Is Chronic Kidney Disease a Critical Health Problem in Madeira Island?

Chronic kidney disease (CKD) is an ever-growing global public health problem affecting more than 10% of the general population worldwide. CKD is associated with an increased risk of cardiovascular disease and all-cause mortality, representing a major burden to the healthcare system. Although multiple studies have determined CKD prevalence in different countries, there is still a significant knowledge gap between epidemiological surveys and real data recorded by healthcare providers. Regarding the Portuguese population, most recent studies revealed a CKD prevalence of 20.9%. However, there is an irregular distribution of CKD prevalence in the country. For example, considering the Madeiran population, a non-published review of lab results of nearly 130,000 patients in our database allowed us an estimation of 20%. Thus, to better comprehend CKD prevalence and its characterization in this region, we designed a study comprising previous studies' strengths as well as aiming to overcome their limitations. The principal objective is to calculate global CKD prevalence in Madeira Island and stratify it by stage of CKD, allowing comparison of our results with recent literature on this subject. We intend to contribute with relevant epidemiological data in the characterization of CKD prevalence in Portugal and, simultaneously, have a more active role in CKD prevention and allocation of resources.

Validity and reliability of the Berlin questionnaire for the detection of moderate or severe obstructive sleep apnea in patients aged 40 years or older detected from primary care.

Background: The obstructive sleep apnea syndrome (OSA) is a highly prevalent condition. In Spain and other countries, only 5%-9% of patients with OSA have been diagnosed and treated. The lack of accessibility to diagnosis is considered the main cause of this situation through easy-to-use screening instruments, it is necessary to check their validity and reliability in the context where they are to be used. Objective: To validate the Spanish translation of the Berlin questionnaire for screening for moderate or severe OSA in patients aged 40 years or more detected in primary care. Methods: A descriptive observational study, with a first qualitative phase of transcultural adaptation to Spanish using the translation-back-translation method. Setting: primary care level of the Spanish National Health System. A total of 255 patients recruited from 7 healthcare centers completed the study. The Berlin questionnaire was administered to the recruited patients, and subsequently, a respiratory polygraphy was performed to confirm the diagnosis of OSA. The concurrent criterion validity of the questionnaire and its reliability in terms of internal consistency and reproducibility (intra-observer agreement) were analyzed. Results: The patients' mean age was 54.76 years (SD: 6.57; 95% CI: 53.53-54.99), and 54.12% were men (95% CI: 47.96-60.27). We found that 61.57% (95% CI: 55.57-67.57) presented OSA (apnea-hypopnea index-AHI >5), and 45.5% (95% CI: 17.05-57.92) presented moderate or severe (AHI >15) OSA. The Berlin questionnaire, with a cut-off point of 4.5, showed a sensitivity of 76.77% (95% CI: 67.94-85.59), a specificity of 74.49% (95% CI: 65.35-83.63), a positive predictive value of 75.25% (95% CI: 66.34-84.16), a negative predictive value of 76.04% (95% CI: 66.98-85.10), and an area under the curve of 0.786 (95% CI: 0.721-0.851). Cronbach's alpha coefficient was 0.730 (95% CI: 0.668-0.784), and the Kappa index was 0.739 (95% CI, 0.384-1.000). Conclusion: The Spanish adaptation of the Berlin questionnaire has good validity and reliability as a test for the diagnostic screening of moderate or severe OSA in patients aged 40 years or older. The findings of our study confirm that primary care physicians should use such screening tools to predict OSA.

Effect of Protective Measures Adopted in the COVID-19 Pandemic on Hemodialysis Patients.

Introduction The use of masks and other preventive measures is nowadays an essential measure to prevent COVID-19 infections, particularly in hemodialysis patients. The aim of this study was to understand whether these protective measures adopted during the COVID-19 pandemic reduced or somehow contained the number of respiratory infections in a population of hemodialysis patients. Methods This was a longitudinal retrospective single-center study of hemodialysis patients with at least six months of follow-up in a central hospital. A total of 103 patients were evaluated for the study. Two groups were defined: a control group that was followed in the year before the beginning of the pandemic and a group that followed in the year after its beginning. Results Patients in the pandemic group had a higher prevalence of previous major cardiovascular events (48.9% vs 8.6%) and heart failure (31.3% vs 12.1%) than those in the control group. Vaccination rates for influenza and pneumococcus as well as the monthly analytical results were similar in both groups. There were no significant differences in lower respiratory infections, hospitalizations caused by lower respiratory infections, and mortality between both groups. However, not accounting for aspiration pneumonias, the pandemic group had half the mortality due to respiratory infections (2.2% vs 5.2%). Conclusion Despite patients in the pandemic group having a similar prevalence of respiratory infections and hospitalizations motivated by lower respiratory infections, they presented about half the mortality of the control group. This suggests that although there was no decrease in the number of infections, protective measures may have contributed to a decreased mortality.

The usefulness of the Spanish version of the STOP-Bang questionnaire for screening for moderate or severe sleep apnea syndrome in primary care.

Rationale: Sleep apnea-hypopnea syndrome (OSA) is a highly prevalent disease and has been related to cardiovascular diseases and occupational and traffic accidents. Currently, it is estimated that there is a significant underdiagnosis of OSA, mainly due to the difficulty accessing the tests for that purpose. Objective: To determine the usefulness of the Spanish version of the STOP-Bang questionnaire (SBQ) for screening for moderate or severe OSA in the adult population attending primary care. Methods: A descriptive observational multicenter study was conducted. Through an opportunistic search, (patients over 18 years old), were recruited in seven primary care centers. The SBQ was applied to them and home respiratory polygraphy (HRP) was subsequently performed to confirm the diagnosis of OSA. The criterion validity of the SBQ was analyzed, comparing the score obtained by the SBQ with the apnea-hypopnea index (AHI) obtained by RP, establishing the diagnosis of OSA for an AHI>5. The reliability of the questionnaire was evaluated. Results: A total of 255 subjects, 54.1% men, with a mean age of 54.76 ± 10 years, were recruited in the study. The results showed that 61.57% (95% Confidence Interval: 55.57-67.57) of the subjects presented OSA, presenting 22.75% (17.57-57.92) a mild OSA (530) (11.54-20.62). The Kuder and Richardson coefficient was 0.623 (0.335-0.788) and Cohen's Kappa coefficient was 0.871 (0.520-1.00; p < 0.001). For moderate/severe OSA screening (AHI>15) the SBQ obtained an ROC curve of 0.769 (0.704-0.833) that with an optimal cutoff of 3, achieved a sensitivity of 84.85% (77.28-92.42) and a specificity of 55.10% (44.74-65.46). Conclusions: The SBQ is very effective for detecting moderate/severe OSA. Its psychometric properties are similar to those obtained in studies on other populations. Because of its ease of use, the SBQ is a very useful tool for primary health care professionals.

Synthesis and dopamine receptor binding of dihydrexidine and SKF 38393 catecholamine-based analogues.

Dopamine is an important neurotransmitter that regulates numerous essential functions, including cognition and voluntary movement. As such, it serves as an important scaffold for synthesis of novel analogues as part of drug development effort to obtain drugs for treatment of neurodegenerative diseases, such as Parkinson's disease. To that end, similarity search of the ZINC database based on two known dopamine-1 receptor (D1R) agonists, dihydrexidine (DHX) and SKF 38393, respectively, was used to predict novel chemical entities with potential binding to D1R. Three compounds that showed the highest similarity index were selected for synthesis and bioactivity profiling. All main synthesis products as well as the isolated intermediates, were properly characterized. The physico-chemical analyses were performed using HRESIMS, GC/MS, LC/MS with UV-Vis detection, and FTIR, 1H NMR and 13C NMR spectroscopy. Binding to D1 and D2 receptors and inhibition of dopamine reuptake via dopamine transporter were measured for the synthesized analogues of DHX and SKF 38393.

Fabry Disease p.M290I Mutation is Related to Organ Involvement: A Case Report.

Fabry disease (FD) is an X-linked hereditary disease. It results from mutations in the GLA gene, leading to deficient activity of the enzyme alpha-galactosidase A (α-Gal A) and progressive accumulation of undegraded glycosphingolipids in cell lysosomes. Enzyme replacement therapy (ERT) can improve the natural course of this disease, but an early diagnosis is crucial for a successful treatment. We describe the case of a female diagnosed with chronic proteinuric kidney disease in the postpartum period. Despite receiving optimal medical treatment, the disease progressed and she started renal replacement therapy (RRT) with peritoneal dialysis (PD). Five years later, she was enrolled in a pilot screening study for FD, and the heterozygous mutation c.870G>C (p.Met290Ile; M290I) in exon six of the GLA gene was found. The family screening revealed the presence of this mutation in the patient's father and daughter. The proband did not meet the criteria for a definitive FD diagnosis, but she remained under follow-up at our nephrology metabolic diseases consultation, as the mutation was described as pathogenic and associated with a classic FD phenotype. Later that same year, reassessment exams revealed a worsening left ventricle mass index (LVMi), a new ischemic cerebral lesion, and a substantial increase in serum globotriaosylsphingosine (LysoGb3) levels. These clinical changes led to a decision to initiate ERT. p.M290I is a previously known but poorly described GLA mutation. To our knowledge, this is the first report of p.M290I mutation-associated disease activity that offers strong evidence of its pathogenicity.

Novel GLA T194A variant causes Fabry disease.

Fabry disease (FD) is an X-linked, systemic lysosomal deposition disease caused by alpha-galactosidase A (AGAL) enzyme deficiency deriving out of changes on the GLA gene. Though several mutations have been described, one must consider that even a specific mutation may present with variable clinical expression within the same family. Typically described as a disease that affects hemizygous men with no residual AGAL activity, we describe a novel FD mutation (first case of GLA T194A variant worldwide) in a 49-year-old woman presenting with a classic phenotype of FD. The patient investigation highlighted a previously not described mutation in exon 4 of the GLA gene, as for the substitution of threonine for alanine. The same mutation was identified in her children, one of them presenting with end-stage kidney disease (ESKD) in early adulthood.

Celiac Disease as a Rare Cause of Membranous Nephropathy: A Case Report.

Membranous nephropathy is the most common cause of nephrotic syndrome in adults. A non-negligible number of cases are associated with systemic conditions. We report a case of a 50-year-old man who presented with nephrotic syndrome six months after being diagnosed with celiac disease. Although the patient showed disappearance of circulating immunoglobulin A (IgA) anti-tissue transglutaminase antibodies following a gluten-free diet, he had a sudden onset of nephrotic syndrome presenting with severe hypoalbuminemia. Other secondary causes were promptly excluded leading to the assumption of celiac disease-associated membranous nephropathy with remission after treatment with angiotensin system blockade and a gluten-free diet. The goal of this case report is to alert the clinic towards this rare association aiming for an early diagnosis and adequate selection of long-term therapy.

Obstructive Acute Kidney Injury with Maintenance of Diuresis: A Case of Ureter Bifidity / Lesión Renal Aguda Obstructiva con Mantenimiento de la Diuresis: Un Caso de BifidezUreteral

Abstract Percutaneous kidney biopsyin transplanted kidneys remains an essential and commonly performed procedure required for diagnostic and prognostic information. Hemorrhage is the main complication of renal graft biopsy. We report a case of a 47-year-old caucasian womanadmitted to perform an ultrasound(US)-guided biopsy of the renal graft. Six hours later, she presented with macroscopic hematuriawhichimproved after urethral catheterization and intravenous hydration. However the hematuria reappeared associated with anemia and worsening of the serum creatinine value. The US study, revealed hydronephrosis with high Doppler derived renal resistive index compatible with clot obstruction.Despite the vesical lavage with drainage of several clots, the patient rapidly progressed to hemorrhagic shock with worsening of renal function. Pelvic computed tomography (CT) revealed calyx and pelvis duplicity and ureter bifidity which merged into a single ureter and inserted into the right anterolateral wall of the bladder. The inferior ureter was enlarged due to an obstructive clot. Most acute obstructive uropathies are associated with significant pain or the abrupt diminution of urine flow. The presence of ureter bifidity in the CT study explained the maintenance of significantdiuresis despite obstruction, located only to the lower ureter but with sufficient functional impact to condition acute kidney injury (AKI).

Resumen La biopsia renal percutánea en riñones trasplantados sigue siendo un procedimiento esencial y común, necesario para obtener información diagnóstica y pronóstica. La hemorragia es la principal complicación de la biopsia de injerto renal. Presentamos un caso de una mujer caucásica de 47 años, quien fue hospitalizada para la realización de una biopsia de injerto renal guiada por ultrasonido (US). Seis horas después, presentó hematuria macroscópica que mejoró después de la cateterización uretral e hidratación intravenosa. Sin embargo, la hematuria reapareció asociada con anemia y empeoramiento del valor sérico de creatinina. El estudio de US reveló, mediante Doppler, una hidronefrosis con alto índice de resistencia renal, compatible con obstrucción por un coágulo. A pesar del lavado vesical con drenaje de varios coágulos, la paciente progresó rápidamente a choque hemorrágico con empeoramiento de la función renal. La tomografía computarizada (TC) pélvica reveló la duplicidad del cáliz y la pelvis y la bifidez ureteral, que se fusionó en un solo uréter y se insertó en la pared anterolateral derecha de la vejiga. El uréter inferior se agrandó debido a un coágulo obstructivo. La mayoría de las uropatías obstructivas agudas están asociadas con dolor significativo o la disminución abrupta del flujo de orina. La presencia de la bifidez del uréter en el estudio de TC explicó el mantenimiento de una diuresis significativa a pesar de la obstrucción, localizada solo en el uréter inferior, pero con suficiente impacto funcional como para provocar insuficiencia renal aguda (IRA).

An Explanation about the Use of (S)-Citronellal as a Chiral Derivatizing Agent (CDA) in 1H and 13C NMR for Sec-Butylamine, Methylbenzylamine, and Amphetamine: A Theoretical-Experimental Study.

A chiral derivatizing agent (CDA) with the aldehyde function has been widely used in discriminating chiral amines because of the easy formation of imines under mild conditions. There is a preference for the use of cyclic aldehydes as a CDA since their lower conformational flexibility favors the differentiation of the diastereoisomeric derivatives. In this study, the imines obtained from the reaction between (S)-citronellal and the chiral amines (sec-butylamine, methylbenzylamine, and amphetamine) were analyzed by the nuclear Overhauser effect (NOE). Through NOE, it was possible to observe that the ends of the molecules were close, suggesting a quasi-folded conformation. This conformation was confirmed by theoretical calculations that indicated the London forces and the molecular orbitals as main justifications for this conformation. This conformational locking explains the good separation of 13C NMR signals between the diastereomeric imines obtained and, consequently, a good determination of the enantiomeric excess using the open chain (S)-citronellal as a CDA.

N, N', N″-trisubstituted guanidines: Synthesis, characterization and evaluation of their leishmanicidal activity.

Leishmaniasis is a group of diseases caused by protozoan parasites from the genus Leishmania. There are estimated 1.3 million new cases annually with a mortality of 20,000-30,000 per year, when patients are left untreated. Current chemotherapeutic drugs available present high toxicity and low efficacy, the latter mainly due to the emergence of drug-resistant parasites, which makes discovery of novel, safe, and efficacious antileishmanial drugs mandatory. The present work reports the synthesis, characterization by ESI-MS, 1H and 13C NMR, and FTIR techniques as well as in vitro and in vivo evaluation of leishmanicidal activity of guanidines derivatives presenting lower toxicity. Among ten investigated compounds, all being guanidines containing a benzoyl, a benzyl, and a substituted phenyl moiety, LQOF-G2 (IC50-ama 5.6 µM; SI = 131.8) and LQOF-G7 (IC50-ama 7.1 µM; SI = 87.1) were the most active against L. amazonensis intracellular amastigote, showing low cytotoxicity to the host cells according to their selectivity index. The most promising compound, LQOF-G2, was further evaluated in an in vivo model and was able to decrease 60% of the parasite load in foot lesions at a dose of 0.25 mg/kg/day. Moreover, this guanidine derivative demonstrated reduced hepatotoxicity compared to other leishmanicidal compounds and did not show nephrotoxicity, as determined by the analyses of biomarkers of hepatic damage and renal function, which make this compound a potential new hit for therapy against leishmaniasis.

Blood pressure and phosphate level in diabetic and non-diabetic kidney disease: Results of the cross-sectional "Low Clearance Consultation" study.

HIGHLIGHTS: A statistically significant and moderate positive correlation was verified between systolic blood pressure and plasma phosphate concentration in the whole sample (diabetic and non-diabetic), due to the diabetic chronic kidney disease group.A statistically significant and moderate positive correlation was verified between the diastolic blood pressure and plasma phosphate concentration in the whole sample (diabetic and non-diabetic), due to the diabetic chronic kidney disease group.A statistically significant and strong negative correlation was found between diastolic blood pressure and estimated glomerular filtration rate in the diabetic chronic kidney disease group, but there was no statistically significant correlation in the whole sample (diabetic and non-diabetic). ABSTRACT: Diabetic kidney disease features certain clinical and laboratorial characteristics that differ from chronic kidney disease of other etiologies. We performed a transversal study comparing some of these characteristics and assessed potential associations among blood pressure, plasma phosphate concentration and estimated glomerular filtration rate between patients with diabetic and non-diabetic chronic kidney disease.We found a positive correlation between both systolic and diastolic blood pressure and the plasma phosphate concentration in the diabetic kidney disease group, but not in the non-diabetic group. Also, diastolic blood pressure was negatively correlated with the estimated glomerular filtration rate in the diabetic group, yet not in the non-diabetic group.In conclusion, these data support the hypothesis of a close link between systolic and diastolic blood pressure and hyperphosphatemia, as well as between diastolic blood pressure and estimated glomerular filtration rate, in patients with diabetic kidney disease. Therapeutic approaches directed at these factors might prove to be important to delay the decline of renal function in the subgroup of patients with diabetic kidney disease.

Bioassay-guided isolation of proanthocyanidins with antioxidant activity from peanut (Arachis hypogaea) skin by combination of chromatography techniques.

Purification and bioassay-guided fractionation were employed to isolate proanthocyanidins with antioxidant activity from peanut skin (Arachis hypogaea Runner 886). The crude extract was prepared with acetone (60% v/v) and purified using chromatographic methods, including a semipreparative HPLC technique. As a result, two proanthocyanidins were isolated and identified using NMR, epicatechin-(2 ß â†’ O → 7, 4 ß â†’ 8)-catechin (proanthocyanidin A1) and epicatechin-(ß â†’ 2 O → 7, 4 ß â†’ 8)-epicatechin (proanthocyanidin A2). Despite the structural similarity, differences were observed in their antioxidant activity. Proanthocyanidin A1 proved to be more active, with EC50 value for DPPH radical scavenging of 18.25 µg/mL and reduction of Fe(3+)-TPTZ complex of 7.59 mmol/g, higher than that of synthetic antioxidant BHT. This compound evaluated by ABTS(+) was similar to that of natural quercetin. Therefore, peanut skin is an important source of bioactive compounds that may be used as a mild antioxidant for food preservation.