Is the cost of the new home dialysis techniques still advantageous compared to in-center hemodialysis? An Italian single center analysis and comparison with experiences from western countries.

Introduction: Potential advantages of home dialysis remained a questionable issue. Three main factors have to be considered: the progressive reduction in the cost of consumables for in-Center hemodialysis (IC-HD), the widespread use of incremental Peritoneal Dialysis (PD), and the renewed interest in home hemodialysis (H-HD) in the pandemic era. Registries data on prevalence of dialysis modalities generally report widespread underemployment of home dialysis despite PD and H-HD could potentially provide clinical benefits, improve quality of life, and contrast the diffusion of new infection among immunocompromised patients. Methods: We examined the economic impact of home dialysis by comparing the direct and indirect costs of PD (53 patients), H-HD (21 patients) and IC-HD (180 patients) in a single hospital of North-west Italy. In order to achieve comparable weekly costs, the average weekly frequency of dialysis sessions based on the dialysis modality was calculated, the cost of individual sessions per patient per week normalized, and the monthly and yearly costs were derived. Results: As expected, PD resulted the least expensive procedure (€ 23,314.79 per patient per year), but, notably, H-HD has a lower average cost than IC-HD (€ 35,535.00 vs. € 40,798.98). A cost analysis of the different dialysis procedures confirms the lower cost of PD, especially continuous ambulatory PD, compared to any extracorporeal technique. Discussion: Among the hemodialysis techniques, home bicarbonate HD showed the lowest costs, while the weekly cost of Frequent Home Hemodialysis was found to be comparable to In-Center Bicarbonate Hemodialysis.

Assessing the steroid-sparing effect of biological agents in randomized controlled trials for lupus: a scoping review.

Prompt disease control of flares in patients with systemic lupus erythematosus (SLE) is a priority in treatment strategy planning. However, the long-term dosage-related collateral effects of glucocorticoids (GCs) have pushed researchers towards the identification and utilization of novel biological agents that could both induce and maintain low disease activity and remission, especially in the context of lupus nephritis (LN). This scoping review aims at assessing the current evidence of the potential steroid-sparing effect of biologic therapies by reviewing phase II and phase III randomized, placebo-controlled trials involving SLE/LN patients. A scoping review of the literature was carried out in accordance with PRISMA-ScR recommendations. Risk of bias was assessed through the utilization of the Cochrane Collaboration's tool for randomized controlled trials (RCTs). Eight RCTs met the inclusion criteria and were included in this analysis (treatment drug, 7 belimumab; 1 anifrolumab). Four studies showed a definite steroid-sparing effect (treatment drug, 3 belimumab; 1 anifrolumab), while in the remaining four RCTs, the steroid-sparing effect was not observed. When focusing on phase III trials, the overall quality of the studies resulted fair or good considering the risk of bias. However, a degree of heterogeneity of steroid regimen protocol (considering initial dosage, tapering and rescue treatment allowance) was observed. While a growing body of evidence is supporting the safety and efficacy of biological treatment in SLE, the evidence on their steroid-sparing effect remains scattered. Future research needs to pursue the identification of precise SLE clusters of patients who would benefit most from a specific treatment protocol with a definite steroid-sparing effect.

Type I interferon pathway activation across the antiphospholipid syndrome spectrum: associations with disease subsets and systemic antiphospholipid syndrome presentation.

Introduction: While the type I interferon (IFN-I) pathway is crucial in autoimmunity, its role in antiphospholipid antibody (aPL)-positive subjects, including aPL carriers and antiphospholipid syndrome (APS) patients, is poorly understood. This study aims at characterizing IFN-I pathway activation within the spectrum of aPL-positive subsets. Methods: A total of 112 patients [29 aPL carriers, 31 primary APS (PAPS), 25 secondary APS (SAPS), 27 systemic lupus erythematosus (SLE) patients without aPL, and 44 healthy controls (HCs)] were recruited. IFI6, IFI44, IFI44L, MX1, IFI27, OAS1, and RSAD2 gene expression was evaluated in whole blood, and a composite index (IFN score) was calculated. Results: An overall activation of the IFN-I pathway was observed across the entire APS spectrum, with differences among genes based on the specific disease subset. The composite score revealed quantitative differences across subsets, being elevated in aPL carriers and PAPS patients compared to HCs (both p < 0.050) and increasing in SAPS (p < 0.010) and SLE patients (p < 0.001). An unsupervised cluster analysis identified three clusters, and correspondence analyses revealed differences in clusters usage across APS subsets (p < 0.001). A network analysis revealed different patterns characterizing different subsets. The associations between IFN-I pathway activation and clinical outcomes differed across APS subsets. Although no differences in gene expression were observed in systemic APS, the network analyses revealed specific gene-gene patterns, and a distinct distribution of the clusters previously identified was noted (p = 0.002). Conclusion: IFN-I pathway activation is a common hallmark among aPL-positive individuals. Qualitative and quantitative differences across the APS spectrum can be identified, leading to the identification of distinct IFN-I signatures with different clinical values beyond traditional categorization.

Lymphatic System and the Kidney: From Lymphangiogenesis to Renal Inflammation and Fibrosis Development.

The lymphatic kidney system plays a crucial role in managing interstitial fluid removal, regulating fluid balance, and tuning immune response. It also assists in the reabsorption of proteins, electrolytes, cytokines, growth factors, and immune cells. Pathological conditions, including tissue damage, excessive interstitial fluid, high blood glucose levels, and inflammation, can initiate lymphangiogenesis-the formation of new lymphatic vessels. This process is associated with various kidney diseases, including polycystic kidney disease, hypertension, ultrafiltration challenges, and complications post-organ transplantation. Although lymphangiogenesis has beneficial effects in removing excess fluid and immune cells, it may also contribute to inflammation and fibrosis within the kidneys. In this review, we aim to discuss the biology of the lymphatic system, from its development and function to its response to disease stimuli, with an emphasis on renal pathophysiology. Furthermore, we explore how innovative treatments targeting the lymphatic system could potentially enhance the management of kidney diseases.

2023 ACR/EULAR classification criteria in existing research cohorts: an international study.

OBJECTIVE: Assessing the impact of the updated ACR/EULAR APS classification criteria to our research cohort. METHODS: Consecutive patients who tested persistently positive for at least one aPL in the last three years were enrolled. The first APS Sydney index event was considered and computed for the comparison between Sydney and 2023 APS criteria. When computing the 2023 APS criteria, additional manifestations were also considered. RESULTS: The cohort comprised 249 patients (185 with APS and 64 aPL carriers according to Sydney criteria). The 185 patients had as first index event VT in 55 cases (29.8%) AT in 63 (34%) and PM in 67 (36.2%). When applying the updated criteria, 90 subjects (48.7%) failed to reach the composite score of the new criteria. The percentage of thrombotic APS per Sydney criteria decreased from 47.3% to 34.9% because of high cardiovascular risk in 23 cases, IgM aPL profile in 6 cases and in 2 patients for both reasons. Patients with PM decreased from 26.9-3.2% (39 cases of recurrent early pregnancy loss and 20 of fetal losses). Consequently, the percentage of aPL carriers increased from 26% to 61%. When looking at the disease evolution at follow-up, 32 additional patients out of 90 (35.6%) fulfilled the new APS criteria, after developing additional clinical manifestation following index event. CONCLUSION: When applying the new APS criteria to our research cohort, not negligible differences exist in patients' classification. A multidisciplinary approach will be mandatory to assess the impact into research and, ultimately, patient's care of new criteria.

Pediatric Presentation of Antiphospholipid Syndrome: A Review of Recent Literature With Estimation of Local Prevalence.

We aimed to investigate the epidemiology, the clinical and laboratory characteristics of the pediatric involvement of antiphospholipid syndrome (APS), by performing a review of the current evidence and reviewing local experience in the Northwest Italy. To achieve this, we performed a detailed literature search to identify articles describing clinical and laboratory characteristics of pediatric APS. In concomitance, we conducted a registry-based study collecting data from the Piedmont and Aosta Valley Rare Disease Registry including pediatric patients diagnosed with APS in the last 11 years. The literature review led to inclusion of six articles with a total of 386 pediatric patients (65% females, 50% with systemic lupus erythematosus (SLE) as concomitant diagnosis). Rates of venous and arterial thrombosis were 57 and 35%, respectively. "Extra-criteria manifestations" included mostly hematologic and neurologic involvement. Almost one-quarter of patients (19%) reported recurrent events and 13% manifested as catastrophic APS. A total of 17 pediatric patients (mean age 15.1 ± 2.8, 76% female) developed APS in the Northwest of Italy. In 29% of cases, SLE was a concomitant diagnosis. Deep vein thrombosis was the most frequent manifestation (28%) followed by catastrophic APS (6%). The estimated prevalence of pediatric APS in Piedmont and Aosta Valley Region is 2.5/100,000 people, whereas the estimated annual incidence is 0.2/100,000 inhabitants. In conclusion, clinical manifestations of pediatric APS seem to be more severe and with a high prevalence of noncriteria manifestations. International efforts are needed to better characterize this condition and to develop new specific diagnostic criteria to avoid missed/delayed diagnosis in children with APS.

The estimated prevalence of antiphospholipid antibodies and criteria-antiphospholipid syndrome in subjects with renal thrombotic microangiopathy.

BACKGROUND: While the prevalence of antiphospholipid antibodies (aPL) in venous and arterial thrombotic events had already been estimated by previous studies, the prevalence of aPL in subjects with Thrombotic Microangiopathy (TMA) is still not fully elucidated. Thus, we conducted a systematic review to estimate the frequency of aPL in subjects with biopsy-proven renal TMA. METHODS: We conducted in the PubMed database a search for English-language studies investigating the presence of aPL in subjects with biopsy-proven renal TMA from January 1985 to December 2022. Keywords used in the search included: 'antiphospholipid syndrome', 'antiphospholipid antibodies' and 'thrombotic microangiopathy'. Cohorts of HUS patients were excluded due to the risk of over-estimating the prevalence of aPL in these populations. The median frequency for positive aPL including anticardiolipin antibodies (aCL), antibodies against ß2-glycoprotein-I (anti-ß2GPI) and lupus anticoagulant (LA) was then calculated. RESULTS: 522 articles were identified through the literature search. Six studies, assessing the prevalence of aPL in 211 subjects with renal TMA, were retrieved. The overall aPL prevalence was estimated as 24.4% (range 22-56). The estimated prevalence of aCL (IgG/IgM), anti-ß2GPI, (IgG/IgM) and LA was 4.0% (range 3-27), 4.0% (range 3-16) and 18.9% (range 13-25), respectively. APS was diagnosed in 16.3% (range 11-29) of the patients. Of note, a high level of heterogeneity was observed when comparing the reported aPL profiles for each study. CONCLUSIONS: This comprehensive systematic analysis of studies investigating the prevalence of aPL in renal TMA showed that, despite the high heterogeneity of the included studies, aPL are present in about one case out of four renal-TMA cases.

[The Cannulation of the Arteriovenous Fistula in the Presence of a Stent: Precautions, Risks, and Possibilities].

A proper management and tailored interventions represented two fundamental steps to ensure a long-term use of the arteriovenous fistula (AVF). AVF failure can be attributed to various factors, with stenosis being the most common cause. Different techniques are employed for treating complications, but percutaneous endovascular procedures are the most widely used. In addition to angioplasty (PTA), the possibility of utilizing stents, particularly stent grafts (SG), has further improved outcomes. However, the insertion of these devices involves commitment to a segment of the vessel, which may vary in length, making the indication necessitate a careful evaluation. The positioning of a stent graft indeed limits the space for needle insertion, and on the other hand, the cannulation of the device is considered off-label according to technical specification. This work addresses the issue of puncturing these devices. Alongside a rapid overview, we describe a clinical case of continuous cannulation of a multiply stented AVF, for over 9 years, which opens up the discussion about the possibility of long-term cannulation through proper planning.

Relevance of next generation sequencing (NGS) data re-analysis in the diagnosis of monogenic diseases leading to organ failure.

BACKGROUND: In 2018, our center started a program to offer genetic diagnosis to patients with kidney and liver monogenic rare conditions, potentially eligible for organ transplantation. We exploited a clinical exome sequencing approach, followed by analyses of in silico gene panels tailored to clinical suspicions, obtaining detection rates in line with what reported in literature. However, a percentage of patients remains without a definitive genetic diagnosis. This work aims to evaluate the utility of NGS data re-analysis for those patients with an inconclusive or negative genetic test at the time of first analysis considering that (i) the advance of alignment and variant calling processes progressively improve the detection rate, limiting false positives and false negatives; (ii) gene panels are periodically updated and (iii) variant annotation may change over time. METHODS: 114 patients, recruited between 2018 and 2020, with an inconclusive or negative NGS report at the time of first analysis, were included in the study. Re-alignment and variant calling of previously generated sequencing raw data were performed using the GenomSys Variant Analyzer software. RESULTS: 21 previously not reported potentially causative variants were identified in 20 patients. In most cases (n = 19), causal variants were retrieved out of the re-classification from likely benign to variants of unknown significance (VUS). In one case, the variant was included because of inclusion in the analysis of a newly disease-associated gene, not present in the original gene panel, and in another one due to the improved data alignment process. Whenever possible, variants were validated with Sanger sequencing and family segregation studies. As of now, 16 out of 20 patients have been analyzed and variants confirmed in 8 patients. Specifically, in two pediatric patients, causative variants were de novo mutations while in the others, the variant was present also in other affected relatives. In the remaining patients, variants were present also in non-affected parents, raising questions on their re-classification. CONCLUSIONS: Overall, these data indicate that periodic and systematic re-analysis of negative or inconclusive NGS data reports can lead to new variant identification or reclassification in a small but significant proportion of cases, with benefits for patients' management.

[Cancer and the Kidney: A Deadly Embrace].

A deadly embrace occurs between cancer and chronic kidney disease. The estimation of kidney function in cancer patients is of utmost interest due to its direct impact on chemotherapy dosing, selection, and eligibility for chemotherapeutics. Overestimating kidney function (determined as estimated glomerular filtration rate -eGFR) can lead to overdosing and drug toxicity, while underestimating kidney function can prevent patients from receiving novel therapies. Notably, the current measures of eGFR are not validated in transplanted patients yet. The field of onconephrology ranges from nephrotoxicity of existing and novel therapeutics, paraproteinemias, and cancer-associated electrolyte imbalance, fluid and acid-base disturbances, the effects of the destruction of cancer cells, and acute and/or chronic kidney injuries. Recently, the therapeutic armamentarium has been enriched with new agents that interfere with specific proteins involved in oncogenesis. These are the so-called target therapies, which although acquired as "targeted" therapies do not have absolute specificity and selectivity and tend to inhibit multiple targets, often involving the kidney. Renal biopsy may be critical in managing these adverse effects. Moreover, primary hematological and oncological disorders can have significant kidney implications in the form of glomerular or nonglomerular diseases presenting with proteinuria, hematuria, hypertension, and kidney function decline, specifically including cast nephropathy or systemic light chain amyloidosis, and paraneoplastic glomerulopathies that occur as a result of occult malignancy, such as Membranous Nephropathy and Minimal Change disease.

[Management of the Oncological Patient with Chronic Renal Failure].

Cancer is a leading cause of death in people with chronic kidney disease (CKD). The incidence of CKD in patients with cancer is higher than in the non-cancer population. Across various populations, CKD is associated with an elevated risk of cancer incidence and cancer death compared with people without CKD, although the risks are cancer site-specific. The potential mechanisms for the increased risk of cancer observed in CKD, include patient factors, disease, and treatment factors. CKD has also a major impact on the treatment of cancer patients. The kidney is the primary route of elimination of many anticancer drugs. Dosing of anticancer agents according to kidney function is essential to avoid undertreatment and toxicity. Because of the systemic exclusion of patients with severe kidney dysfunction from clinical cancer trials, data are lacking to guide dosing of anticancer drugs in patients with chronic kidney disease. As a consequence, many therapies are denied to CKD patients due to their possible toxicities. An orchestrated effort by all stakeholders is required to fill the knowledge gap and improve the outcome of cancer patients with kidney dysfunction.

[Renal Replacement Therapy in Cancer Patients with AKI].

Acute renal failure (AKI) is a high-prevalence complication in patients with cancer. The risk of AKI after cancer diagnosis is 18% in the first year, 27% in the fifth year, and 40% of critically ill patients with cancer require renal replacement therapy. The causes of AKI may be pre-renal due to hemodynamic problems, related to the cancer, metabolic complications, and drug or surgical treatment. One must preventively protect renal function by hydration, use of non-nephrotoxic drugs, correction of anemia, prevention of contrast agent-induced AKI (CI-AKI), and adjustment of cancer therapy in patients with CKD. It is essential to check basal renal function, creatinine trend, electrolytes, urinalysis and proteinuria, perform imaging, renal biopsy if necessary. The evaluation of patients should be multidisciplinary and timely including the initiation of renal replacement treatment (RRT). There are different modalities of replacement treatment depending on the clinical picture of the patient with AKI and cancer: intermittent hemodialysis (IHD), intermittent prolonged replacement therapy (PIRRT), and continuous replacement therapy (CRRT). The concept of dose administered, as opposed to prescribed dose, as well as the anticoagulation of extracorporeal circuits, which must be regional with citrate (RCA) as the first choice in the management of CRRT, turns out to be fundamental in order to achieve optimal circuit anticoagulation, with reduction of coagulation episodes and downtime, while maintaining the patient's coagulation status. The onco-nephrologic multidisciplinary approach is crucial to reduce the mortality rate, which is still high in this category of patients.

[Renal Side Effects of Novel Molecular Targeted Oncologic Agents].

The introduction of innovative therapies has changed the scenario of complications. The delay in the recognition of kidney adverse effects is partly due to the timing of the development of the kidney damage which occurs later than the observation period of registration studies, and partly to the exclusion of patients with known kidney impairment from registration trials. Renal disease has a significant impact on the management of cancer patients and often leads to discontinuation of therapy. Histological evaluations of kidney disorders induced by targeted/immunotherapy are very limited. Renal biopsy is critical for the management of renal toxicities and should be especially encouraged for patients showing adverse renal effects to novel cancer agents. We recently examined the histological features of patients treated with new cancer agents who underwent renal biopsy for new onset renal failure and/or urinary abnormalities. The cohort included 42 patients. The most frequently administered therapies were immunotherapy (54.8%) and anti-angiogenic treatments (45.2%). The most common adverse effect was tubular interstitial nephritis in the first group and thrombotic microangiopathy in the second one. Based on histological findings, definitive discontinuation of treatment could be restricted to a very limited number of patients. All of them had anti-VEGF-related TMA. Treatment discontinuation was unneeded in patients treated with ICIs. In patients treated with multidrug therapy, the histological findings made it possible to identify the weight of drug-related specific injury. Based on this data, renal biopsy should be considered in every cancer patient who develops urinary abnormalities or shows a worsening of renal function during treatment with immunotherapy or targeted therapy.

[Management of Cast Nephropathy].

Myeloma cast nephropathy is the most common cause of acute kidney injury in patients affected by multiple myeloma. The mainstay of management of cast nephropathy is the clone-based therapy by reducing production and thereby precipitation of light chains. Adjuvant therapy consists of inducing high urine volume flow and alkalinisation, where possible. Extracorporeal removal of light chains is still debated and the advantages of these procedures are not established. The use of safe and low expensive membranes may encourage their use and address their utility.

Thrombosis and APS: Lessons Learned from Another Black Swan Tale.

Antiphospholipid syndrome (APS) is a chronic systemic autoimmune disease characterized by venous, arterial, and microvascular thromboses and/or recurrent pregnancy morbidity, that occur in the persistent presence of antiphospholipid antibodies (aPL). APS can present with a wide range of clinical manifestations often reffered as "extra-criteria". These features, although apparently less common, can severely impact patients' outcome. Here, we report the case of a patient with a newly diagnosed APS. He previously experienced a recurrence of venous thrombosis after discontinuation of anticoagulant therapy in association with cutaneous ulcerations as presenting symptoms. Interestingly, skin lesions did not improve with full anticoagulant treatment. Due to concomitant presence of thrombotic and microvascular involvement, immunomodulatory therapy with steroid pulses followed by intravenous injections of belimumab was started, with progressive and significant amelioration, leading to complete recovery. Following the presentation of the current case report, we highlight the importance of suspecting APS in young patients experiencing unprovoked thrombosis. We also emphasized the critical issue of testing aPL during anticoagulant treatment and focused on the need of aPL retesting in patients with positivity at high titers. We also highlight the double nature of aPL-mediated clinical manifestations. While most patients presented with pure thrombotic complications, one should always remember that APS is an autoimmune-mediated disease, which can benefit from alternative therapeutic approaches beyond anticoagulation.

Complement levels during the first trimester predict disease flare and adverse pregnancy outcomes in systemic lupus erythematosus: A network meta-analysis on 532 pregnancies.

BACKGROUND: Complement levels have been proposed as candidate biomarkers of disease activity and obstetric risk in systemic lupus erythematosus (SLE) pregnancies, but their reliability has been questioned due to the physiologic fluctuations of complement during gestation. Thus, this network meta-analysis aimed at assessing the clinical significance of complement fluctuations in lupus pregnant women. METHODS: Corresponding authors of 19 studies meeting inclusion criteria were invited to contribute with additional data including C3 and C4 levels [before pregnancy, at conception, in every trimester (T) and 3 months after delivery]; data were pooled together in a network meta-analysis. RESULTS: A total of 532 lupus women from four studies were included in the analysis. In SLE women, C3 and C4 increased progressively during gestation: levels remained stable during T1 and peaked in T2 to decrease in T3. Patients with previous lupus nephritis (LN) and those who experienced flares during pregnancy had significantly lower mean levels of C3 and C4 at all timepoints. The lowest levels of complement were observed, particularly during T1, in patients with LN and gestational flare. Both reduction and the lack of increase of C3 and C4 levels at T1 versus conception were associated with gestational flares, particularly in LN patients. Pregnancies with flare had a statistically significant higher rate of maternal and fetal complications(60% versus 50.3%; p = 0.03). CONCLUSIONS: Low complement levels, particularly in T1, were associated with a higher frequency of gestational flare. Either reduction or smaller increase of C3 and/or C4 levels, even within normal range, might predict flares especially in early gestation.

From inflammation to renal fibrosis: A one-way road in autoimmunity?

Renal fibrosis is now recognized as a main determinant of renal pathology to include chronic kidney disease. Deposition of pathological matrix in the walls of glomerular capillaries, the interstitial space, and around arterioles predicts and contributes to the functional demise of the nephron and its surrounding vasculature. The recent identification of the major cell populations of fibroblast precursors in the kidney interstitium such as pericytes and tissue-resident mesenchymal stem cells, or bone-marrow-derived macrophages, and in the glomerulus such as podocytes, parietal epithelial and mesangial cells, has enabled the study of the fibrogenic process thought the lens of involved immunological pathways. Besides, a growing body of evidence is supporting the role of the lymphatic system in modulating the immunological response potentially leading to inflammation and ultimately renal damage. These notions have moved our understanding of renal fibrosis to be recognized as a clinical entity and new main player in autoimmunity, impacting directly the management of patients.

Mayo Clinic consensus report on membranous nephropathy: proposal for a novel classification.

Membranous nephropathy (MN) is a pattern of injury caused by autoantibodies binding to specific target antigens, with accumulation of immune complexes along the subepithelial region of glomerular basement membranes. The past 20 years have brought revolutionary advances in the understanding of MN, particularly via the discovery of novel target antigens and their respective autoantibodies. These discoveries have challenged the traditional classification of MN into primary and secondary forms. At least 14 target antigens have been identified, accounting for 80%-90% of cases of MN. Many of the forms of MN associated with these novel MN target antigens have distinctive clinical and pathologic phenotypes. The Mayo Clinic consensus report on MN proposes a 2-step classification of MN. The first step, when possible, is identification of the target antigen, based on a multistep algorithm and using a combination of serology, staining of the kidney biopsy tissue by immunofluorescence or immunohistochemistry, and/or mass spectrometry methodology. The second step is the search for a potential underlying disease or associated condition, which is particularly relevant when knowledge of the target antigen is available to direct it. The meeting acknowledges that the resources and equipment required to perform the proposed testing may not be generally available. However, the meeting consensus was that the time has come to adopt an antigen-based classification of MN because this approach will allow for accurate and specific MN diagnosis, with significant implications for patient management and targeted treatment.

Mayo Clinic Consensus Report on Membranous Nephropathy: Proposal for a Novel Classification.

Membranous nephropathy (MN) is a pattern of injury caused by autoantibodies binding to specific target antigens, with accumulation of immune complexes along the subepithelial region of glomerular basement membranes. The past 20 years have brought revolutionary advances in the understanding of MN, particularly via the discovery of novel target antigens and their respective autoantibodies. These discoveries have challenged the traditional classification of MN into primary and secondary forms. At least 14 target antigens have been identified, accounting for 80%-90% of cases of MN. Many of the forms of MN associated with these novel MN target antigens have distinctive clinical and pathologic phenotypes. The Mayo Clinic consensus report on MN proposes a 2-step classification of MN. The first step, when possible, is identification of the target antigen, based on a multistep algorithm and using a combination of serology, staining of the kidney biopsy tissue by immunofluorescence or immunohistochemistry, and/or mass spectrometry methodology. The second step is the search for a potential underlying disease or associated condition, which is particularly relevant when knowledge of the target antigen is available to direct it. The meeting acknowledges that the resources and equipment required to perform the proposed testing may not be generally available. However, the meeting consensus was that the time has come to adopt an antigen-based classification of MN because this approach will allow for accurate and specific MN diagnosis, with significant implications for patient management and targeted treatment.