sFLC) reduction in observational cohorts, an association that mainly reflects the hematologic response to chemotherapy; the incremental benefit of removing circulating sFLCs by extracorporeal means remains uncertain, and this narrative review is organized around that question in the current era of effective antimyeloma therapy. Plasma exchange was tested in three small randomized trials before proteasome inhibitors were available, the largest finding no benefit, and two randomized trials of high-cutoff hemodialysis on a bortezomib backbone, MYRE and EuLITE, found no benefit for their primary renal endpoints, with more pulmonary infections in the high-cutoff arm of EuLITE. Medium-cutoff membranes, polymethylmethacrylate adsorptive dialyzers, and hemodiafiltration with endogenous reinfusion have achieved substantial sFLC reduction with less albumin loss in small uncontrolled series, without any randomized comparison against conventional dialysis. Daratumumab-containing induction lowers sFLCs within days and may further narrow the residual rationale for enhanced clearance. Conventional high-flux hemodialysis combined with prompt antimyeloma therapy is therefore the evidence-based standard kidney-replacement modality when dialysis is indicated; the patient subsets in which a time-limited enhanced-removal strategy might still be tested are proposed as hypotheses for prospective trials, without validated thresholds.

Cryptococcosis, an opportunistic fungal infection predominantly caused by Cryptococcus neoformans, is the third most common invasive fungal disease in solid organ transplant recipients. While well-characterized in adult kidney transplant (KT) patients, pediatric data remain sparse. This article compares clinical presentation, immune response, renal involvement, and management strategies of cryptococcosis between adult and pediatric KT recipients. In adults, the disease typically presents as cryptococcal meningitis or pulmonary infection, often complicated by delayed diagnosis and high mortality. In contrast, children frequently exhibit non-specific respiratory symptoms or disseminated disease, reflecting immune immaturity and increased susceptibility to hematogenous spread. Key immunopathological differences include impaired Th1 type responses, macrophage dysfunction, and variable complement activity across age groups. Management involves similar antifungal regimens such as liposomal amphotericin B, flucytosine, and fluconazole, but requires weight-based dosing and careful toxicity monitoring in pediatric patients. Early diagnosis through serum cryptococcal antigen screening, appropriate adjustment of immunosuppressive therapy, and coordinated multidisciplinary care are essential. The findings underscore the need for pediatric specific research and clinical vigilance, emphasizing tailored antifungal dosing and individualized immune management to improve outcomes in this vulnerable population.

Hypercalcemia is defined as a serum calcium concentration higher than 10.5 mg/gL or 2.6 mmol/L. Only 50% of serum calcium is active, presented as ionized calcium. The remaining half is bound to albumin, phosphate, and other serum anions, and their changes can affect the serum calcium concentration. Thus, to discriminate true hypercalcemia from pseudo hypercalcemia, an ionized calcium concentration higher than 1.3 mmol/L might be more appropriate. Many variables can lead to hypercalcemia, and managing them is necessary to treat this ion disorder. Indeed, it can be caused by malignancies, hematologic disorders, or genetic diseases such as familial hypocalciuric hypercalcemia, or it can be related to hormone disorders involving parathormone or vitamin D. For this condition, the correct diagnostic algorithm should be followed. In this review, we summarize the diagnostic steps to follow and detail each clinical pathway is involved in hypercalcemia.

The integrity of the glomerular filtration barrier maintains protein excretion below 150 mg/day. When urinary proteins increase, this indicates damage to the filtration barrier. However, proteinuria is not only a marker of kidney damage but also exacerbates it through various mechanisms involving the glomerular and tubulointerstitial compartments. Therefore, it is essential to intervene with renoprotective action that reduces the proteinuria. In this context, Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers are cornerstone treatments. Recent advancements include sodium–glucose cotransporter 2 inhibitors, initially used for glycemic control, now recognized for their renoprotective properties in both diabetic and non-diabetic populations. Another drug, Finerenone, a selective non-steroidal mineralocorticoid receptor antagonist, has emerged as a promising agent, offering anti-inflammatory and antifibrotic benefits with fewer side effects than traditional steroidal options. Finally, dual inhibition of angiotensin II and endothelin-1 receptors through agents like Sparsentan presents a novel approach with significant antiproteinuric effects in IgA nephropathy and focal segmental glomerulosclerosis. This brief review summarizes the mechanisms by which proteinuria promotes kidney damage and the renoprotective therapeutic approaches available, which can be combined with lifestyle modifications and specific treatments for underlying diseases to mitigate the progression of chronic kidney disease.

Background: Pregnancy involves complex hemodynamic and immune adaptations to support the developing fetus. The kidney assumes a pivotal role in orchestrating these mechanisms. However, renal disease poses a potential risk for adverse maternal–fetal outcomes. While kidney function, hypertension, and proteinuria are recognized as key influencers of risk, the mere presence of glomerular disease, independent of these factors, may wield significant impact. Methods: A brief review of the existing literature was conducted to synthesize current knowledge regarding the interplay between glomerulonephritis and pregnancy. Results: The review underscores the centrality of the kidney in the context of pregnancy and highlights the role of glomerular disease, particularly when active. It emphasizes multifaceted risk modulators, including kidney function, hypertension, and proteinuria. Conclusion: Understanding the dynamics between pregnancy and glomerulonephritis is crucial for optimizing maternal and fetal outcomes. Preconception counseling and collaborative nephro-gynecological management emerge as pivotal components in addressing the unique challenges posed by this medical interplay.

Membranous nephropathy is an autoimmune disease affecting the glomeruli and is one of the most common causes of nephrotic syndrome. In the absence of any therapy, 35% of patients develop end-stage renal disease. The discovery of autoantibodies such as phospholipase A2 receptor 1, antithrombospondin and neural epidermal growth factor-like 1 protein has greatly helped us to understand the pathogenesis and enable the diagnosis of this disease and to guide its treatment. Depending on the complications of nephrotic syndrome, patients with this disease receive supportive treatment with diuretics, ACE inhibitors or angiotensin-receptor blockers, lipid-lowering agents and anticoagulants. After assessing the risk of progression of end-stage renal disease, patients receive immunosuppressive therapy with various drugs such as cyclophosphamide, steroids, calcineurin inhibitors or rituximab. Since immunosuppressive drugs can cause life-threatening side effects and up to 30% of patients do not respond to therapy, new therapeutic approaches with drugs such as adrenocorticotropic hormone, belimumab, anti-plasma cell antibodies or complement-guided drugs are currently being tested. However, special attention needs to be paid to the choice of therapy in secondary forms or in specific clinical contexts such as membranous disease in children, pregnant women and patients undergoing kidney transplantation.

The ongoing glomerular damage of infections is not limited to the most widely known form of post-streptococcal glomerulonephritis, which is today less common in the Western world; other forms of glomerulonephritis are associated with several bacterial, viral and parasitic pathogens. The mechanisms responsible range from the direct damage of glomerular cells to the formation and deposition of immunocomplexes to molecular mimicry to the secretion of superantigens. Similarly, in the course of glomerular disease, infections are more frequent than in the general population due to the loss of immunoglobulins in urine and the immunosuppressive agents used to treat the autoimmune disease that decrease the activity of the immune system. Recognizing this two-way link, understanding its pathogenetic mechanism, and identifying the most appropriate therapeutic choice are essential for the personalized management of patients. In this continuously developing field, this short review summarizes the current state of the art as support for physicians, who are increasingly involved in managing patients with glomerular disease and infections.

Hyperphosphatemia is a common complication in advanced chronic kidney disease and contributes to cardiovascular morbidity and mortality. The present narrative review focuses on the management of phosphatemia in uremic patients receiving peritoneal dialysis. These patients frequently develop hyperphosphatemia since phosphate anion behaves as a middle-size molecule despite its low molecular weight. Accordingly, patient transporter characteristics and peritoneal dialysis modalities and prescriptions remarkably influence serum phosphate control. Given that phosphate peritoneal removal is often insufficient, especially in lower transporters, patients are often prescribed phosphate binders whose use in peritoneal dialysis is primarily based on clinical trials conducted in hemodialysis because very few studies have been performed solely in peritoneal dialysis populations. A crucial role in phosphate control among peritoneal dialysis patients is played by diet, which must help in reducing phosphorous intake while preventing malnutrition. Moreover, residual renal function, which is preserved in most peritoneal dialysis patients, significantly contributes to maintaining phosphate balance. The inadequate serum phosphate control observed in many patients on peritoneal dialysis highlights the need for large and well-designed clinical trials including exclusively peritoneal dialysis patients to evaluate the effects of a multiple therapeutic approach on serum phosphate control and on hard clinical outcomes in this high-risk population.