Oral administration of a recombinant modified RBD antigen of SARS-CoV-2 as a possible immunostimulant for the care of COVID-19.

BACKGROUND: Developing effective vaccines against SARS-CoV-2 that consider manufacturing limitations, equitable access, and acceptance is necessary for developing platforms to produce antigens that can be efficiently presented for generating neutralizing antibodies and as a model for new vaccines. RESULTS: This work presents the development of an applicable technology through the oral administration of the SARS-CoV-2 RBD antigen fused with a peptide to improve its antigenic presentation. We focused on the development and production of the recombinant receptor binding domain (RBD) produced in E. coli modified with the addition of amino acids extension designed to improve antigen presentation. The production was carried out in shake flask and bioreactor cultures, obtaining around 200 mg/L of the antigen. The peptide-fused RBD and peptide-free RBD proteins were characterized and compared using SDS-PAGE gel, high-performance chromatography, and circular dichroism. The peptide-fused RBD was formulated in an oil-in-water emulsion for oral mice immunization. The peptide-fused RBD, compared to RBD, induced robust IgG production in mice, capable of recognizing the recombinant RBD in Enzyme-linked immunosorbent assays. In addition, the peptide-fused RBD generated neutralizing antibodies in the sera of the dosed mice. The formulation showed no reactive episodes and no changes in temperature or vomiting. CONCLUSIONS: Our study demonstrated the effectiveness of the designed peptide added to the RBD to improve antigen immunostimulation by oral administration.

Meropenem allergy testing performed at the bedside of hospitalized patients labelled with a penicillin allergy.

BACKGROUND: Meropenem is a widely prescribed beta-lactam for hospitalized patients. There are few data on meropenem allergy assessments in inpatients with a reported history of penicillin allergy who require a treatment with meropenem. This can lead to the use of less effective second-line antibiotics that may increase antibiotic resistances. We aimed to evaluate the clinical outcomes of a meropenem allergy assessment in admitted patients with a reported history of penicillin allergy that required meropenem for the treatment of an acute infection. METHODS: A retrospective analysis was performed on 182 inpatients labelled with a penicillin-allergy who received meropenem after an allergy assessment. The allergy study was performed bedside if meropenem was required urgently. The study included skin prick tests (SPTs) followed by an intradermal skin test (IDT) to meropenem, and a meropenem drug challenge test (DCT). If a non-immediate reaction to a beta-lactam was suspected, it was initiated with patch tests. RESULTS: The median age of the patients was 59.7 years (range 28-95) and 80 (44%) were women. A total of 196 sets of diagnostic workups were performed, with 189 (96.4%) of them being tolerated. Only two patients had a positive meropenem IV DCT, both presenting a non-severe cutaneous reaction that completely resolved after treatment. CONCLUSIONS: This study evidenced that a bedside meropenem allergy assessment of hospitalized patients labelled with a 'penicillin allergy' who require a broad-spectrum antibiotic for empiric coverage is a safe and effective procedure, avoiding the use of second-line antimicrobial agents.

Regulation of zinc homeostatic genes by environmental pH in the filamentous fungus Aspergillus fumigatus.

Aspergillus fumigatus can grow over a broad range of pH values even though zinc availability is greatly conditioned by ambient pH. It has been previously shown that regulation of zinc homeostatic genes in this fungus relies on the transcription factor ZafA. In addition, their expression is further modulated by the transcription factor PacC depending on ambient pH, which allows this fungus to grow in diverse types of niches, including soils and the lungs of immunosuppressed hosts. In this work the regulation by PacC of genes zrfB and zrfC that are expressed, respectively, under acidic and alkaline zinc-limiting conditions have been analysed in detail. Thus, data that extend the current model for PacC function, including the role of the full-length PacC72 protein and the PacC processed forms (PacC53 and PacC27 ) on gene expression has been provided, and a new mechanism for the repression of acid-expressed genes in alkaline media based on interference with the start of transcription has been described. Moreover, it was proposed that the transcription of both acid-expressed and alkaline-expressed genes under zinc-limiting conditions might also rely on a third factor (putatively Pontin/Reptin), which may be required to integrate the action of PacC and ZafA into gene specific transcriptional responses.

Treatment with low-dose prednisone in refractory obstetric antiphospholipid syndrome: A retrospective cohort study and meta-analysis.

BACKGROUND: Glucocorticoids have been suggested as a potential therapy in refractory obstetric antiphospholipid syndrome (oAPS). Our aims were to describe a cohort of patients with oAPS treated with low-dose glucocorticoids and to perform a systematic review and meta-analysis evaluating the effects of additional glucocorticoids on the pregnancy outcomes in oAPS patients. METHODS: Retrospective study that included 11 women diagnosed with primary antiphospholipid syndrome. The meta-analysis was conducted by fitting random effects models and was checked for heterogeneity. RESULTS: All women had suffered from early pregnancy losses and two also had a history of fetal deaths. We studied 47 pregnancies that resulted in 32 abortions (68.1%) and 3 fetal deaths (6.4%). Twenty-six pregnancies were under treatment, mainly LDA and LMWH. Low-dose glucocorticoids were indicated in 13 pregnancies (always in association with LDA and LMWH). There was a decrease in pregnancy loss in those patients treated with LDA and LMWH. Treatment with glucocorticoids significantly increased the rate of successful pregnancy (38.5% abortions in treated vs 85.3% abortions in non-treated pregnancies; p=0.003). After multivariate GEE analysis, only glucocorticoids remained inversely associated with pregnancy loss (OR=0.157, (CI 0.025-0.968, p=0.046)). The meta-analysis showed that glucocorticoids tended to improve the frequency of successful pregnancy (OR= 0.509 (0.252-1.028), p=0.06). Three cases of gestational diabetes and one of preeclampsia were observed in our cohort. The meta-analysis, which mostly included studies using high-dose steroids, showed that glucocorticoids increased not only the frequency of preeclampsia and gestational diabetes, but also the rate of pre-term birth. CONCLUSIONS: The efficacy of low-dose glucocorticoids in addition to the standard therapy in patients with refractory oAPS should be confirmed in well-designed clinical trials. However, high doses of steroids significantly increase the frequency of maternal and fetal morbidities, making their use strongly inadvisable.

Intralesional Infiltrations of Arteriosclerotic Tissue Cells-Free Filtrate Reproduce Vascular Pathology in Healthy Recipient Rats.

Lower-extremity arterial disease is a major health problem with increasing prevalence, often leading to non-traumatic amputation, disability and mortality. The molecular mechanisms underpinning abnormal vascular wall remodeling are not fully understood. We hypothesized on the existence of a vascular tissue memory that may be transmitted through soluble signaling messengers, transferred from humans to healthy recipient animals, and consequently drive the recapitulation of arterial wall thickening and other vascular pathologies. We examined the effects of the intralesional infiltration for 6 days of arteriosclerotic popliteal artery-derived homogenates (100 µg of protein) into rats' full-thickness wounds granulation tissue. Animals infiltrated with normal saline solution or healthy brachial arterial tissue homogenate obtained from traumatic amputation served as controls. The significant thickening of arteriolar walls was the constant outcome in two independent experiments for animals receiving arteriosclerotic tissue homogenates. This material induced other vascular morphological changes including an endothelial cell phenotypic reprogramming that mirrored the donor's vascular histopathology. The immunohistochemical expression pattern of relevant vascular markers appeared to match between the human tissue and the corresponding recipient rats. These changes occurred within days of administration, and with no cross-species limitation. The identification of these "vascular disease drivers" may pave novel research avenues for atherosclerosis pathobiology.

Integrative overview of antibodies against SARS-CoV-2 and their possible applications in COVID-19 prophylaxis and treatment.

SARS-CoV-2 is a novel ß-coronavirus that caused the COVID-19 pandemic disease, which spread rapidly, infecting more than 134 million people, and killing almost 2.9 million thus far. Based on the urgent need for therapeutic and prophylactic strategies, the identification and characterization of antibodies has been accelerated, since they have been fundamental in treating other viral diseases. Here, we summarized in an integrative manner the present understanding of the immune response and physiopathology caused by SARS-CoV-2, including the activation of the humoral immune response in SARS-CoV-2 infection and therefore, the synthesis of antibodies. Furthermore, we also discussed about the antibodies that can be generated in COVID-19 convalescent sera and their associated clinical studies, including a detailed characterization of a variety of human antibodies and identification of antibodies from other sources, which have powerful neutralizing capacities. Accordingly, the development of effective treatments to mitigate COVID-19 is expected. Finally, we reviewed the challenges faced in producing potential therapeutic antibodies and nanobodies by cell factories at an industrial level while ensuring their quality, efficacy, and safety.

Treatment Adherence and Clinical Outcomes of Patients with Inflammatory Bowel Disease on Biological Agents During the SARS-CoV-2 Pandemic.

BACKGROUND: The outbreak of COVID19 evolved rapidly into a global pandemic, forcing hospitals, including inflammatory bowel disease (IBD) referral units, to change their practices to ensure quality of care. AIMS: To describe the clinical outcomes and the fulfilment of the treatment schedule of patients with IBD treated with biological agents in a single-center of a red-zone of the pandemic, and to report the patients' perceptions about COVID-19 and the measures adopted at our center. METHODS: Therapeutic adherence and clinical outcomes were collected for all patients undergoing treatment with intravenous biologicals and subcutaneous biologicals at our center. A telephone survey was also performed to assess these patients' perceptions of the COVID pandemic and the related measures adopted at their IBD unit. RESULTS: A total of 234 patients were included (117 on intravenous and 117 on subcutaneous biologicals). Only 10% of patients postponed intravenous infusions intentionally and 5% postponed the collection of subcutaneous biologicals at the hospital pharmacy. Only five confirmed COVID-19 cases were registered (2.1%), all of them of mild severity. One hundred and fifty-five patients participated in the survey (77 on intravenous and 78 on subcutaneous drugs). Fear of going to the hospital was the most common reason for postponing biological administrations. Among those on combination therapy, only 7% admitted to have withdrawn immunosuppressants. CONCLUSIONS: Adherence to intravenous and subcutaneous biological therapies during the pandemic was high in a single-center cohort of IBD patients even though the cumulative incidence of confirmed COVID-19 was low.

Chronic interstitial nephritis of nontraditional causes in Salvadoran agricultural communities.

In El Salvador, a form of chronic kidney disease (CKD) of nontraditional causes (CKDnt) affecting farmers is being reported. Its behavior has been epidemic and is responsible for tens of thousands of deaths. This article summarizes the results obtained from a series of studies conducted to identify the epidemiology and clinical behavior of this disease, proposing a case definition and an etiopathogenic hypothesis. Methods included a survey of CKD in agricultural communities studying 2,388 people ≥ 18 years and 1,755 < 18, a descriptive clinical study followed by histopathological assessment conducted in 46 possible cases of CKDnt ≥ 18 years, and a national survey to study the prevalence of CKD and associated risk factors in 4,817 participants ≥ 20 years followed by a nested case-control study. In the agricultural communities, the prevalence of CKD in adults was 18% (men: 23.9%, women: 13.9%), 26.8% in agricultural workers (non-agricultural 13.8%), CKDnt accounted for 51.9% of cases. CKD in the population < 18 years was 3.9% (mean estimated glomerular filtration rate > 160 mL/1.73m2). The national CKD prevalence was 12.6% (urban: 11.3%; rural: 14.4%; males: 17.8%, females 8.5%), and CKDnt was only 3.8%; with associations between CKD and exposure to agrochemicals. The clinical study revealed the presence of markers of kidney damage (A3 albuminuria: 80.4%; ß2-microglobulin: 78.2%), urine electrolyte anomalies (100% hypermagnesuria, 45.7% hypernatriuria, 43.5% osmotic polyuria), abnormal osteotendinous reflexes (45.7%), sensorineural hearing loss (56.5%), and damage of the tibial arteries by Doppler imaging (66.7%). Biopsies revealed a chronic tubulointerstitial nephropathy. The etiopathogenesis of CKDnt is possibly multifactorial, including environmental contamination by agrochemicals, heat stress, and dehydration.

COVID-19 and inflammatory bowel disease: questions arising from patient care and follow-up during the initial phase of the pandemic (February-April 2020). / COVID-19 y enfermedad inflamatoria intestinal: preguntas surgidas de la atención y seguimiento de los pacientes durante la fase inicial de la pandemia (febrero-abril 2020).

COVID-19 is a disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which was described in China in late 2019. There are currently more than three million diagnosed cases, constituting a pandemic which has caused a worldwide crisis. The devastating effects of this infection are due to its highly contagious nature and although mild forms predominate, in absolute values, the rates for severe forms and mortality are very high. The information on the characteristics of the infection in inflammatory bowel disease is of special interest, as these patients have higher attendance at health centres, which may increase their risk of infection. Furthermore, the treatments used to control the inflammatory activity may modify the disease course of COVID-19. The Spanish Working Group on Crohn's Disease and Ulcerative Colitis and the Spanish Nurses Working Group on Inflammatory Bowel Disease have prepared this document as a practical response to some common questions about the treatment of these patients.

Impact of pain associated with the subcutaneous administration of adalimumab.

BACKGROUND: There is limited information regarding the impact of patients' perception of injection pain on adherence to treatments, specifically in inflammatory bowel disease (IBD) patients. Therefore, we aimed to determine the impact of the pain associated with the subcutaneous administration of adalimumab in patients with IBD treated with the old formulation and the new low-volume/citrate-free formulation. METHODS: A specifically-designed questionnaire was completed by 76 patients with IBD, who started treatment with adalimumab before the availability of the low-volume/citrate-free formulation and were switched to this new formulation. Intensity of pain was measured by using visual analog scales (VAS). RESULTS: A total of 62 patients (82%) experienced injection-related pain with the initial formulation. The perception of pain was associated with a decreased adherence to the treatment (37%), an increase in pre-administration anxiety (25%) or, as a consequence, the patient required someone else to carry out the injection (21%). Younger age was the only factor associated with pain perception. After switching to the new formulation, perception of pain persisted only in 2 patients (3%). Among those who felt pain with the initial formulation, pre-administration anxiety disappeared in 44%; 32% and 42% stated that the new formulation eased adherence and self-administration. CONCLUSIONS: The perception of pain related to the subcutaneous administration of therapy negatively impacts on treatment adherence in IBD patients. Improved formulations for subcutaneous administration of drugs can positively impact patients' convenience and adherence.

Enterovirus A71 Infection and Neurologic Disease, Madrid, Spain, 2016.

We conducted an observational study from January 2016 through January 2017 of patients admitted to a reference pediatric hospital in Madrid, Spain, for neurologic symptoms and enterovirus infection. Among the 30 patients, the most common signs and symptoms were fever, lethargy, myoclonic jerks, and ataxia. Real-time PCR detected enterovirus in the cerebrospinal fluid of 8 patients, nasopharyngeal aspirate in 17, and anal swab samples of 5. The enterovirus was genotyped for 25 of 30 patients; enterovirus A71 was the most common serotype (21/25) and the only serotype detected in patients with brainstem encephalitis or encephalomyelitis. Treatment was intravenous immunoglobulins for 21 patients and corticosteroids for 17. Admission to the pediatric intensive care unit was required for 14 patients. All patients survived. At admission, among patients with the most severe disease, leukocytes were elevated. For children with brainstem encephalitis or encephalomyelitis, clinicians should look for enterovirus and not limit testing to cerebrospinal fluid.

The interplay between zinc and iron homeostasis in Aspergillus fumigatus under zinc-replete conditions relies on the iron-mediated regulation of alternative transcription units of zafA and the basal amount of the ZafA zinc-responsiveness transcription factor.

Aspergillus fumigatus is a saprophyte fungus that typically grows on organic decaying matter but can also parasitize immunosuppressed hosts. This is explained, in part, by its great ability to take up Zn2+ ions from living tissues, which is induced by the ZafA transcription factor. This study shows that the ZafA-mediated regulation of fungal growth is also influenced by iron availability and that A. fumigatus is well adapted to grow in zinc-limiting and zinc-replete media with Zn:Fe ratios lower in the former than in the latter. Accordingly, this indicates that iron availability appears to be more critical for fungal growth in zinc-replete than in zinc-limiting environments. Interestingly, the cross-regulation of zinc/iron homeostasis under zinc-replete conditions relies on an unprecedented iron-mediated regulation of different zafA transcription units that, along with a limited transcript translation, allows synthesizing the right basal amount of ZafA dependent on iron availability. We posit that this regulatory strategy has evolved in fungi as a mechanism to adjust zinc intake to iron availability under zinc-replete conditions. Thus, fungal growth is enhanced in zinc- and iron-replete media but restricted by reducing zinc intake under iron starvation to prevent the noxious side effects of an intracellular zinc excess during iron deficiency.

Association of salivary alpha-amylase and salivary flow rate with working memory functioning in healthy children.

The aim of this study was to examine the association between auditory and visual working memory (WM) performance and salivary alpha-amylase (sAA) and salivary flow rate (SFR) in a sample of 63 children (38 boys). WM was assessed by means of WISC-V subtests: four auditory subtests (Digit Span and Letter-Number Sequencing) and one visual subtest (Picture Span). SAA activity, output, and SFR were measured at baseline (10 min prior to testing), one minute prior to testing, one minute after the end of the auditory WM subtests and one minute after the end of the visual WM subtest. Our statistical analyses showed an association among SAA activity, output and SFR levels and the number of recalled digits in the last attempt score in Letter-Number Sequencing subtest. Specifically, our results showed that working performance in this task was associated with a concurrent decrease in SFR (r(63) = -0.423, p < .05). This salivary measure was the best predictor of this specific index of working memory performance (ß = -0.423, p < .05). These results show that the changes in SFR, which represents changes in parasympathetic tone, could be employed in future studies as a noninvasive marker of working memory performance in child studies.

Development and validation of the QUECOMIICAT questionnaire: a tool to assess disease-related knowledge in patients with inflammatory bowel disease.

INTRODUCTION: adequate knowledge of inflammatory bowel disease (IBD) is essential for a successful patient-centered management of IBD. OBJECTIVE: due to the scarcity of up-to-date tools for measuring IBD literacy, this single-center, prospective study aimed to develop and validate a new questionnaire to assess IBD-related knowledge. MATERIAL AND METHODS: the study included patients followed up at the Crohn-Colitis Care Unit (UACC) at the Hospital Vall d'Hebron (Barcelona, Spain). Patients admitted to the UACC for the first time were subsequently enrolled into a standard IBD educational program. A pilot questionnaire was developed and validated in 92 IBD patients by determining the internal consistency reliability (Cronbach's α test), feasibility, construct validity (correlation with the Crohn's and Colitis Knowledge [CCKNOW] questionnaire and a knowledge visual analog scale [VAS]) and sensitivity (score change before and after a standard IBD educational program). The questionnaire, named "Qüestionari Coneixements Malaltia Inflamatòria Intestinal Catalunya" (IBD-knowledge questionnaire Catalonia) (QUECOMIICAT) was written in Spanish and had 25 items addressing six dimensions: general concepts, clinic, treatment, surgery, habits and social context. RESULTS: the median (interquartile range) completion time was 15 (10-20) minutes and the floor and ceiling effects were 1.1% and 2.1%, respectively. The Cronbach's α coefficient was α = 0.75. QUECOMIICAT significantly correlated with the VAS (rho = 0.34, p < 0.01) and CCKNOW questionnaires (rho = 0.74, p < 0.01). Patient knowledge significantly increased 24 hours after attending a standard IBD educational program and remained statistically significant one month later (Pearson's test-retest correlation coefficient r = 0.81, p < 0.001). CONCLUSION: in conclusion, the QUECOMIICAT questionnaire is a new up-to-date tool to assess IBD-related knowledge with good feasibility and validation results for use in the routine clinical practice.

Novel Zinc-Attenuating Compounds as Potent Broad-Spectrum Antifungal Agents with In Vitro and In Vivo Efficacy.

An increase in the incidence of rare but hard-to-treat invasive fungal pathogens as well as resistance to the currently available antifungal drugs calls for new broad-spectrum antifungals with a novel mechanism of action. Here we report the identification and characterization of two novel zinc-attenuating compounds, ZAC307 and ZAC989, which exhibit broad-spectrum in vitro antifungal activity and in vivo efficacy in a fungal kidney burden candidiasis model. The compounds were identified serendipitously as part of a drug discovery process aimed at finding novel inhibitors of the fungal plasma membrane proton ATPase Pma1. Based on their structure, we hypothesized that they might act as zinc chelators. Indeed, both fluorescence-based affinity determination and potentiometric assays revealed these compounds, subsequently termed zinc-attenuating compounds (ZACs), to have strong affinity for zinc, and their growth inhibitory effects on Candida albicans and Aspergillus fumigatus could be inactivated by the addition of exogenous zinc to fungal growth media. We determined the ZACs to be fungistatic, with a low propensity for resistance development. Gene expression analysis suggested that the ZACs interfere negatively with the expression of genes encoding the major components of the A. fumigatus zinc uptake system, thus supporting perturbance of zinc homeostasis as the likely mode of action. With demonstrated in vitro and in vivo antifungal activity, low propensity for resistance development, and a novel mode of action, the ZACs represent a promising new class of antifungal compounds, and their advancement in a drug development program is therefore warranted.

RNAi promotes heterochromatic silencing through replication-coupled release of RNA Pol II.

Heterochromatin comprises tightly compacted repetitive regions of eukaryotic chromosomes. The inheritance of heterochromatin through mitosis requires RNA interference (RNAi), which guides histone modification during the DNA replication phase of the cell cycle. Here we show that the alternating arrangement of origins of replication and non-coding RNA in pericentromeric heterochromatin results in competition between transcription and replication in Schizosaccharomyces pombe. Co-transcriptional RNAi releases RNA polymerase II (Pol II), allowing completion of DNA replication by the leading strand DNA polymerase, and associated histone modifying enzymes that spread heterochromatin with the replication fork. In the absence of RNAi, stalled forks are repaired by homologous recombination without histone modification.

Therapeutic requirements in active ulcerative proctitis: A single-centre study.

BACKGROUND: Ulcerative proctitis (UP) presents distinctive clinical characteristics, outcomes and therapeutic approaches as compared to left-sided and extensive ulcerative colitis (UC). AIM: To describe the current therapeutic requirements and clinical outcomes in patients with active UP. METHODS: Retrospective observational study conducted in a referral IBD centre. Patients with UP in follow-up between 1989 and 2014 were included. The clinical characteristics, as well as the different treatments and drug formulations administered to treat flares, were recorded. RESULTS: Out of 687 UC patients, 101 patients (15%) with UP were included. Median follow-up was 8 years (IQR 3-14) and 49% of patients presented disease activity during the study period. Topical mesalazine monotherapy (90%) was the most commonly administered treatment for disease activity (mostly as suppositories), followed by topical steroids (47%) and oral mesalazine (56%) in monotherapy or combination therapy. Only 14% and 16% of patients required oral prednisone and beclomethasone, respectively. CONCLUSIONS: In clinical practice, active UP presents mostly favourable outcomes. Mesalazine suppositories are by far the most used treatment for these patients.

Nucleosomal organization of replication origins and meiotic recombination hotspots in fission yeast.

In Schizosaccharomyces pombe, DNA replication origins (ORIs) and meiotic recombination hotspots lack consensus sequences and show a bias towards mapping to large intergenic regions (IGRs). To explore whether this preference depended on underlying chromatin features, we have generated genome-wide nucleosome profiles during mitosis and meiosis. We have found that meiotic double-strand break sites (DSBs) colocalize with nucleosome-depleted regions (NDRs) and that large IGRs include clusters of NDRs that overlap with almost half of all DSBs. By contrast, ORIs do not colocalize with NDRs and they are regulated independently of DSBs. Physical relocation of NDRs at ectopic loci or modification of their genomic distribution during meiosis was paralleled by the generation of new DSB sites. Over 80% of all meiotic DSBs colocalize with NDRs that are also present during mitosis, indicating that the recombination pattern is largely dependent on constitutive properties of the genome and, to a lesser extent, on the transcriptional profile during meiosis. The organization of ORIs and of DSBs regions in S. pombe reveals similarities and differences relative to Saccharomyces cerevisiae.

Clinical characteristics of chronic kidney disease of non-traditional causes in women of agricultural communities in El Salvador.

INTRODUCTION: A chronic kidney disease of non-traditional causes (CKDu) has emerged in Central America and elsewhere, predominantly affecting male farmworkers. In El Salvador (2009), it was the second cause of death in men > 18 years old. Causality has not been determined. Most available research focused on men and there is scarce data on women. OBJECTIVES: Describe the clinical and histopathologic characteristics of CKDu in women of agricultural communities in El Salvador. METHODOLOGY: A descriptive study was carried out in 10 women with CKDu stages 2, 3a, and 3b. Researchers studied demographics, clinical examination; hematological and biochemical analyses, urine sediment, renal injury markers, and assessed renal, cardiac, and peripheral arteries, liver, pancreas, and lung anatomy and functions. Kidney biopsy was performed in all. Data was collected on the Lime Survey platform and exported to SPSS 19.0. RESULTS: Patient distribution by stages: 2 (70%), 3a (10%), 3b (20%). Occupation: agricultural 7; non-agricultural 3. RISK FACTORS: agrochemical exposure 100%; farmworkers 70%; incidental malaria 50%, NSAIDs use 40%; hypertension 40%. SYMPTOMS: nocturia 50%; dysuria 50%; arthralgia 70%; asthenia 50%; cramps 30%, profuse sweating 20%. Renal markers: albumin creatinine ratio (ACR) > 300 mg/g 90%; ß microglobulin and neutrophil gelatinase- associated lipocalin (NGAL) presence in 40%. Kidney function: hypermagnesuria 100%; hyperphosphaturia 50%, hypercalciuria 40%; hypernatriuria 30%; hyponatremia 60%, hypocalcemia 50%. Doppler: tibial artery damage 40%. Neurological: reflex abnormalities 30%; Babinski and myoclonus 20%. Neurosensorial hypoacusis 70%. Histopathology: damage restricted mostly to the tubulo-interstitium, urine was essentially bland. CONCLUSIONS: CKDu in women is a chronic tubulointerstitial nephropathy with varied extrarenal symptoms.