Kidney physiology shows diurnal variation, and a disrupted circadian rhythm is associated with kidney disease. However, it remains largely unknown whether glomeruli, the filtering units in the kidney, are under circadian control. Here, we investigated core circadian clock components in glomeruli, together with their rhythmic targets and modes of regulation. With clock gene reporter mice, cell-autonomous glomerular clocks which likely govern rhythmic fluctuations in glomerular physiology were identified. Using circadian time-series transcriptomic profiling, the first circadian glomerular transcriptome with 375 rhythmic transcripts, enriched for extracellular matrix and glucocorticoid receptor signaling ontologies, were identified. Subsets of rhythmic matrix-related genes required for basement membrane assembly and turnover, and circadian variation in matrix ultrastructure, coinciding with peak abundance of rhythmic basement membrane proteins, were uncovered. This provided multiomic evidence for interactions between glomerular matrix and intracellular time-keeping mechanisms. Furthermore, glucocorticoids, which are frequently used to treat glomerular disease, reset the podocyte clock and induce rhythmic expression of potential glomerular disease genes associated with nephrotic syndrome that included NPHS1 (nephrin) and NPHS2 (podocin). Disruption of the clock with pharmacological inhibition altered the expression of these disease genes, indicating an interplay between clock gene expression and key genes required for podocyte health. Thus, our results provide a strong basis for future investigations of the functional implications and therapeutic potential of chronotherapy in glomerular health and disease.

Extracellular vesicles, small membrane-bound packages secreted by virtually all cells of the body, have become a focus of interest in nephrology over the recent years. After the first characterization of their proteomic and transcriptomic content, the scientific attention shifted toward their potential as biomarkers for kidney diseases both as diagnostic and monitoring tools. More recently, researchers have begun exploring whether extracellular vesicles mediate intercellular signaling inside the nephron and between the kidney and other organs throughout the body. Nevertheless, the field of extracellular vesicle research has struggled to translate major findings to the clinical context due to numerous methods to separate extracellular vesicles, yielding fractions of different sizes and varying purity, unclear terminology, and, hence, limitations concerning reproducibility. The International Society of Extracellular Vesicles, therefore, has striven to reduce these barriers by an ongoing initiative to increase rigor and standardization of extracellular vesicle research. The "Minimal Information for Studies of Extracellular Vesicles" guideline is the result of this initiative and, in its now third iteration, provides the most concise suggestions for investigating extracellular vesicles to date. This mini review illustrates the advances made in extracellular vesicle research in nephrology so far using informative examples, outlines the advances made by the former Minimal Information for Studies of Extracellular Vesicles guidelines, and shows what potential using the latest iteration holds.

Patients with glomerular disease are at high risk of cardiovascular disease but the contribution of immunosuppression to this risk is unclear. In this retrospective cohort study of 1912 patients (comprised of 759 with IgA nephropathy, 540 with focal segmental glomerulosclerosis, 387 with membranous nephropathy and 226 with minimal change disease) from British Columbia, Canada, we evaluated the association between exposure to specific immunosuppressive medications and a composite outcome including coronary artery, cerebrovascular and peripheral arterial events. Survival models were adjusted for baseline cardiovascular risk factors, type of glomerular disease, estimated glomerular filtration rate (eGFR) and proteinuria over time. During a median follow-up of 6.8 years, 212 patients (11.1%) experienced the primary outcome. Corticosteroid exposure was not significantly associated with the primary outcome after adjusting for cardiovascular risk factors. In fully adjusted models, cumulative calcineurin inhibitor exposure at modest (150-300 defined daily doses [DDD]) and higher (300 or more DDD) doses were associated with a 2-fold higher risk of cardiovascular events (hazard ratio 2.98, 95% confidence interval 1.27-6.95) and (2.78, 1.32-5.84), respectively. A peak daily dose of antimetabolite (azathioprine, mycophenolate mofetil and mycophenolate sodium) of 0.5 or more DDD was associated with higher risk of cardiovascular events after adjustment for baseline risk factors and type of glomerular disease, but not after adjusting for time-varying eGFR and proteinuria (1.70, 0.91-3.20). Each 10 grams of cumulative cyclophosphamide exposure was associated with a 1.5-fold higher risk of cardiovascular events in a fully adjusted model (1.46, 1.22-1.75) Thus, our findings suggest that immunosuppressive therapies used in the treatment of glomerular disease may have different cardiovascular risk profiles, which should be considered when deciding on immunosuppression for individual patients and as a safety endpoint in future clinical trials.

Dialysis vascular access thrombosis poses a substantial challenge for individuals undergoing hemodialysis. The efficacy and safety of apixaban, a direct oral coagulation factor Xa inhibitor, in preventing recurrent access thrombosis have yet to be explored. Here, a multicenter randomized control study (NCT04489849) enrolled hemodialysis patients to evaluate this who underwent successful endovascular thrombectomy within 48 hours. Participants were assigned to standard care or standard care plus apixaban, 2.5 mg twice daily for three months. The trial design involved open-label administration, with independent adjudication of endpoints. The primary efficacy endpoint was recurrent access thrombosis within three months after thrombectomy. A total of 186 patients with well-balanced baseline characteristics were enrolled, 93 randomized to the apixaban group and 93 to the control group. The apixaban group demonstrated a significantly lower rate of access thrombosis at three months than the control group (24.0% vs. 40.8%; hazard ratio, 0.52 [95% confidence interval 0.31-0.88]), along with a significantly better primary patency failure rate (32.2% vs. 49.5%, 0.57 [0.36-0.91]). Safety outcomes showed comparable death rates and major bleeding incidents but significantly higher incidence of minor bleeding in the apixaban group (22.6% vs. 7.5%). The effect of apixaban did not show interaction in subgroups of different access types, antiplatelet usage, severity of comorbidities, or history of thrombosis. Thus, apixaban effectively reduced the risk of recurrent thrombosis in hemodialysis vascular access post-thrombectomy. Despite a minor increase in bleeding adverse effects, the net clinical benefit favors the use of apixaban in this context.

The course of proliferative lupus nephritis is characterized by flares of activity alternating with periods of quiescence against a background of chronic immune dysregulation. An accurate assessment of disease activity is of unassailable importance to tailor therapy. In the present communication, we discuss the available clinical, serologic, and histologic tools to evaluate disease activity and how they may be applied to redefine the treatment goals in lupus nephritis. Traditionally, treatment response is judged by the degree of proteinuria reduction and improvement of kidney function, but this fails to differentiate ongoing inflammatory disease from chronic damage. Despite intensive research, no novel biomarker has proved useful for clinical practice, and we continue to rely on anti-double-stranded DNA antibody levels to assess serologic activity. Repeat kidney biopsies sometimes reveal persistent inflammation despite apparent clinical remission, giving credibility to the conviction that histologic remission should be a treatment goal and protocol biopsies be part of the decision-making process. However, the discrepancies between clinical and histologic responses to therapy can be explained by persistent systemic autoimmunity with low-grade immune complex deposition or, alternatively, by delayed clearance of intrarenal inflammation once immunologic remission has been achieved. Because persistent immune dysregulation is the motor of disease activity in lupus nephritis, it should be the principal focus of therapy and monitoring. We propose to replace the traditional induction-remission maintenance protocol by a more dynamic and individualized approach and aim for 3 treatment goals, concomitantly rather than sequentially: (i) clinical remission, by attenuating renal inflammation, using microscopic hematuria, proteinuria, estimated glomerular filtration rate, and complement levels as biomarkers; (ii) immunologic remission, by decreasing immune complex generation, using anti-double-stranded DNA antibody as a biomarker; and (iii) preservation of kidney function, by curtailing chronic kidney damage, using estimated glomerular filtration rate slope as a biomarker.

Glomeruli filter blood through the coordination of podocytes, mesangial cells, fenestrated endothelial cells, and the glomerular basement membrane. Cellular changes, such as podocyte loss, are associated with pathologies like diabetic kidney disease. However, little is known regarding the in situ molecular profiles of specific cell types and how these profiles change with disease. Matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI IMS) is well-suited for untargeted tissue mapping of a wide range of molecular classes. Importantly, additional imaging modalities can be integrated with MALDI IMS to associate these biomolecular distributions to specific cell types. Here, we integrated workflow combining MALDI IMS and multiplexed immunofluorescence (MxIF) microscopy. High spatial resolution MALDI IMS (5 μm) was used to determine lipid distributions within human glomeruli from a normal portion of fresh-frozen kidney cancer nephrectomy tissue revealing intra-glomerular lipid heterogeneity. Mass spectrometric data were linked to specific glomerular cell types and substructures through new methods that enable MxIF microscopy to be performed on the same tissue section following MALDI IMS, without sacrificing signal quality from either modality. Machine learning approaches were combined enabling cell type segmentation and identification based on MxIF data. This was followed by mining of cell type or cluster-associated MALDI IMS signatures using classification and interpretable machine learning. This allowed automated discovery of spatially specific molecular markers for glomerular cell types and substructures as well as lipids correlated to deep and superficial glomeruli. Overall, our work establishes a toolbox for probing molecular signatures of glomerular cell types and substructures within tissue microenvironments providing a framework applicable to other kidney tissue features and organ systems.

Endoplasmic Reticulum (ER) stress is a condition in which the ER is overwhelmed and unable to manage its protein load properly. The precise activation mechanisms and role of ER stress in kidney disease remain unclear. To study this, we performed unbiased transcriptomics analysis to demonstrate ER stress in kidneys of patients with chronic kidney disease and in mouse models of acute and chronic kidney injury (cisplatin and unilateral ureteral obstruction and reanalyzed previously published data on folic acid and mitochondrial transcription factor A(TFAM) knockout mice). Inhibiting the protein kinase RNA-like ER kinase (PERK) arm of ER stress but not activating transcription factor 6 or inositol-requiring enzyme 1, protected mice from kidney fibrosis. The stimulator of interferon genes (STING) was identified as an important upstream activator of ER stress in kidney tubule cells. STING and PERK were found to physically interact, and STING agonists induced PERK activation in kidney tubule cells. Mice with a STING activating mutation presented with ER stress and kidney fibroinflammation. We also generated mice with a tubule specific STING deletion that were resistant to ER stress and kidney fibrosis. Human kidney spatial transcriptomics highlighted a spatial correlation between STING, ER stress and fibrotic gene expression. Thus, our results indicate that STING is an important upstream regulator of PERK and ER stress in tubule cells during kidney fibrosis development.

Human pluripotent stem cell-derived kidney organoids hold promise for future applications in regenerative medicine. However, significant biological hurdles need to be overcome to enable their use as a transplantable stem cell-derived therapeutic graft. Current kidney organoid protocols do not recapitulate a complete integrated developing kidney, but embryonic kidney transplantations have provided clues for advancing maturation and functionality of kidney organoids. Transplantation, subsequent vascularization and blood perfusion of kidney organoids improve nephron patterning and maturation, suggesting a role for angiocrine factors as well as metabolic wiring in these processes. Transplanted organoids exhibit filtration, but the resulting filtrate has no apparent exit path for excretion. Improved in vitro patterning of kidney organoids may be required such that a more structurally correct tissue is formed prior to transplant. Here we review current progress with kidney organoid transplantation, their engraftment and integration, and identify the key obstacles to therapeutic success and how these might be achieved.

Can direct activation of soluble guanylyl cyclase (sGC) provide kidney-protection? To answer this, we tested the kidney-protective effects of a sGC activator, which functions independent of nitric oxide and with oxidized sGC, in an acute kidney injury (AKI) model with transition to chronic kidney disease (CKD). We hypothesize this treatment would provide protection of kidney microvasculature, kidney blood flow, fibrosis, inflammation, and kidney damage. Assessment took place on days three, seven, 14 (acute phase) and 84 (late phase) after unilateral ischemia reperfusion injury (IRI) in rats. Post-ischemia, animals received vehicle or the sGC activator BAY 60-2770 orally. In the vehicle group, medullary microvessels narrowed and cortical microvessels showed hypertrophic inward remodeling. The mRNA levels of acute injury markers (Kim-1, Ngal) were high in the acute phase but declined in the late phase. Kidney weight decreased after the acute phase, while fibrosis started after day seven. Abundance of fibrotic (Col1a, Tgf-β1) and inflammatory markers (Il-6, Tnf-α) remained elevated throughout, along with mononuclear cell invasion, with elevated plasma cystatin C and creatinine. BAY 60-2770 treatment increased tissue cGMP concentration, dilated kidney microvasculature, and enhanced blood flow and oxygenation. This intervention significantly attenuated kidney weight loss, cell damage, fibrosis, and inflammation. Plasma cystatin C and creatinine improved significantly with sGC activator treatment indicating functional recovery, though possible GFR increase above kidney reserve in uninjured kidneys could not be excluded. In cultured human tubular cells (HK-2 cells) exposed to hypoxia or profibrotic TGF-b, BAY 60-2770 improved abundance patterns of pathologically relevant genes. Overall, our results show that sGC activation may provide effective kidney-protection and attenuate the AKI-to-CKD transition.

Podocytes can undergo PANoptosis (apoptosis, pyroptosis, and necroptosis). Diabetic kidney disease (DKD) is the leading cause of kidney failure, and podocyte loss is a major event leading to the progression of DKD. Here, we compared single cell RNA sequencing (scRNA-seq) data between three normal and three DKD human kidney samples and found a significant increase of TNFSF10 and TNFRSF10B expression in podocytes of patients with DKD. Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), coded by TNFSF10, belongs to the TNF superfamily members and TNFRSF10B codes for death receptor 5 (DR5). We confirmed that expression of TRAIL and DR5 increased in podocytes of patients with DKD and correlated with the severity of DKD. In vitro, TNF-α stimulated TRAIL and DR5 expression in cultured human podocytes. Silence of TRAIL or DR5 by small interfering RNA alleviated TNF-α-stimulated podocytes PANoptosis, while overexpression of TRAIL, treatment with recombinant human TRAIL (rh-TRAIL) or the DR5 activator (Bioymifi) enhanced podocytes PANoptosis. In vivo, podocyte-specific deletion of TNFSF10 or TNFRSF10B alleviated podocyte and glomerular injury in high fat diet and streptozotocin-induced obese diabetic mice and was associated with decreased podocyte PANoptosis. Conversely, the induction of TNFSF10 overexpression specifically in podocytes exacerbated albuminuria and kidney injury in diabetic mice with increased podocyte PANoptosis. Additionally, administration of soluble DR5-Fc, an inhibitor of DR5, resulted in a marked reduction in albuminuria and glomerular injury in BTBR ob/ob mice. Our findings suggest a critical autocrine role of TRAIL/DR5 in inducing podocyte injury in DKD via activation of PANoptosis.

Idiopathic nephrotic syndrome (INS), the most common glomerular disorder in children, has long been considered an immune-mediated disease based on the efficacy of glucocorticoids at inducing remission. Nevertheless, the immune processes leading to podocytopathy have largely remained elusive. The success of B cell-depletion with rituximab, descriptions of B cell dysregulation during active disease, and the most recent discovery of autoantibodies targeting the major podocyte antigen Nephrin denote an autoimmune humoral etiology for INS. Research into the immune factors involved in INS pathogenesis have uncovered common features with other autoimmune disorders that will aid in prognostication and in guiding the expansion of our glucocorticoid-sparing therapeutic arsenal. In this review, we discuss the emerging autoimmune architecture of INS, with a specific focus on pediatric steroid-sensitive disease, including the podocyte-reactive B cell response that gives rise to anti-podocyte antibodies (APAs), the predisposing genetic factors that shape the podocyte-reactive immune landscape, and the immune triggers driving active disease.

While epidemiological and experimental studies have demonstrated kidney-protective effects of estrogen and female sex in adulthood, some epidemiological data showed deterioration of kidney function during puberty when estrogen production increases. However, molecular mechanisms explaining these conflicting phenomena remain unknown. Here, we showed that the pubertal sex hormone surge in female mice increases susceptibility to kidney ischemia reperfusion injury partly via downregulation of insulin-like growth factor 1 receptor (IGF-1R) expression in proximal tubules. Adult mice ovariectomized pre-pubertally (at postnatal day 21) showed strong tolerance to kidney ischemia, which was partly reversed by the administration of 17β-estradiol, while adult mice ovariectomized post-pubertally (at 8 weeks of age) were vulnerable to kidney ischemia. Kidney tubular IGF-1R protein expression decreased during postnatal growth but was highly expressed in adult mice ovariectomized pre-pubertally and in infant mice, which might be partly explained by different expression of an E3 ligase (MDM2) of IGF-1R. Mice deficient of Igf-1r in proximal tubules (iIGF-1RKO mice) during postnatal kidney growth showed increased susceptibility to ischemic injury. RNA-seq and western blotting analysis using proximal tubular cells from pre-pubertally ovariectomized iIGF-1RKO and control mice revealed altered expression of cell cycle-associated molecules such as cyclin D1. These results suggest that Igf-1r deletion during postnatal growth renders proximal tubular cells susceptible to ischemia possibly via altered cell cycle regulation. Thus, our findings provide evidence that exposure to pubertal sex hormones leads to increased susceptibility to kidney ischemia, which is partly mediated by modulation of IGF-1R signaling.

Based on the hypothesis that hyperuricemia is a modifiable risk factor for chronic kidney disease (CKD) progression, there is an expectation that urate-lowering therapy (ULT) could delay the progression of CKD. Here, we investigated changes in kidney function and the association of the serum uric acid (sUA) level and kidney function during ULT in patients with gout. To do this we conducted post-hoc analysis on patients who received ULT with either febuxostat or allopurinol for more than six months in the CARES trial. The estimated glomerular filtration rate (eGFR) slope (annual rate of change in eGFR) was calculated using the CKD- EPI creatinine equation and linear mixed modeling. Among the 5,002 patients with gout, 3,264 (65.3%) demonstrated an increased eGFR while receiving ULT over a median follow-up of 2.5 years. Increased average sUA levels were significantly associated with declines in eGFR slope (per 1 mg/dL increase, (adjusted beta of -0.1912). Propensity score matched analysis demonstrated a significant association between low average sUA levels below 6 mg/dL during ULT and a reduced risk of eGFR decline (adjusted odds ratio: 0.66, 95% confidence interval 0.57-0.77). Despite the well-documented natural decline of eGFR over time in the general population, more than half of the patients enrolled in the CARES trial did not experience declines in eGFR while receiving ULT. Thus, our study shows maintaining low sUA levels with ULT was significantly associated with a decreased risk of CKD progression in patients with gout.

Onset, progression and cardiovascular outcome of chronic kidney disease (CKD) are influenced by the concomitant sterile inflammation. The pro-inflammatory cytokine family interleukin (IL)-1 is crucial in CKD with the key alarmin IL-1 playing an additional role as an adhesion molecule that facilitates immune cell tissue infiltration and consequently inflammation. Here, we investigate calcium ion and reactive oxygen species (ROS)-dependent regulation of different aspects of IL-1-mediated inflammation. We show that human CKD monocytes exhibit altered purinergic calcium ion signatures. Monocyte IL-1 release was reduced when inhibiting P2X7, and to a lesser extent P2X4, two ATP-receptors that were found upregulated compared to monocytes from healthy people. In murine CKD models, deleting P2X7 (P2X7-/-) abolished IL-1 release but increased IL-1 surface presentation by bone marrow derived macrophages and impaired immune cell infiltration of the kidney without protecting kidney function. In contrast, immune cell infiltration into injured wild type and P2X7-/- hearts was comparable in a myocardial infarction model, independent of previous kidney injury. Both the chimeric mouse line harboring P2X7-/- immune cells in wild type recipient mice, and the inversely designed chimeric line showed less acute inflammation. However, only the chimera harboring P2X7-/- immune cells showed a striking resistance against injury-induced cardiac remodeling. Mechanistically, ROS measurements reveal P2X7-induced mitochondrial ROS as an essential factor for IL-1 release by monocytes. Our studies uncover a dual role of P2X7 in regulating IL-1 biogenesis with consequences for inflammation and inflammation-induced deleterious cardiac remodeling that may determine clinical outcomes in CKD therapies.

Hypotension is a common cause of acute kidney injury (AKI), with strong associations between the duration and magnitude of hypotension seen across a range of situations including major surgery. However, it is less clear whether targeting higher intraoperative MAP results in lower rates of AKI. In a prespecified analysis of the Perioperative Ischemic Evaluation-3 (POISE-3) randomized controlled trial, this question is addressed for noncardiac major surgery. Despite an increase in cessation of antihypertensive medications and higher intraoperative mean arterial blood pressure in the intervention arm, no differences were seen in the rates of postoperative AKI. This commentary discusses the strengths and weaknesses of the trial, as well as providing some interpretation of results and their relevance to clinical practice.

The MTOR inhibitors have demonstrated antiviral properties, and prior non-randomized studies have suggested they may have a suppressive effect on BKPyV replication. Here, in this randomized, multicenter, controlled trial (BKEVER study), we sought to evaluate the impact of everolimus (EVR) in facilitating the clearance of BKPyV compared to simply reducing immunosuppression among kidney transplant recipients (KTRs). All together, 130 KTRs presenting with BKPyV DNAemia were randomized 1:1 into two groups. The EVR group, in which mycophenolate mofetil (MMF) was replaced by EVR along with a decrease in calcineurin inhibitor trough levels and secondly the MMF group, in which the MMF dose was decreased by half along with a similar lowering of calcineurin inhibitor levels. The primary endpoint was the proportion of patients achieving viral clearance at six months. Secondary endpoints included the kinetics of BKPyV replication over time, the incidence of BKPyV-associated nephropathy, kidney graft function, the incidence of kidney graft rejection, and medication tolerability over two years. Significantly, BKPyV clearance was achieved in 55.7% of patients in the EVR group compared to 81.3% of patients in the MMF group at six months. The reduction in BKPyV DNA load was significantly more rapid in the MMF group. Calcineurin inhibitor trough levels were within expected target ranges and did not differ meaningfully between the two groups from randomization through month six. Two grafts were lost, and four patients died. Eleven patients in the EVR group and six patients in the MMF group developed biopsy-proven BKPyV nephropathy. Thus, in KTRs with BKPyV DNAemia, replacing MMF with EVR along with lowering calcineurin inhibitor levels did not lead to more frequent or faster clearance of BKPyV.

In this pre-specified sub-study of the POISE-3 trial, we examined the effect of a perioperative hypotension-avoidance strategy versus a hypertension-avoidance strategy on the risk of postoperative acute kidney injury (AKI). Altogether, 7307 patients were included from 110 hospitals in 22 countries. Patients were 45 years and older, had or were at risk of atherosclerotic disease, took at least one antihypertensive medication, and were scheduled for noncardiac surgery. Hypotension-avoidance strategy: (i) target intraoperative mean arterial pressure (MAP) 80 mm Hg or over, (ii) on day of surgery and for two days after, hold renin-angiotensin-aldosterone system inhibitors and use other antihypertensives in stepwise fashion if systolic blood pressure (SBP) 130 mm Hg or more. Hypertension-avoidance strategy: (i) target intraoperative MAP 60 mm Hg or more, (ii) continue all antihypertensives before and after surgery. Primary outcome: postoperative AKI, an increase in serum creatinine concentration of either 26.5 μmol/L or more (0.3 mg/dL or more) within 48 hours of randomization or 50% or more within seven days of randomization. The hypotension-avoidance group (3654 patients) used fewer antihypertensive medications than the hypertension-avoidance group (3653 patients); specifically, 6% vs. 38% used an ACEI or ARB on the day of surgery, and 6% vs. 47% and 7% vs. 50% one and two days after surgery, respectively. Patients also spent about half as much intraoperative time with a MAP under 80 mm Hg (27 vs. 60 minutes, respectively), but had little difference in average BP before or after surgery. There was no significant difference in AKI risk (15.1% vs. 14.4%). Results were consistent with other definitions of AKI and in patients with preexisting chronic kidney disease. Thus, a hypotension-avoidance strategy targeting a MAP greater than 80 mm Hg in the operating room and discontinued blood pressure medication during the perioperative period did not confer a lower risk of AKI compared to a hypertension avoidance strategy. Clinical trial registration number: NCT03505723.

The neonatal Fc receptor (FcRn) was initially discovered as the receptor that allowed passive immunity in newborns by transporting maternal IgG through the placenta and enterocytes. Since its initial discovery, FcRn has been found to exist throughout all stages of life and in many different cell types. Beyond passive immunity, FcRn is necessary for intrinsic albumin and IgG recycling and is important for antigen processing and presentation. Given its multiple important roles, FcRn has been utilized in many disease treatments including a new class of agents that were developed to inhibit FcRn for treatment of a variety of autoimmune diseases. Certain cell populations within the kidney also express high levels of this receptor. Specifically, podocytes, proximal tubule epithelial cells, and vascular endothelial cells have been found to utilize FcRn. In this review, we summarize what is known about FcRn and its function within the kidney. We also discuss how FcRn has been used for therapeutic benefit, including how newer FcRn inhibiting agents are being used to treat autoimmune diseases. Lastly, we will discuss what renal diseases may respond to FcRn inhibitors and how further work studying FcRn within the kidney may lead to therapies for kidney diseases.