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.

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.

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.

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.

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.

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.

COVID-19 presenting with persistent hiccup and myocardial infarction in a peritoneal dialysis patient: A case report.

BACKGROUND: Persistent hiccups, lasting more than 48 h, have been described as an atypical presentation of coronavirus disease 19 (COVID-19) in the general population. To the best of our knowledge, this is the first report of persistent hiccups and non-ST elevation myocardial injury (NSTEMI) as an atypical presentation of COVID-19 in a peritoneal dialysis (PD) patient. CASE SUMMARY: A 70-year old man, who had been on PD for 3 years with a history of ischemic heart failure and reduced ejection fraction, presented for a scheduled radionuclide myocardial scan. Upon arrival, he complained of anorexia, nausea for 5 d, and unremitting hiccups for the previous 48 h. Clinical and laboratory examinations revealed an NSTEMI plus a positive nasopharyngeal reverse transcriptase polymerase chain reaction testing for severe acute respiratory syndrome coronavirus 2. COVID-19 lung involvement was mild and was resolved without specific treatment. Myocardial injury was managed by coronary catheterization and stenting, while hiccups responded only to baclofen per os. CONCLUSION: Persistent hiccups and NSTEMI can be atypical presentations of COVID-19 in peritoneal dialysis patients, which may be due to involvement of the central nervous system and myocardial injuries.

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.

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.

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.

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.

Clinical presentation and outcomes of chronic dialysis patients with COVID-19: A single center experience from Greece.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is still a menacing pandemic, especially in vulnerable patients. Morbidity and mortality from COVID-19 in maintenance hemodialysis (MHD) patients are considered worse than those in the general population, but vary across continents and countries in Europe. AIM: To describe the clinical course and outcomes of hospitalized MHD patients with COVID-19 in a retrospective observational single center study in Greece. METHODS: We correlated clinical, laboratory, and radiological data with the clinical outcomes of MHD patients hospitalized with COVID-19 during the pandemic. The diagnosis was confirmed by real-time polymerase chain reaction. Outcome was determined as survivors vs non-survivors and "progressors" (those requiring oxygen supplementation because of COVID-19 pneumonia worsening) vs "non-progressors". RESULTS: We studied 32 patients (17 males), with a median age of 75.5 (IQR: 58.5-82) years old. Of those, 12 were diagnosed upon screening and 20 with related symptoms. According to the World Health Organization (WHO) score, the severity on admission was mild disease in 16, moderate in 13, and severe in 3 cases. Chest computed tomography (CT) showed 1-10% infiltrates in 24 patients. Thirteen "progressors" were recorded among included patients. The case fatality rate was 5/32 (15.6%). Three deaths occurred among "progressors" and two in "non-progressors", irrespective of co-morbidities and gender. Predictors of mortality on admission included frailty index, chest CT findings, WHO severity score, and thereafter the increasing values of serum LDH and D-dimers and decreasing serum albumin. Predictors of becoming a "progressor" included increasing number of neutrophils and neutrophils/lymphocytes ratio. CONCLUSION: Patients on MHD seem to be at higher risk of COVID-19 mortality, distinct from the general population. Certain laboratory parameters on admission and during follow-up may be helpful in risk stratification and management of patients.

Pregnancy in Women With Preexisting Glomerular Diseases: A Single-Center Experience.

AIM: Women with glomerular diseases are often of childbearing age. Besides lupus nephritis, data regarding pregnancy in patients with glomerular diseases are limited, posing a challenging task to attending nephrologists. This study aimed to investigate the pregnancy outcomes and the impact on the underlying glomerular disease among women followed in our institution. METHODS: A single-center retrospective cohort study of women with biopsy-proven glomerular diseases who experienced pregnancy between 2010 and 2020. We analyzed data before, during, and after gestation. RESULTS: A total of 22 women, 13 women with primary and 9 women with secondary glomerular diseases, were included in this study. Most patients (82%) had received immunosuppressive treatment at various times before pregnancy. All the women were in remission, either complete (62%) or partial (38%), with well-preserved renal function (82%) before conception. A total of 30 live births and 1 stillbirth were recorded; the rate of preterm delivery was 23%. Renal function and proteinuria remained stable during pregnancy. Preeclampsia was observed in 6.7% of patients and disease relapse in 6.9% of the pregnancies. CONCLUSION: Pregnancy was associated with a low frequency of adverse events in women with underlying glomerular diseases, provided they have quiescent disease and preserved renal function.

Plasma Exchange in ANCA-Associated Vasculitis: A Narrative Review.

Therapeutic plasma exchange (TPE) is an adjunctive intervention to immunosuppression for the treatment of severe renal involvement or lung hemorrhage in patients with ANCA-associated vasculitis (AAV). Patients with AAV have an increased risk for progression to end-stage kidney disease (ESKD) or death despite advances in immunosuppressive therapy. The potential pathogenicity of ANCA makes TPE a reasonable treatment approach for the life-threatening complications of AAV. The efficacy of intensive TPE in rapidly progressive glomerulonephritis was originally described in small studies almost four decades ago. Further randomized trials examined the addition of TPE to standard of care, exhibiting mixed results in both patient and renal survival. The largest clinical trial to date, PEXIVAS, failed to demonstrate a clear benefit for TPE in severe AAV. In light of new evidence, the role of TPE remains controversial across the vasculitis medical community. The purpose of this review is to summarize the clinical indications and the current available data for the use of TPE in patients with severe AAV.

Hypocomplementemia at Diagnosis of Pauci-immune Glomerulonephritis Is Associated With Advanced Histopathological Activity Index and High Probability of Treatment Resistance.

INTRODUCTION: Recent evidence suggests that complement activation is important in the pathogenesis of pauci-immune (PI) vasculitis. This is a retrospective investigation of the frequency of hypocomplementemia at pauci-immune glomerulonephritis (PIGN) diagnosis, in relation to vasculitic manifestations, renal histopathology, and treatment outcomes. METHODS: A total of 115 patients with biopsy-proven PIGN were categorized based on their serum complement C3 (sC3). Histopathology evaluation included activity and chronicity indexes. The primary outcome of interest was treatment resistance, defined as a progressive decline in kidney function, with persistently active urine sediment, leading to dialysis dependency or vasculitis-related death. RESULTS: In all, 20.9% of patients had low sC3 levels associated with more advanced renal impairment (P < 0.01), requiring acute dialysis (P < 0.01) more frequently compared to patients with normal sC3. Within 1 year, 85.7% of patients with normal sC3 responded to therapy, versus 58.3% of those with low sC3 (P = 0.001). The probability of treatment resistance was strongly associated with low sC3 (P = 0.004), high serum creatinine (P < 0.001), acute dialysis requirement (P < 0.001), and high histopathological score of chronicity (P < 0.01). Advanced histopathological activity was related to more intense interstitial leukocyte infiltration (P = 0.005) and higher likelihood of fibrinoid necrosis documentation in a vessel wall (P = 0.02). The probability of treatment resistance was higher in patients with low sC3 (odds ratio [OR] = 6.47, 95% confidence interval [CI] 1.47-28.35, P = 0.013), oliguria (OR = 29.57, 95% CI = 4.74-184, P < 0.0001), and high chronicity score (OR = 1.77, 95% CI = 1.23-2.54, P = 0.002). CONCLUSION: Low sC3 is emerging as an independent predictor of treatment resistance in patients with PIGN associated with higher index of histopathological activity at diagnosis compared to normal sC3.