Multidisciplinary approach to lupus nephritis: Clinical pearls, pitfalls, and positioning of newly-approved agents.

Lupus nephritis (LN) is a major course of morbidity and mortality in patients with systemic lupus erythematosus (SLE), best managed by a multidisciplinary group. To this end, we gathered a group of rheumatologists, nephrologists and a nephropathologist to review current evidence regarding diagnosis and management of LN. In this consensus paper, we summarize the key points from this meeting and provide practice guidelines for the management of kidney involvement in SLE, in view of emerging new data concerning novel agents approved recently. Renal biopsy is indispensable for the management of LN. Yet, important pearls and pitfalls need to be considered regarding indications and interpretation, which are summarized in informative tables. In new-onset LN, experts agreed that, although belimumab may be added from disease onset, patients with moderate to severe proliferative nephritis (defined as: NIH activity index > 5 plus ≥ 1 of the following: (i) NIH chronicity index > 2, (ii) proteinuria > 3 g/24 h, and (iii) increase in serum creatinine > 20%) may be more likely to benefit the most. In all other patients who have already started standard-of-care treatment with either mycophenolate mofetil (MMF) or cyclophosphamide (CY), belimumab could be considered in cases with an inadequate clinical response by 3 months, or in cases that experience a nephritic flare following initial response, or have an inability to reduce the dose of glucocorticoids. In all circumstances, the drug should be given as add-on therapy, that is, in combination with a standard-of-care therapy (MMF or CY). Voclosporin could be considered for up to 3 years, in combination with MMF, in patients with heavy proteinuria (well above the nephrotic range), wherein a quick reduction of protein loss in urine is desirable to avoid the complications of the nephrotic syndrome, either as part of the initial regimen, or in cases of inadequate reduction of proteinuria with MMF. In view of the potential scarring effects, long-term administration beyond the first year requires further documentation.

A past medical history of autoimmune disease predicts a future with fewer relapses in patients with ANCA-associated vasculitis.

OBJECTIVES: To explore the frequency and impact of an autoimmune disease past-medical history (PMH) in the clinical picture and outcomes of patients with antineutrophil cytoplasmic autoantibodies (ANCA) associated vasculitis (AAV). METHODS: This was a retrospective study of patients with biopsy-proven AAV, >16 years old, with detailed information about their PMH. Outcomes of interest included remission, treatment resistance, relapse, end-stage kidney disease (ESKD), and death. RESULTS: 206 patients with biopsy-proven AAV and available information regarding their PMH were studied. 63(30.6%) of them had a history of autoimmune disease prior to AAV diagnosis. The mean age overall was 54.1 years. One hundred and five patients (51%) were positive for PR3-ANCA, 101 (49%) for MPO-ANCA. Granulomatosis with polyangiitis was diagnosed in 79 (38.3%), microscopic polyangiitis in 97 (47.1%) and renal-limited vasculitis in 30 (14.6%) individuals. Remission rate was similar among patients with and without a PMH of autoimmune disease. Time-to-event analysis indicated that the relapse-free survival was significantly longer in patients with PMH of autoimmune disease (148.2 vs. 61.9 months, p-value <0.001). After adjusting for covariates, autoimmune disease history was associated with significantly lower risk of relapse (HR: 0.33, 95% CI: 0.15-0.72), which remained significant in males, patients ≥60 years old and those with C/PR3-ANCA, kidney and lung involvement. CONCLUSIONS: Patients with a PMH of autoimmune disease, prior to AAV diagnosis, experienced significantly fewer relapses after achievement of remission, compared to patients without such a history, underlining the importance of individualisation of maintenance immunosuppressive therapy, given the different aetiopathogenetic settings the disease was developed.

Pathogenesis and Management of Acute Kidney Injury in Patients with Nephrotic Syndrome Due to Primary Glomerulopathies.

Acute kidney injury in the context of nephrotic syndrome is a serious and alarming clinical problem. Largely, acute kidney injury is a relatively frequent complication among patients with comorbidities while it has been independently associated with an increased risk of adverse outcomes, including death and chronic kidney disease. Nephrotic syndrome, without hematuria or with minimal hematuria, includes a list of certain glomerulopathies; minimal change disease, focal segmental glomerulosclerosis and membranous nephropathy. In the light of primary nephrotic syndrome, pathophysiology of acute kidney injury is differentiated by the nature of the primary disease and the severity of the nephrotic state. This review aims to explore the clinical circumstances and pathogenetic mechanisms of acute kidney injury in patients with nephrotic syndrome due to primary glomerulopathies, focusing on newer perceptions regarding the pathogenesis and management of this complicated condition, for the prompt recognition and timely initiation of appropriate treatment in order to restore renal function to its baseline level. Prompt recognition of the precise cause of acute kidney injury is crucial for renal recovery. Clinical characteristics, laboratory and serological findings along with histopathological findings, if required, will reveal the implicated pathway leading to individualized approach and management.

Cyclophosphamide followed by rituximab for aggressive multiple-relapsing antineutrophil cytoplasmic antibody-associated vasculitis.

OBJECTIVES: To evaluate the long-term outcomes of patients with multi-relapsing antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), who received sequentially therapy with cyclophosphamide and rituximab, upon new onset of aggressive vasculitis. METHODS: We retrospectively studied patients with multiple-relapsing AAV, who were treated with the standard regimen plus rituximab, given in sequence, upon a major relapse, compared to historical patients, who had been treated with the standard regimen alone in the same setting. The main outcomes of interest were relapse rates and frequency of adverse events. RESULTS: Of 147 patients with biopsy proven AAV, 35 (23.8%) experienced at least one major relapse, of whom, 14 (9.5%) received the sequential regimen and were compared to 21 (14.3%) historic patients, who had received the standard regimen alone for the same reason. Patients in both groups achieved remission in similar rates, but those treated with the sequential regimen experienced a significant decline in the relapse rate afterwards, compared to their corresponding rate prior to study entry [0.07 episodes of relapse per patient-year (95%CI: 0.03-0.2) vs. 0.38 (95%CI: 0.35-0.60) respectively, (p=0.004)]. The need for cyclophosphamide was significantly decreased in patients in whom cyclophosphamide was followed by rituximab [3.3(0-10.5) grams vs. 14.5 (4-177) grams, (p<0.0001)] but not in controls [17.2(0-108) grams vs. 14.5(0-63) grams, p=0.61]. CONCLUSIONS: Our data show that sequential therapy with cyclophosphamide and rituximab, upon a major relapse, in patients with frequently relapsing AAV, is associated with prolonged remission, allowing minimization of the ultimate exposure to cyclophosphamide.

Patients with primary membranous nephropathy are at high risk of cardiovascular events.

Here we conducted a retrospective study to examine the risk of cardiovascular events (CVEs) relative to that of end-stage renal disease (ESRD) in patients with primary membranous nephropathy, in a discovery cohort of 404 patients. The cumulative incidence of CVEs was estimated in the setting of the competing risk of ESRD with risk factors for CVEs assessed by multivariable survival analysis. The observed cumulative incidences of CVEs were 4.4%, 5.4%, 8.2%, and 8.8% at 1, 2, 3, and 5 years respectively in the primary membranous nephropathy cohort. In the first 2 years after diagnosis, the risk for CVEs was similar to that of ESRD in the entire cohort, but exceeded it among patients with preserved renal function. Accounting for traditional risk factors and renal function, the severity of nephrosis at the time of the event (hazard ratio 2.1, 95% confidence interval 1.1 to 4.3) was a significant independent risk factor of CVEs. The incidence and risk factors of CVEs were affirmed in an external validation cohort of 557 patients with primary membranous nephropathy. Thus early in the course of disease, patients with primary membranous nephropathy have an increased risk of CVEs commensurate to, or exceeding that of ESRD. Hence, reduction of CVEs should be considered as a therapeutic outcome measure and focus of intervention in primary membranous nephropathy.

Predictors of renal histopathology in antineutrophil cytoplasmic antibody associated glomerulonephritis.

OBJECTIVES: Prompt, aggressive therapy is vital for anti-neutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis. In this regard, we aimed to identify predictors of distinct renal histopathological classes at the time of clinical diagnosis. PATIENTS & METHODS: An inception cohort of patients with biopsy proven ANCA-associated glomerulonephritis was studied retrospectively. Demographics, clinical, laboratory, serological and radiological parameters were analyzed. Patients were classified on the basis of renal histopathology. A risk score was developed for each histopathological class using univariate and stepwise logistic regression analyses. RESULTS: Variables independently associated with focal class included disease duration up to diagnosis <8 weeks, absence of erythrocyte casts by urine microscopy and eGFR >49 ml/min/1.73 m(2); with crescentic class >40 erythrocytes/hpf, identification of erythrocyte casts in urine, upper respiratory tract involvement and eGFR <49 ml/min/1.73 m(2); with mixed class age >54 years, male gender, and absence of upper respiratory tract involvement. In the presence of these risk factors a predictive risk score for each histopathological classes was calculated: odds ratio, 95% confidence intervals (CI), for focal class (≥2 risk factors, 20.8 (95% CI: 5.1-84.2), p < 0.0001, and 441.0 (95% CI: 16.8-11,590), p = 0.0003 for crescentic class (≥3 risk factors) while the small number of patients in the mixed and sclerotic class precluded any estimates. CONCLUSION: We propose a predictive algorithm of specific histolopathological classes of ANCA-associated glomerulonephritis, which might provide a crude estimation of the disease activity in the glomeruli at presentation. This tool might assist the clinician in making decisions regarding the level of intensity of inductive immunosuppressive therapy at clinical diagnosis.

Individualized scheme of immunoadsorption for the recurrence of idiopathic focal segmental glomerulosclerosis in the graft: a single center experience.

OBJECTIVES: To explore the role of immunoadsorption (IA) for the treatment of idiopathic focal segmental glomerulosclerosis (FSGS) recurrence in the renal allograft, if applied in a personalized manner. METHODS: We studied patients with end-stage renal disease (ESRD) due to idiopathic FSGS, transplanted between 2001 and 2010. Patients with FSGS recurrence were treated with daily sessions of IA for the first week, followed by an every other day scheme and then individualized tapering until discontinuation. Complete remission was defined as a reduction of 24-h proteinuria to ≤ 0.5 g/day and partial remission as a reduction of 24-h proteinuria to 50% or more from baseline. RESULTS: Of the 18 renal transplant recipients with ESRD due to idiopathic FSGS, 12 (66.7%) experienced disease recurrence in a mean time of 0.75 months post-transplantation (KTx), with a mean proteinuria of 8.9 g/day at the time of recurrence. The mean recipient age was 30.8 years; the mean donor age was 47.4 years, while living related donors provided the allograft in seven cases. Four of the patients received therapy with rituximab in addition to IA. During a mean time of follow-up of 48.3 months, seven patients (58.3%) achieved complete remission, and five (41.7%) partial remission. At the end of follow-up, eight patients (66.7%) had functioning grafts, being in sustained remission, in contrast to four patients (33.3%), who ended up in ESRD because of FSGS recurrence. CONCLUSIONS: IA was shown efficacious in a small series of patients with recurrent FSGS in the graft. Renal function remained stable in eight of the 12 patients with FSGS recurrence.

Kidney transplantation outcomes from expanded criteria donors, standard criteria donors or living donors older than 60 years.

OBJECTIVES: To evaluate outcomes in kidney allograft recipients from donors with expanded criteria (ECD) versus standard criteria (SCD) or living donors (LD) >60 years. METHODS: We studied all patients who received a kidney between 2005 and 2011, focusing in recipients of kidneys from deceased ECD, SCD and LD >60 years. ECD was any deceased donor >60 years or >50 years with two of the following: hypertension (HTN), stroke as the cause of death, or serum creatinine >1.5 mg/dL. We recorded characteristics of the transplant procedure, patient, graft survival and renal function 1 year after transplantation and at the end of follow-up. RESULTS: Six-hundred and five patients were transplanted between 2005 and 2011 in our department. There were 142 (25.1%) transplantations from ECD, 192 (33.98%) from SCD and 96 (16.99%) from LDs older than 60 years. In a mean follow-up time of 36.4 months, graft survival rates were similar for all groups. Calculated GFR was found statistically different between the ECD and SCD groups, but still satisfactory at first year, and at end of follow-up time. Comparison of the patients, who received transplants from ECD, even older than 70 years, and those from LD >60 years revealed equivalent renal function in short and long term. CONCLUSIONS: Utilization of marginal kidneys effectively doubled our deceased transplant volume in the period 2005-2011. Patients' and graft survival were shown similar at the end of follow-up for all groups. Renal outcomes were shown equivalent between the ECD and LD >60 years groups, and although significantly lower between the ECD and the SCD group, were still very satisfactory.

Nephrotic Syndrome Associated With Heavy Metals Exposure: A Case Report and Literature Review.

Heavy metals are found in many products used in everyday life. In addition, many workers are exposed to higher concentrations of such metals in their work environment. Many of these metals may cause toxic effects in humans and there are many reports relating them to the occurrence of kidney disorders such as nephrotic syndrome. In this study, we present a case of a 38-year-old woman with nephrotic syndrome suspected to be related to heavy metal toxicity, after ruling out all other secondary causes. At the same time, she proved refractory to multiple therapies. Furthermore, a related literature review regarding the occurrence of nephrotic syndrome in patients with heavy metal exposure is presented with emphasis on the importance of considering them as a secondary cause, especially in cases that appear resistant to treatment.

Classification of antineutrophil cytoplasmic autoantibody vasculitides: the role of antineutrophil cytoplasmic autoantibody specificity for myeloperoxidase or proteinase 3 in disease recognition and prognosis.

OBJECTIVE: To compare the usefulness of 3 currently used classification systems in predicting the outcomes of treatment resistance, disease relapse, end-stage renal disease (ESRD), and death in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). METHODS: Three classification systems were applied to 502 patients with biopsy-proven AAV: 1) the Chapel Hill Consensus Conference (CHCC) definition with categories for granulomatosis with polyangiitis (GPA) (Wegener's), microscopic polyangiitis (MPA), and kidney-limited disease; 2) the European Medicines Agency (EMA) system with categories for GPA and MPA; and 3) classification based on ANCA with specificity for myeloperoxidase (MPO ANCA) versus ANCA with specificity for proteinase 3 (PR3 ANCA). Outcomes included treatment resistance, relapse, ESRD, and death. Proportional hazards models were compared between systems using an information-theoretic approach to rank models by predictive fit. Hazard ratios (HRs) with 95% confidence intervals (95% CIs) and P values are reported. RESULTS: ANCA specificity was predictive of relapse, with PR3 ANCA-positive patients almost twice as likely to relapse as those with MPO ANCA (HR 1.89 [95% CI 1.33-2.69], P = 0.0004), and ANCA specificity had the best predictive model fit (model rank 1) compared to the CHCC and EMA systems. The CHCC and EMA systems did not predict relapse. By ANCA specificity, categories of GPA, MPA, and kidney-limited disease did not distinguish differences in probability of relapse-free survival. None of the systems predicted treatment resistance, ESRD, or death. CONCLUSION: ANCA specificity independently predicts relapse among patients with AAV with renal disease. Classification and diagnostic systems that incorporate ANCA specificity, such as PR3 ANCA-positive MPA and MPO ANCA-positive MPA, provide a more useful tool than the clinical pathologic category alone for predicting relapse.

Incidence and clinical significance of de novo donor specific antibodies after kidney transplantation.

Kidney transplantation has evolved over more than half a century and remarkable progress has been made in patient and graft outcomes. Despite these advances, chronic allograft dysfunction remains a major problem. Among other reasons, de novo formation of antibodies against donor human leukocyte antigens has been recognized as one of the major risk factors for reduced allograft survival. The type of treatment in the presence of donor specific antibodies (DSA) posttransplantation is largely related to the clinical syndrome the patient presents with at the time of detection. There is no consensus regarding the treatment of stable renal transplant recipients with circulating de novo DSA. On the contrast, in acute or chronic allograft dysfunction transplant centers use various protocols in order to reduce the amount of circulating DSA and achieve long-term graft survival. These protocols include removal of the antibodies by plasmapheresis, intravenous administration of immunoglobulin, or depletion of B cells with anti-CD20 monoclonal antibodies along with tacrolimus and mycophenolate mofetil. This review aims at the comprehension of the clinical correlations of de novo DSA in kidney transplant recipients, assessment of their prognostic value, and providing insights into the management of these patients.

IgA Nephropathy: Current Treatment and New Insights.

IgA Nephropathy (IgAN) is the most common cause of primary glomerulonephritis worldwide. Despite the histopathologic hallmark of mesangial IgA deposition, IgAN is a heterogenous autoimmune disease not only in terms of clinical presentation but also in long-term disease progression. The pathogenesis of the disease is complex and includes the generation of circulating IgA immune complexes with chemical and biological characteristics that favor mesangial deposition and reaction to mesangial under-glycosylated IgA1 accumulation, which leads to tissue injury with glomerulosclerosis and interstitial fibrosis. Patients with proteinuria over 1 g, hypertension, and impaired renal function at diagnosis are considered to be at high risk for disease progression and end-stage kidney disease (ESKD). Glucocorticoids have been the mainstay of treatment for these patients for years, but without long-term benefit for renal function and accompanied by several adverse events. A better understanding of the pathophysiology of IgAN in recent years has led to the development of several new therapeutic agents. In this review, we summarize the current therapeutic approach for patients with IgAN as well as all novel investigational agents.

Rapidly Progressive Pauci-Immune Glomerulonephritis with Aberrant Fibrinoid Necrosis Associated with Atezolizumab, an Immune Check Point Inhibitor: A Case Report and Review of Literature.

Stimulation of the antitumor activity of the immune system using immune checkpoint inhibitors (ICIs) has proven efficacy in the treatment of multiple types of cancer, inducing the speedily expanding approval of therapeutic indications for ICIs. The literature regarding the immune-related toxicities and nephrotoxicity of ICIs is limited. Herein, we present a patient with lung cancer treated with atezolizumab, an IgG1 monoclonal antibody aimed at the programmed death ligand 1 (PD-L1), who presented with vasculitic skin rash and rapidly deteriorating renal function, new onset of significant glomerular hematuria and proteinuria. The renal biopsy revealed acute necrotizing pauci-immune vasculitis, with fibrinoid necrosis. The patient received a course of high-dose glucocorticoids with recovery of renal function and skin lesions. Further immunosuppressive therapy was withheld, due to active malignancy in the lung, while oncology consultation recommended the continuation of treatment with atezolizumab, as the patient had shown substantial response.

Acute Renal Vein Thrombosis Following COVID-19 in a Lupus Patient: A Case Report and Review of the Literature.

Purpose: The association between COVID-19 and hypercoagulability is well established. This is a case of a patient with systemic lupus erythematosus (SLE) who developed unilateral renal vein thrombosis following COVID-19, the third case described in the international literature so far. Methods: Clinical, laboratory characteristics and outcomes of the patient were described in detail. Literature review was performed on MEDLINE database via Pubmed. Search items included COVID-19, renal infarction, and renal thrombosis. A total of fifty-three cases were located. Of these, only two patients had renal vein thrombosis but none of them carried a diagnosis of SLE. However, six cases have been published so far involving SLE patients in whom thromboembolic events developed following COVID-19, but none of them experienced renal vein thrombosis. Conclusion: The present case adds a new piece to the emerging puzzle of COVID-19 associated hypercoagulability, especially among patients with autoimmune diseases.

Drug-Induced Podocytopathies: Report of Four Cases and Review of the Literature.

Kidney injury due to medications is a well-known clinical entity. Although drug-induced tubulointerstitial disease is commonly encountered, there are few reports in the literature associated with glomerular injury due to medications. The recognition of this type of kidney injury is crucial, as rapid discontinuation of the offending agent is critical to maximizing the likelihood of quick and effective renal function recovery. In this article, we present four cases that presented with nephrotic syndrome and were diagnosed with biopsy-proven podocytopathies, associated with exposure to a certain medication. All of them experienced complete resolution of nephrotic syndrome within days or weeks after discontinuation of the offending drug. We also present the data, which were found in a Medline search from the year 1963 until the present, regarding cases with podocytopathies associated with penicillamine, tamoxifen and the combination of pembrolizumab-axitinib, including only adult cases from the English literature. The Medline search revealed nineteen cases of penicillamine-induced minimal-change disease (MCD), one case of tamoxifen-induced MCD, and none associated with pembrolizumab-axitinib therapy. We also searched for the largest studies and meta-analyses regarding drug-induced podocytopathies after a Medline search from 1967 to the present of the English literature.

Impaired cerebral autoregulation in Fabry disease: A case-control study.

BACKGROUND AND PURPOSE: Cerebral small vessel disease is a common manifestation among patients with Fabry disease (FD). As a biomarker of cerebral small vessel disease, the prevalence of impaired cerebral autoregulation as assessed by transcranial Doppler (TCD) ultrasonography was evaluated in FD patients and healthy controls. METHODS: TCD was performed to assess pulsatility index (PI) and vasomotor reactivity expressed by breath-holding index (BHI) for the middle cerebral arteries of included FD patients and healthy controls. Prevalence of increased PI (>1.2) and decreased BHI (<0.69) and ultrasound indices of cerebral autoregulation were compared in FD patients and controls. The potential association of ultrasound indices of impaired cerebral autoregulation with white matter lesions and leukoencephalopathy on brain MRI in FD patients was also evaluated. RESULTS: Demographics and vascular risk factors were similar in 23 FD patients (43% women, mean age: 51 ± 13 years) and 46 healthy controls (43% women, mean age: 51 ± 13 years). The prevalence of increased PI (39%; 95% confidence interval [CI]: 20%-61%), decreased BHI (39%; 95% CI: 20%-61%), and the combination of increased PI and/or decreased BHI (61%; 95% CI: 39%-80%) was significantly (p < .001) higher in FD patients compared to healthy controls (2% [95% CI: 0.1%-12%], 2% [95% CI: 0.1%-12%], and 4% [95% CI: 0.1%-15%], respectively). However, indices of abnormal cerebral autoregulation were not associated independently with white matter hyperintensities and presented a low-to-moderate predictive ability for the discrimination of FD patients with and without white matter hyperintensities. CONCLUSIONS: Impaired cerebral autoregulation as assessed by TCD appears to be highly more prevalent among FD patients compared to healthy controls.

A Meta-Analysis of the Safety and Efficacy of Maintenance Therapies for Antineutrophil Cytoplasmic Antibody Small-Vessel Vasculitis.

Introduction: To compare the efficacy and safety of different regimens used for maintenance of remission in patients with antineutrophil cytoplasmic antibody (ANCA) vasculitis. Methods: This network meta-analysis studied adult patients with ANCA vasculitis in complete remission, who were maintained with various regimens, excluding patients with eosinophilic granulomatosis with polyangiitis (GPA) and those who have ended up in end-stage kidney disease. Outcomes of interest included relapse (any/major), relapse-free survival, and adverse effects. PubMed, Scopus, Web of Science, Cochrane Central Register of Controlled Trials (CENTRAL), ClinicalTrials.gov, and Google Scholar were systematically searched from inception. Results: Overall, the meta-analysis was based on 10 reports, describing the outcomes of 7 randomized controlled trials (RCTs) including 752 patients with ANCA vasculitis. Relapse-free survival was significantly worse with the use of azathioprine (hazard ratio [HR]: 2.11, 95% CI: 1.19-3.74), methotrexate (HR: 2.51, 95% CI: 1.24-5.08), and mycophenolate mofetil (HR: 3.57, 95% CI: 1.70-7.46) compared with the use of rituximab. Outcomes estimated for azathioprine (HR: 0.59, 95% CI: 0.37-0.94), cyclophosphamide (HR: 0.39, 95% CI: 0.20-0.75), and leflunomide (HR: 0.30, 95% CI: 0.11-0.84) were better than those for mycophenolate mofetil. When examining relapse-free survival, relapses were more likely with use of azathioprine (odds ratio [OR]: 2.15, 95% CI: 1.00-4.59) and mycophenolate mofetil (OR: 4.42, 95% CI: 1.63-11.94) compared with the use of rituximab. The risk of major relapse calculated for azathioprine (OR: 2.39, 95% CI: 1.10-5.19), methotrexate (OR: 3.18, 95% CI: 1.14-8.89), and mycophenolate mofetil (OR: 5.20, 95% CI: 1.65-16.37) was higher than that for rituximab. The rates of serious adverse effects did not differ significantly among interventions. Conclusion: Rituximab appears predominant in maintaining remission in patients with ANCA vasculitis with no cost in adverse events.

MPO-ANCA-Positive Granulomatosis with Polyangiitis with Rapidly Progressive Glomerulonephritis and Saddle-Nose Deformity: A Case Report.

Early diagnosis and initiation of appropriate immunosuppressive treatment remain the cornerstone of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis at the cost of significant toxicity. In this report, we present a case of a 69-year-old female who presented with advanced renal insufficiency and evidence of pulmonary hemorrhage and was MPO-ANCA-positive with a clinical phenotype of granulomatosis with polyangiitis. Organ involvement included rapidly progressive glomerulonephritis (GN), along with extrarenal manifestations (skin, upper and lower respiratory system involvement, and onset of saddle-nose deformity). Kidney biopsy established the diagnosis of pauci-immune crescentic, sclerotic GN. She received therapy with glucocorticoids and cyclophosphamide, mainly due to life-threatening extra-renal manifestations, such as pulmonary hemorrhage. She avoided vasculitis-related death but she developed severe therapy-related toxicity, resulting in the discontinuation of immunosuppressive therapy. Continuous re-evaluation of patients with ANCA-associated vasculitis in terms of response to immunosuppressive therapy and treatment-related toxicity is crucial for their management.

Calciphylaxis: A Long Road to Cure with a Multidisciplinary and Multimodal Approach.

Calciphylaxis is a rare yet potentially fatal condition, resulting from ectopic calcification of the small arterioles of the dermis with resulting necrotic lesions infection, sepsis, and death. In hemodialysis patients, its prevalence ranges between 1 and 4%, while mortality amounts to 30-80%. We present in here a 45-year-old female on chronic dialysis with morbid obesity, who was admitted for painful nodules in the lower abdomen and necrotic lesions at the lower extremities. Severe uremia and uncontrolled secondary hyperparathyroidism were the main characteristics in this patient, and thus, a clinical diagnosis of calciphylaxis was made. Treatment modalities included wound care plus antibiotics and analgesics, daily hemodialysis, and strategies targeting calcification with sodium thiosulfate, cinacalcet, and non-calcium-containing binders. A crucial factor for overcoming the infection-lesion vicious circle is thorough and daily care of the lesions. Nursing attention was focused on the motivation of her self-care, for the prevention of institutionalization and the psychological support of the patient and her family. The most intriguing feature was the fact that she experienced several exacerbations during the follow-up time. During the final relapse, she was prescribed hyperbaric oxygen sessions that actually put the disease under control thereafter. The good outcome for this patient was probably related to the combination of close follow-up along with a multidisciplinary approach.

Direct Oral Anticoagulants in Patients on Chronic Dialysis and Concomitant Atrial Fibrillation: A Common Clinical Impasse.

The most frequent arrhythmia treated is atrial fibrillation (AF), which necessitates the use of oral anticoagulants (OACs) to reduce the risk of thromboembolism and stroke. Patients with chronic kidney disease are more likely to develop AF, with a 10% frequency among those on chronic dialysis. Warfarin is the most widely prescribed OAC for individuals with end-stage kidney disease (ESKD). On the other hand, direct OACs (DOACs) are generally safer than warfarin, with fewer fatal bleeding events and a fixed dose that does not require close international normalized ratio (INR) monitoring. For those patients, warfarin and apixaban appear to be FDA-approved, whereas dabigatran, rivaroxaban, and edoxaban are not recommended yet. Due to a lack of large randomized studies, data from major trials cannot be extended to dialysis patients. In this review, we summarize the available data and literature referring to patients on chronic hemodialysis with concomitant AF. Due to the scarcity of data, we try to assist clinicians in selecting the appropriate therapy according to the specific characteristics of each patient. Finally, future directions are provided in two key areas of focus: left atrial appendage closure therapies and genetic research.