There is a growing concern within the medical community about the potential burden of microplastics on human organs and tissues. In this study, we investigated by microRaman spectroscopy the presence of microplastics in human kidneys and urine. Moreover, an open-access software was developed and validated for the project, which enabled the comparison between the investigated spectra and a self-created spectral database, thus enhancing the ability to characterize polymers and pigments in biological matrices. Healthy portions of ten kidneys obtained from nephrectomies, as well as ten urine samples from healthy donors were analyzed: 26 particles in both kidney and urine samples were identified, with sizes ranging from 3 to 13 μm in urine and from 1 to 29 μm in kidneys. The most frequently determined polymers are polyethylene and polystyrene, while the most common pigments are hematite and Cu-phthalocyanine. This preclinical study proves the presence of microplastics in renal tissues and confirms their presence in urine, providing the first evidence of kidney microplastics deposition in humans.

In this work we model the glomerular filtration barrier, the structure responsible for filtering the blood and preventing the loss of proteins, using human podocytes and glomerular endothelial cells seeded into microfluidic chips. In long-term cultures, cells maintain their morphology, form capillary-like structures and express slit diaphragm proteins. This system recapitulates functions and structure of the glomerulus, including permselectivity. When exposed to sera from patients with anti-podocyte autoantibodies, the chips show albuminuria proportional to patients’ proteinuria, phenomenon not observed with sera from healthy controls or individuals with primary podocyte defects. We also show its applicability for renal disease modeling and drug testing. A total of 2000 independent chips were analyzed, supporting high reproducibility and validation of the system for high-throughput screening of therapeutic compounds. The study of the patho-physiology of the glomerulus and identification of therapeutic targets are also feasible using this chip.

Plastic pollution became a main challenge for human beings as demonstrated by the increasing dispersion of plastic waste into the environment. Microplastics (MPs) have become ubiquitous and humans are exposed daily to inhalation or ingestion of plastic microparticles. Recent studies performed using mainly spectroscopy or spectrometry-based techniques have shown astounding evidence for the presence of MPs in human tissues, organs and fluids. The placenta, meconium, breast milk, lung, intestine, liver, heart and cardiovascular system, blood, urine and cerebrovascular liquid are afflicted by MPs’ presence and deposition. On the whole, obtained data underline a great heterogeneity among different tissue and organs of the polymers characterized and the microparticles’ dimension, even if most of them seem to be below 50–100 µm. Evidence for the possible contribution of MPs in human diseases is still limited and this field of study in medicine is in an initial state. However, increasing studies on their toxicity in vitro and in vivo suggest worrying effects on human cells mainly mediated by oxidative stress, inflammation and fibrosis. Nephrological studies are insufficient and evidence for the presence of MPs in human kidneys is still lacking, but the little evidence present in the literature has demonstrated histological and functional alteration of kidneys in animal models and cytotoxicity through apoptosis, autophagy, oxidative stress and inflammation in kidney cells. Overall, the manuscript we report in this review recommends urgent further study to analyze potential correlations between kidney disease and MPs’ exposure in human.

Significance Statement: Children with frequently relapsing, steroid-dependent nephrotic syndrome (FRSDNS) often require multiple courses of rituximab. However, long-term effects from repeated treatments remain unknown. In this international, multicenter study of 346 children receiving 1149 courses of rituximab, the risk of relapse decreased and relapse-free survival significantly improved with repeated treatments. Important side effects, including hypogammaglobulinemia, neutropenia, and infections, were mostly mild, but significant adverse events could occur. The incidence of side effects did not increase with more treatment courses nor a higher cumulative dose of rituximab. These findings suggest that repeating rituximab therapy is an effective and reasonably safe approach for most children with FRSDNS. Background: Long-term outcomes after multiple courses of rituximab among children with frequently relapsing, steroid-dependent nephrotic syndrome (FRSDNS) are unknown. Methods: A retrospective cohort study at 16 pediatric nephrology centers from ten countries in Asia, Europe, and North America included children with FRSDNS who received two or more courses of rituximab. Primary outcomes were relapse-free survival and adverse events. Results: A total of 346 children (age, 9.8 years; IQR, 6.6–13.5 years; 73% boys) received 1149 courses of rituximab. A total of 145, 83, 50, 28, 22, and 18 children received two, three, four, five, six, and seven or more courses, respectively. Median (IQR) follow-up was 5.9 (4.3–7.7) years. Relapse-free survival differed by treatment courses (clustered log-rank test P<0.001). Compared with the first course (10.0 months; 95% CI, 9.0 to 10.7 months), relapse-free period and relapse risk progressively improved after subsequent courses (12.0–16.0 months; HR_adj, 0.03–0.13; 95% CI, 0.01 to 0.18; P<0.001). The duration of B-cell depletion remained similar with repeated treatments (6.1 months; 95% CI, 6.0 to 6.3 months). Adverse events were mostly mild; the most common adverse events were hypogammaglobulinemia (50.9%), infection (4.5%), and neutropenia (3.7%). Side effects did not increase with more treatment courses nor a higher cumulative dose. Only 78 of the 353 episodes of hypogammaglobulinemia were clinically significant. Younger age at presentation (2.8 versus 3.3 years; P=0.05), age at first rituximab treatment (8.0 versus 10.0 years; P=0.01), and history of steroid resistance (28% versus 18%; P=0.01) were associated with significant hypogammaglobulinemia. All 53 infective episodes resolved, except for one patient with hepatitis B infection and another with EBV infection. There were 42 episodes of neutropenia, associated with history of steroid resistance (30% versus 20%; P=0.04). Upon last follow-up, 332 children (96%) had normal kidney function. Conclusions: Children receiving repeated courses of rituximab for FRSDNS experience an improving clinical response. Side effects appear acceptable, but significant complications can occur. These findings support repeated rituximab use in FRSDNS.

Erythropoietin (EPO) is a glycoprotein produced mainly by the adult kidney in response to hypoxia and is the crucial regulator of red blood cell production. EPO receptors (EPORs), however, are not confined to erythroid cells, but are expressed by many organs including the heart, brain, retina, pancreas, and kidney, where they mediate EPO‐induced, erythropoiesis‐independent, tissue‐protective effects. Some of these tissues also produce and locally release small amounts of EPO in response to organ injury as a mechanism of self‐repair. Growing evidence shows that EPO possesses also important immune‐modulating effects. Monocytes can produce EPO, and autocrine EPO/EPOR signaling in these cells is crucial in maintaining immunologic self‐tolerance. New data in mice and humans also indicate that EPO has a direct inhibitory effect on effector/memory T cells, while it promotes formation of regulatory T cells. This review examines the nonerythropoietic effects of EPO, with a special emphasis on its modulating activity on innate immune cells and T cells and on how it affects transplant outcomes.

Podocytopathies represent a group of glomerular disorders associated with minimal changes (MC) or focal segmental glomerulosclerosis (FSGS) lesion patterns at biopsy and heterogeneous responses to steroids. Anti-nephrin antibodies were previously found in such patients, suggesting an autoimmune form of podocytopathy. High resolution confocal microscopy on kidney biopsies of a cohort of 128 pediatric patients revealed localization of IgG along the slit diaphragm in 30% of patients with MC and 25% of those with FSGS, but not in other lesion patterns. Anti-nephrin IgG ELISA assay in the serum and stimulated emission depletion microscopy of kidney biopsies showed IgG-nephrin co-localization only in 77.8% of cases. Similar observations were obtained in a cohort of 48 adult patients with MC or FSGS at kidney biopsy, where IgG-nephrin colocalization was only 44.4%, suggesting the existence of autoantibodies binding to other slit proteins. Patients with anti-slit antibodies showed nephrotic syndrome at onset in 94.4% of cases. Patients with primary steroid-resistance had anti-slit antibodies in 27%, while those with secondary steroid-resistance in 87.5% of cases, irrespective of the histopathological lesion pattern. Steroid-resistant patients with anti-slit antibodies responded to second-line immunosuppressants in 92.3% vs. only 20% of patients that were anti-slit negative. No patient with anti-slit antibodies developed kidney failure vs. 51.7% of those negative for antibodies (66.7% with a genetic cause and 41.2% with a non-genetic cause). Thus, the detection of anti-slit antibodies can identify patients with an autoimmune podocytopathy responsive to treatment with second-line immunosuppressants, irrespective of the histopathological lesion pattern at biopsy.