Consensus recommendations for the treatment and management of patients with Fabry disease on migalastat: a modified Delphi study.

Objective: Fabry disease is a progressive disorder caused by deficiency of the α-galactosidase A enzyme (α-Gal A), leading to multisystemic organ damage with heterogenous clinical presentation. The addition of the oral chaperone therapy migalastat to the available treatment options for Fabry disease is not yet universally reflected in all treatment guidelines. These consensus recommendations are intended to provide guidance for the treatment and monitoring of patients with Fabry disease receiving migalastat. Methods: A modified Delphi process was conducted to determine consensus on treatment decisions and monitoring of patients with Fabry disease receiving migalastat. The multidisciplinary panel comprised 14 expert physicians across nine specialties and two patients with Fabry disease. Two rounds of Delphi surveys were completed and recommendations on the use of biomarkers, multidisciplinary monitoring, and treatment decisions were generated based on statements that reached consensus. Results: The expert panel reached consensus agreement on 49 of 54 statements, including 16 that reached consensus in round 1. Statements that reached consensus agreement are summarized in recommendations for migalastat treatment and monitoring, including baseline and follow-up assessments and frequency. All patients with Fabry disease and an amenable mutation may initiate migalastat treatment if they have evidence of Fabry-related symptoms and/or organ involvement. Treatment decisions should include holistic assessment of the patient, considering clinical symptoms and organ involvement as well as patient-reported outcomes and patient preference. The reliability of α-Gal A and globotriaosylsphingosine as pharmacodynamic response biomarkers remains unclear. Conclusion: These recommendations build on previously published guidelines to highlight the importance of holistic, multidisciplinary monitoring for patients with Fabry disease receiving migalastat, in addition to shared decision-making regarding treatments and monitoring throughout the patient journey. GRAPHICAL ABSTRACT.

Leukocyte Imbalances in Mucopolysaccharidoses Patients.

Mucopolysaccharidoses (MPSs) are rare inherited lysosomal storage diseases (LSDs) caused by deficient activity in one of the enzymes responsible for glycosaminoglycans lysosomal degradation. MPS II is caused by pathogenic mutations in the IDS gene, leading to deficient activity of the enzyme iduronate-2-sulfatase, which causes dermatan and heparan sulfate storage in the lysosomes. In MPS VI, there is dermatan sulfate lysosomal accumulation due to pathogenic mutations in the ARSB gene, leading to arylsulfatase B deficiency. Alterations in the immune system of MPS mouse models have already been described, but data concerning MPSs patients is still scarce. Herein, we study different leukocyte populations in MPS II and VI disease patients. MPS VI, but not MPS II patients, have a decrease percentage of natural killer (NK) cells and monocytes when compared with controls. No alterations were identified in the percentage of T, invariant NKT, and B cells in both groups of MPS disease patients. However, we discovered alterations in the naïve versus memory status of both helper and cytotoxic T cells in MPS VI disease patients compared to control group. Indeed, MPS VI disease patients have a higher frequency of naïve T cells and, consequently, lower memory T cell frequency than control subjects. Altogether, these results reveal MPS VI disease-specific alterations in some leukocyte populations, suggesting that the type of substrate accumulated and/or enzyme deficiency in the lysosome may have a particular effect on the normal cellular composition of the immune system.

Kala-Azar: A Case Report.

Leishmaniasis is a zoonosis caused by unicellular protozoans Leishmania. The transmission can be zoonotic or anthroponotic, depending on the species, and the main vector is the phlebotomine sandfly. The disease is endemic in the tropics of Asia and Africa but is considered rare in Portugal, especially in immunocompetent hosts. Its main clinical syndromes constitute cutaneous leishmaniasis, mucocutaneous disease, and visceral leishmaniasis. The latter is also known as kala-azar and is caused by the infection of the phagocytes of the reticuloendothelial system, causing the typical symptoms: fever, hepatosplenomegaly, and pancytopenia. The clinical manifestations are non-specific, frequently causing a delay in the diagnosis, especially in nonendemic areas and immunocompetent hosts. Early diagnosis and treatment are essential, given the high mortality rate in untreated patients. The diagnosis is based on the direct visualization of the protozoan and molecular methods, such as polymerase chain reaction tests. Amphotericin B is considered the first-line treatment. We present a case of visceral leishmaniasis in an immunocompetent patient with fever, hepatosplenomegaly, and pancytopenia.

Hemophagocytic Lymphohistiocytosis Secondary to Chronic Lymphocytic Leukemia Progression.

Hemophagocytic lymphohistiocytosis (HLH) is an acute, rare systemic hyperinflammatory disorder caused by a dysregulated immune cell function and massive cytokine release, often leading to multiple organ involvement and failure. Fever, hepatosplenomegaly, cytopenia, elevated liver enzymes, hypertriglyceridemia, and hyperferritinemia are the hallmarks of the disease. Its primary (genetic) form is typically observed in pediatric patients and its secondary, acquired form is seen in adult patients with an underlying autoimmune, malignant, or infectious disease. It is not frequently reported in patients with chronic lymphocytic leukemia (CLL) without an infectious or pharmacological trigger. We present a case of a 71-year-old patient with hemophagocytic lymphohistiocytosis due to the progression of chronic lymphocytic leukemia.

Phenotype of BTK-lacking myeloid cells during prolonged COVID-19 and upon convalescent plasma.

XLA patient with 7-month course of COVID-19 with persistent plasma SARS-CoV-2 load revealed a sustained non-inflammatory profile of myeloid cells in association with contained severity of disease, arguing in favor of the use of BTK inhibitors in SARS-COV-2 infection.

Do clinical guidelines facilitate or impede drivers of treatment in Fabry disease?

BACKGROUND: Variable disease progression confounds accurate prognosis in Fabry disease. Evidence supports the long-term benefit of early intervention with disease-specific therapy, but current guidelines recommend treatment initiation based on signs that may present too late to avoid irreversible organ damage. Findings from the 'PRoposing Early Disease Indicators for Clinical Tracking in Fabry Disease' (PREDICT-FD) initiative included expert consensus on 27 early indicators of disease progression in Fabry disease and on drivers of and barriers to treatment initiation in Fabry disease. Here, we compared the PREDICT-FD indicators with guidance from the European Fabry Working Group and various national guidelines to identify differences in signs supporting treatment initiation and how guidelines themselves might affect initiation. Finally, anonymized patient histories were reviewed by PREDICT-FD experts to determine whether PREDICT-FD indicators supported earlier treatment than existing guidance. RESULTS: Current guidelines generally aligned with PREDICT-FD on indicators of renal involvement, but most lacked specificity regarding cardiac indicators. The prognostic significance of neurological indicators such as white matter lesions (excluded by PREDICT-FD) was questioned in some guidelines and excluded from most. Some PREDICT-FD patient-reported signs (e.g., febrile crises) did not feature elsewhere. Key drivers of treatment initiation in PREDICT-FD were: (A) male sex, young age, and clinical findings (e.g., severe pain, organ involvement), (B) improving clinical outcomes and preventing disease progression, and (C) a family history of Fabry disease (especially if outcomes were severe). All guidelines aligned with (A) and several advocated therapy for asymptomatic male patients. There was scant evidence of (B) in current guidance: for example, no countries mandated ancillary symptomatic therapy, and no guidance advocated familial screening with (C) when diagnosis was confirmed. Barriers were misdiagnosis and a lack of biomarkers to inform timing of treatment. Review of patient histories generally found equal or greater support for treatment initiation with PREDICT-FD indicators than with other guidelines and revealed that the same case and guideline criteria often yielded different treatment recommendations. CONCLUSIONS: Wider adoption of PREDICT-FD indicators at a national level could promote earlier treatment in Fabry disease. Clearer, more concise guidance is needed to harmonize treatment initiation in Fabry disease internationally.

Neurosyphilis: The Great Imitator.

Syphilis is a sexually transmitted disease caused by spirochete Treponema pallidum, with a growing incidence documented in recent years. Its clinical course is divided into three phases - primary, secondary, and tertiary syphilis - and virtually any organ can be affected, resulting in diverse clinical manifestations, making the diagnosis challenging. Neurosyphilis is a progressive, destructive disease of the central nervous system (CNS) that can develop at any stage of the infection, leading to meningeal involvement, meningovascular disease, or parenchymal syphilis (including tabes dorsalis and general paresis). Its clinical manifestations are heterogeneous and vary from focal neurologic signs to neuropsychiatric manifestations. The diagnosis is based mainly on the clinical picture and study of cerebrospinal fluid. Neuroimaging is helpful and sometimes essential, with magnetic resonance imaging being the most sensitive radiologic method, although there are no pathognomonic radiologic signs. Treatment of all forms of neurosyphilis is based on parenteral penicillin. We present a case of neurosyphilis in a patient presenting with a subacute confusional state and initial imaging findings suggestive of metastatic CNS lesions.

Progressive Multifocal Leukoencephalopathy in a Chemotherapy-Naive Patient With Chronic Lymphocytic Leukemia: A Case Report.

Progressive multifocal leukoencephalopathy is a rare, progressive demyelinating disease of the central nervous system caused by reactivation and replication of the John Cunningham (JC) virus in cerebral oligodendrocytes. The JC virus is a small ubiquitous polyomavirus that can be detected in up to 50% of the adult population. It affects almost exclusively immunocompromised patients and is generally observed in patients with acquired immunodeficiency syndrome and patients with hematologic malignancies and autoimmune or chronic inflammatory diseases medicated with immunosuppressive and immunomodulatory drugs. However, it is rarely described in patients with hematologic malignancies, not undergoing chemotherapy or immunosuppressive therapy. It has a poor prognosis, and the treatment is based on restoring the immune system, given that no specific antiviral treatment is available. We present a case of a chemotherapy-naive patient with chronic lymphocytic leukemia associated with progressive multifocal leukoencephalopathy.

Therapeutic Options in Refractory Evans Syndrome: A Case Report.

Evans syndrome is a rare autoimmune disease, characterized by at least two immune cytopenias, most frequently anemia and thrombocytopenia and rarely immune neutropenia. It has a variable clinical presentation and is rarely diagnosed in adults. It can be idiopathic or secondary to lymphoproliferative disease, infections, autoimmune diseases, drugs, and immunodeficiencies in about 50% of cases. It is characterized by a chronic, relapsing, potentially fatal course due to its hemorrhagic complications as well as complications associated with the long-term immunosuppressive treatment required to control the disease, such as infectious diseases, and cardiovascular and renal complications. Its prognosis depends on the underlying cause. Because of its rarity, the treatment is empirical, based mostly on case series and recommendations for the treatment of other immune cytopenias. The underlying disease and demographic characteristics also play an important role in choosing the treatment, which should be adapted individually to each patient. We present a case of an elderly patient with idiopathic autoimmune hemolytic anemia and thrombocytopenia, refractory to various treatment options.

Congenital Lobar Emphysema in Early Adulthood.

Congenital lobar emphysema (CLE) is a rare developmental abnormality of the lower respiratory tract. This disease is caused by cartilage or connective tissue defects, leading to overdistention of a pulmonary lobe. CLE is mainly diagnosed in early childhood, though it might be rarely found in young adults. Due to its rarity, it can be misdiagnosed with other conditions. Here we report a case of a previously healthy young female complaining of dyspnea and thoracic pain after a commercial flight. Physical and radiological examinations were consistent with the diagnosis of CLE.

Early indicators of disease progression in Fabry disease that may indicate the need for disease-specific treatment initiation: findings from the opinion-based PREDICT-FD modified Delphi consensus initiative.

OBJECTIVES: The PRoposing Early Disease Indicators for Clinical Tracking in Fabry Disease (PREDICT-FD) initiative aimed to reach consensus among a panel of global experts on early indicators of disease progression that may justify FD-specific treatment initiation. DESIGN AND SETTING: Anonymous feedback from panellists via online questionnaires was analysed using a modified Delphi consensus technique. Questionnaires and data were managed by an independent administrator directed by two non-voting cochairs. First, possible early indicators of renal, cardiac and central/peripheral nervous system (CNS/PNS) damage, and other disease and patient-reported indicators assessable in routine clinical practice were compiled by the cochairs and administrator from panellists' free-text responses. Second, the panel scored indicators for importance (5-point scale: 1=not important; 5=extremely important); indicators scoring ≥3 among >75% of panellists were then rated for agreement (5-point scale: 1=strongly disagree; 5=strongly agree). Indicators awarded an agreement score ≥4 by >67% of panellists achieved consensus. Finally, any panel-proposed refinements to consensus indicator definitions were adopted if >75% of panellists agreed. RESULTS: A panel of 21 expert clinicians from 15 countries provided information from which 83 possible current indicators of damage (kidney, 15; cardiac, 15; CNS/PNS, 13; other, 16; patient reported, 24) were compiled. Of 45 indicators meeting the importance criteria, consensus was reached for 29 and consolidated as 27 indicators (kidney, 6; cardiac, 10; CNS/PNS, 2; other, 6; patient reported, 3) including: (kidney) elevated albumin:creatinine ratio, histological damage, microalbuminuria; (cardiac) markers of early systolic/diastolic dysfunction, elevated serum cardiac troponin; (CNS/PNS) neuropathic pain, gastrointestinal symptoms suggestive of gastrointestinal neuropathy; (other) pain in extremities/neuropathy, angiokeratoma; (patient-reported) febrile crises, progression of symptoms/signs. Panellists revised and approved proposed chronologies of when the consensus indicators manifest. The panel response rate was >95% at all stages. CONCLUSIONS: PREDICT-FD captured global opinion regarding current clinical indicators that could prompt FD-specific treatment initiation earlier than is currently practised.

Retinal Vascular Reactivity in Type 1 Diabetes Patients Without Retinopathy Using Optical Coherence Tomography Angiography.

Purpose: We hypothesize that patients with type 1 diabetes (T1D) may have abnormal retinal vascular responses before diabetic retinopathy (DR) is clinically evident. Optical coherence tomography angiography (OCTA) was used to dynamically assess the retinal microvasculature of diabetic patients with no clinically visible retinopathy. Methods: Controlled nonrandomized interventional study. The studied population included 48 eyes of 24 T1D patients and 24 demographically similar healthy volunteers. A commercial OCTA device (AngioVue) was used, and two tests were applied: (1) the hypoxia challenge test (HCT) and (2) the handgrip test to induce a vasodilatory or vasoconstrictive response, respectively. The HCT is a standardized test that creates a mild hypoxic environment equivalent to a flight cabin. The handgrip test (i.e., isometric exercise) induces a sympathetic autonomic response. Changes in the parafoveal superficial and deep capillary plexuses in both tests were compared in each group. Systemic cardiovascular responses were also comparatively evaluated. Results: In the control cohort, the vessel density of the median parafoveal superficial and deep plexuses increased during hypoxia (F1,23 = 15.69, P < 0.001 and F1,23 = 16.26, P < 0.001, respectively). In the T1D group, this physiological response was not observed in either the superficial or the deep retinal plexuses. Isometric exercise elicited a significant decrease in vessel density in both superficial and deep plexuses in the control group (F1,23 = 27.37, P < 0.0001 and F1,23 = 27.90, P < 0.0001, respectively). In the T1D group, this response was noted only in the deep plexus (F1,23 = 11.04, P < 0.01). Conclusions: Our work suggests there is an early impairment of the physiological retinal vascular response in patients with T1D without clinical diabetic retinopathy.

Lipid Antigen Presentation by CD1b and CD1d in Lysosomal Storage Disease Patients.

The lysosome has a key role in the presentation of lipid antigens by CD1 molecules. While defects in lipid antigen presentation and in invariant Natural Killer T (iNKT) cell response were detected in several mouse models of lysosomal storage diseases (LSD), the impact of lysosomal engorgement in human lipid antigen presentation is poorly characterized. Here, we analyzed the capacity of monocyte-derived dendritic cells (Mo-DCs) from Fabry, Gaucher, Niemann Pick type C and Mucopolysaccharidosis type VI disease patients to present exogenous antigens to lipid-specific T cells. The CD1b- and CD1d-restricted presentation of lipid antigens by Mo-DCs revealed an ability of LSD patients to induce CD1-restricted T cell responses within the control range. Similarly, freshly isolated monocytes from Fabry and Gaucher disease patients had a normal ability to present α-Galactosylceramide (α-GalCer) antigen by CD1d. Gaucher disease patients' monocytes had an increased capacity to present α-Gal-(1-2)-αGalCer, an antigen that needs internalization and processing to become antigenic. In summary, our results show that Fabry, Gaucher, Niemann Pick type C, and Mucopolysaccharidosis type VI disease patients do not present a decreased capacity to present CD1d-restricted lipid antigens. These observations are in contrast to what was observed in mouse models of LSD. The percentage of total iNKT cells in the peripheral blood of these patients is also similar to control individuals. In addition, we show that the presentation of exogenous lipids that directly bind CD1b, the human CD1 isoform with an intracellular trafficking to the lysosome, is normal in these patients.

A Protocol to Evaluate Retinal Vascular Response Using Optical Coherence Tomography Angiography.

INTRODUCTION: Optical coherence tomography angiography (OCT-A) is a novel diagnostic tool with increasing applications in ophthalmology clinics that provides non-invasive high-resolution imaging of the retinal microvasculature. Our aim is to report in detail an experimental protocol for analyzing both vasodilatory and vasoconstriction retinal vascular responses with the available OCT-A technology. METHODS: A commercial OCT-A device was used (AngioVue®, Optovue, CA, United States), and all examinations were performed by an experienced technician using the standard protocol for macular examination. Two standardized tests were applied: (i) the hypoxia challenge test (HCT) and (ii) the handgrip test, in order to induce a vasodilatory and vasoconstriction response, respectively. OCT-A was performed at baseline conditions and during the stress test. Macular parafoveal vessel density of the superficial and deep plexuses was assessed from the en face angiograms. Statistical analysis was performed using STATA v14.1 and p < 0.05 was considered for statistical significance. RESULTS: Twenty-four eyes of 24 healthy subjects (10 male) were studied. Mean age was 31.8 ± 8.2 years (range, 18-57 years). Mean parafoveal vessel density in the superficial plexus increased from 54.7 ± 2.6 in baseline conditions to 56.0 ± 2.0 in hypoxia (p < 0.01). Mean parafoveal vessel density in the deep plexuses also increased, from 60.4 ± 2.2 at baseline to 61.5 ± 2.1 during hypoxia (p < 0.01). The OCT-A during the handgrip test revealed a decrease in vessel density in both superficial (55.5 ± 2.6 to 53.7 ± 2.9, p < 0.001) and deep (60.2 ± 1.8 to 56.7 ± 2.8, p < 0.001) parafoveal plexuses. DISCUSSION: In this work, we detail a simple, non-invasive, safe, and non-costly protocol to assess a central nervous system vascular response (i.e., the retinal circulation) using OCT-A technology. A vasodilatory response and a vasoconstriction response were observed in two physiologic conditions-mild hypoxia and isometric exercise, respectively. This protocol constitutes a new way of studying retinal vascular changes that may be applied in health and disease of multiple medical fields.

Biomarkers of Myocardial Fibrosis: Revealing the Natural History of Fibrogenesis in Fabry Disease Cardiomyopathy.

BACKGROUND: Cardiomyopathy is a major determinant of overall Fabry disease (FD) prognosis, with the worst outcomes in patients with myocardial fibrosis. Late gadolinium enhancement is currently the gold standard for evaluation of replacement myocardial fibrosis; however, this event is irreversible, thus identification of biomarkers of earlier diffuse fibrosis is paramount. METHODS AND RESULTS: Type I collagen synthesis and degradation biomarkers (PICP [carboxyterminal propeptide of procollagen type I], ICTP [carboxyterminal telopeptide of type I collagen], and MMP1 [matrix metalloproteinase 1] and MMP2) and markers of bone synthesis and degradation were evaluated (to adjust type I collagen metabolism to bone turnover) in FD patients and controls. FD patients were grouped by cardiomyopathy severity, according to echocardiogram: (1) normal, (2) tissue Doppler abnormalities, (3) left ventricular hypertrophy. A significant increase in PICP and a significant decrease in matrix metalloproteinases were observed in FD patients; even the group with normal echocardiogram had a significant increase in PICP. We also found a significant correlation between left ventricular mass and PICP (ρ=0.378, P=0.003) and MMP1 (ρ=-0.484, P<0.001). PICP (adjusted for bone turnover) was the better predictor of left ventricular mass in multivariable regression, and its diagnostic accuracy to predict late gadolinium enhancement was also significant. CONCLUSIONS: Collagen type I synthesis is increased in FD cardiomyopathy, even in the earlier stages of the disease, and this profibrotic state has good predictive value for and is likely to be critical to the development of overt left ventricular hypertrophy. Moreover, inhibition of enzymes involved in collagen type I cleavage also seems crucial to myocardial collagen deposition.

Biomarkers and Imaging Findings of Anderson-Fabry Disease-What We Know Now.

Anderson-Fabry disease (AFD) is an X-linked lysosomal storage disorder, caused by deficiency or absence of the alpha-galactosidase A activity, with a consequent glycosphingolipid accumulation. Biomarkers and imaging findings may be useful for diagnosis, identification of an organ involvement, therapy monitoring and prognosis. The aim of this article is to review the current available literature on biomarkers and imaging findings of AFD patients. An extensive bibliographic review from PubMed, Medline and Clinical Key databases was performed by a group of experts from nephrology, neurology, genetics, cardiology and internal medicine, aiming for consensus. Lyso-GB3 is a valuable biomarker to establish the diagnosis. Proteinuria and creatinine are the most valuable to detect renal damage. Troponin I and high-sensitivity assays for cardiac troponin T can identify patients with cardiac lesions, but new techniques of cardiac imaging are essential to detect incipient damage. Specific cerebrovascular imaging findings are present in AFD patients. Techniques as metabolomics and proteomics have been developed in order to find an AFD fingerprint. Lyso-GB3 is important for evaluating the pathogenic mutations and monitoring the response to treatment. Many biomarkers can detect renal, cardiac and cerebrovascular involvement, but none of these have proved to be important to monitoring the response to treatment. Imaging features are preferred in order to find cardiac and cerebrovascular compromise in AFD patients.

New biomarkers defining a novel early stage of Fabry nephropathy: A diagnostic test study.

BACKGROUND: Renal involvement in Fabry disease is a major determinant of overall disease prognosis and early enzyme replacement therapy seems effective in preventing progression of kidney injury. Gb3 storage, glomerular sclerosis and tubulo-interstitial fibrosis may occur with minimal or no changes on standard renal tests, hence alternative markers of renal dysfunction are crucial. In this study we compared several biomarkers with albuminuria in the identification of incipient Fabry nephropathy and their diagnostic accuracy to identify chronic kidney disease (CKD) stage≥2. METHODS: In this multicentre, prospective, cross-sectional and diagnostic test study, a cohort of 78 Fabry patients and 25 healthy controls was consecutively recruited. Patients were grouped by severity of nephropathy: 1) albuminuria<30mg/g; 2) albuminuria 30-299mg/g; 3) albuminuria>300mg/g; 4) glomerular filtration rate (GFR)<60mL/min/1.73m2. Several index tests, namely biomarkers of glomerular (transferrin and type IV collagen) and tubular (α1-microglobulin, N-acetyl-ß-glucosaminidase and alanine aminopeptidase) dysfunction were compared with the reference standard (albuminuria). RESULTS: Significant increase of all tested biomarkers in Fabry patients, even in the subgroup of patients without evidence of nephropathy. We also found inverse significant correlations between estimated GFR and collagen type IV (ρ=-0.289; p=0.003) or N-acetyl-ß-glucosaminidase (ρ=-0.448; p<0.001), which were stronger than with albumin (ρ=-0.274; p=0.019). There was also better diagnostic accuracy of N-acetyl-ß-glucosaminidase to predict CKD stage≥2. CONCLUSIONS: These results suggest that studied biomarkers may overcome the limitations of albuminuria as sensitive marker of early renal dysfunction and as marker for CKD progression risk. These biomarkers may also define novel early stages of nephropathy characterized by mesangial expansion and/or tubular damage.

Anderson-Fabry Disease: A Rare Disease That Mimics Common Cardiac, Neurological, Renal, and Other Disorders: Approach for the Differential Diagnosis and Follow-Up

Abstract Anderson-Fabry disease (AFD) is a rare inherited X-linked disease, caused by mutations of the gene encoding the α-galactosidase A enzyme, that leads to a deficiency or absence of its activity with consequent accumulation of globotriaosylceramide (Gb3) and other glycosphingolipids in the lysosomes of several cells types in the organism, mainly the endothelial, nervous system, cardiac, and renal cells. Its heterogeneous and nonspecific presentation, similar to other common pathologies, delays the diagnosis and leads to incorrect therapy. In the presence of attenuated phenotypes with predominant involvement of an organ, it is even harder to identify patients with AFD. It is highly important to be aware of this diagnosis, since enzyme replacement therapy is currently available. This review aims to approach the clinical manifestations of AFD and the phenotypes related to the differential diagnosis for each manifestation and the frequency of follow-up recommended.

Cystatin C: A Promising Marker of Renal Function in Patients with Systemic Lupus Erythematosus?

PURPOSE: Cystatin C has a higher correlation with glomerular filtration rate and a more significant clinical prognosis than creatinine. We sought to determine whether it is a marker of renal function different from creatinine (cystatin C potentially superior to creatinine), in patients with systemic lupus erythematosus. MATERIAL AND METHODS: 37 patients with systemic lupus erythematosus were evaluated. Serum cystatin C was determined by nephelometry and creatinine by modified Jaffe method. We compared five formulas: Chronic Kidney Disease â Epidemiology Collaboration cystiatin; Chronic Kidney Disease â Epidemiology Collaboration creatinine-cystatin; Cockcroft-Gault; Modification of Diet in Renal Disease and Chronic Kidney Disease â Epidemiology Collaboration creatinine, using the latter as a reference. We analyzed the influence of clinical and laboratory factors in cystatin C variation, using multivariate linear regression. RESULTS: Cystatin C was singly elevated in ten participants, versus none isolated creatinine elevation, and this difference was significant (p = 0.002). There was a difference between the estimated glomerular filtration rate by Chronic Kidney Disease â Epidemiology Collaboration cystatin and by Chronic Kidney Disease â Epidemiology Collaboration creatinine (-6.0541 mL/min/1.73 m², p = 0.07), more pronounced for lower glomerular filtration rate. Consequently, Chronic Kidney Disease â Epidemiology Collaboration cystatin reclassified 4 patients as having chronic kidney disease de novo and 1 patient as not having chronic kidney disease (p = 0.375). Cystatin C was only significantly influenced by age (p < 0.001). DISCUSSION: Several reports showed cystatin C as a better marker to define chronic kidney disease, allowing more accurate classification and risk stratification, compared with creatinine. In this study, Cystatin C revealed as a promisor marker of renal function in patient with lupus, mainly in patients with lower glomerular filtration rates. The correlation between age and cystatin C seems to be a confounding factor, as glomerular filtration rate physiologically declines with ageing. CONCLUSION: Cystatin C was potentially superior to creatinine and in this study and cystatin C seems to detect changes in glomerular filtration rate earlier than creatinine and may be a better screening method for chronic kidney disease in systemic lupus erythematosus.

Introdução: A cistatina C possui uma correlação superior com a taxa de filtrado glomerular e um prognóstico clínico mais significativo do que a creatinina. Procurou-se averiguar se constitui um marcador de função renal diferente da creatinina (cistatina C potencialmente superior à creatinina), em doentes com lúpus eritematoso sistémico.Material e Métodos: Foram avaliados 37 doentes com lúpus eritematoso sistémico, sem evidência de nefrite lúpica activa. Determinouse a cistatina C sérica por nefelometria e a creatinina pelo método de Jaffe modificado. Compararam-se cinco fórmulas: Chronic Kidney Disease â Epidemiology Collaboration cystatin; Chronic Kidney Disease â Epidemiology Collaboration creatinine-cystatin; Cockcroft-Gault, Modification of Diet in Renal Disease e Chronic Kidney Disease â Epidemiology creatinine, utilizando-se esta última como referência. Analisou-se a influência de factores clínicos e laboratoriais na variação da cistatina C, por regressão linear multivariada. Resultados: A cistatina C encontrava-se isoladamente elevada em dez participantes, ao invés de nenhuma elevação isolada dacreatinina, sendo esta diferença significativa (p = 0,002). Verificou-se uma diferença entre a taxa de filtrado glomerular estimada pela Chronic Kidney Disease â Epidemiology Collaboration cystatin e pela Chronic Kidney Disease â Epidemiology Collaboration creatinine (-6,0541 mL/min/1,73 m2, p = 0,07), mais acentuada para taxas de filtração glomerular mais baixas. Assim, a fórmula Chronic Kidney Disease â Epidemiology Collaboration cystatin reclassificou 4 doentes como tendo doença renal crónica de novo e um doente como não tendo doença renal crónica (p = 0,375). A cistatina C foi influenciada significativamente apenas pela idade (p < 0,001).Discussão: Vários estudos demonstraram que a cistatina C melhora a definição de doença renal crónica, permitindo uma classificação e uma estratificação do risco mais exactas, comparativamente à creatinina. A cistatina C revelou-se, neste estudo, um marcador de função renal promissor nos doentes com lupus, principalmente para taxas de filtrado glomerular mais baixas. A correlação da cistatina C com a idade para ser um factor confundente, na medida em que existe um declínio fisiológico da taxa de filtração glomerular com o envelhecimento.Conclusão: A cistatina C foi potencialmente superior à creatinina e nesta amostra a cistatina C pareceu detectar mais precocemente do que a creatinina alterações na taxa de filtrado glomerular, podendo ser um melhor método de rastreio de doença renal crónica no lúpus eritematoso sistémico.