Is just enzyme replacement therapy enough for Fabry disease treatment? Have we missed a trick? / ¿Es suficiente la terapia enzimática para tratar la enfermedad de Fabry? ¿Nos falta algún detalle?

Background and aim: In Fabry disease (FD), primary factors such as glycosphingolipid deposition that initiate kidney damage and secondary factors that advance kidney damage to fibrosis are different. Periostin is a molecule of proven importance in renal inflammation and fibrosis. It was previously shown that periostin plays an essential role in the process leading to renal fibrosis and its expression is increased in many kidney diseases. In the present study, we aimed to reveal the relationship between periostin and Fabry nephropathy. Material-method: This cross-sectional study included 18 FD patients (10 males, 8 females) with enzyme replacement therapy (ERT) indications and 22 healthy control patients of similar age and gender. At the time of diagnosis, plasma alpha-galactosidase A (α-gal-A) and globotriaosylsphingosine (lyso-Gb3), proteinuria, and kidney function tests of all FD patients before ERT were scanned from the hospital system. Periostin was studied from serum samples collected and stored before ERT. Parameters related to serum periostin levels in Fabry disease were investigated. Results: In FD patients, serum periostin was negatively correlated with age of first symptom and GFR; and positively correlated with proteinuria and lyso-Gb3. In regression analysis, we found that serum periostin was the only independent determinant of proteinuria in patients with Fabry disease. The serum periostin levels were significantly lower in patients with low proteinuria, and the serum periostin levels were correlated with proteinuria. Discussion: Periostin may be a valuable marker of Fabry nephropathy and proteinuria. Periostin seems to be one of the molecules that may have an important role in the management of the fibrotic process in Fabry nephropathy. We think that the role of periostin among these mechanisms is worth investigating... (AU)

Antecedente y objetivo: En la enfermedad de Fabry (EF), son diferentes los factores primarios tales como el depósito de glicoesfingolípidos que inicia el daño renal, y los factores secundarios que progresan de daño renal a fibrosis. Periostina es una molécula de importancia probada en la inflamación renal y la fibrosis. Se ha demostrado previamente que periostina juega un papel esencial en el proceso que causa la fibrosis renal, y que su expresión se incrementa en muchas enfermedades renales. En el presente estudio, nuestro objetivo fue revelar la relación entre la periostina y la nefropatía de Fabry. Material y método: Este estudio transversal incluyó 18 pacientes con EF (10 varones y 8 mujeres) con indicación de terapia enzimática (ERT) y 22 controles sanos con edad y sexo similares. En el momento del diagnóstico se escanearon del sistema hospitalario las pruebas de alfa-galactosidasa A (α-gal-A) plasmática y globotriaosilsfingosina (lyso-Gb3), proteinuria y función renal de todos los pacientes con EF antes de la ERT. Se analizó el nivel de periostina en las muestras séricas recogidas y almacenadas antes de realizar la ERT. Se investigaron los parámetros relacionados con los niveles séricos de periostina en la enfermedad de Fabry. Resultados: En los pacientes con EF, el nivel de periostina sérica se correlacionó negativamente con la edad del primer síntoma y la GFR, y positivamente con proteinuria y lyso-Gb3. En el análisis de regresión, encontramos que el nivel de periostina sérico fue el único determinante independiente de proteinuria en los pacientes con EF. Los niveles séricos de periostina fueron significativamente menores en los pacientes con baja proteinuria, correlacionándose los niveles séricos de periostina con proteinuria. Discusión: La periostina puede ser un marcador valioso de nefropatìa de Fabry y proteinuria.... (AU)

Overlooked factor in the etiology of pruritus in hemodialysis patients: Ultrafiltration volume.

INTRODUCTION: This study investigated the relationship between ultrafiltration (UF) volume and pruritus severity based on the idea that skin perfusion and inflammatory changes occur in dialysis patients with high UF volume. MATERIALS AND METHODS: This observational study included 392 patients. Patients filled out the Numerical Rating Scale, Verbal Rating Scale, and Visual Analogue Scale, showing the severity of pruritis. UF volumes in the last 12 sessions were recorded and averaged. RESULTS: The rate of patients with pruritis was between 59.4% and 67.5% in the three scales. In three pruritis scales, the severity of pruritis, age, body mass index (BMI), UF volume, and UF volume/body weight ratio were positively correlated. UF volume/body weight ratio, age, and BMI were independent predictors of pruritis severity. CONCLUSION: Limiting interdialytic weight gain may be an important treatment approach in pruritus control.

Tonic-Clonic Seizure in Patient With SLE: Posterior Reversible Encephalopathy Syndrome, or a Neuropsychiatric Manifestation of SLE?

Posterior reversible encephalopathy syndrome (PRES) is a clinically and radiologically diagnosed reversible sudden onset disease with many neurological symptoms. SLE is the most common cause of PRES among autoimmune diseases. Many factors, such as SLE activity, hypertension, hematological and renal diseases, lymphopenia dyslipidemia, and immunosuppressive treatments, can trigger PRES in SLE. We wanted to draw attention to the difference between neuropsychiatric systemic lupus erythematosus (SLE) and PRES in a patient with SLE and the triggers for developing PRES in SLE by presenting a hypertensive patient on immunosuppressive therapy who had just started haemodialysis treatment and had generalised tonic-clonic seizures.

Unknown criminals for kidney: Acute interstitial nephritis due to lavender tea.

INTRODUCTION: Spanish Lavender is an herbal from the lavender family and is widely used among people for the belief that it cures various diseases. Acute interstitial nephritis (AIN) is one of the common causes of acute kidney injury (AKI). Although drugs are the most common cause of AIN, the frequency of reporting AIN cases due to various herbals has been increasing in recent years. CASE PRESENTATION: We present a 24-year-old male patient who developed AKI after consuming Spanish lavender tea to treat upper respiratory tract infection symptoms and was diagnosed with AIN. AIM AND DISCUSSION: With this case report, we wanted to explain the fact that medicinal herbs, which are used frequently and carelessly today, can have serious consequences, as in acute interstitial nephritis associated with Spanish lavender.

Sclerostin and TNF-related weak inducer of apoptosis: can they be important in the patients with glomerulonephritis?

OBJECTIVE: Sclerostin is a protein produced by osteocytes, kidneys, and vascular cells and has many effects on kidney and vascular structures. Soluble TNF-related weak inducer of apoptosis is a proinflammatory cytokine that may cause glomerular and tubular injury and increase sclerostin expression. This study aimed to investigate serum sclerostin and soluble TNF-related weak inducer of apoptosis levels in patients with glomerulonephritis and the effects they may be associated with. METHODS: This cross-sectional study included 93 patients, 63 of whom were glomerulonephritis and 30 were healthy controls. Serum sclerostin, soluble TNF-related weak inducer of apoptosis, and 24-h urinary protein excretion were measured, and pulse wave velocity was calculated for arterial stiffness. RESULTS: Serum sclerostin and soluble TNF-related weak inducer of apoptosis were higher in glomerulonephritis patients than in the control group, and serum sclerostin and soluble TNF-related weak inducer of apoptosis levels were correlated with both proteinuria and pulse wave velocity. In addition, in the regression analysis, serum sclerostin and soluble TNF-related weak inducer of apoptosis levels were found to be independent predictors of proteinuria in patients with glomerulonephritis. CONCLUSION: This is the first study to show that serum sclerostin and soluble TNF-related weak inducer of apoptosis are elevated in glomerulonephritis patients, and these two markers correlate with arterial stiffness and proteinuria in these patients. Considering the effects of sclerostin and soluble TNF-related weak inducer of apoptosis in patients with glomerulonephritis, we think these mechanisms will be the target of both diagnosis and new therapies.

Is just enzyme replacement therapy enough for Fabry disease treatment? Have we missed a trick?

BACKGROUND AND AIM: In Fabry disease (FD), primary factors such as glycosphingolipid deposition that initiate kidney damage and secondary factors that advance kidney damage to fibrosis are different. Periostin is a molecule of proven importance in renal inflammation and fibrosis. It was previously shown that periostin plays an essential role in the process leading to renal fibrosis and its expression is increased in many kidney diseases. In the present study, we aimed to reveal the relationship between periostin and Fabry nephropathy. MATERIAL-METHOD: This cross-sectional study included 18 FD patients (10 males, 8 females) with enzyme replacement therapy (ERT) indications and 22 healthy control patients of similar age and gender. At the time of diagnosis, plasma alpha-galactosidase A (α-gal-A) and globotriaosylsphingosine (lyso-Gb3), proteinuria, and kidney function tests of all FD patients before ERT were scanned from the hospital system. Periostin was studied from serum samples collected and stored before ERT. Parameters related to serum periostin levels in Fabry disease were investigated. RESULTS: In FD patients, serum periostin was negatively correlated with age of first symptom and GFR; and positively correlated with proteinuria and lyso-Gb3. In regression analysis, we found that serum periostin was the only independent determinant of proteinuria in patients with Fabry disease. The serum periostin levels were significantly lower in patients with low proteinuria, and the serum periostin levels were correlated with proteinuria. DISCUSSION: Periostin may be a valuable marker of Fabry nephropathy and proteinuria. Periostin seems to be one of the molecules that may have an important role in the management of the fibrotic process in Fabry nephropathy. We think that the role of periostin among these mechanisms is worth investigating. In addition to standard ERTs, periostin-reducing therapies may contribute to better kidney survival in Fabry disease. Progressive fibrosis processes caused by periostin in patients with Fabry disease are still a hidden issue waiting to be clarified. Progressive fibrosis processes caused by periostin in Fabry patients are still a hidden issue waiting to be clarified.

Can eculizumab be an option in traditional treatment-resistant ulcerative colitis?

Atypical/complement-mediated hemolytic uremic syndrome (A-HUS/CM-HUS) is a hereditary or sporadic disease with thrombotic microangiopathy (TMA). Diarrhea is a trigger that can cause attacks of CM-HUS. Although there are opinions that complement system activation plays a role in intestinal inflammation in patients with inflammatory bowel disease, the association of TMA with inflammatory bowel disease (IBD) has rarely been reported. In our case, a CM-HUS case that developed without an additional triggering factor in the course of ulcerative colitis (UC) was successfully treated with eculizumab, and then UC remission was also achieved. In this context, we would like to point out that the irregularities in the alternative pathway of the complement system may cause clinical findings in extra-renal organs, and the complement system may also play a role in the pathogenesis of inflammatory bowel disease. In addition, we think that our case may guide further studies on the usability of anti-complement therapies in treating patients with IBD who are resistant to conventional treatments.

Liver-Spleen Ratio: Can It Be Used for the Prediction of Coronary Artery Disease?

BACKGROUND: Considering that ectopic fat accumulation in various organs, especially the heart and liver, is a cardiometabolic risk factor, the need for easily accessible markers of ectopic fat accumulation is inevitable. The main starting point of the study is based on the hypothesis of predicting cardiovascular disease risk through the link that can be established between the liver-spleen ratio, which is one of the strong indicators of hepa- tosteatosis, and epicardial adipose tissue volume. METHODS: This was a retrospective study. The records of 283 consecutive patients who underwent coronary computed tomography angiography in our Radiology Department were reviewed retrospectively from our hospital's system. All patients' epicardial adipose tissue volume and liver-spleen ratio were calculated using appropriate criteria on non- contrast computed tomography images. Additionally, the Coronary Artery Disease- Reporting and Data System was calculated on contrast computed tomography images. The participating patients were divided into groups according to the liver-spleen ratio and Coronary Artery Disease-Reporting and Data System score. RESULTS: We found that while there was a negative correlation between the liver-spleen ratio and epicardial adipose tissue volume in the hepatosteatosis group, this relationship was not observed in the non-steatosis group. In addition, we observed that the family his- tory of cardiovascular disease and the frequency of cardiovascular disease were higher in the hepatosteatosis group than in the other group, and there was a correlation between cardiovascular disease and the liver-spleen ratio. Also, we found that age and liver- spleen ratio values were found to be independent predictors of coronary artery disease. CONCLUSION: In our study, we found that the frequency of cardiovascular disease was lower in patients with a high liver-spleen ratio. We also demonstrated in the study that the liver-spleen ratio, which indicates a low level of epicardial adipose tissue volume accumulation, is an independent predictor of cardiovascular disease. In addition, the use of liver-spleen ratio, which is more valuable than liver attenuation in predicting hepatic steatosis, may be more useful in evaluating the risk of hepatosteatosis-related cardio- vascular disease.

The relationship between FGF23 and anemia in HD and renal transplant patients.

PURPOSE: Recent studies claim that FGF23 is also associated with anemia and inflammation. In this study, the relationship between FGF23 and anemia in hemodialysis (HD) and renal transplantation patients (RTx patients) patients was investigated. METHODS: This was a cross-sectional study involving 40 RTx patients (13 females, 27 males; mean age, 45.93 ± 12.49 years) who had transplantation at least 6 months before, 25 HD patients (12 females, 13 males; mean age, 54.72 ± 15.5 years), and 20 healthy control subjects (13 females, 7 males; mean age, 36.7 ± 9.38 years). FGF23 was studied using Elisa method. Parameters such as iron, ferritin, total iron binding capacity, and transferrin saturation were assessed. RESULTS: FGF23 level was significantly higher in HD patients when compared with the RTx patients and control groups. In the bivariate correlation analysis, hemoglobin was positively correlated with albumin (r = 0.681, p = 0.000), ferritin (r = 0.446, p = 0.043), and negatively correlated with CRP (r = - 0.476, p = 0.016) and FGF23 (r = 0.493, p = 0.043). FGF23 was found to be an independent predictor of decreased hemoglobin in HD patients. In addition, this association was observed to disappear after transplantation. CONCLUSION: While FGF23 is closely related to hemoglobin levels in HD patients, we have shown that this relationship disappears after transplantation.

Nephrological factors may cause kidney dysfunction in patients with common variable immunodeficiency

Background/aim: Common variable immunodeficiency (CVID) is a heterogeneous primary deficiency characterized by hypogammaglobulinemia, recurrent infections, an increased risk of autoimmune disease, malignancy, and chronic inflammation. Proteinuria is one of the most important prognostic factors causing progression in kidney disease. Proteinuria causes tubulotoxicity, activates inflammatory markers that cause fibrosis, and consequently nephropathy progression. The data is scant in the literature regarding the inflammation and nephropathy in CVID. Hence, in the present study, we aimed to investigate the relationship between tubular dysfunction, proteinuria, and inflammation in patients with CVID. Materials and methods: This was a cross-sectional study involving 27 patients with CVID (15 females, 12 males; mean age, 39.88 ± 13.47 years) and 18 control subjects (10 females, 8 males; mean age, 33.83 ± 7.97 years). Patients were evaluated for kidney functions including glomerular filtration rate, fractional excretion of sodium, metabolic acidosis, serum/urine anion gap, 24-h urine proteinuria and, were grouped in terms of proteinuria. Blood samples obtained from the patients with CVID were taken into 2 mL EDTA tube to evaluate peripheral NK cell subgroups according to CD56 and CD16 expression and CD3, CD4, CD 8 expression to determine subtypes T cells. These cells were evaluated by flow cytometry technique. Results: Urinary density, fractional excretion of sodium, proteinuria, and metabolic acidosis are found to be higher in patients with CVID when compared to healthy controls. In the bivariate correlation analysis, proteinuria was positively correlated with age (r = 0.496, p = < 0.001), CD8+T cells percentage (r = 0.427, p = 0.02). Albumin, CRP, and CD8+T cell percentage were found to be independent variables of proteinuria. Conclusion: Increased chronic ongoing inflammation was found to be associated with proteinuria in patients with CVID. Hence, in routine outpatient clinics, proteinuria should not be overlooked in this group of patients.

C3 glomerulopathy and atypical hemolytic uremic syndrome: an updated review of the literature on alternative complement pathway disorders.

The complement system plays a significant role within the pathological process of C3 glomerulopathy (C3GP) and atypical hemolytic uremic syndrome (aHUS). In daily practice, clinicians should differentiate the subgroups of C3GP because of they should apply different treatment modalities. In the past, C3GP was considered as a part of membranoproliferative glomerulonephritis (MPGN). MPGN is defined as glomerular capillary thickening secondary to the synthesis of the new glomerular basement membrane and mesangial cellular hyperplasia with mesangial matrix expansion. Atypical hemolytic uremic syndrome is an ultra-rare disease that can be outlined by the triad of Coombs negative microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury. Recent advances demonstrated that these diseases share common abnormalities of the control of the alternative complement system. Therefore, nowadays, most researchers advocate that there may be overlap in the pathogenesis of C3GP and aHUS. This review will provide recent novel mechanisms and treatment options in these diseases. For the purposes that we mentioned above and to help clinicians, we aimed to describe the etiology, pathophysiology, and treatment of C3GP and aHUS in this comprehensive review.

Are Kidney Donor Risk Index/Kidney Donor Profile Index Scores Predictor of Future Graft Function?

Kidney donor profile index (KDPI) is a method developed to assess donor kidney quality for cadaveric transplants. We investigated the relationship between kidney donor risk index (KDRI) and KDPI scores of cadaveric transplants in the last five years in our clinic and current graft conditions. Forty people (12 females, 28 males; mean age, 46.35 + 8.94 years), who underwent cadaveric transplantation between January 2013 and March 2018, were participated in this study. At the same time, the KPDI and KDRI scores of the donor's kidneys were calculated and then compared with that of the recipients' data. The mean KDRI value of donors was 1.11 ± 0.33 and the median KDPI value was 60.50%. KDRI/KDPI scores were found to be high in women (P = 0.021) and, when the posttransplant findings of the recipients were evaluated by bivariate correlation analysis KDRI/KDPI scores were positively correlated with the day when creatinine (Cr) values started to fall off spontaneously (r = 0.457, P = 0.003). It was observed that recipients who were transplanted from the donors with high KDRI/KDPI scores had higher Cr levels (P <0.01) and this relationship did not change over time (P = 0.115). When the donors were grouped as the standard-criteria donor and expanded-criteria donor (ECD); we found that the relationship between KDRI/KDPI, creatinine, and time was more significant in the ECD group (P = 0.04). KDRI/KDPI scores are closely related to graft outcomes especially in recipients that have kidneys from marginal donors. Therefore, evaluation of KDRI/KDPI scores might be required in marginal donors.

The Relationship Between Visceral Adiposity Index and Epicardial Adipose Tissue in Patients with Type 2 Diabetes Mellitus.

INTRODUCTION AND AIM: Cardiovascular diseases remain the most common cause of morbidity and mortality in patients with diabetes. Epicardial adipose tissue (EAT), visceral fat depot of the heart, was found to be associated with coronary artery disease in cardiac and non-cardiac patients. Increased visceral adiposity is associated with proinflammatory activity, impaired insulin sensitivity, increased risk of atherosclerosis and high mortality. In the present study we aimed to investigate the relationship between EAT and visceral adiposity index (VAI) in patients with diabetes. METHODS: This was a cross-sectional study involving 128 patients with type 2 diabetes mellitus (73 females, 55 males; mean age, 54.09+±+9.17 years) and 32 control subjects (23 females, 9 males; mean age, 50.09+±+7.81 years). EAT was measured by using a trans-thoracic echocardiograph. Parameters such as waist circumference (WC), body mass index (BMI), triglyceride and high density lipoprotein (HDL) cholesterol were used to calculate VAI. RESULT: EAT and VAI measurements were significantly higher in patients with diabetes when compared to control subjects. In the bivariate correlation analysis, VAI was positively correlated with uric acid level (r=0.214, p=0.015), white blood cell count (r= 0.262, p=0.003), platelet count (r=0.223, p=0.011) and total cholesterol levels (r= 0.363, p<0.001). Also, VAI was found to be the independent predictor of EAT. CONCLUSION: Simple calculation of VAI was found to be associated with increased EAT in patients with type 2 diabetes.

The effect of Ramadan fasting on kidney function in patients with chronic kidney disease.

PURPOSE: Because of the increase in globalization, clinicians all over the world are confronted the questions about safety of Ramadan fasting. However, there is no clear information about whether there is an obstacle for fasting patients with chronic disease. Hence, in the present study, we aimed to investigate the effects of Ramadan fasting on kidney and the factors affecting this relationship in patients with chronic kidney disease. METHODS: This study involving 117 patients [36 females, 81 males; mean age, 60 (46.0-70.0) years] with stage 2-3 chronic kidney and fasting. Patients were evaluated every 10 days for acute kidney injury (AKI) in Ramadan month. And, patients with acute kidney injury and patients without AKI were grouped. RESULTS: When the patients were evaluated for AKI, we observed that in 27 patients had acute kidney injury. While patients without AKI fasted for more days (p < 0.001), urea levels and frequency of hypertension were higher in the group with AKI (p = 0.019; p = 0.025 respectively). We also performed univariate and multiple binary logistic regression analysis to identify the risk factors of AKI. Hypertension and number of fasting day were found to be predictive of AKI (p = 0.02; p < 0.001 respectively). CONCLUSIONS: We found a significant relationship between hypertension, the number of fasting days and acute kidney injury. Patients with chronic kidney damage and hypertension should be evaluated more carefully, informed about the importance of hydration after fasting and should be followed frequently for AKI.

The characteristics of patients returning to hemodialysis due to nonfunctioning graft in Turkey.

Renal transplantation is the most effective treatment modality for end-stage renal failure. According to the Ministry of Health Organ Transplant Registration System, despite the presence of 14,936 renal transplant recipients in Turkey, there are not enough data about the prognosis of these patients. Therefore, we aimed to ascertain the rate of patients returning to hemodialysis (HD) due to nonfunctioning graft in our country. One thousand four hundred and ninety-eight (males: 826, females: 672) HD patients who undergo HD at 22 HD centers in total, from different geographical regions to represent our country were examined retrospectively. The informations were obtained from patient registry files and anamnesis which were in HD centers. The number of patients returning to HD due to the loss of graft function was 77 (males: 56, females: 21). Eleven of the patients had transplantation from cadavers (14%) and 66 from living donors (86%). Prevelance of patients, who return to HD after the failure of renal transplantation, between HD patients was 5.1. The mean duration of return to HD after renal transplantation was 6.7 ± 5.9 years for all patients. There was no significant difference in the duration without HD after transplantation between two groups when cadaveric and living donor transplants were compared (P = 0.759). There was no statistically significant difference in duration without HD after transplantation between patients receiving HD treatment before transplantation and preemptive transplant (P = 0.212). The prevelance of patients, who return to HD due to nonfunctioning graft among HD patients was 5.1. The duration without HD were similar after transplantation from both cadavers and living donors. The duration without HD was found longer among those who were operated before 2000.

The relationship between coronary artery calcium scores and left atrium size in hemodialysis patients.

PURPOSE: Hemodialysis patients have extremely increased cardiovascular mortality. The coronary artery calcification score (CACS) in uremic patients receiving hemodialysis reflects the severity of atherosclerotic vascular disease and predicts the cardiovascular events. In cardiac conditions, left atrial (LA) size has a prognostic importance. In this study, relationship between coronary artery calcification and left atrial size was investigated. METHODS: This was a cross-sectional study involving 32 hemodialysis patients (16 females, 16 males; mean age, 52.4 ± 14.1 years) receiving HD for ≥6 months. Coronary artery calcium scoring was performed by a 16-MDCT scanner, and CACS was calculated by Agatston score. A calcification was defined as a minimum of two adjacent pixels (>0.52 mm2) with a density over 130 Hounsfield units. Patients were divided into two subgroups (group 1: CACS ≤ 45.85, n = 16 and group 2: CACS > 45.85, n = 16) according to median CACS value. RESULTS: Mean CACS value of 32 hemodialysis patients was 245.57 ± 373.91. LA size was significantly higher in patients with CACS > 45.85 (group 2) than in patients with CACS ≤ 45.85 (group 1). In the bivariate correlation analysis, total CACS was positively correlated with left atrium size (r = 0.47, p = 0.006). Total CACS was positively correlated with age (r = 0.43, p = 0.014). LA size was positively correlated with diastolic blood pressure (r = 0.42, p = 0.016) and negatively correlated with ejection fraction (r = -0.42, p = 0.016). The clinical parameters such as BMI, duration of dialysis, blood pressure, ejection fraction, serum levels of calcium, phosphorus, uric acid, albumin, CRP, triglyceride, cholesterol, hemoglobin and ferritin were not independently associated with total CACS. CONCLUSIONS: We found a positive relationship between the CACS and LA size measured by echocardiography in hemodialysis patients. Therefore; echocardiography, which is cheaper and non-invasive than tomographic examinations, might be considered for the risk stratification of coronary artery disease in hemodialysis patients.

How effective are the 6 European Society of Immunodeficiency warning signs for primary immunodeficiency disease?

BACKGROUND: The European Society of Immunodeficiency (ESID) developed 6 warning signs to promote the awareness of adult primary immunodeficiency disease (PID). OBJECTIVE: To screen adult patients for the presence of PID using these 6 warning signs to determine the effectiveness of this protocol. METHODS: Questions related to the ESID warning signs for adult PID were added to the standard outpatient clinic file system and asked of 3,510 patients who were admitted to our clinic for any reason. Patients with signs and/or suspicion of PID based on their medical history underwent immunologic investigation. RESULTS: In total, 24 patients were diagnosed as having a PID. The most common reason that patients with PID were admitted was frequent infection (n=18 [75%]), and the most common PID subgroup was common variable immunodeficiency (n=12 [50%]). Twenty patients with PID had at least one positive finding according to the ESID warning signs. Two patients with gastrointestinal concerns and 2 with dermatologic symptoms were also diagnosed as having a PID, although they did not have any of the ESID warning signs. CONCLUSION: The ESID warning signs do not specify the need for symptoms to diagnose a PIDs and do not include a comprehensive list of all signs and symptoms of PIDs. As a result, more than infection-centric questions are needed to identify adult patients with immunodeficiencies.