The effect of sleep disorders on quality of life in patients with epilepsy: A multicenter study from Turkey.

OBJECTIVE: We aimed to investigate sleep disorders in patients with epilepsy (PWE) and to investigate the effects of sleep disorders on quality of life. METHODS: In our multicenter study conducted in Turkey, 1358 PWE were evaluated. The demographic and clinical data of the patients were recorded. The Insomnia Severity Index (ISI), Epworth Sleepiness Scale (ESS), Pittsburgh Sleep Quality Index (PSQI), Beck Depression Inventory (BDI), and Quality of Life in Epilepsy Inventory-10 (QOLIE-10) were administered. RESULTS: The mean age of 1358 patients was 35.92 ±â€¯14.11 (range, 18-89) years. Seven hundred fifty-one (55.30 %) were women. Some 12.7 % of the patients had insomnia (ISI > 14), 9.6 % had excessive daytime sleepiness (ESS > 10), 46.5 % had poor sleep quality (PSQI > 5), and 354 patients (26.1 %) had depressive symptoms (BDI > 16). The mean QOLIE-10 score was 22.82 ±â€¯8.14 (10-48). Resistant epilepsy was evaluated as the parameter with the highest risk affecting quality of life Adjusted odds ratio (AOR = 3.714; 95 % confidence interval (CI): [2.440-5.652] < 0.001)). ISI (AOR = 1.184; 95 % CI: [1.128-1.243]; p < 0.001), ESS (AOR = 1.081; 95 % CI: [1.034-1.130]; p < 0.001), PSQI (AOR = 0.928; 95 % CI: [0.867 - 0.994]; p = 0.034), BDI (AOR = 1.106; 95 % CI: [1.084-1.129]; p < 0.001), epilepsy duration (AOR = 1.023; 95 % CI: [1.004-1.041]; p = 0.014), were determined as factors affecting quality of life. SIGNIFICANCE: Sleep disorders are common in PWE and impair their quality of life. Quality of life can be improved by controlling the factors that may cause sleep disorders such as good seizure control, avoiding polypharmacy, and correcting the underlying mood disorders in patients with epilepsy.

Evaluation of the relationship between the morphometric structure of the pituitary gland and fatigue in patients with multiple sclerosis.

BACKGROUND: The correlation between fatigue and disability in multiple sclerosis (MS) with the hypothalamus-pituitary-adrenal axis is known. This study aimed to investigate the relationship between the morphometric dimensions of the pituitary gland with fatigue and disability. METHOD: This research, designed as a prospective and case-control study, included 85 MS patients and 45 healthy controls. The disability was evaluated using the expanded disability rating scale (EDSS), while fatigue was determined using the fatigue severity scale (FSS) and the neurological fatigue index (NFI-MS). The morphometric structure of the pituitary gland was measured using a coronal, T2-weighted, turbo-spin-echo sequence of magnetic resonance imaging. RESULTS: FSS and NFI-MS scores were higher in MS patients than in the control group (p = 0.001). Patients with a progressive and moderate-to-severe disability had a higher FSS score (p = 0.015; p = 0.002, respectively). A positive correlation was determined between disease duration, attack frequency, and EDSS and physical fatigue subscale score (p = 0.001; r = 0.383; 0.373; 0.545, respectively). The height and width of the pituitary gland were higher in MS patients (p = 0.021; p = 0.001, respectively). Pituitary gland height was higher in fatigued patients (p = 0.041). A low-positive correlation was determined between the number of attacks and the height of the pituitary gland (p = 0.027, r = 0.231). CONCLUSION: The difference in the dimensions of the pituitary gland in MS patients, especially in the fatigued group, supports the relationship of fatigue with morphometric features as well as the hypothalamus-pituitary-adrenal axis.

The Relationship Between Age Shock Index, and Severity of Stroke and In-Hospital Mortality in Patients with Acute Ischemic Stroke.

BACKGROUND: Shock index (SI) has been reported to help us predict adverse prognosis in patients with acute ischemic stroke (AIS). However, the prognostic value of age SI and age modified shock index (MSI) in acute ischemic stroke is unknown. In our study, we aimed to examine the association between the severity of the stroke and in-hospital mortality, age SI and age MSI in patients with AIS. METHODS: A total of 256 patients were enrolled in this study. The National Institutes of Health Stroke Scale (NIHSS) was used to determine the severity of stroke. Patients were divided into two groups according to the NIHSS score calculated during hospitalization (NIHSS>14: severe disability group, NIHSS<15: moderate and mild disability group). Shock indexes were calculated using the blood pressure and heart rate values measured as a result of the cardiovascular examinations of the patients. We looked for correlations between increased NIHSS and in-hospital mortality with age shock index and age modified shock index. RESULTS: Age SI and age MSI values were higher in the severe disability group than those without severe disability, and the results were statistically significant (p<0.001, p<0.001, respectively). Also, a positive correlation was determined between the height of NIHSS and the age SI and the age MSI (p=0.002, r=0.197, p=0.001, r=0.215, respectively). Thirty-two (12.5%) of 256 patients included in the study died during hospitalization. Patients who died were older (77.1±11.0 vs. 67.5±13.5, respectively; p<0.001). According to Point-Biserial correlation analysis, there was a positive correlation between mortality and age SI, and age MSI (p<0.001, r=0.258 ve p<0.001, r=0.274, respectively). CONCLUSIONS: As a result of our study, the relationship between stroke severity and increasing age SI and age MSI was significant and there was a positive correlation. In addition, there was a significant and positive relationship between in-hospital mortality and age SI and age MSI.

Investigation of 3D-printed chitosan-xanthan gum patches.

In this study, using a new polymer combination of Chitosan(CH)/Xanthan Gum(XG) has been exhibited for wound dressing implementation by the 3D-Printing method, which was fabricated due to its biocompatible, biodegradable, improved mechanical strength, low degradation rate, and hydrophilic nature to develop cell-mimicking, cell adhesion, proliferation, and differentiation. Different concentrations of XG were added to the CH solution as 0.25, 0.50, 0.75, 1, and 2 wt% respectively in the formic acid/distilled water (1.5:8.5) solution and rheologically characterized to evaluate their printability. The results demonstrated that high mechanical strength, hydrophilic properties, and slow degradation rate were observed with the presence and increment of XG concentration within the 3D-Printed patches. Moreover, in vitro cell culture research was conducted by seeding NIH 3T3 fibroblast cells on the patches, proving the cell proliferation rate, viability, and adhesion. Finally, 1% XG and 4% CH containing 3D-Printed patches were great potential for wound dressing applications.

Evaluation of diagnostic components and management of childhood pulmonary tuberculosis: a prospective study from Istanbul, Turkey.

INTRODUCTION: The diagnosis of childhood tuberculosis is difficult and most of the patients are diagnosed clinically. The objective of this study is to reveal the diagnostic and therapeutic components of childhood pulmonary tuberculosis and to analyze the changes that occurred in our country over the years. METHODOLOGY: All patients diagnosed with tuberculosis between 2006 and 2016 were included. Demographic characteristics, diagnostic and treatment outcomes were recorded and patients were followed up prospectively. RESULTS: A total of 492 patients were included in the study. 97% had Bacillus Calmette-Guerin vaccine, 36% were diagnosed with microbiologically-confirmed tuberculosis and 64% were diagnosed with clinically-proven tuberculosis. 94% of the patients had symptoms consistent with tuberculosis, all patients had radiologic findings, 74% had a history of tuberculosis contact and 63% had tuberculin skin test positivity. The diagnoses included primary tuberculosis in 62%, secondary tuberculosis in 21%, progressive primary tuberculosis in 13% and miliary tuberculosis in 4%. 48% of the patients received a treatment regimen containing three drugs as the initial treatment, and drug-related side effects developed in 12%. Isoniazid resistance was detected in 13% of the patients and rifampicin resistance was detected in 8%. None of the patients died due to tuberculosis. In the last 50 years in Turkey, the rates of Bacillus Calmette-Guerin vaccination and diagnosis of tuberculosis cases have increased and the mortality rates have decreased over the years. CONCLUSIONS: Our study is one of the few prospective studies and revealed the differences between the recent data and the past 50 years in childhood tuberculosis in Turkey.

SARS-CoV-2 Mutations and their Viral Variants.

Mutations in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) occur spontaneously during replication. Thousands of mutations have accumulated and continue to since the emergence of the virus. As novel mutations continue appearing at the scene, naturally, new variants are increasingly observed. Since the first occurrence of the SARS-CoV-2 infection, a wide variety of drug compounds affecting the binding sites of the virus have begun to be studied. As the drug and vaccine trials are continuing, it is of utmost importance to take into consideration the SARS-CoV-2 mutations and their respective frequencies since these data could lead the way to multi-drug combinations. The lack of effective therapeutic and preventive strategies against human coronaviruses (hCoVs) necessitates research that is of interest to the clinical applications. The reason why the mutations in glycoprotein S lead to vaccine escape is related to the location of the mutation and the affinity of the protein. At the same time, it can be said that variations should occur in areas such as the receptor-binding domain (RBD), and vaccines and antiviral drugs should be formulated by targeting more than one viral protein. In this review, a literature survey in the scope of the increasing SARS-CoV-2 mutations and the viral variations is conducted. In the light of current knowledge, the various disguises of the mutant SARS-CoV-2 forms and their apparent differences from the original strain are examined as they could possibly aid in finding the most appropriate therapeutic approaches.

The impact of Technetium-99m dimercapto-succinic acid scintigraphy on DNA damage and oxidative stress in children.

BACKGROUND: Technetium-99m-dimercapto succinic acid (Tc-99m DMSA) scintigraphy is a commonly used imaging modality in children with urological abnormalities. The radiopharmaceuticals, which have the effects of ionising radiation, are used in this method. This study aimed to investigate the impact of the Tc-99m DMSA scan on renal oxidative stress and mononuclear leukocyte (MNL) DNA damage. METHODS: Children, who were followed up by paediatric nephrology at Bezmialem Vakif University and underwent Tc-99m DMSA scintigraphy between April 2015 and January 2016 with the indication of detection of renal scars, were included in this study. The exclusion criteria were nephrolithiasis, history of premature birth and recent urinary tract infection 3 months prior to scintigraphy or antibiotic use in the last 1 month. 3 mL heparinised blood samples were obtained just before, immediately after and 1 week after the scintigraphy. MNL DNA damage, total antioxidant status (TAS) and total oxidant status (TOS) were measured in the blood samples. The oxidative stress index (OSI) was calculated. Spot urine samples were obtained from each patient before and within 3 days after performing the scintigraphy. TAS/Creatinine (TAS/Cr), TOS/Creatinine (TOS/Cr) and N-acetyl-glucosaminidase/creatinine (NAG/Cr) levels were measured in the urine samples. RESULTS: Twenty-seven children were evaluated. The values between TAS, TOS and OSI levels in serum samples at baseline, immediately after and 1 week after the scintigraphy (P = .105, P = .913, and P = .721, respectively) showed no statistically significant difference. The levels of TAS/Cr, TOS/Cr, NAG/Cr ratios and OSI, which were evaluated from urine samples before and within 3 days after the scintigraphy scan were also similar (P = .391, P = .543, P = .819 and P = .179, respectively). The levels of DNA damage only increased following scintigraphy scan and decreased a week later (P < .05). CONCLUSIONS: The effect of Tc-99m DMSA scintigraphy is insufficient to create oxidative damage, but it can cause DNA damage via the direct impact of ionising radiation which can be repaired again in a short time.

The relationship between dysphagia, respiratory functions and anthropometry in patients with multiple sclerosis.

BACKGROUND: It is known that many body systems are affected as a result of dysphagia. The aim of this study is to investigate the relationship between clinical features, respiratory functions, anthropometric measurements and dysphagia in patients with multiple sclerosis (MS). METHOD: Seventy-five MS patients and 50 healthy controls were included in this prospective case-control study. Disability was assessed with expanded disability status scale (EDSS), and swallowing was assessed with questionnaire for the assessment of dysphagia (solid, liquid and total) for disease. Respiratory functions were demonstrated with computerized spirometry device. Body weight, height, waist, hip, and mid-arm circumference are measured. Body mass index and body fat percentage were calculated. The relationship of all these parameters with disease activity and dysphagia was investigated. RESULTS: There were 75 MS patients with a mean age of 38.40 ± 11.27 years, and 50 (66.70%) were female in the study. The all type of dysphagia scores were higher in MS patients than control group (p = 0.001). Many respiratory function test scores and only hip circumference were lower in MS patients. However, especially low forced expiratory volume-1st second (FEV1), forced vital capacity (FVC) and peak expiratory flow (PEF) values were associated with disability. In addition, dysphagia scores were higher in progressive MS patients with severe disability and high frequency attacks (p = 0.001). Increased severity of dysphagia are associated with many lower anthropometric measurements (not height-especially mid-arm circumference) and respiratory function test scores. CONCLUSION: MS affects swallowing and respiratory systems functions. They are associated with MS disease activity. Dysphagia and its severity are associated with many anthropometric measurements and respiratory functions test scores.

The Impact of the COVID-19 Lockdown on the Quality of Life in Chronic Neurological Diseases: The Results of a COVQoL-CND Study.

BACKGROUND: Coronavirus disease 2019 (COVID-19) pandemic and lockdown period may induce an impairment in quality of life (QoL), disruption in treatment (DIT), and posttraumatic stress disorder (PTSD) in chronic neurological diseases (CNDs). To reach this information, a multicenter, cross-sectional study (COVQoL-CND) was planned. Parkinson's disease (PD), headache (HA), multiple sclerosis (MS), epilepsy (EP), polyneuropathy (PNP), and cerebrovascular disease (CVD) were selected as the CND. METHODS: The COVQoL-CND study includes demographic data, the World Health Organization Quality of Life short form (WHOQOL-BREF), and Impact of Event Scale-Revised (IES-R) forms. RESULTS: The mean age of a total of 577 patients was 49 ± 17 (19-87 years), and the ratio of female/male was 352/225. The mean age of patients with PD, HA, MS, EP, PNP, and CVD were 65 ± 11, 39 ± 12, 38 ± 10, 47 ± 17, 61 ± 12, and 60 ± 15 years, respectively. The IES-R scores were found to be higher in the younger group, those with comorbid disease, contacted with CO-VID-19 patients, or diagnosed with COVID-19. In the group with a high IES-R score, the rate of DIT was found to be high. IES-R scores were negatively correlated with QoL. IES-R total scores were found highest in the CVD group and lowest in the PD group. The ratio of DIT was found highest in the PNP group and the lowest in the EP group. Contact with CO-VID-19 patients was high in the EP and HA group. CONCLUSIONS: The results of the COVQoL-CND study showed that lockdown causes posttraumatic stress and deterioration in the QoL in CND.

Is there a relationship between anxiety and depression with respiratory functions in patients with relapsing-remitting multiple sclerosis?

BACKGROUND: Psychiatric symptoms are common in multiple sclerosis. The relationship of emotional state with respiratory function is unclear in these patients. We aimed to evaluate the relationship between the clinical characteristics, anxiety and depression status, and respiratory functions of patients with relapsing-remitting multiple sclerosis (RRMS). METHOD: The research was planned as a prospective case-control study. Ninety RRMS patients and 50 healthy controls were included in the study. The MS diagnosis was confirmed according to the revised 2017 McDonald's criteria. Disability was divided into two subgroups according to the Expanded Disability Status Scale (EDSS) (under 3.5 and 3.5-5.5). Beck anxiety and Beck depression inventories evaluated. A pulmonary function test was performed with a computerized spirometry device. Forced expiratory volume-1st second (FEV1), forced vital capacity (FVC), FEV/FVC, peak expiratory flow (PEF), maximal expiratory flow (MEF), peak inspiratory flow (PIF), and maximal inspiratory flow (MIF) values were obtained. RESULTS: There were 90 RRMS patients with a mean age of 38.68±10.95 years, and 58 (64.40%) were female in the study. The anxiety and depression scores of the patients were significantly higher than the control group (p=0.02, 0.002). FVC and FEV1 values were lower in patients with higher Beck depression scores (p=0.012, 0.007). FVC, FEV1, MEF50, and PIF values were lower in patients with higher Beck anxiety scores (p=0.002, 0.002, 0.030, 0.027). When EDSS and number of attacks were fixed, there was a low to moderate correlation between anxiety and FEV1-FVC (p=0.001, r=-367, -0.360 respectively), and a low negative correlation between depression and FEV1 (p=0.045, r=-0.214). CONCLUSION: Anxiety and depression scores are higher in patients with RRMS. Depression and anxiety are particularly associated with low FVC and FEV1 in patients.

Association of Myeloperoxidase Gene Polymorphism With Iron Deficiency Anemia in Turkish Children.

This study was performed to investigate the gene polymorphisms of the myeloperoxidase (MPO) enzyme and to determine whether MPO gene polymorphisms influence the response to iron therapy in pediatric patients with iron deficiency anemia (IDA). In this case-control study, 50 Turkish children with IDA and 50 healthy controls were enrolled. Three MPO gene alleles were selected for genotyping in the study: GG, AG, and AA. The relationships of alleles with IDA were analyzed and compared in patients and controls. Pretreatment and posttreatment laboratory parameters and gene polymorphisms were compared in the patient group. There was a significant difference between patients with IDA and controls regarding genotype frequencies of the AA, GG, and AG alleles (P=0.005). However, the AG allele was found to be associated with variations in hemoglobin, red blood cell, hematocrit, mean corpuscular volumes, and mean corpuscular Hb concentrations levels. The frequency of AA, GG, and AG alleles of the MPO gene was potentially associated with changes in iron metabolism and the AG allele led to variations in various hemogram parameters.

Decrease in Pulse Wave Velocity is Associated with Clinical Improvement in Patients with Ischemic Stroke.

BACKGROUND: Arterial stiffness is an independent determinant of cardiovascular and cerebrovascular risks. The relationship between the increase in arterial stiffness parameters and the severity of stroke has been shown in previous studies. We aimed to investigate the association between clinical improvement and changes in arterial stiffness parameters in patients presenting acute ischemic stroke. METHODS: A total of 107 patients were enrolled in this study. On the first and seventh day of the hospitalization, 24 h non-invasive blood pressure was monitored and arterial stiffness parameters were measured. The National Institutes of Health Stroke Scale (NIHSS) was used to determine the severity of stroke, and the Modified Rankin Scale was used to determine dependency and to evaluate functional improvements. RESULTS: Arterial stiffness parameters of augmentation index (AIx@75) and pulse wave velocity (PWV) were significantly higher in patients who died during hospitalization than patients who were discharged (respectively p <0.001, p = 0.04). In the group with clinical improvement, PWV values measured on the seventh day were significantly lower than PWV values measured on the first day (p = 0.032). When the changes in PWV value measured on the first and seventh day for both groups were analyzed using mixed ANOVA test, p value were significant (p = 0.033). Multivariate binary logistic regression analyses showed that negatively change in PWV and CDBP independently predicts the clinical improvement. CONCLUSIONS: Increased AIx@75 and PWV appear to be associated with higher in-hospital mortality rates in patients with acute ischemic stroke. Additionally, clinical improvement in patients with ischemic stroke is associated with a decrease in PWV .

A 13-Year-Old Boy Who Has Kawasaki Disease Shock Syndrome Presents with Parotitis.

We report a 13-year-old boy who (initially) had symptoms of toxic shock-like syndrome and mumps. Then, the patient was hospitalized in the pediatric intensive care unit (PICU) because of his ongoing hemodynamic instability (low blood pressure of 70/30 mm Hg and capillary refill time of > 4 seconds). During his stay in the PICU, the patient was treated with fluid resuscitation and vasoactive infusion and at the same time was diagnosed with Kawasaki disease shock syndrome (KDSS), when giant right coronary artery aneurysms were detected on echocardiographic examination. This case illustrates the risk of KDSS in patient who carries both parotitis and toxic shock-like syndrome. The clinicians should be cautious about detecting any types of coronary artery aneurysms in such patients. This is the first case of KDSS associated with parotitis reported in the literature.

The relationship between severity of disease and vitamin D levels in children with atopic dermatitis.

INTRODUCTION: Atopic dermatitis (AD) is a chronic relapsing inflammatory skin disorder. Vitamin D is a liposoluble vitamin synthesized mainly in the skin. Vitamin D has several effects on the skin. AIM: To assess the serum level of vitamin D in children with AD and determine its relation to AD severity. MATERIAL AND METHODS: Sixty patients with AD were enrolled in the study. We evaluated disease severity using the SCORing Atopic Dermatitis (SCORAD) index. The control group consisted of 37 healthy subjects. RESULTS: The mean serum concentration of 25(OH)D3 in patients with AD was not statistically different from control subjects (p = 0.065). The vitamin D level was significantly lower in moderate and severe AD compared with mild AD, and this difference was statistically significant (p = 0.001 and p = 0.004). Vitamin D showed a negative correlation with serum total IgE levels (p = 0.007). There was no significant correlation between total IgE levels and SCORAD scores (p = 0.089). CONCLUSIONS: This study suggests that a low serum vitamin D level is inversely associated with severity of AD in children. Vitamin D has not been included in the routine treatment of AD because of the conflicting results of various studies. Thus, there is a need for more detailed and prospective studies.

Spontaneous evisceration of umbilical hernia in a patient with congenital nephrotic syndrome.

Congenital nephrotic syndrome is a term used to describe a condition in babies who develop severe proteinuria and hypoalbuminaemia within their first three months of life. They generally have oedema and ascites from birth which, because of increased intra-abdominal pressure, can result in an umbilical hernia. The report presents a five-month old infant with congenital nephrotic syndrome who had spontaneous umbilical hernia rupture with evisceration. The approach to umbilical hernias is usually conservative, but in selected cases elective surgery may be indicated.

Evaluation of autonomic nervous system function in children with overactive bladder syndrome.

PURPOSE: We aimed to evaluate the autonomic nervous system activity in children with overactive bladder (OAB) syndrome. METHODS: Included in the study were 40 children with overactive bladder and 28 healthy controls. Autonomic tests were performed on all participants, including heart rate interval variation (RRIV), heart rate response to valsalva maneuver, and sympathetic skin response (SSR). RESULTS: Mean valsalva rates in the overactive bladder and control groups were 1.53 ± 0.29 and 1.30 ± 0.18, respectively, a statistically significant difference (P < 0.001). Also significantly different were deep breathing RRIV values of the study and control groups: 56.65 ± 14.66 and 47.92 ± 10.15, respectively (P = 0.008). No statistical differences were found in SSR when OAB patients were compared with controls (P > 0.05). CONCLUSIONS: This study demonstrated a parasympathetic hyperactivity in children with OAB, results suggesting a dysfunction in their autonomic nervous systems. Neurourol. Urodynam. 36:673-676, 2017. © 2016 Wiley Periodicals, Inc.

The different cutaneous presentations in three cases of Kawasaki disease as confounding factor of diagnosis.

We report three paediatric cases of Kawasaki disease (KD). Erythema multiforme (EM) was the presenting cutaneous feature in two patients, with young age (43 days old), macular rash and meningitis in the third patient. Diagnosis of KD was difficult due either to initial misdiagnosis of drug eruption, incomplete presentation, or the young age of the patient. Clinicians should be aware of these cutaneous presentations to prevent KD complications.

Renal tubular function and urinary N-acetyl-ß-d-glucosaminidase and kidney injury molecule-1 levels in asthmatic children.

BACKGROUND: Asthma is a chronic inflammatory disorder of the airways which results in chronic hypoxia. Chronic hypoxia and inflammation can affect renal tubular function. OBJECTIVES: The aim of this study was to investigate renal tubular function and early kidney injury molecules such as urinary N-acetyl-betaglucosaminidase (NAG) and kidney injury molecule-1 (KIM-1) excretion in children with asthma. METHODS: Enrolled in the study were 73 children diagnosed with asthma and 65 healthy age- and gender-matched control subjects. Urine pH, sodium, phosphorus, potassium, microalbumin, creatinine, NAG, KIM-1, and serum creatinine, sodium, phosphorus were evaluated. The diagnosis of asthma and classification of mild or moderate were done according to the Global Initiative for Asthma guidelines. RESULTS: Serum sodium, phosphorus, creatinine, and urinary microalbumin were within normal levels in the both groups. Urinary pH, sodium, potassium, phosphorus, microalbumin, and KIM-1 excretions were similar between the control and study groups. Tubular phosphorus reabsorption was within normal limits in two groups. Urine NAG was elevated in the study group (P = 0.001). Urinary KIM-1 and NAG levels were positively correlated (r = 0.837; P = 0.001). When children with mild and moderate asthma were compared, all of the parameters were similar (P >0.05). CONCLUSIONS: This study showed that chronic asthma can lead to subtle renal impacts. We suggest that in children with asthma, urinary NAG level is a more valuable parameter to show degree of renal tubular injury than markers such as microalbumin and KIM-1. Chronic hypoxy and inflammation probably contributes to these subclinical renal effects.