Focus: Rare Disease: Chronic Pulmonary Aspergillosis: A Brief Review

Chronic Pulmonary Aspergillosis (CPA) is a destructive pulmonary disease caused by a fungal infection, affecting mainly individuals with prior or concurrent pulmonary conditions. It has a global prevalence of 42 per 100,000 population, but in the US and Europe, prevalence is less than 1 per 100,000. The clinical definition of CPA is based on various factors accounting for comorbidities, clinical presentation, and duration. It may be categorized into five subtypes that the disease may evolve between over time. Based on global consensus covering the spectrum of low-resource to high-resource settings, diagnosis is a multi-factorial process that involves a combination of clinical presentation persisting over 3 months, radiological findings, positive culture growth, and serological tests. CPA remains underdiagnosed due to a lack of awareness and is often misdiagnosed due to the comorbidities present. Treatment options are limited due to a lack of research. Furthermore, associated comorbidities and drug interactions further complicate treatment plans. Follow-up throughout treatment should be based on understanding the predictors of mortality. Identification of potential relapse or resistance to antifungal therapy is crucial to limit the low long-term survival rate. Awareness surrounding this devastating disease needs to be raised further to enable earlier identification, improve understanding of patient factors associated with prognosis, and the future potential for targeted therapies. This review aims to raise awareness of this rare condition among practitioners, by providing an overview of common risk factors influencing the prevalence and incidence of the disease. We further discuss current approaches and recent advancements in CPA diagnosis and treatment.     

Focus: Rare Disease: Differential Diagnosis of a Case of Dercum’s Disease with Possible Familial Involvement and Review of Literature

Dercum’s disease (DD), also described as adiposis dolorosa, is a poorly understood and rare adipose tissue disorder involving obesity and painful adipose tissue masses. Patients may have associated bruising and constitutional symptoms such as fatigue, difficulty concentrating, and sleep disturbance. DD was initially described in 1888 by Francis Xavier Dercum, and was classified into four subtypes, including generalized diffuse, generalized nodular, localized nodular, and juxta-articular subtypes. While this disease has been described for more than 130 years, its etiology and treatment remain elusive. We describe a case of a patient with DD who presented to Ochsner Medical Center, New Orleans, LA, for evaluation of treatment options. We review current knowledge on this rare disease and data on modern treatment methods.     

Focus: Rare Disease: Pulmonary Alveolar Microlithiasis – A Review

Pulmonary Alveolar Microlithiasis (PAM) is a rare genetic disorder causing widespread deposition of calcium-phosphate crystals in the alveolar space. A hallmark of the disease is the discrepancy between perceived symptoms upon diagnosis compared with the extensive, sandstorm-like appearance of the microliths on chest X-ray or HRCT. Caused by a defective sodium-dependent phosphate transport protein due to loss-of-function variants of the SLC34A2 gene, PAM is an autosomal recessive transmitted disorder, and as such has a high correlation to consanguinity. The most common variants of the SLC34A2 gene are single nucleotide biallelic changes, but larger deletions are described. Initial suspicion of PAM on radiological examination should be followed by genetic testing to verify the diagnosis and identify the disease-causing variant. When not available, the diagnosis can be made by means of invasive techniques, such as transbronchial forceps or cryobiopsy, or a surgical lung biopsy. In families with a history of PAM, genetic counseling should be offered, as well as preimplantation/prenatal testing if necessary. As of writing this review, no definitive treatment exists, and PAM may in some cases progress to severe pulmonary disease with respiratory failure and potential death. Patients with PAM should be offered preventative and symptomatic treatments such as vaccinations and oxygen therapy when needed. In some cases, lung transplantation may be required.     

Focus: Rare Disease: Patients as Partners in Rare Disease Diagnosis and Research

There is great value in understanding the patient perspective in rare disease diagnosis and research, and in partnering actively with patients and their families throughout the process. Meaningful and respectful interaction between patients and researchers leads to learning on both sides, and ultimately, to better research outcomes. Researchers can help patients understand how research is conducted and what the latest advances and perceived gaps in research are, and patients, who have direct experience living with their health conditions, can impart to researchers what is most important to them. We describe our engagement with patients in the Undiagnosed Diseases Network (UDN) program, as well as the lessons we have learned to date. In the UDN, patients have been instrumental in bringing meaning to the work of clinicians and researchers, building patient communities, making the network aware of unmet patient needs, advocating for additional research funding, and disseminating UDN research findings. Although patient engagement in the UDN has already had a significant positive impact on our work, we continue to strive to involve patients earlier in the process, in the research design itself, and in addressing power dynamics that may arise between clinicians, researchers, and patients.     

Focus: Rare Disease: Histopathologic Analysis of Surgically Resected Lungs of Patients with Non-tuberculous Mycobacterial Lung Disease: a Retrospective and Hypothesis-generating Study

Non-tuberculous mycobacterial lung disease (NTM-LD) is most commonly due to species within the Mycobacterium avium complex (MAC) and Mycobacterium abscessus complex (MAbC). Surgical lung resection, typically a lobectomy or segmentectomy, is occasionally undertaken for individuals with recalcitrant but localized NTM-LD. Since the growth characteristics of MAC (slow growers) and MAbC (rapid growers) as well as their drug susceptibility patterns are significantly different, the objective of this study is to characterize and compare the histopathologic features of the resected lungs due to these two major NTM groups. From 1996 to 2017, 356 patients with NTM-LD due to MAC (n=270), MAbC (n=54), or both (n=32) underwent a total of 404 lobar resections (with the lingula counted as a separate lobe) at the University of Colorado Hospital. We analyzed by microscopy the existing surgical lung tissue sections for bronchiolitis, bronchiolectasis, bronchiectasis, non-necrotizing granuloma (airway, parenchymal, and total), necrotizing granuloma (airway, parenchymal, and total), peri-airway fibrosis, fibrous pleuritis, and lymphoid follicles. There were no significant differences in the presence or absence of most of the histopathologic features of surgically removed lungs due to MAC, MAbC, or both MAC + MAbC. However, there were significantly more necrotizing granulomas (airway, parenchymal, and total) and fibrous pleuritis in MAC compared to MAbC lung diseases. Since necrotizing granulomas may be a sign of inadequate control of the infection, we posit that their presence may be an indication of increased chronicity, increased virulence of MAC compared to MAbC, and/or impaired host immunity against the NTM. Futures studies to determine the root cause of such differences in histopathologic findings in MAC versus MAbC lung disease may spawn new leads on differential pathogenic mechanisms with different NTM, with the goal of aiming for more targeted therapy against both the NTM and the lung damage induced by them.     

Focus: Rare Disease: Sinonasal Glomangiopericytoma: Review of Imaging Appearance and Clinical Management Update for a Rare Sinonasal Neoplasm

Introduction: Glomangiopericytoma (GPC) is a rare tumor in the nasal cavity or paranasal sinuses with low malignant potential. Initially deemed a hemangiopericytoma, in 2005 it was classified as a distinct entity by the World Health Organization (WHO). Case Presentation: A male patient in his early 60s presented with new-onset right arm and leg weakness/numbness, who was incidentally found to have a left ethmoid sinus mass with extension in the olfactory fossa. On CT and MRI, the mass enhanced with well-defined borders and eroded the bone, but without dural enhancement. The mass was surgically excised, and pathology confirmed the diagnosis of glomangiopericytoma by microscopic appearance and staining. Discussion: Glomangiopericytoma has less than 0.5% incidence of all neoplasms of the sinonasal cavity, making it rare. Most diagnosed patients are in their 6th or 7th decade of age, with a slight female predominance. Treatment is complete surgical excision, with excellent prognosis, although there is up to 17% local recurrence. Despite the non-specific appearance on CT and MRI, imaging can help provide differential diagnosis, tumor extent, size, and reassuring non-aggressive characteristics of the tumor prior to surgery. GPC tumors are relatively resistant to radiation and chemotherapy. Conclusion: It is important to recognize glomangiopericytoma in the differential of masses of the nasal cavities or paranasal sinuses, as they rarely warrant aggressive treatment beyond local excision. Each reported case of glomangiopericytoma helps to build guidance for imaging and treatment since GPC is rare and not well-represented in the medical literature.     

Focus: Rare Disease: Desmoplastic Small Round Cell Tumor in a Pregnant Woman: A Case Report and Literature Review

Background: Desmoplastic small round cell tumor (DSRCT) is an aggressive malignant tumor commonly found in young men; most occurs in the abdominal cavity. Here we conducted an in-depth analysis of a pregnant patient in our hospital and explored all the case information in the literature on small round cell carcinoma of women. Case presentation: A 27-year-old pregnant woman underwent tumor resection in our hospital at 29 weeks gestational age for a large progressive shoulder lump. The postoperative pathology showed that the mass was a DSRCT. Genetic testing found no fusion gene. At 36 weeks gestation, a painful mass was found in the breast and proved to be a metastatic focus of the desmoplastic small round cell tumor. Twenty days after a successful cesarean section at 40 weeks gestation, she received the VAC-IE chemotherapy regimen, successfully completed the first course, but when awaiting the next chemotherapy, unfortunately, the patient died during follow-up due to tumor recurrence and metastasis. Conclusion: The treatment of DSRCT in pregnant women requires a multidisciplinary consultation, and the treatment and examination during pregnancy are subject to many constraints, which may have a negative impact on the patient’s prognosis. Also, a review of the literature found that there is still no standard treatment protocol for DSRCT, and its prognosis in female patients is independent of age and tissue origin.     

Focus: Rare Disease: Oxytocin and Oxytocin Receptor Gene Regulation in Williams Syndrome: A Systematic Review

Williams Syndrome (WS) is a rare genetic multisystem disorder that occurs because of a deletion of approximately 25 genes in the 7q11.23 chromosome region. This causes dysmorphic facial appearances, multiple congenital cardiovascular defects, delayed motor skills, and abnormalities in connective tissues and the endocrine system. The patients are mostly diagnosed with mild to moderate mental retardation, however, they have a hyper sociable, socially dis-inhibited, and outgoing personality, empathetic behavior, and are highly talkative. Oxytocin (OT), a neuropeptide synthesized at the hypothalamus, plays an important role in cognition and behavior, and is thought to be affecting WS patients’ attitudes at its different amounts. Oxytocin receptor gene (OXTR), on chromosome 3p25.3, is considered regulating oxytocin receptors, via which OT exerts its effect. WS is a crucial disorder to understand gene, hormone, brain, and behavior associations in terms of sociality and neuropsychiatric conditions. Alterations to the WS gene region offer an opportunity to deepen our understandings of autism spectrum disorder, schizophrenia, anxiety, or depression. We aim to systematically present the data available of OT/OXTR regulation and expression, and the evidence for whether these mechanisms are dysregulated in WS. These results are important, as they predict strong epigenetic control over social behavior by methylation, single nucleotide polymorphisms, and other alterations. The comparison and collaboration of these studies may help to establish a better treatment or management approach for patients with WS if backed up with future research.     

Focus: Vaccines: Healthcare Economics of a Coronavirus Disease 2019 Pop-Up Vaccination Center

Introduction: Creation of pop-up vaccination sites at trusted community locations has been encouraged to address vaccine hesitancy and provide equitable access to COVID-19 vaccination in minority communities. This study sought to study the healthcare economics of a community-based COVID-19 pop-up vaccination center in terms of the following: costs associated with operating the vaccination center, analysis of billing data from patients who received the Moderna COVID-19 vaccine, and costs of hospitalization for COVID-19 which may be avoided with widespread vaccination. Methods: The pop-up vaccination center was located in Port Jefferson Station, NY, USA. Costs associated with operation of the COVID-19 pop-up vaccination center were quantified, itemized, and tabulated. Current Procedural Technology codes were used to identify patients who received the Moderna COVID-19 vaccine. Billing data were quantified for the cohort as well as per each patient to receive the vaccine. Costs associated with provision of urgent care, emergency, and hospital services to patients with COVID-19 were obtained. Results: The total cost to operate the vaccination center was $25,880. The vaccination center administered the initial dose of the Moderna COVID-19 vaccine to N=251 patients between March and May, 2021. The standard hospital costs for patients admitted to the medical ICU due to COVID-19 ranged from $8,913 to $190,714, per patient. Conclusion: Since the Moderna COVID-19 vaccine series is effective in preventing hospitalization for 93% of patients, this community-based vaccination center’s administration of the vaccine series to 240 patients meant aversion of hospitalization due to COVID-19 related morbidity for 223 patients. Therefore, the true impact of this vaccination center, measured in averted hospital costs, ranges from $1,987,599 to $42,529,222.     

Focus: Rare Disease: Psychosocial Functioning in Siblings of Children With Rare Disorders Compared to Controls

Siblings of children with chronic disorders are at increased risk of psychosocial problems. The risk may be exacerbated when the chronic disorder is rare and limited medical knowledge is available, due to more uncertainty and feelings of isolation. We examined mental health, parent-child communication, child-parent relationship quality, and social support among 100 children aged 8 to 16 years (M age 11.5 years, SD = 2.2; 50.0% boys, 50.0% girls). Fifty-six were siblings of children with rare disorders, and 44 were controls. The siblings of children with rare disorders (herein, siblings) were recruited from a resource centre for rare disorders and comprised siblings of children with a range of rare disorders including neuromuscular disorders and rare chromosomal disorders with intellectual disability. Controls were recruited from schools. Self-reported child mental health was significantly poorer for siblings compared to controls (effect size difference d = 0.75). Parent-reported child mental health was not significantly different between the groups (d = -0.06 to 0.16). Most child-parent relationships (anxiety/avoidance; mothers/fathers) were significantly poorer for siblings compared to controls (d = 0.47 to 0.91). There was no difference between groups in anxious relation with mother. Parent-child communication was significantly poorer for siblings compared to controls (d = -0.87 to -0.75). Social support was significantly poorer for siblings compared to controls (d = 0.61). We conclude that siblings of children with rare disorders display more psychosocial problems than controls. Interventions are indicated to prevent further maladjustment for siblings.     

Focus: Rare Disease: Behçet’s Disease and Pregnancy: A Retrospective Case-control Study

Background: Behçet’s disease (BD) is a rare chronic multisystemic vasculitis of unknown etiology. It is usually diagnosed between the 2^nd and 4^th decades of life, so its association with pregnancy is not unusual. This study aims to characterize the evolution of pregnancy in a group of pregnant women with BD and the impact of this pathology in embryo-fetal morbidity. Methods: A retrospective case-control study included 49 pregnancies in women suffering from BD, followed in our institution. Pregnancy outcomes were compared with a control group of healthy pregnant women. Two controls per case were randomly selected. Statistical analysis used SPSS 25.0, and a p-value of 0.05 was considered statistically significant. Results: Forty-nine pregnancies were included in 27 patients with BD. BD exacerbation occurred in 32.6% of the pregnancies. There were no significant statistical differences between the two groups regarding the rate of preterm delivery, gestational diabetes, and preeclampsia (p>0.05). In the BD group, we found a higher rate of miscarriage (24.5%) and fetal growth restriction (FGR, 13.3%, p<0.05). In the study group, 13 (32.5%) of the pregnant patients did not need treatment. The cesarean rate was significantly higher in the BD group (43.2% vs 20.4% in the control group, p<0.05), and there were no significant differences in median gestational age at the time of delivery (p>0.05). The birth weight of newborns did not differ significantly between the groups. There was no association of BD with maternal morbidity and neonatal complications. Conclusion: In this study, the majority of pregnant with BD did not present clinical exacerbation of their pathology. However, BD may have an adverse influence on pregnancy outcomes. FGR and miscarriage rates were significantly higher in the study group.     

Focus: Rare Disease: The Embryological Landscape of Mayer-Rokitansky-Kuster-Hauser Syndrome: Genetics and Environmental Factors

Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is a disorder caused by Müllerian ducts dysgenesis affecting 1 in 5000 women with a typical 46,XX karyotype. The etiology of MRKH syndrome is complex and largely unexplained. Familial clustering suggests a genetic component and the spectrum of clinical presentations seems consistent with an inheritance pattern characterized by incomplete penetrance and variable expressivity. Mutations of several candidate genes have been proposed as possible causes based on genetic analyses of human patients and animal models. In addition, studies of monozygotic twins with discordant phenotypes suggest a role for epigenetic changes following potential exposure to environmental compounds. The spectrum of clinical presentations is consistent with intricate disruptions of shared developmental pathways or signals during early organogenesis. However, the lack of functional validation and translational studies have limited our understanding of the molecular mechanisms involved in this condition. The clinical management of affected women, including early diagnosis, genetic testing of MRKH syndrome, and the implementation of counseling strategies, is significantly impeded by these knowledge gaps. Here, we illustrate the embryonic development of tissues and organs affected by MRKH syndrome, highlighting key pathways that could be involved in its pathogenesis. In addition, we will explore the genetics of this condition, as well as the potential role of environmental factors, and discuss their implications to clinical practice.     

Proenkephalin and risk of developing chronic kidney disease: the Prevention of Renal and Vascular End-stage Disease study

Background: Proenkephalin (pro-ENK) was recently found to be associated with low estimated glomerular filtration rate (eGFR). The association of pro-ENK with urinary albumin excretion (UAE), another marker for chronic kidney disease (CKD), has not been investigated. We examined the association of pro-ENK with eGFR and UAE as markers of CKD.

Methods: We included 4375 subjects of the Prevention of Renal and Vascular End-Stage Disease (PREVEND) study. CKD_eGFR was defined as development of eGFR?<60?ml/min/1.73 m² and CKD_UAE as albuminuria?>30?mg/24?h.

Results: Baseline median pro-ENK was 52.2 (IQR: 44.9–60.5) pmol/L. After a median follow-up of 8.4 (IQR: 7.9–8.9) years, 183 subjects developed CKD_eGFR and 371 developed CKD_UAE. The association of pro-ENK with CKD_eGFR was modified by sex (P_interaction?SD increase in ¹⁰log-transformed pro-ENK, 1.65; 95% CI: 1.15–2.36) and not in women (0.83; 0.58–1.20). No significant association was observed between pro-ENK and CKD_UAE risk (0.83; 0.58–1.20).

Conclusions: High pro-ENK is associated with increased risk of CKD_eGFR in men, but not in women. No association of pro-ENK with CKD_UAE was observed. These results should be interpreted with caution, since residual confounding and potential overfitting of models could have influenced the results.     

Focus: Rare Disease: Necrotizing Fasciitis: Association with Pregnancy-related Risk Factors Early in Life

Background: Pregnancy-related risk factors for necrotizing fasciitis are poorly understood. We investigated pregnancy-related characteristics associated with the long-term risk of developing necrotizing fasciitis, a rare life-threatening infectious disease. Methods: We analyzed a longitudinal cohort of 1,344,996 parous women in Quebec, Canada between 1989 and 2020. The main exposure measures included complications of pregnancy such as gestational diabetes, preterm delivery, metabolic disorder, and other maternal characteristics. We followed the women over time to identify future hospitalizations for necrotizing fasciitis up to three decades after delivery. We estimated adjusted hazard ratios (HR) and 95% confidence intervals (CI) for the association of pregnancy characteristics with risk of necrotizing fasciitis in time-varying Cox proportional hazards regression models. Results: A total of 420 women were hospitalized for necrotizing fasciitis during follow-up, including 83 (19.8%) with diabetes-related necrotizing fasciitis. The incidence of necrotizing fasciitis was elevated for women with gestational diabetes (2.9 per 100,000 person-years), preterm delivery (3.2 per 100,000 person-years), and metabolic disorders (5.4 per 100,000 person-years), compared with no pregnancy complication (1.1 per 100,000 person-years). Compared with no pregnancy complication, gestational diabetes was associated with 1.87 times the risk (95% CI 1.38-2.53), preterm delivery with 2.10 times the risk (95% CI 1.65-2.66), and metabolic disorder with 3.72 times the risk (95% CI 2.92-4.74) of developing necrotizing fasciitis over time. Pregnancy complications were more strongly associated with the risk of necrotizing fasciitis 5 years or more after delivery. Conclusions: Complications of pregnancy may be associated with the long-term risk of necrotizing fasciitis in women.     

Focus: Rare Disease: Prostatic Schwannoma Presenting with Prostate-specific Antigen Elevation: A Case Report

Introduction: Schwannoma of the male genital system is very uncommon and is mostly treated by surgery. However, prostatic schwannoma presenting with elevated prostate-specific antigen (PSA) level and treated conservatively are extremely rare. Case presentation: Herein, we present a rare case of a prostatic schwannoma in a 65-year-old man who initially presented with an elevated PSA level. Digital rectal examination revealed an enlarged prostate with a palpable hard nodule on the left side. Transrectal ultrasonography revealed an enlarged prostate with a well-defined homogeneously hypoechoic nodule in the left peripheral lobe. Biopsy was done, and histopathology revealed a prostatic schwannoma. Conservative treatment with regular image follow-up was done per the patient’s preference. Mild PSA progression but no worsening of symptoms was found in 6 years of follow-up. Conclusions: PSA elevation could be a rare presentation of prostatic schwannoma. Treatment options other than surgery, such as conservative treatment with close observation, could be feasible for these rare tumors and long-term survivorship can be achieved.     

Focus: Rare Disease: mEDUrare: Supporting Integrated Care for Rare Diseases by Better Connecting Health and Education Through Policy

Rare diseases affect an estimated 6-10% of the Australian population, a prevalence similar to that seen in other regions worldwide. These multi-system conditions are often severely debilitating and affect multiple domains of a person’s life. A salient necessity for effective care provision thus, is holistic care, achieved by appropriate and continual multi-disciplinary and cross-sectoral collaboration. Synonymous with this priority for collaborative care, is the need for increased partnerships between the health and education sectors. This partnership has the potential to benefit people with rare disease of all educational ages, but in particular, school-aged children and young adults. More than 70% of rare diseases affect children, and this population often experiences difficulties with overall well-being and functioning, including impaired school performance and confounding mental and social comorbidities. Ensuring adequate schooling needs and experiences along with provision of adequate medical care, is crucial in ensuring overall well-being for this population. For this, effective partnerships between the health and education sectors are paramount. This article highlights fundamental elements of health and education priorities, ingrained in current strategic documents, to build a policy foundation that informs and supports increased inter-sectoral partnerships between health and education services. Shared priorities identified in both sectors’ guidelines, co-developed with those with lived experience of rare diseases, build a strong policy base for future advocative initiatives to mold better integration between the sectors, a partnership which is vital to improving the overall quality of life, experiences and journeys of people living with rare disease.     

Focus: Rare Disease: Neuromonitoring in Rare Disorders of Metabolism

Inborn errors of metabolism (IEM) are a unique class of genetic diseases due to mutations in genes involved in key metabolic pathways. The combined incidence of IEM has been estimated to be as high as 1:1000. Urea Cycle disorders (UCD), one class of IEM, can present with cerebral edema and represent a possible target to explore the utility of different neuromonitoring techniques during an hyperammonemic crisis. The last two decades have brought advances in the early identification and comprehensive management of UCD, including further understanding of neuroimaging patterns associated with neurocognitive function. Nonetheless, very important questions remain about the potential acute neurotoxic effects of hyperammonemia to better understand how to treat and prevent secondary brain injury. In this review, we describe existing neuromonitoring techniques that have been used in rare metabolic disorders to assess and allow amelioration of ongoing brain injury. Directions of future research should be focused on identifying new diagnostic approaches in the management of metabolic crises to optimize care and reduce long term morbidity and mortality in patients with IEM.     

Focus: Personalized Medicine: Taking Control of Castleman Disease: Leveraging Precision Medicine Technologies to Accelerate Rare Disease Research

Castleman disease (CD) is a rare and heterogeneous disorder characterized by lymphadenopathy that may occur in a single lymph node (unicentric) or multiple lymph nodes (multicentric), the latter typically occurring secondary to excessive proinflammatory hypercytokinemia. While a cohort of multicentric Castleman disease (MCD) cases are caused by Human Herpes Virus-8 (HHV-8), the etiology of HHV-8 negative, idiopathic MCD (iMCD), remains unknown. Breakthroughs in “omics” technologies that have facilitated the development of precision medicine hold promise for elucidating disease pathogenesis and identifying novel therapies for iMCD. However, in order to leverage precision medicine approaches in rare diseases like CD, stakeholders need to overcome several challenges. To address these challenges, the Castleman Disease Collaborative Network (CDCN) was founded in 2012. In the past 3 years, the CDCN has worked to transform the understanding of the pathogenesis of CD, funded and initiated genomics and proteomics research, and united international experts in a collaborative effort to accelerate progress for CD patients. The CDCN’s collaborative structure leverages the tools of precision medicine and serves as a model for both scientific discovery and advancing patient care.     

MXRA5 is a TGF‐β1‐regulated human protein with anti‐inflammatory and anti‐fibrotic properties

Current therapy for chronic kidney disease (CKD) is unsatisfactory because of an insufficient understanding of its pathogenesis. Matrix remodelling‐associated protein 5 (MXRA5, adlican) is a human protein of unknown function with high kidney tissue expression, not present in rodents. Given the increased expression of MXRA5 in injured tissues, including the kidneys, we have suggested that MXRA5 may modulate kidney injury. MXRA5 immunoreactivity was observed in tubular cells in human renal biopsies and in urine from CKD patients. We then explored factors regulating MXRA5 expression and MXRA5 function in cultured human proximal tubular epithelial cells and explored MXRA5 expression in kidney cancer cells and kidney tissue. The fibrogenic cytokine transforming growth factor‐β1 (TGFβ1) up‐regulated MXRA5 mRNA and protein expression. TGFβ1‐induced MXRA5 up‐regulation was prevented by either interference with TGFβ1 activation of the TGFβ receptor 1 (TGFBR1, ALK5) or by the vitamin D receptor agonist paricalcitol. By contrast, the pro‐inflammatory cytokine TWEAK did not modulate MXRA5 expression. MXRA5 siRNA‐induced down‐regulation of constitutive MXRA5 expression resulted in higher TWEAK‐induced expression of chemokines. In addition, MXRA5 down‐regulation resulted in a magnified expression of genes encoding extracellular matrix proteins in response to TGFβ1. Furthermore, in clear cell renal cancer, von Hippel–Lindau (VHL) regulated MXRA5 expression. In conclusion, MXRA5 is a TGFβ1‐ and VHL‐regulated protein and, for the first time, we identify MXRA5 functions as an anti‐inflammatory and anti‐fibrotic molecule. This information may yield clues to design novel therapeutic strategies in diseases characterized by inflammation and fibrosis.