Antineutrophil cytoplasmic antibody-associated vasculitis.

PURPOSE OF REVIEW: This review focuses on latest developments in managing antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV), a systemic autoimmune condition characterized by inflammation and necrosis of small blood vessels due to circulating autoantibodies that target neutrophilic granules. RECENT FINDINGS: Our understanding of AAV pathogenesis has evolved in the past decades highlighting the central pathogenic roles of autoantibodies and complement activation. In parallel, the appreciation for glucocorticoid toxicity has led the research on crucial steroid-sparing therapeutic alternatives. Complement inhibitors (like avacopan) that have emerged are associated with better preservation of kidney function in AAV patients with severe kidney impairment. The role of plasma-exchange (PLEX) was revisited in updated guidelines that recommended its potential use in the context of diffuse alveolar hemorrhage associated hypoxia and severe kidney involvement, particularly with a serum creatinine level above 3.4 mg/dl. The ANCA Kidney Risk Score risk prediction and Glucocorticoid Toxicity Index score aid in identifying high-risk patients and individualizing management plans. SUMMARY: Kidney involvement in AAV requires prompt diagnosis and initiation of immunosuppression to prevent irreversible nephron loss. Newer therapeutic targets are on the horizon and offer hope for personalized treatment strategies.

Calciphylaxis in a Patient With Lupus Nephritis and Acute Kidney Injury: A Rare Case Report and Literature Review.

Calciphylaxis is a rare and severe disease characterized by calcification, fibrosis, and thrombosis of small blood vessels. Although it primarily affects patients with end-stage renal disease (ESRD) on dialysis, limited cases have been reported of calciphylaxis in patients with acute kidney injury (AKI) and lupus. This case report describes the occurrence of calciphylaxis in a 35-year-old female recently diagnosed with lupus nephritis class IV and AKI requiring dialysis.

Evolution of Therapy for ANCA-Associated Vasculitis with Kidney Involvement.

ANCA-associated vasculitis (AAV) belongs to a group of small vessel systemic vasculitides characterized by granulomatous and neutrophilic inflammation of various tissues. Patients often have circulating autoantibodies targeting neutrophilic antigens. Although AAV was once associated with severe end-organ damage and extremely high mortality rates, the use of glucocorticoids and cyclophosphamide led to a paradigm change in its treatment. Over the past 20 years, significant progress in understanding the immunopathogenesis of AAV has enabled development of targeted immunotherapies, providing a much better prognosis for patients. This review describes the evolution of treatment of AAV, particularly for patients with kidney involvement.

Current Understanding of Complement Proteins as Therapeutic Targets for the Treatment of Immunoglobulin A Nephropathy.

Immunoglobulin A nephropathy (IgAN) is the most common primary glomerulonephritis worldwide and a frequent cause of kidney failure. Currently, the diagnosis necessitates a kidney biopsy, with routine immunofluorescence microscopy revealing IgA as the dominant or co-dominant immunoglobulin in the glomerular immuno-deposits, often with IgG and sometimes IgM or both. Complement protein C3 is observed in most cases. IgAN leads to kidney failure in 20-40% of patients within 20 years of diagnosis and reduces average life expectancy by about 10 years. There is increasing clinical, biochemical, and genetic evidence that the complement system plays a paramount role in the pathogenesis of IgAN. The presence of C3 in the kidney immuno-deposits differentiates the diagnosis of IgAN from subclinical glomerular mesangial IgA deposition. Markers of complement activation via the lectin and alternative pathways in kidney-biopsy specimens are associated with disease activity and are predictive of poor outcome. Levels of select complement proteins in the circulation have also been assessed in patients with IgAN and found to be of prognostic value. Ongoing genetic studies have identified at least 30 loci associated with IgAN. Genes within some of these loci encode complement-system regulating proteins that can interact with immune complexes. The growing appreciation for the central role of complement components in IgAN pathogenesis highlighted these pathways as potential treatment targets and sparked great interest in pharmacological agents targeting the complement cascade for the treatment of IgAN, as evidenced by the plethora of ongoing clinical trials.

Wearable Sensor Data Classification for Identifying Missing Transmission Sequence Using Tree Learning.

Wearable Sensor (WS) data accumulation and transmission are vital in analyzing the health status of patients and elderly people remotely. Through specific time intervals, the continuous observation sequences provide a precise diagnosis result. This sequence is however interrupted due to abnormal events or sensor or communicating device failures or even overlapping sensing intervals. Therefore, considering the significance of continuous data gathering and transmission sequence for WS, this article introduces a Concerted Sensor Data Transmission Scheme (CSDTS). This scheme endorses aggregation and transmission that aims at generating continuous data sequences. The aggregation is performed considering the overlapping and non-overlapping intervals from the WS sensing process. Such concerted data aggregation generates fewer chances of missing data. In the transmission process, allocated first-come-first-serve-based sequential communication is pursued. In the transmission scheme, a pre-verification of continuous or discrete (missing) transmission sequences is performed using classification tree learning. In the learning process, the accumulation and transmission interval synchronization and sensor data density are matched for preventing pre-transmission losses. The discrete classified sequences are thwarted from the communication sequence and are transmitted post the alternate WS data accumulation. This transmission type prevents sensor data loss and reduces prolonged wait times.

The Gut and Kidney Crosstalk in Immunoglobulin A Nephropathy.

Immunoglobulin A nephropathy(IgAN) is the most common primary glomerulonephritis worldwide. The working model for the pathogenesis of IgAN involves a multistep process starting from the production of galactose-deficient and polymeric immunoglobulin A-1 (gd-IgA1) that enters systemic circulation from gut-associated lymphoid tissue (GALT). Galactose-deficient IgA are targeted by endogenous IgG, leading to the formation of circulating immune complexes that deposit in the mesangium and resulting in glomerular inflammation. Disease onset and relapses are often associated with gut infections, supporting the hypothesis that the gut plays an important pathogenic role. In the presence of microbial pathogens or food antigens, activated dendritic cells in the gut mucosa induce T cell dependent and independent B cell differentiation into IgA secreting plasma cells. In IgAN patients, this promotes the systemic release of mucosal gd-IgA1. Not all bacterial strains have the same capacity to elicit IgA production, and little is known about the antigen specificity of the pathogenic gd-IgA1. However, efficacy of treatments targeting gut inflammation support a pathogenic link between the bowel immune system and IgAN. Herein, we review the evidence supporting the role of gut inflammation in IgAN pathogenesis.

Advocating for in-center hemodialysis patients via anonymous survey.

We conducted an anonymous survey in 9 of our university affiliated outpatient dialysis units to address the concern that many in-center hemodialysis patients may not feel comfortable sharing their experiences. Major goals of this study: Investigating level of patient satisfaction with their care; Evaluating the subjective perception of the level of understanding of patients regarding pertinent issues of their disease and its management; Identifying potential avenues for care improvement. Survey was conducted in English, paper-based, with answer choices to individual questions for patient satisfaction and education graded using a 5-point Likert scale. Regarding potential areas of improvement, patients were asked to choose as many areas as deemed appropriate. To ensure anonymity, the completed surveys were folded and dropped into a box. Overall, 253 out of 516 (49%) screened patients were eligible and completed the survey. Patients expressed favorable responses regarding satisfaction (mean rating > 4 in each of 14 questions) and education (mean rating > 4 in 8 questions, > 3.5 in 2 questions) regarding hemodialysis. About 62% of overall study participants identified at least one area where they felt additional information would result in improvement of care. Our results indicate that patients undergoing outpatient hemodialysis were overall satisfied and had a good perceptive understanding about their health. Based on the patients' input, strategies focused on addressing pain and discomfort, privacy, providing information about palliative care/hospice, mental health resources, and the process of kidney transplantation may promote improvement in overall quality of care.

Performance comparison of solar still with inbuilt condenser and agitator over conventional solar still with energy and exergy analysis.

Demand for fresh water increases day by day. Solar desalination is one of the promising technologies to meet this demand in an economical fashion which uses solar still. For the current study, single-basin single-slope conventional solar still and a modified single-basin single-slope solar still with inbuilt condenser and agitator were designed and fabricated. Both the stills were tested under the same ambient conditions to compare the performance. Through experimental results, it was found that modified still with inbuilt condenser and agitator had 98.69% more productivity than conventional solar still. Modified still productivity was recorded as 4.856 L/m2/day and that of conventional still was 2.44 L/m2/day. The agitation effect caused by the agitator in the modified still led to an increase in the rate of evaporation. The increase in condensing area for the same evaporation area of the modified still improved the condensation rate. These two synergized effects resulted in an overall performance improvement of the modified still over the conventional still. An energy analysis revealed that modified still is 24.42% more efficient than its counterpart. The energy efficiency of modified and conventional stills was calculated as 4.82% and 2.04% respectively.

Lactated Ringer's solution and risk of hyperkalemia in patients with reduced kidney function.

BACKGROUND: Emerging evidence supports the superiority of balanced crystalloids such as Lactated Ringer's (LR) compared to normal saline but concerns for the development of hyperkalemia have limited its use. Although LR inherently contains potassium, there exists a paucity of evidence to suggest that LR could potentiate hyperkalemia. To address this, we evaluated the effect of LR on serum potassium in patients with reduced kidney function who are at risk of developing hyperkalemia. METHODS: We conducted a single-center, retrospective cohort-based observational clinical study that included 293 clinical encounters who were hospitalized with an estimated glomerular filtration rate (eGFR) of < 30 ml/min/1.73m2, at the time of hospital admission. Subjects must have received a minimum of 500 ml of LR continuously during the admission. Only those with a minimum of one lab report within 24 hours prior to-, and post-LR administration that reported serum measurements of potassium, glucose, and bicarbonate levels were included. Other potential risk factors for developing hyperkalemia including medication, tube feeds, potassium supplements, and red blood cell transfusion during or within 24 hours after LR administration were recorded. RESULTS: Serum potassium prior to LR use was highly correlated and predictive of the serum potassium after LR use [P < 0.0001; Odds Ratio 6.77 (3.73 - 12.28)]. Sixteen encounters (5%) developed de-novo hyperkalemia following LR use. No significant positive correlation between the amount of LR administered and the development of hyperkalemia was found. CONCLUSIONS: LR use was not independently associated with the development of hyperkalemia in patients with reduced kidney function.

Blockchain Enabled Anonymous Privacy-Preserving Authentication Scheme for Internet of Health Things.

The Internet of Health Things (IoHT) has emerged as an attractive networking paradigm in wireless communications, integrated devices and embedded system technologies. In the IoHT, real-time health data are collected through smart healthcare sensors and, in recent years, the IoHT has started to have an important role in the Internet of Things technology. Although the IoHT provides comfort in health monitoring, it also imposes security challenges in maintaining patient data confidentiality and privacy. To overcome such security issues, in this paper, a novel blockchain-based privacy-preserving authentication scheme is proposed as an approach for achieving efficient authentication of the patient without the involvement of a trusted entity. Moreover, a secure handover authentication mechanism that ensures avoiding the patient re-authentication in multi-doctor communication scenarios and revoking the possible malicious misbehavior of medical professionals in the IoHT communication with the patient is developed. The performance of the proposed authentication and handover scheme is analyzed concerning the existing state-of-the-art authentication schemes. The results of the performance analyses reveal that the proposed authentication scheme is resistant to different types of security attacks. Moreover, the results of analyses show that the proposed authentication scheme outperforms similar state-of-the-art authentication schemes in terms of having lower computational, communication and storage costs. Therefore, the novel authentication and handover scheme has proven practical applicability and represents a valuable contribution to improving the security of communication in IoHT networks.

Updated Pathway to Micro-elimination of Hepatitis C Virus in the Hemodialysis Population.

Chronic hepatitis C virus (HCV) infection continues to be transmitted to hemodialysis (HD) patients within HD facilities globally. The goal of the World Health Organization to micro-eliminate HCV infection from the HD population by the year 2030 is not on target to be achieved. Obstacles to eliminate HCV in HD settings remain daunting due to a complex system created by a confluence of guidelines, legislation, regulation, and economics. HCV prevalence remains high and seroconversion continues among the HD patient population globally as a result of the HD procedure. Preventive strategies that effectively prevent HCV transmission, treatment-as-prevention, and rapid referral to treatment balanced with kidney transplant candidacy should be added to the current universal precautions approach. A safer system must be designed before HCV transmission can be halted and eliminated from the HD population.

An Update on the Current State of Management and Clinical Trials for IgA Nephropathy.

IgA nephropathy remains the most common primary glomerular disease worldwide. It affects children and adults of all ages, and is a leading cause of end-stage kidney disease, making it a considerable public health issue in many countries. Despite being initially described over 50 years ago, there are still no disease specific treatments, with current management for most patients being focused on lifestyle measures and renin-angiotensin-aldosterone system blockade. However, significant advances in the understanding of its pathogenesis have been made particularly over the past decade, leading to great interest in developing new therapeutic strategies, and a significant rise in the number of interventional clinical trials being performed. In this review, we will summarise the current state of management of IgAN, and then describe major areas of interest where new therapies are at their most advanced stages of development, that include the gut mucosal immune system, B cell signalling, the complement system and non-immune modulators. Finally, we describe clinical trials that are taking place in each area and explore future directions for translational research.

IgA Nephropathy: An Interesting Autoimmune Kidney Disease.

Immunoglobulin A nephropathy (IgAN) is the most common primary glomerulonephritis worldwide. It is a leading cause of chronic kidney disease and progresses to end-stage kidney disease in up to 40% of patients about 20 years after diagnosis. Additionally, IgAN is associated with significant mortality. The diagnosis currently necessitates a kidney biopsy, as no biomarker sufficiently specific and sensitive is available to supplant the procedure. Patients display significant heterogeneity in the epidemiology, clinical manifestations, renal progression, and long-term outcomes across diverse racial and ethnic populations. Recent advances in understanding the underlying pathophysiology of the disease have led to the proposal of a four-hit hypothesis supporting an autoimmune process. To date, there is no disease-specific treatment but, with a better understanding of the disease pathogenesis, new therapeutic approaches are currently being tested in clinical trials. In this review, we examine the multiple facets and most recent advances of this interesting disease.

Impact of autologous stem cell transplantation on long term renal function and associated progression-free and overall survival in multiple myeloma.

The long-term impact of Autologous hematopietic stem cell transplantation (ASCT) on renal function, and the impact of renal function on progression-free survival (PFS) and overall survival (OS) in patients with multiple myeloma are not known. We retrospectively reviewed the records of 885 patients at our institution. We used linear mixed effect models to study the change in estimated glomerular filtration rate (eGFR) and a joint model approach to assess associations between the eGFR, PFS and OS. Sensitivity analyses were conducted at days 0, 100, 180, and 365 post-SCT. eGFR post-ASCT was significantly lower than at day 0 but stabilized at approximately 80 mL/min/1.73 m2. There was no association between eGFR and PFS or OS.; However, relapsed disease and ISS stage were associated with shorter PFS and OS. This data suggests that although there is a modest decline in eGFR post-ASCT, it is not associated with an adverse impact on PFS or OS. KEY POINTS Advanced MM stage at diagnosis was associated with reduced eGFR at all stages of chronic kidney disease. eGFR was not associated with PFS or OS in any of the analyses, but disease-related factors prior to ASCT were all associated with reduced eGFR, PFS and OS. ASCT did not adversely impact kidney function and mitigated the risk of CKD on outcomes in MM.

Primary myelofibrosis associated glomerulopathy: significant improvement after therapy with ruxolitinib.

BACKGROUND: Primary myelofibrosis (PMF) is a type of myeloproliferative neoplasm (MPN) characterized by the predominant proliferation of megakaryocytes and granulocytes in the bone marrow, leading to the deposition of fibrous tissue, and by a propensity toward extramedullary hematopoiesis. Renal involvement in PMF is rare, but kidney tissue samples from these patients reveal MPN-related glomerulopathy, a recently discovered condition, in the late stages of the disease. CASE PRESENTATION: We present the first case described in the medical literature of a patient with early renal glomerular involvement in PMF/MPN. A 60-year-old man with stage 4 chronic kidney disease and a recent diagnosis of PMF (within 4 weeks of presentation at our renal division) presented with generalized body swelling, acute kidney injury, and massive nephrotic-range proteinuria. Kidney biopsy was performed to determine the etiology of the patient's renal dysfunction and revealed early renal glomerular involvement that was histologically characteristic of MPN-related glomerulopathy. Early diagnosis and prompt medical management returned the patient's kidney functionality to the levels seen on initial presentation at our hospital. CONCLUSION: Large studies with long follow-up durations are necessary to identify and categorize the risk factors for the development of MPN-related glomerulopathy, to standardize therapeutic regimens, and to determine whether aggressive management of the myelofibrosis slows the progression of kidney disease.

APOL1 risk variants predict histopathology and progression to ESRD in HIV-related kidney disease.

With earlier institution of antiretroviral therapy, kidney diseases other than HIV-associated nephropathy (HIVAN) predominate in HIV-infected persons. Outcomes for these diseases are typically worse among those infected with HIV, but the reasons for this are not clear. Here, we examined the role of APOL1 risk variants in predicting renal histopathology and progression to ESRD in 98 HIV-infected African Americans with non-HIVAN kidney disease on biopsy. We used survival analysis to determine time to ESRD associated with APOL1 genotype. Among the 29 patients with two APOL1 risk alleles, the majority (76%) had FSGS and 10% had hypertensive nephrosclerosis. In contrast, among the 54 patients with one APOL1 risk allele, 47% had immune-complex GN as the predominant lesion and only 23% had FSGS. Among the 25 patients with no APOL1 risk allele, 40% had immune-complex GN and 12% had FSGS. In 310 person-years of observation, 29 patients progressed to ESRD. In adjusted analyses, individuals with two APOL1 risk alleles had a nearly three-fold higher risk for ESRD compared with those with one or zero risk alleles (P=0.03). In summary, these data demonstrate an association between APOL1 variants and renal outcomes in non-HIVAN kidney disease, suggesting a possible use for APOL1 genotyping to help guide the care of HIV-infected patients.