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This thesis focused on uncovering the intricate interactions between the proximal tubule (PT) and disease mediators through the development and application of in vitro models. For this, we extensively reviewed the currently available PT in vitro models, followed by the application of a series of in vitro PT models designed to address the factors contributing to injury. Our initial focus was on understanding the interactions between uremic toxins (UTs), particularly those bound to albumin (PBUTs), and drugs prescribed for treatment of CKD complications. Our findings revealed that certain drugs, including angiotensin receptor blockers and the diuretic, furosemide, may inadvertently compromise PBUTs uptake, thus leading to their accumulation and kidney function deterioration. Additionally, this finding has implications in the efficacy of the bioartificial kidney (BAK), designed to complement conventional dialysis by removing PBUTs. To advance its clinical application, we investigated the performance of a BAK functional unit in conditions that mimic dialysis. Our results showed that dialysis fluid, a solution used in dialysis to aid waste product removal and maintain patients’ electrolyte levels, is cytocompatible with the BAK-containing cells and does not interfere with PBUTs clearance. Furthermore, given the high mitochondrial density found in PT required for ATP production, and needed for transport and metabolism functions, we explored the implications of impaired mitochondrial function, as a result of ischemia and hyperglycemia. In response to this damage, we employed therapeutic strategies, including stem cell therapy and diabetes medication. Our findings showcase that stem cell therapy successfully restored the bioenergetic profile of ischemic PT cells, while a diabetes drug effectively reduced the secretion of kidney injury markers. Altogether, the comprehensive findings of this thesis contribute to an enhanced understanding of the PT as a prime target for diseas

Introduction: Acute kidney injury is an early-stage renal damage that can be detected by neutrophilic gelatinase-associated lipocalin protein. Aim: To evaluate the usefulness of neutrophilic gelatinase-associated lipocalin protein as an early marker of Acute Kidney Inju r y. Methodology: narrative review following the PRISMA statement criteria. PubMed, Scopus, and LILACS were the databases consulted. Results: 23 articles published in the last five years were identified. The evidence shows that this protein has biochemical characteristics useful in the early diagnosis of renal injury in different situations and populations. Discussion: The behavior of NGAL has demonstrated its increase in plasma up to 2 hours after the onset of renal impairment. Likewise, its synthesis is not affected by variables such as sex, body mass index, high protein intake, excess physical activity, and alteration in glomerular filtration, which do modify Crs concentrations. Conclusions: Neutrophilic gelatinase-associated lipocalin meets the criteria to become an early biomarker for Acute Kidney Introduction: Acute kidney injury is an early-stage renal damage that can be detected by neutrophilic gelatinase-associated lipocalin protein. Aim: To evaluate the usefulness of neutrophilic gelatinase-associated lipocalin protein as an early marker of Acute Kidney Inju r y. Methodology: narrative review following the PRISMA statement criteria. PubMed, Scopus, and LILACS were the databases consulted. Results: 23 articles published in the last five years were identified. The evidence shows that this protein has biochemical characteristics useful in the early diagnosis of renal injury in different situations and populations. Discussion: The behavior of NGAL has demonstrated its increase in plasma up to 2 hours after the onset of renal impairment. Likewise, its synthesis is not affected by variables such as sex, body mass index, high protein intake, excess physical activity, and alteration in glomerular f, Introducción: La lesión renal aguda es un daño renal en etapa temprana que, se postula, podría ser detectada por la proteína lipocalina asociada a gelatina neutrofílica. Objetivo: Evaluar la utilidad de la proteína lipocalina asociada a gelatina neutrofílica como marcador precoz de Lesión Renal Aguda. Metodología: revisión narrativa siguiendo los criterios de la declaración PRISMA. PubMed, Scopus y LILACS fueron las bases de datos consultadas. Resultados: se identificó un total de 23 artículos publicados en los últimos cinco años. Las evidencias muestran que esta proteína posee características bioquímicas útiles en el diagnóstico precoz de lesión renal en diferentes situaciones y poblaciones. Discusión:El comportamiento de NGAL ha demostrado su aumento en plasma hasta 2 horas después de iniciarse la deficiencia renal. Asimismo, su síntesis no se ve afectada por variables como el sexo, el índice de masa corporal, el alto consumo de proteína, el exceso de actividad física y la alteración en la filtración glomerular, que sí modifican las concentraciones de la Crs. Conclusiones: La lipocalina asociada a gelatinasa neutrofílica cumple con los criterios requeridos para convertirse en un biomarcador precoz para Lesión Renal Aguda.

MRI plays an important role in the evaluation of kidney allografts for vascular complications as well as parenchymal insults. Transplant renal artery stenosis, the most common vascular complication of kidney transplant, can be evaluated by MRA using gadolinium and nongadolinium contrast agents as well as by unenhanced MRA techniques. Parenchymal injury occurs through a variety of pathways, including graft rejection, acute tubular injury, BK polyomavirus infection, drug-induced interstitial nephritis, and pyelonephritis. Investigational MRI techniques have sought to differentiate among these causes of dysfunction as well as to assess the degree of interstitial fibrosis or tubular atrophy (IFTA)-the common end pathway for all of these processes-which is currently evaluated by invasively obtained core biopsies. Some of these MRI sequences have shown promise in not only assessing the cause of parenchymal injury but also assessing IFTA noninvasively. This review describes current clinically used MRI techniques and previews promising investigational MRI techniques for assessing complications of kidney grafts.

Managing patients with kidney allografts largely depends on biopsy diagnosis which is based on semiquantitative assessments of rejection features and extent of acute and chronic changes within the renal parenchyma. Current methods lack reproducibility while digital image data-driven computational models enable comprehensive and quantitative assays. In this study we aimed to develop a computational method for automated assessment of histopathology transformations within the tubulointerstitial compartment of the renal cortex. Whole slide images of modified Picrosirius red-stained biopsy slides were used for the training (n = 852) and both internal (n = 172) and external (n = 94) tests datasets. The pipeline utilizes deep learning segmentations of renal tubules, interstitium, and peritubular capillaries from which morphometry features were extracted. Seven indicators were selected for exploring the intrinsic spatial interactions within the tubulointerstitial compartment. A principal component analysis revealed two independent factors which can be interpreted as representing chronic and acute tubulointerstitial injury. A K-means clustering classified biopsies according to potential phenotypes of combined acute and chronic transformations of various degrees. We conclude that multivariate analyses of tubulointerstitial morphometry transformations enable extraction of and quantification of acute and chronic components of injury. The method is developed for renal allograft biopsies; however, the principle can be applied more broadly for kidney pathology assessment.

BACKGROUND: Pathology reports contain key information about the patients diagnosis as well as important gross and microscopic findings. These information-rich clinical reports offer an invaluable resource for clinical studies, but data extraction and analysis from such unstructured texts is often manual and tedious. While neural information retrieval systems (typically implemented as deep learning methods for natural language processing) are automatic and flexible, they typically require a large domain-specific text corpus for training, making them infeasible for many medical subdomains. Thus, an automated data extraction method for pathology reports that does not require a large training corpus would be of significant value and utility. OBJECTIVE: To develop a language model-based neural information retrieval system that can be trained on small datasets and validate it by training it on renal transplant-pathology reports to extract relevant information for two predefined questions: (1) What kind of rejection does the patient show?; (2) What is the grade of interstitial fibrosis and tubular atrophy (IFTA)? METHODS: Kidney BERT was developed by pre-training Clinical BERT on 3.4K renal transplant pathology reports and 1.5M words. Then, exKidneyBERT was developed by extending Clinical BERTs tokenizer with six technical keywords and repeating the pre-training procedure. This extended the models vocabulary. All three models were fine-tuned with information retrieval heads. RESULTS: The model with extended vocabulary, exKidneyBERT, outperformed Clinical BERT and Kidney BERT in both questions. For rejection, exKidneyBERT achieved an 83.3% overlap ratio for antibody-mediated rejection (ABMR) and 79.2% for T-cell mediated rejection (TCMR). For IFTA, exKidneyBERT had a 95.8% exact match rate. CONCLUSION: ExKidneyBERT is a high-performing model for extracting information from renal pathology reports. Additional pre-training of BERT language models on specialized small domains

BACKGROUND: Low protein intake (LPI) has been suggested as a treatment for chronic kidney disease (CKD). However, protein intake is essential for bone health. METHODS: We studied the database of the National Health and Nutrition Examination Survey, 2005-2010. Basic variables, metabolic diseases, and bone density of different femoral areas were stratified into four subgroups according to different protein intake (DPI) (that is, <0.8, 0.8-1.0, 1.0-1.2, and >1.2 g/kg/day). RESULTS: Significant differences were found among all lumbar area bone mineral density (BMD) and T-scores (p < 0.0001). There was an apparent trend between a decreasing BMD in the CKD groups with increasing DPI in all single lumbar spines (L1, L2, L3, and L4) and all L spines (L1-L4). Compared with DPI (0.8-1.0 g/day/kg), higher risks of osteoporosis were noticed in the subgroup of >1.2 g/day/kg over L2 (relative risk (RR)=1.326, 95% confidence interval (CI)=1.062-1.656), subgroup >1.2 g/day/kg over L3 (RR = 1.31, 95%CI = 1.057-1.622), subgroup <0.8 g/day/kg over L4 (RR = 1.276, 95%CI = 1.015-1.605), subgroup <0.8 g/day/kg over all L spines (RR = 11.275, 95%CI = 1.051-1.548), and subgroup >1.2 g/day/kg over all L spines (RR = 0.333, 95%CI = 1.098-1.618). However, a higher risk of osteoporosis was observed only in the non-CKD group. There was an apparent trend of higher DPI coexisting with lower BMD and T scores in patients with CKD. For osteoporosis (reference:0.8-1.0 g/day/kg), lower (<0.8 g/day/kg) or higher DPI (>1.2 g/day/kg) was associated with higher risks in the non-CKD group, but not in the CKD group. CONCLUSIONS: In the CKD group, LPI for renal protection was safe without threatening L spine bone density and without causing a higher risk of osteoporosis.

BACKGROUND: Leveraging the Accelerating Medicines Partnership (AMP) Lupus Nephritis (LN) dataset, we evaluated longitudinal patterns, rates, and predictors of response to standard-of-care therapy in patients with lupus nephritis. METHODS: Patients from US academic medical centers with class III, IV, and/or V LN and a baseline urine protein/creatinine (UPCR) ratio ≥ 1.0 (n = 180) were eligible for this analysis. Complete response (CR) required the following: (1) UPCR < 0.5; (2) normal serum creatinine (≤ 1.3 mg/dL) or, if abnormal, ≤ 125% of baseline; and (3) prednisone ≤ 10 mg/day. Partial response (PR) required the following: (1) > 50% reduction in UPCR; (2) normal serum creatinine or, if abnormal, ≤ 125% of baseline; and (3) prednisone dose ≤ 15 mg/day. RESULTS: Response rates to the standard of care at week 52 were CR = 22.2%; PR = 21.7%; non-responder (NR) = 41.7%, and not determined (ND) = 14.4%. Only 8/180 (4.4%) patients had a week 12 CR sustained through week 52. Eighteen (10%) patients attained a week 12 PR or CR and sustained their responses through week 52 and 47 (26.1%) patients achieved sustained PR or CR at weeks 26 and 52. Week 52 CR or PR attainment was associated with baseline UPCR > 3 (ORadj = 3.71 [95%CI = 1.34-10.24]; p = 0.012), > 25% decrease in UPCR from baseline to week 12 (ORadj = 2.61 [95%CI = 1.07-6.41]; p = 0.036), lower chronicity index (ORadj = 1.33 per unit decrease [95%CI = 1.10-1.62]; p = 0.003), and positive anti-dsDNA antibody (ORadj = 2.61 [95%CI = 0.93-7.33]; p = 0.069). CONCLUSIONS: CR and PR rates at week 52 were consistent with the standard-of-care response rates observed in prospective registrational LN trials. Low sustained response rates underscore the need for more efficacious therapies and highlight how critically important it is to understand the molecular pathways associated with response and non-response.

Individuals afflicted with advanced kidney dysfunction who require dialysis for medical management exhibit different degrees of native kidney function, called residual kidney function (RKF), ranging from nil to appreciable levels. The primary focus of this manuscript is to delve into the concept of RKF, a pivotal yet under-represented topic in nephrology. To begin, we unpack the definition and intrinsic nature of RKF. We then juxtapose the efficiency of RKF against that of hemodialysis in preserving homeostatic equilibrium and facilitating physiological functions. Given the complex interplay of RKF and overall patient health, we shed light on the extent of its influence on patient outcomes, particularly in those living with advanced kidney dysfunction and on dialysis. This manuscript subsequently presents methodologies and measures to assess RKF, concluding with the potential benefits of targeted interventions aimed at preserving RKF.

There is a need to reconsider the acceptance of organs from donors considered suboptimal, in the absence of data. Toxoplasma antibody-positive donors (TPD) constitute one such group. The objective of our study was to compare graft survival in deceased donor renal transplant (Tx) recipients, stratified by Toxoplasma IgG status, using the Organ Procurement and Transplantation Network (OPTN) database. A log-linear event history regression model for graft failure categorized by Toxoplasma IgG status, adjusting for confounders was applied to first kidney-only Tx recipients from 2018 to 2022. Of the 51,422 Tx, 4,317 (8.4%) were from TPD. Acute rejection and graft failure (5% each) were similar between groups. Crude graft failure was 7.3 failures per 100 person-years for TPD recipients compared to 6.5 failures per 100 person-years for the Toxoplasma-negative group (p 0.008). The crude failure rate ratio was 1.14 with an adjusted hazard rate ratio of 1.04 (95% CI: 0.94, 1.15, p 0.39). In renal Tx recipients, TPD graft recipients have comparable survival to Tx from Toxoplasma-negative recipients. While caution and close monitoring of recipients post-Tx for surveillance of disseminated toxoplasmosis are still warranted, our study suggests that patients can be successfully managed using TPD organs.

With the increasing incidence of kidney diseases, there is an urgent need to develop therapeutic strategies to combat post-injury fibrosis. Immune cells, including platelets, play a pivotal role in this repair process, primarily through their released cytokines. However, the specific role of platelets in kidney injury and subsequent repair remains underexplored. Here, the detrimental role of platelets in renal recovery following ischemia/reperfusion injury and its contribution to acute kidney injury  to chronic kidney disease transition is aimed to investigated. In this study, it is shown that depleting platelets accelerates injury resolution and significantly reduces fibrosis. Employing advanced single-cell and spatial transcriptomic techniques, macrophages as the primary mediators modulated by platelet signals is identified. A novel subset of macrophages, termed cycling M2, which exhibit an M2 phenotype combined with enhanced proliferative activity is uncovered. This subset emerges in the injured kidney during the resolution phase and is modulated by platelet-derived thrombospondin 1 (THBS1) signaling, acquiring profibrotic characteristics. Conversely, targeted inhibition of THBS1 markedly downregulates the cycling M2 macrophage, thereby mitigating fibrotic progression. Overall, this findings highlight the adverse role of platelet THBS1-boosted cycling M2 macrophages in renal injury repair and suggest platelet THBS1 as a promising therapeutic target for alleviating inflammation and kidney fibrosis.

Objective: Diabetes Mellitus (DM) is a metabolic disease characterized by hyperglycemia due to insufficiency of insulin function. One of the complications caused by DM is Diabetic Nephropathy. This study aims to determine the profile of diabetic nephropathy patients at Waled General Hospital, Cirebon Regency, Indonesia.   Methods: A descriptive observational study was conducted at Waled General Hospital, Cirebon Regency, Indonesia. All patients diagnosed with diabetic nephropathy at Internal Medicine Polyclinic from January 2018 to December 2021 were recruited. The inclusion criteria were adult diabetic nephropathy patients (aged >17 years).   Results: There were 58 patients recruited into the sample, consisting of 37.9% male and 62.1% female. The majority of the sample were aged 55-64 years (44.8%) and housewives (60.3%). We also found that 87.9% of sample were productive age group (<65 years). A total of 79.4% sample had hypertension stage 1 and 2. Based on body mass index (BMI), it was found that 15.5% of the sample were overweight and 10.3% were obese. More than half (51.7%) had Random Blood Glucose (RBG) 200-300 mg/dL and about 32.8% had RBG >300 mg/dL.   Conclusion: It can be concluded that diabetic nephropathy is mostly suffered productive age group <65 years, female, housewives, uncontrolled hypertension, lipid and blood glucose. Efforts to prevent DM and diabetic nephropathy need to be carried out in productive age groups, female and housewives by avoiding sedentary lifestyle, maintaining ideal body weight, preventing hypertension, dyslipidemia and optimal blood gulcose control.

BACKGROUND: An accurate, rapid estimate of glomerular filtration rate (GFR) in kidney transplant patients affords early detection of transplant deterioration and timely intervention. This study compared the performance of serum creatinine (Cr) and cystatin C (CysC)-based GFR equations to measured GFR (mGFR) using iohexol among pediatric kidney transplant recipients. METHODS: CysC, Cr, and mGFR were obtained from 45 kidney transplant patients, 1-18 years old. Cr- and CysC-estimated GFR (eGFR) was compared against mGFR using the Cr-based (Bedside Schwartz, U25-Cr), CysC-based (Gentian CysC, CAPA, U25-CysC), and Cr-CysC combination (CKiD Cr-CysC, U25 Cr-CysC) equations in terms of bias, precision, and accuracy. Bland-Altman plots assessed the agreement between eGFR and mGFR. Secondary analyses evaluated the formulas in patients with biopsy-proven histological changes, and K/DOQI CKD staging. RESULTS: Bias was small with Gentian CysC (0.1 ml/min/1.73 m2); 88.9% and 37.8% of U25-CysC estimations were within 30% and 10% of mGFR, respectively. In subjects with histological changes on biopsy, Gentian CysC had a small bias and U25-CysC were more accurate-both with 83.3% of and 41.7% of estimates within 30% and 10% mGFR, respectively. Precision was better with U25-CysC, CKiD Cr-CysC, and U25 Cr-CysC. Bland-Altman plots showed the Bedside Schwartz, Gentian CysC, CAPA, and U25-CysC tend to overestimate GFR when > 100 ml/min/1.72 m2. CAPA misclassified CKD stage the least (whole cohort 24.4%, histological changes on biopsy 33.3%). CONCLUSIONS: In this small cohort, CysC-based equations with or without Cr may have better bias, precision, and accuracy in predicting GFR.

Background Thermal ablation (TA) with radiofrequency (RFA) or cryoablation (CA) are established treatments for small renal masses (≤4 cm). Microwave ablation (MWA) has several potential benefits (decreased ablation time, less susceptibility to heat-sink, higher lesion temperatures than RFA) but is still considered experimental considering the available small-sample studies with short follow-up. Purpose To evaluate technique efficacy and complications of our initial experience of renal tumors treated using percutaneous MWA with a curative intent. Material and Methods A total of 105 renal tumors (in 93 patients) were treated between April 2014 and August 2017. MWA was performed percutaneously with computed tomography (CT) guidance under conscious sedation (n=82) or full anesthesia. Patients were followed with contrast-enhanced CT scans at six months and yearly thereafter for a minimum of five years. The mean follow-up time was 2.1 years. The percentage of tumors completely ablated in a single session (primary efficacy rate) and those successfully treated after repeat ablation (secondary efficacy rate) were recorded. Patient and tumor characteristics as well as complications were collected retrospectively. Results The median patient age was 70 years and median tumor size was 25 mm. Primary efficacy rate was 96.2% (101/105 tumors). After including two residual tumors for a second ablation session, secondary efficacy was 97.1% (102/105). Periprocedural complications were found in 5.2% (5/95) sessions: four Clavien-Dindo I and one Clavien-Dindo IIIa. One postprocedural Clavien-Dindo II complication was found. Conclusion MWA has high efficacy rates and few complications compared to other TA methods at a mean follow-up of two years., Title in the list of papers of Vanessa Acosta Ruiz's thesis: Percutaneous CT guided microwave ablation of 105 T1a-T1b renal tumors: technique efficacy with a mean 2-year follow-up

Sarcopenia, defined as the loss of muscle mass, is a growing public health concern, and is an underrecognized problem in adults with Chronic Kidney Disease (CKD). The clinical diagnosis of sarcopenia can be made via measurement of appendicular lean mass index (ALMi, indexed to height by m2), traditionally obtained through whole-body dual-energy X-ray absorptiometry (DXA) scans, however these are not frequently performed. As a result, large population studies examining the relationship between CKD and sarcopenia are lacking. Using databases held at the Manitoba Centre for Health Policy, we identified adults who had at least one DXA scan linkable to serum creatinine values within 365 days, between 2007 and 2022. Serum creatinine was used to calculate estimated glomerular filtration rate, and estimated ALMi (eALMi) was calculated through central DXA scans via a previously developed algorithm. We constructed Linear, logistic, and Cox proportional hazards models to examine the relationship between CKD, sarcopenia, and adverse clinical outcomes. Our CKD cohort contained 24,660 individuals (64.4 ± 12.5 years, 84.4% female), with 3,204 individuals (13.0%) having eALMi indicating sarcopenia. 22,648 individuals (91.8%) had eGFR <= 60, and 2,012 (8.2%) had eGFR < 60. After adjustment for age, sex, estimated central mass index, and comorbid conditions, both sarcopenia and declining eALMi were also associated with adverse clinical outcomes including hospitalization and emergency room visits, home care use, long-term care use, and all-cause mortality. Additionally, the presence of eGFR < 60 was associated with higher odds of sarcopenia (OR: 1.39; 95% CI: 1.16–1.67), and lower eALMi (-0.057; 95% CI: -0.081, -0.034). In individuals with two DXA scans (n=2,985), eGFR < 60 at baseline was associated with a larger decline in eALMi compared to individuals with preserved eGFR (OR: 1.61; 95% CI: 1.05–2.45). Our results show that CKD is associated with sarcopenia and leads to more rapid d

Background Thermal ablation (TA) with radiofrequency (RFA) or cryoablation (CA) are established treatments for small renal masses (≤4 cm). Microwave ablation (MWA) has several potential benefits (decreased ablation time, less susceptibility to heat-sink, higher lesion temperatures than RFA) but is still considered experimental considering the available small-sample studies with short follow-up. Purpose To evaluate technique efficacy and complications of our initial experience of renal tumors treated using percutaneous MWA with a curative intent. Material and Methods A total of 105 renal tumors (in 93 patients) were treated between April 2014 and August 2017. MWA was performed percutaneously with computed tomography (CT) guidance under conscious sedation (n=82) or full anesthesia. Patients were followed with contrast-enhanced CT scans at six months and yearly thereafter for a minimum of five years. The mean follow-up time was 2.1 years. The percentage of tumors completely ablated in a single session (primary efficacy rate) and those successfully treated after repeat ablation (secondary efficacy rate) were recorded. Patient and tumor characteristics as well as complications were collected retrospectively. Results The median patient age was 70 years and median tumor size was 25 mm. Primary efficacy rate was 96.2% (101/105 tumors). After including two residual tumors for a second ablation session, secondary efficacy was 97.1% (102/105). Periprocedural complications were found in 5.2% (5/95) sessions: four Clavien-Dindo I and one Clavien-Dindo IIIa. One postprocedural Clavien-Dindo II complication was found. Conclusion MWA has high efficacy rates and few complications compared to other TA methods at a mean follow-up of two years., Title in the list of papers of Vanessa Acosta Ruiz's thesis: Percutaneous CT guided microwave ablation of 105 T1a-T1b renal tumors: technique efficacy with a mean 2-year follow-up

Background Thermal ablation (TA) with radiofrequency (RFA) or cryoablation (CA) are established treatments for small renal masses (≤4 cm). Microwave ablation (MWA) has several potential benefits (decreased ablation time, less susceptibility to heat-sink, higher lesion temperatures than RFA) but is still considered experimental considering the available small-sample studies with short follow-up. Purpose To evaluate technique efficacy and complications of our initial experience of renal tumors treated using percutaneous MWA with a curative intent. Material and Methods A total of 105 renal tumors (in 93 patients) were treated between April 2014 and August 2017. MWA was performed percutaneously with computed tomography (CT) guidance under conscious sedation (n=82) or full anesthesia. Patients were followed with contrast-enhanced CT scans at six months and yearly thereafter for a minimum of five years. The mean follow-up time was 2.1 years. The percentage of tumors completely ablated in a single session (primary efficacy rate) and those successfully treated after repeat ablation (secondary efficacy rate) were recorded. Patient and tumor characteristics as well as complications were collected retrospectively. Results The median patient age was 70 years and median tumor size was 25 mm. Primary efficacy rate was 96.2% (101/105 tumors). After including two residual tumors for a second ablation session, secondary efficacy was 97.1% (102/105). Periprocedural complications were found in 5.2% (5/95) sessions: four Clavien-Dindo I and one Clavien-Dindo IIIa. One postprocedural Clavien-Dindo II complication was found. Conclusion MWA has high efficacy rates and few complications compared to other TA methods at a mean follow-up of two years., Title in the list of papers of Vanessa Acosta Ruiz's thesis: Percutaneous CT guided microwave ablation of 105 T1a-T1b renal tumors: technique efficacy with a mean 2-year follow-up

Background Thermal ablation (TA) with radiofrequency (RFA) or cryoablation (CA) are established treatments for small renal masses (≤4 cm). Microwave ablation (MWA) has several potential benefits (decreased ablation time, less susceptibility to heat-sink, higher lesion temperatures than RFA) but is still considered experimental considering the available small-sample studies with short follow-up. Purpose To evaluate technique efficacy and complications of our initial experience of renal tumors treated using percutaneous MWA with a curative intent. Material and Methods A total of 105 renal tumors (in 93 patients) were treated between April 2014 and August 2017. MWA was performed percutaneously with computed tomography (CT) guidance under conscious sedation (n=82) or full anesthesia. Patients were followed with contrast-enhanced CT scans at six months and yearly thereafter for a minimum of five years. The mean follow-up time was 2.1 years. The percentage of tumors completely ablated in a single session (primary efficacy rate) and those successfully treated after repeat ablation (secondary efficacy rate) were recorded. Patient and tumor characteristics as well as complications were collected retrospectively. Results The median patient age was 70 years and median tumor size was 25 mm. Primary efficacy rate was 96.2% (101/105 tumors). After including two residual tumors for a second ablation session, secondary efficacy was 97.1% (102/105). Periprocedural complications were found in 5.2% (5/95) sessions: four Clavien-Dindo I and one Clavien-Dindo IIIa. One postprocedural Clavien-Dindo II complication was found. Conclusion MWA has high efficacy rates and few complications compared to other TA methods at a mean follow-up of two years., Title in the list of papers of Vanessa Acosta Ruiz's thesis: Percutaneous CT guided microwave ablation of 105 T1a-T1b renal tumors: technique efficacy with a mean 2-year follow-up

Background: Agricultural workers in Mexico endure physically demanding work in a hot environment, increasing the risk for kidney injury and impaired kidney function. They are also exposed to nephrotoxic metal(loid)s such as arsenic, cadmium, chromium, lead, mercury, nickel, and uranium from natural and anthropogenic sources. However, few studies have investigated how combined exposures of heat and metal(loid)s impact kidney injury and functioning. Objectives: To fill this research gap, we assessed the combined effects of exposure to metal(loid)s and heat on acute kidney injury (AKI) and kidney function over time. Methods: Biological samples, anthropometric measurements, and questionnaires were collected from a cohort of adult males working at a Sonoran grape farm and a control group of non-farmworkers in a nearby city. Acute heat strain was assessed using inner ear temperature and heart rate to calculate the physiological strain index (PSI). Urine samples were analyzed for toxic metal(loid)s, specific gravity, and neutrophil gelatinase-associated lipocalin (uNGAL), while blood samples were analyzed for creatinine levels to calculate estimated glomerular filtration rate (eGFR). Descriptive statistics were computed, linear regression models were used to assess the relationship between socioeconomic variables and metal exposure, and linear mixed effect (LME) and linear regression models were used to evaluate the impact of metal(loid)s and PSI on kidney injury and function. Additionally, we examined an interaction term between each metal(loid) and sampling period as well as each metal(loid) and acute heat (PSI) in each of the LME models. Results: Agricultural workers reported lower education rates (93.5% < high school vs. 19%) and pay (69% less than $100USD/month vs. 0%), higher rates of migration for work (100% vs. 24%), and a greater proportion of Indigenous language speakers (27% vs. 4.8%) compared to non-agricultural workers. Creatinine-adjusted uNGAL levels among a

Background Thermal ablation (TA) with radiofrequency (RFA) or cryoablation (CA) are established treatments for small renal masses (≤4 cm). Microwave ablation (MWA) has several potential benefits (decreased ablation time, less susceptibility to heat-sink, higher lesion temperatures than RFA) but is still considered experimental considering the available small-sample studies with short follow-up. Purpose To evaluate technique efficacy and complications of our initial experience of renal tumors treated using percutaneous MWA with a curative intent. Material and Methods A total of 105 renal tumors (in 93 patients) were treated between April 2014 and August 2017. MWA was performed percutaneously with computed tomography (CT) guidance under conscious sedation (n=82) or full anesthesia. Patients were followed with contrast-enhanced CT scans at six months and yearly thereafter for a minimum of five years. The mean follow-up time was 2.1 years. The percentage of tumors completely ablated in a single session (primary efficacy rate) and those successfully treated after repeat ablation (secondary efficacy rate) were recorded. Patient and tumor characteristics as well as complications were collected retrospectively. Results The median patient age was 70 years and median tumor size was 25 mm. Primary efficacy rate was 96.2% (101/105 tumors). After including two residual tumors for a second ablation session, secondary efficacy was 97.1% (102/105). Periprocedural complications were found in 5.2% (5/95) sessions: four Clavien-Dindo I and one Clavien-Dindo IIIa. One postprocedural Clavien-Dindo II complication was found. Conclusion MWA has high efficacy rates and few complications compared to other TA methods at a mean follow-up of two years., Title in the list of papers of Vanessa Acosta Ruiz's thesis: Percutaneous CT guided microwave ablation of 105 T1a-T1b renal tumors: technique efficacy with a mean 2-year follow-up

Background: Hypertension, characterized by elevated blood pressure (≥140/90 mmHg), leads to kidney and heart damage. Hypertension causes increased heart rate, heart enlargement, risk of heart failure, and damage to kidney blood vessels. One way to treat hypertension is by administering drugs such as herbal medicines. Pamelo oranges (Citrus maxima) are starting to be developed in the treatment of diseases. The ethanol extract of pomelo orange peel (EEKJP) contains flavonoid compounds which have antihypertensive activity as a natural Angiotensin Converting Enzyme (ACE) inhibitor, diuretic, increases Nitric Oxide Synthase (NOS) activity and activates Endothelium Derived Relaxing Factor (EDRF). Objectives: This study aims to examine the effect of ethanol extract of pomelo orange peel on the macroscopic features of the heart and kidneys of hypertensive rats (Rattus norvegicus). Methods: This research uses The Posttest-Only Control Group Design. Thirty rats were divided into six groups, namely naive control, negative control (NaCMC 1%), positive control (Captopril 0,45 mg/200 gramBB), EEKJP 100 mg/KgBW group, EEKJP 150 mg/KgBW group, and EEKJP 200 mg/KgBW group. Hypertension condition through induction with prednisone 1.5 mg/KgBW and NaCl 2% for 21th days. The test preparation was administered orally for 14th days. Next, all rats were dissected to remove the heart and kidney organs for macroscopic observations. Results: The results of the study showed that ethanol extract of pomelo (Citrus maxima) orange peel had a varied effect on the macroscopic appearance of the heart and kidneys of rats with hypertension. The heart organ shows structural improvements, while the kidneys have not shown any improvement. Conclusions: Extract with a dose of 100 mg/KgBW has no changes in the macroscopic appearance of the heart so it is thought to be able to repair damage to the heart organ.

Background: Hypertension, characterized by elevated blood pressure (≥140/90 mmHg), leads to kidney and heart damage. Hypertension causes increased heart rate, heart enlargement, risk of heart failure, and damage to kidney blood vessels. One way to treat hypertension is by administering drugs such as herbal medicines. Pamelo oranges (Citrus maxima) are starting to be developed in the treatment of diseases. The ethanol extract of pomelo orange peel (EEKJP) contains flavonoid compounds which have antihypertensive activity as a natural Angiotensin Converting Enzyme (ACE) inhibitor, diuretic, increases Nitric Oxide Synthase (NOS) activity and activates Endothelium Derived Relaxing Factor (EDRF). Objectives: This study aims to examine the effect of ethanol extract of pomelo orange peel on the macroscopic features of the heart and kidneys of hypertensive rats (Rattus norvegicus). Methods: This research uses The Posttest-Only Control Group Design. Thirty rats were divided into six groups, namely naive control, negative control (NaCMC 1%), positive control (Captopril 0,45 mg/200 gramBB), EEKJP 100 mg/KgBW group, EEKJP 150 mg/KgBW group, and EEKJP 200 mg/KgBW group. Hypertension condition through induction with prednisone 1.5 mg/KgBW and NaCl 2% for 21th days. The test preparation was administered orally for 14th days. Next, all rats were dissected to remove the heart and kidney organs for macroscopic observations. Results: The results of the study showed that ethanol extract of pomelo (Citrus maxima) orange peel had a varied effect on the macroscopic appearance of the heart and kidneys of rats with hypertension. The heart organ shows structural improvements, while the kidneys have not shown any improvement. Conclusions: Extract with a dose of 100 mg/KgBW has no changes in the macroscopic appearance of the heart so it is thought to be able to repair damage to the heart organ.

Background: Hypertension, characterized by elevated blood pressure (≥140/90 mmHg), leads to kidney and heart damage. Hypertension causes increased heart rate, heart enlargement, risk of heart failure, and damage to kidney blood vessels. One way to treat hypertension is by administering drugs such as herbal medicines. Pamelo oranges (Citrus maxima) are starting to be developed in the treatment of diseases. The ethanol extract of pomelo orange peel (EEKJP) contains flavonoid compounds which have antihypertensive activity as a natural Angiotensin Converting Enzyme (ACE) inhibitor, diuretic, increases Nitric Oxide Synthase (NOS) activity and activates Endothelium Derived Relaxing Factor (EDRF). Objectives: This study aims to examine the effect of ethanol extract of pomelo orange peel on the macroscopic features of the heart and kidneys of hypertensive rats (Rattus norvegicus). Methods: This research uses The Posttest-Only Control Group Design. Thirty rats were divided into six groups, namely naive control, negative control (NaCMC 1%), positive control (Captopril 0,45 mg/200 gramBB), EEKJP 100 mg/KgBW group, EEKJP 150 mg/KgBW group, and EEKJP 200 mg/KgBW group. Hypertension condition through induction with prednisone 1.5 mg/KgBW and NaCl 2% for 21th days. The test preparation was administered orally for 14th days. Next, all rats were dissected to remove the heart and kidney organs for macroscopic observations. Results: The results of the study showed that ethanol extract of pomelo (Citrus maxima) orange peel had a varied effect on the macroscopic appearance of the heart and kidneys of rats with hypertension. The heart organ shows structural improvements, while the kidneys have not shown any improvement. Conclusions: Extract with a dose of 100 mg/KgBW has no changes in the macroscopic appearance of the heart so it is thought to be able to repair damage to the heart organ.

Due to the shortage of kidneys donated for transplantation, surgeons are forced to use the organs with an elevated risk of poor function or even failure. Although the existing methods for pre-transplant quality evaluation have been validated over decades in population cohort studies across the world, new methods are needed as long as delayed graft function or failure in a kidney transplant occurs. In this study, we explored the potential of utilizing photoacoustic (PA) imaging during normothermic machine perfusion (NMP) as a means of evaluating kidney quality. We closely monitored twenty-two porcine kidneys using 3D PA imaging during a two-hour NMP session. Based on biochemical analyses of perfusate and produced urine, the kidneys were categorized into ‘non-functional’ and ‘functional’ groups. Our primary focus was to quantify oxygenation (sO2) within the kidney cortical layer of depths 2 mm, 4 mm, and 6 mm using two-wavelength PA imaging. Next, receiver operating characteristic (ROC) analysis was performed to determine an optimal cortical layer depth and time point for the quantification of sO2 to discriminate between functional and non-functional organs. Finally, for each depth, we assessed the correlation between sO2 and creatinine clearance (CrCl), oxygen consumption (VO2), and renal blood flow (RBF). We found that hypoxia of the renal cortex is associated with poor renal function. In addition, the determination of sO2 within the 2 mm depth of the renal cortex after 30 min of NMP effectively distinguishes between functional and non-functional kidneys. The non-functional kidneys can be detected with the sensitivity and specificity of 80% and 85% respectively, using the cut-off point of sO2 < 39%. Oxygenation significantly correlates with RBF and VO2 in all kidneys. In functional kidneys, sO2 correlated with CrCl, which is not the case for non-functional kidneys. We concl, Biomechanical Engineering

Background: Thermal ablation (TA) with radiofrequency (RFA) or cryoablation (CA) are established treatments for small renal masses (≤4 cm). Microwave ablation (MWA) has several potential benefits (decreased ablation time, less susceptibility to heat-sink, higher lesion temperatures than RFA) but is still considered experimental considering the available small-sample studies with short follow-up. Purpose: To evaluate technique efficacy and complications of our initial experience of renal tumors treated using percutaneous MWA with a curative intent. Material and Methods: A total of 105 renal tumors (in 93 patients) were treated between April 2014 and August 2017. MWA was performed percutaneously with computed tomography (CT) guidance under conscious sedation (n=82) or full anesthesia. Patients were followed with contrast-enhanced CT scans at six months and yearly thereafter for a minimum of five years. The mean follow-up time was 2.1 years. The percentage of tumors completely ablated in a single session (primary efficacy rate) and those successfully treated after repeat ablation (secondary efficacy rate) were recorded. Patient and tumor characteristics as well as complications were collected retrospectively. Results: The median patient age was 70 years and median tumor size was 25 mm. Primary efficacy rate was 96.2% (101/105 tumors). After including two residual tumors for a second ablation session, secondary efficacy was 97.1% (102/105). Periprocedural complications were found in 5.2% (5/95) sessions: four Clavien-Dindo I and one Clavien-Dindo IIIa. One postprocedural Clavien-Dindo II complication was found. Conclusion: MWA has high efficacy rates and few complications compared to other TA methods at a mean follow-up of two years.

In autosomal dominant polycystic kidney disease (ADPKD) with germline mutations in a PKD1 or PKD2 gene, innumerable cysts develop from tubules, and renal function deteriorates. Second-hit somatic mutations and renal tubular epithelial (RTE) cell death are crucial features of cyst initiation and disease progression. Here, we use established RTE lines and primary ADPKD cells with disease-associated PKD1 mutations to investigate genomic instability and DNA damage responses. We found that ADPKD cells suffer severe chromosome breakage, aneuploidy, heightened susceptibility to DNA damage, and delayed checkpoint activation. Immunohistochemical analyses of human kidneys corroborated observations in cultured cells. DNA damage sensors (ATM/ATR) were activated but did not localize at nuclear sites of damaged DNA and did not properly activate downstream transducers (CHK1/CHK2). ADPKD cells also had the ability to transform, as they achieved high saturation density and formed colonies in soft agar. Our studies indicate that defective DNA damage repair pathways and the somatic mutagenesis they cause contribute fundamentally to the pathogenesis of ADPKD. Acquired mutations may alternatively confer proliferative advantages to the clonally expanded cell populations or lead to apoptosis. Further understanding of the molecular details of aberrant DNA damage responses in ADPKD is ongoing and holds promise for targeted therapies.

PURPOSE OF REVIEW: Kidney dysfunction is challenging in liver transplant candidates to determine whether it is reversible or not. This review focuses on the pertinent data on how to best approach liver transplant candidates with kidney dysfunction in the current era after implementing the simultaneous liver kidney (SLK) allocation policy and safety net. RECENT FINDINGS: The implementation of the SLK policy inverted the steady rise in SLK transplants and improved the utilization of high-quality kidneys. Access to kidney transplantation following liver transplant alone (LTA) increased with favorable outcomes. Estimating GFR in liver transplant candidates remains challenging, and innovative methods are needed. SLK provided superior patient and graft survival compared to LTA only for patients with advanced CKD and dialysis at least 3 months. SLK can provide immunological protection against kidney rejection in highly sensitized candidates. Post-SLK transplant care is complex, with an increased risk of complications and hospitalization. SUMMARY: The SLK policy improved kidney access and utilization. Transplant centers are encouraged, under the safety net, to reserve SLK for liver transplant candidates with advanced CKD or dialysis at least 3 months while allowing lower thresholds for highly sensitized patients. Herein, we propose a practical approach to liver transplant candidates with kidney dysfunction.

BACKGROUND: Kidney transplant (KT) candidates with HIV face higher mortality on the waitlist compared with candidates without HIV. Because the HIV Organ Policy Equity (HOPE) Act has expanded the donor pool to allow donors with HIV (D + ), it is crucial to understand whether this has impacted transplant rates for this population. METHODS: Using a linkage between the HOPE in Action trial (NCT03500315) and Scientific Registry of Transplant Recipients, we identified 324 candidates listed for D + kidneys (HOPE) compared with 46 025 candidates not listed for D + kidneys (non-HOPE) at the same centers between April 26, 2018, and May 24, 2022. We characterized KT rate, KT type (D + , false-positive [FP; donor with false-positive HIV testing], D - [donor without HIV], living donor [LD]) and quantified the association between HOPE enrollment and KT rate using multivariable Cox regression with center-level clustering; HOPE was a time-varying exposure. RESULTS: HOPE candidates were more likely male individuals (79% versus 62%), Black (73% versus 35%), and publicly insured (71% versus 52%; P < 0.001). Within 4.5 y, 70% of HOPE candidates received a KT (41% D + , 34% D - , 20% FP, 4% LD) versus 43% of non-HOPE candidates (74% D - , 26% LD). Conversely, 22% of HOPE candidates versus 39% of non-HOPE candidates died or were removed from the waitlist. Median KT wait time was 10.3 mo for HOPE versus 60.8 mo for non-HOPE candidates ( P < 0.001). After adjustment, HOPE candidates had a 3.30-fold higher KT rate (adjusted hazard ratio = 3.30, 95% confidence interval, 2.14-5.10; P < 0.001). CONCLUSIONS: Listing for D + kidneys within HOPE trials was associated with a higher KT rate and shorter wait time, supporting the expansion of this practice for candidates with HIV.

Milk urea (MU) concentration is proposed as an indicator trait for breeding toward reduced nitrogen (N) emissions and leaching in dairy. We selected 20 German Holstein cows based on MU breeding values, with 10 cows each having low (LMUg) and high (HMUg) MU genetic predisposition. Using RNA-seq, we characterized these cows to unravel molecular pathways governing post-absorptive body N pools focusing on renal filtration and reabsorption of nitrogenous compounds, hepatic urea formation and mammary gland N excretion. While we observed minor adjustments in cellular energy metabolism in different tissues associated with different MU levels, no transcriptional differences in liver ammonia detoxification were detected, despite significant differences in MU between the groups. Differential expression of AQP3 and SLC38A2 in the kidney provides evidence for higher urea concentration in the collecting duct of LMU cows than HMU cows. The mammary gland exhibited the most significant differences, particularly in tricarboxylic acid (TCA) cycle genes, amino acid transport, tRNA binding, and casein synthesis. These findings suggest that selecting for lower MU could lead to altered urinary urea (UU) handling and changes in milk protein synthesis. However, given the genetic variability in N metabolism components, the long-term effectiveness of MU-based selection in reducing N emissions remains uncertain.

With a high incidence of acute kidney injury among hospitalized COVID-19 patients, considerable attention has been focussed on whether SARS-CoV-2 specifically targets kidney cells to directly impact renal function, or whether renal damage is primarily an indirect outcome. To date, several studies have utilized kidney organoids to understand the pathogenesis of COVID-19, revealing the ability for SARS-CoV-2 to predominantly infect cells of the proximal tubule (PT), with reduced infectivity following administration of soluble ACE2. However, the immaturity of standard human kidney organoids represents a significant hurdle, leaving the preferred SARS-CoV-2 processing pathway, existence of alternate viral receptors, and the effect of common hypertensive medications on the expression of ACE2 in the context of SARS-CoV-2 exposure incompletely understood. Utilizing a novel kidney organoid model with enhanced PT maturity, genetic- and drug-mediated inhibition of viral entry and processing factors confirmed the requirement for ACE2 for SARS-CoV-2 entry but showed that the virus can utilize dual viral spike protein processing pathways downstream of ACE2 receptor binding. These include TMPRSS- and CTSL/CTSB-mediated non-endosomal and endocytic pathways, with TMPRSS10 likely playing a more significant role in the non-endosomal pathway in renal cells than TMPRSS2. Finally, treatment with the antihypertensive ACE inhibitor, lisinopril, showed negligible impact on receptor expression or susceptibility of renal cells to infection. This study represents the first in-depth characterization of viral entry in stem cell-derived human kidney organoids with enhanced PTs, providing deeper insight into the renal implications of the ongoing COVID-19 pandemic.

Background This post-hoc study investigated whether biomarkers reflecting extracellular matrix (ECM) turnover predicted cardiovascular disease (CVD), mortality, and progression of diabetic kidney disease (DKD) in individuals with type 2 diabetes (T2D) and microalbuminuria. Methods Serum levels of specific ECM turnover biomarkers were assessed in 192 participants with T2D and microalbuminuria from an observational study conducted at Steno Diabetes Center Copenhagen from 2007 to 2008. Endpoints included CVD events, mortality, and DKD progression, defined as decline in estimated glomerular filtration rate (eGFR) of >30 %. Results Participants had a mean age of 59 years, with 75 % males. Over a median follow-up of 4.9 to 6.3 years, the study recorded 38 CVD events, 24 deaths, and 40 DKD events. Elevated levels of a degradation fragment of collagen type I (C1M) were associated with an increased risk of >30 % eGFR decline, although this association was not independent of other risk factors. No significant associations were found between other ECM turnover biomarkers and DKD progression, mortality, or CVD risk. Conclusion Elevated C1M levels were linked to DKD progression in individuals with T2D and microalbuminuria, but not independently of other risk factors. None of the ECM turnover biomarkers were associated with CVD or mortality., Background: This post-hoc study investigated whether biomarkers reflecting extracellular matrix (ECM) turnover predicted cardiovascular disease (CVD), mortality, and progression of diabetic kidney disease (DKD) in individuals with type 2 diabetes (T2D) and microalbuminuria. Methods: Serum levels of specific ECM turnover biomarkers were assessed in 192 participants with T2D and microalbuminuria from an observational study conducted at Steno Diabetes Center Copenhagen from 2007 to 2008. Endpoints included CVD events, mortality, and DKD progression, defined as decline in estimated glomerular filtration rate (eGFR) of >30 %. Results: Participants had a mean age of 59 years, with 75 % males. Over a median follow-up of 4.9 to 6.3 years, the study recorded 38 CVD events, 24 deaths, and 40 DKD events. Elevated levels of a degradation fragment of collagen type I (C1M) were associated with an increased risk of >30 % eGFR decline, although this association was not independent of other risk factors. No significant associations were found between other ECM turnover biomarkers and DKD progression, mortality, or CVD risk. Conclusion: Elevated C1M levels were linked to DKD progression in individuals with T2D and microalbuminuria, but not independently of other risk factors. None of the ECM turnover biomarkers were associated with CVD or mortality.

Background: Lupus nephritis (LN) occurs in ~50% of patients with SLE and is the most common, but not the only, cause of kidney injury in SLE. Men with SLE tend to have more aggressive disease with higher rates of renal and cardiovascular involvement and are more likely to develop kidney failure than women. Methods: This systematic review focused on full-text English literature published between 2014 and 2024 using the PRISMA 2020 guidelines. Editorials and review pieces published in the same journal as the submission without a DOI were not accepted. The literature was compiled using PubMed, ScienceDirect, and SagePub, among other online venues. Result: Five publications were found to be directly related to our ongoing systematic examination after a rigorous three-level screening approach. Subsequently, a comprehensive analysis of the complete text was conducted, and additional scrutiny was given to these articles. Conclusion: Achieving a complete clinical response to treatment is critical to preserving long-term kidney health.

Background: Lupus nephritis (LN) occurs in ~50% of patients with SLE and is the most common, but not the only, cause of kidney injury in SLE. Men with SLE tend to have more aggressive disease with higher rates of renal and cardiovascular involvement and are more likely to develop kidney failure than women. Methods: This systematic review focused on full-text English literature published between 2014 and 2024 using the PRISMA 2020 guidelines. Editorials and review pieces published in the same journal as the submission without a DOI were not accepted. The literature was compiled using PubMed, ScienceDirect, and SagePub, among other online venues. Result: Five publications were found to be directly related to our ongoing systematic examination after a rigorous three-level screening approach. Subsequently, a comprehensive analysis of the complete text was conducted, and additional scrutiny was given to these articles. Conclusion: Achieving a complete clinical response to treatment is critical to preserving long-term kidney health.

With a high incidence of acute kidney injury among hospitalized COVID-19 patients, considerable attention has been focussed on whether SARS-CoV-2 specifically targets kidney cells to directly impact renal function, or whether renal damage is primarily an indirect outcome. To date, several studies have utilized kidney organoids to understand the pathogenesis of COVID-19, revealing the ability for SARS-CoV-2 to predominantly infect cells of the proximal tubule (PT), with reduced infectivity following administration of soluble ACE2. However, the immaturity of standard human kidney organoids represents a significant hurdle, leaving the preferred SARS-CoV-2 processing pathway, existence of alternate viral receptors, and the effect of common hypertensive medications on the expression of ACE2 in the context of SARS-CoV-2 exposure incompletely understood. Utilizing a novel kidney organoid model with enhanced PT maturity, genetic- and drug-mediated inhibition of viral entry and processing factors confirmed the requirement for ACE2 for SARS-CoV-2 entry but showed that the virus can utilize dual viral spike protein processing pathways downstream of ACE2 receptor binding. These include TMPRSS- and CTSL/CTSB-mediated non-endosomal and endocytic pathways, with TMPRSS10 likely playing a more significant role in the non-endosomal pathway in renal cells than TMPRSS2. Finally, treatment with the antihypertensive ACE inhibitor, lisinopril, showed negligible impact on receptor expression or susceptibility of renal cells to infection. This study represents the first in-depth characterization of viral entry in stem cell-derived human kidney organoids with enhanced PTs, providing deeper insight into the renal implications of the ongoing COVID-19 pandemic.

The gene for adrenomedullin (AM), a multifunctional peptide hormone, is expressed in mammalian renal tissue and has been shown to stimulate renin release. The exact cell source of this peptide and its gene-related partner, proadrenomedullin N-terminal 20 peptide (PAMP), in kidney is still uncertain. In the present study we have identified PAMP-immunoreactive cells in the kidney of different mammalian species, including man, by light microscopy. In addition, these cells have been further studied in mouse kidney by both light and electron microscopic techniques. At the light microscopic level, PAMP immunolabeling is preferentially located in the subendothelial cells of the enlarged glomerular afferent arterioles, that is, in the juxtaglomerular cells. However, these cells do not show immunolabeling for AM. At the electron microscopic level, the immunostaining appears inside the renin-containing secretory granules of the juxtaglomerular cells. These results confirm the direct link between renin and the AM peptide family and provide a morphological basis for studying the potential modulatory function of AM and PAMP in the control of renin activity. In contrast, neither AM nor PAMP immunoreactivities were detected in the kidney of nonmammalian vertebrates, other than in blood vessels of particular species, providing a new phylogenetic difference in the juxtaglomerular apparatus between mammalian and nonmammalian vertebrates., Depto. de Biología Celular, Fac. de Medicina, TRUE, pub

To examine the origin and development of the renal plexus and its relationship to the renal vessels in embryos and early human fetuses. Serial sections of 34 human embryos (stages 16 to 23 of Carnegie, 4 or 5–8 weeks) and 38 fetuses (9–19 weeks) were analyzed. Throughout the embryonic period, the kidney was not innervated by the renal plexus. Those nerves appeared at the beginning of the early fetal period (9 weeks) as branches given off by the immature autonomic abdominal plexus. The renal nerves started to approach to the kidney during the early fetal period at 9–10 weeks of development. They were distributed in close proximity to the renal arteries and their branches. They were observed first with the settlement of the renal veins. The renal artery is present as a branch of the abdominal aorta at stage 19 (between 6 and 7 weeks) prior to development of the renal plexus. The renal veins were not present during the embryonic period but appeared at the start of the fetal period, along with the renal nerves that emerged from segmented sympathetic para-aortic bodies (SPBs). In conclusion, the renal plexus starts to form during the early fetal period, which coincides with the establishment of the definitive renal veins, 2 weeks after the definitive renal arteries are identified. The disposition of the renal vessels and renal nerves in adults could be explained by the disposition and progress of the structures during prenatal development, Depto. de Anatomía y Embriología, Fac. de Medicina, TRUE, pub

Artículo aceptado en el año 2013, tal y como queda reflejado en la propia publicación., We investigated the renal effects of a high-intensity exercise (HIE) program based on strength training. 20 Wistar rats were randomly assigned to 2 experimental groups performing HIE or control over 12 weeks. Urinary volume, pH, citrate and calcium, and plasma urea, total proteins, creatinine, albumin, lactate dehydrogenase, creatine kinase (CK), calcium, magnesium, corticosterone and testosterone were measured. We also studied renal morphology with the Fibrosis HR(®) software. Plasma urea and CK concentrations were higher in the HIE compared to the control group (p < 0.05), whereas plasma creatinine was lower (p < 0.01). Plasma corticosterone was higher (p < 0.05) and testosterone lower (p < 0.01) in the HIE group. Except for the higher urinary volume found in the HIE group (p < 0.05), no differences between groups were observed in the rest of urinary parameters analyzed. Renal interstitial connective tissue was ~30% higher in the HIE group (p < 0.05). Glomerular tufts and mesangial areas were also higher in the HIE group (all, p < 0.05). No differences between groups were observed in the glomerular area. Overall, HIE promoted a worse morphological renal profile that might be associated with a higher risk for incidence of kidney disease in the long-term. The stress induced by the type of exercise performed could be on the basis of this worse morphological renal status., Ministerio de Ciencia e Innovación, Ministerio de Educación, Depto. de Fisiología, Fac. de Medicina, TRUE, pub

Authors’ contributions AG and MMB designed the study. RC, AG and JC did most of the array experiments and performed the statistical analyses. AG, MMB, JFFG carried out the infection experiments and cared for the fsh. ARB performed the histopathological studies. LJ performed the statistical analyses. The manuscript was written by AG and RC, and critically reviewed by JC, MMB and JFFG who contributed to writing the manuscript. All authors read and approved the final manuscript., Lactococcus garvieae is a significant pathogen in aquaculture with a potential zoonotic risk. To begin to characterize the late immune response of trout to lactococcosis, we selected infected individuals showing clinical signs of lactococcosis. At the time lactococcosis clinical signs appeared, infection by L. garvieae induced a robust inflammatory response in the spleen of rainbow trout, which correlated with abundant granulomatous lesions. The response in kidney goes in parallel with that of spleen, and most of the gene regulations are similar in both organs. A correlation existed between the early inflammatory granulomas in spleen (containing macrophages with internalized L. garvieae) and up-regulated gene sets, which defined the presence of macrophages and neutrophils. This is the first analysis of the immune transcriptome of rainbow trout following L. garvieae infection during the initiation of adaptive immune mechanisms and shows a ranscriptome induction of antibody response by both IgM (+) and IgT (+) spleen B cells to respond to systemic infection. These results increase our understanding of lactococcosis and pave the way for future research to improve control measures of lactococcosis on fish farms., Ministerio Español de Economía y Competitividad (AGL 2012-35419 y AGL2014-51773-C3-3-R ), Comunidad de Madrid (S2013/ABI-2747 (TAVS-CAM)), Unión Europea, Depto. de Sanidad Animal, Fac. de Veterinaria, TRUE, pub

El artículo ha sido comentado muy positivamente en "Persu A, Maes F, Renkin J, Pathak A. Renal Denervation in Hypertensive Patients: Back to Anatomy? Hypertension. 2020 Oct;76(4):1084-1086. doi: 10.1161/HYPERTENSIONAHA.120.15834. Epub 2020 Sep 9. PMID: 32903105; PMCID: PMC7480938.", Despite the use of renal denervation to treat hypertension, the anatomy of the renal nervous system remains poorly understood. We performed a detailed quantitative analysis of the human renal nervous system anatomy with the goal of optimizing renal denervation procedural safety and efficacy. Sixty kidneys from 30 human cadavers were systematically microdissected to quantify anatomic variations in renal nerve patterns. Contrary to current clinical perception, not all renal innervation followed the main renal artery. A significant portion of the renal nerves (late arriving nerves) frequently reached the kidney (73% of the right kidney and 53% of the left kidney) bypassing the main renal artery. The ratio of the main renal artery length/aorta-renal hilar distance proved to be a useful variable to identify the presence/absence of these late arriving nerves (odds ratio, 0.001 (95% CI, 0.00002–0.0692; P: 0.001) with a cutoff of 0.75 (sensitivity: 0.68, specificity: 0.83, area under ROC curve at threshold: 0.76). When present, polar arteries were also highly associated with the presence of late arriving nerve. Finally, the perivascular space around the proximal main renal artery was frequently occupied by fused ganglia from the solar plexus (right kidney: 53%, left kidney: 83%) and/or by the lumbar sympathetic chain (right kidney: 63%, left kidney: 60%). Both carried innervation to the kidneys but importantly also to other abdominal and pelvic organs, which can be accidentally denervated if the proximal renal artery is targeted for ablation. These novel anatomic insights may help guide future procedural treatment recommendations to increase the likelihood of safely reaching and destroying targeted nerves during renal denervation procedures., Medtronic, Depto. de Anatomía y Embriología, Fac. de Medicina, TRUE, pub

Gut microbiome research has increased dramatically in the last decade, including in renal health and disease. The field is moving from experiments showing mere association to causation using both forward and reverse microbiome approaches, leveraging tools such as germ-free animals, treatment with antibiotics, and fecal microbiota transplantations. However, we are still seeing a gap between discovery and translation that needs to be addressed, so that patients can benefit from microbiome-based therapies. In this guideline paper, we discuss the key considerations that affect the gut microbiome of animals and clinical studies assessing renal function, many of which are often overlooked, resulting in false-positive results. For animal studies, these include suppliers, acclimatization, baseline microbiota and its normalization, littermates and cohort/cage effects, diet, sex differences, age, circadian differences, antibiotics and sweeteners, and models used. Clinical studies have some unique considerations, which include sampling, gut transit time, dietary records, medication, and renal phenotypes. We provide best-practice guidance on sampling, storage, DNA extraction, and methods for microbial DNA sequencing (both 16S rRNA and shotgun metagenome). Finally, we discuss follow-up analyses, including tools available, metrics, and their interpretation, and the key challenges ahead in the microbiome field. By standardizing study designs, methods, and reporting, we will accelerate the findings from discovery to translation and result in new microbiome-based therapies that may improve renal health.

Background: Intrarenal hypoxia has been suggested a unifying pathway to chronic kidney disease (CKD) and increased mitochondria leak respiration, which increases mitochondrial oxygen usage and is one important mechanism contributing to the development of the hypoxia. Previous studies indicate that angiotensin II (Ang II) effects on mitochondria function could be dose dependent. We investigated how moderate and high levels of Ang II affect kidney mitochondria function and pathways of leak respiration. Methods: C57 black 6 mice were treated with either vehicle or Ang II in low dose (400 ng/kg/min) or high dose (1,000 ng/kg/min) for 4 weeks. The function of kidney cortex mitochondria was measured by high-resolution respirometry. Ang II effects on gene expression in kidney tissue were measured by quantitative real-time PCR. Thiobarbituric acids reactive substances were determined as a marker of oxidative stress, and urinary protein excretion was measured as a maker of kidney injury. Results: Low-dose Ang II induced overall mitochondria respiration, without compromising capacity of ATP production. Mitochondrial leak respiration was increased, and levels of oxidative stress were unchanged. However, high-dose Ang II decreased overall mitochondria respiration and reduced mitochondrial capacity for ATP production. Mitochondrial leak respiration was decreased, and oxidative stress increased in kidney tissue. Furthermore, gene expression of mediators that stimulate vasoconstriction and ROS production was increased, while components of counteracting pathways were decreased. Conclusions: In conclusion, Ang II dose-dependently affects mitochondrial function and leak respiration. Thus, Ang II has the potential to directly affect cellular metabolism during conditions of altered Ang II signaling.

Background: Intrarenal hypoxia has been suggested a unifying pathway to chronic kidney disease (CKD) and increased mitochondria leak respiration, which increases mitochondrial oxygen usage and is one important mechanism contributing to the development of the hypoxia. Previous studies indicate that angiotensin II (Ang II) effects on mitochondria function could be dose dependent. We investigated how moderate and high levels of Ang II affect kidney mitochondria function and pathways of leak respiration. Methods: C57 black 6 mice were treated with either vehicle or Ang II in low dose (400 ng/kg/min) or high dose (1,000 ng/kg/min) for 4 weeks. The function of kidney cortex mitochondria was measured by high-resolution respirometry. Ang II effects on gene expression in kidney tissue were measured by quantitative real-time PCR. Thiobarbituric acids reactive substances were determined as a marker of oxidative stress, and urinary protein excretion was measured as a maker of kidney injury. Results: Low-dose Ang II induced overall mitochondria respiration, without compromising capacity of ATP production. Mitochondrial leak respiration was increased, and levels of oxidative stress were unchanged. However, high-dose Ang II decreased overall mitochondria respiration and reduced mitochondrial capacity for ATP production. Mitochondrial leak respiration was decreased, and oxidative stress increased in kidney tissue. Furthermore, gene expression of mediators that stimulate vasoconstriction and ROS production was increased, while components of counteracting pathways were decreased. Conclusions: In conclusion, Ang II dose-dependently affects mitochondrial function and leak respiration. Thus, Ang II has the potential to directly affect cellular metabolism during conditions of altered Ang II signaling.

Background: Intrarenal hypoxia has been suggested a unifying pathway to chronic kidney disease (CKD) and increased mitochondria leak respiration, which increases mitochondrial oxygen usage and is one important mechanism contributing to the development of the hypoxia. Previous studies indicate that angiotensin II (Ang II) effects on mitochondria function could be dose dependent. We investigated how moderate and high levels of Ang II affect kidney mitochondria function and pathways of leak respiration. Methods: C57 black 6 mice were treated with either vehicle or Ang II in low dose (400 ng/kg/min) or high dose (1,000 ng/kg/min) for 4 weeks. The function of kidney cortex mitochondria was measured by high-resolution respirometry. Ang II effects on gene expression in kidney tissue were measured by quantitative real-time PCR. Thiobarbituric acids reactive substances were determined as a marker of oxidative stress, and urinary protein excretion was measured as a maker of kidney injury. Results: Low-dose Ang II induced overall mitochondria respiration, without compromising capacity of ATP production. Mitochondrial leak respiration was increased, and levels of oxidative stress were unchanged. However, high-dose Ang II decreased overall mitochondria respiration and reduced mitochondrial capacity for ATP production. Mitochondrial leak respiration was decreased, and oxidative stress increased in kidney tissue. Furthermore, gene expression of mediators that stimulate vasoconstriction and ROS production was increased, while components of counteracting pathways were decreased. Conclusions: In conclusion, Ang II dose-dependently affects mitochondrial function and leak respiration. Thus, Ang II has the potential to directly affect cellular metabolism during conditions of altered Ang II signaling.

In this study we use comparative genomics to uncover a gene with uncharacterized function (1700011H14Rik/C14orf105/CCDC198), which we hereby name FAME (Factor Associated with Metabolism and Energy). We observe that FAME shows an unusually high evolutionary divergence in birds and mammals. Through the comparison of single nucleotide polymorphisms, we identify gene flow of FAME from Neandertals into modern humans. We conduct knockout experiments on animals and observe altered body weight and decreased energy expenditure in Fame knockout animals, corresponding to genome-wide association studies linking FAME with higher body mass index in humans. Gene expression and subcellular localization analyses reveal that FAME is a membrane-bound protein enriched in the kidneys. Although the gene knockout results in structurally normal kidneys, we detect higher albumin in urine and lowered ferritin in the blood. Through experimental validation, we confirm interactions between FAME and ferritin and show co-localization in vesicular and plasma membranes.

Background: Intrarenal hypoxia has been suggested a unifying pathway to chronic kidney disease (CKD) and increased mitochondria leak respiration, which increases mitochondrial oxygen usage and is one important mechanism contributing to the development of the hypoxia. Previous studies indicate that angiotensin II (Ang II) effects on mitochondria function could be dose dependent. We investigated how moderate and high levels of Ang II affect kidney mitochondria function and pathways of leak respiration. Methods: C57 black 6 mice were treated with either vehicle or Ang II in low dose (400 ng/kg/min) or high dose (1,000 ng/kg/min) for 4 weeks. The function of kidney cortex mitochondria was measured by high-resolution respirometry. Ang II effects on gene expression in kidney tissue were measured by quantitative real-time PCR. Thiobarbituric acids reactive substances were determined as a marker of oxidative stress, and urinary protein excretion was measured as a maker of kidney injury. Results: Low-dose Ang II induced overall mitochondria respiration, without compromising capacity of ATP production. Mitochondrial leak respiration was increased, and levels of oxidative stress were unchanged. However, high-dose Ang II decreased overall mitochondria respiration and reduced mitochondrial capacity for ATP production. Mitochondrial leak respiration was decreased, and oxidative stress increased in kidney tissue. Furthermore, gene expression of mediators that stimulate vasoconstriction and ROS production was increased, while components of counteracting pathways were decreased. Conclusions: In conclusion, Ang II dose-dependently affects mitochondrial function and leak respiration. Thus, Ang II has the potential to directly affect cellular metabolism during conditions of altered Ang II signaling.

BACKGROUND: The appearance of renal swelling during an acute obstruction of the urinary tract could be caused by hydronephrosis or an increase of the parenchymal volume. To the best of our knowledge no studies have been performed regarding renal parenchymal volume change during an acute urinary tract obstruction. PURPOSE: To investigate the change in renal parenchymal volume during an acute urinary tract obstruction and to correlate any such volume change to the degree of secondary signs of obstruction. MATERIAL AND METHODS: In total, 20 patients with obstructive ureterolithiasis were retrospectively and randomly included. Two observers measured the parenchymal volume of the obstructed and the contralateral kidney in CT examinations before, during, and after obstruction. Hydronephrosis, hydroureter, perirenal stranding, and thickening of the renal fascia were graded and correlated to volume change. RESULTS: A decreased volume was noted after obstruction in the obstructed kidneys (-24%) (P < 0.0001) and in the contralateral kidneys (-5%) (P = 0.0110) with a positive correlation of change in volume (P = 0.011). The volume of the obstructed kidneys was larger than the contralateral kidneys during obstruction (P < 0.0001) but not after obstruction (P = 0.559). No significant difference in volume was found before compared to after obstruction. Secondary signs of obstruction did not correlate to volume change. CONCLUSION: The parenchymal volume increases in the obstructed kidneys as well as in the contralateral kidneys during obstruction. The increase in volume was larger in the obstructed kidneys compared to the contralateral kidneys. After obstruction the kidneys regained their original volume. Secondary signs did not correlate to volume change., De två första författarna delar förstaförfattarskapet

Introduction: The recurrence of renal lithiasis has been increasing, making it necessary to implement preventive strategies involving the recognition of the main risk factors.Objective: To determine the factors associated with renal lithiasis and its recurrence in patients in the city of Cartagena.Material and Methods: A cross-sectional descriptive study was conducted in patients between 18 and 80 years of age with renal lithiasis and recurrence during 2018 and 2019 in Cartagena. The sample was composed of 163 patients who met the eligibility criteria. The source of information for the study is a mixed source, which was obtained by a semi-structured instrument and the review of the clinical history of patients who attended the outpatient and surgery services. Univariate and bivariate analyses were performed with risk calculations for the recurrence of this pathology.Results: In the study population, 44.6% presented lithiasis in the first episode; 38.9% showed recurrence of this event in the second episode, and 16.6% presented recurrence in the third episode. The variables associated with recurrence of renal lithiasis were overweight, hypertension, and consumption of coffee and dairy products such as milk. Consumption of pain medication and citric juices were present in this group of patients.Conclusions: Overweight and hypertension are risk factors for both a first episode and recurrence of renal lithiasis, this recurrence is increased by dietary habits such as consumption of citrus fruits, dairy products and drug abuse., Introducción: La recurrencia de la litiasis renal ha venido en aumento haciendo necesario implementar estrategias preventivas que impliquen el reconocimiento de los principales factores de riesgo.Objetivo: Determinar los factores asociados con litiasis renal y su recurrencia en pacientes de la ciudad de Cartagena.Material y Métodos: Se realizó un estudio descriptivo transversal en pacientes entre 18 y 80 años con litiasis renal y recurrencia durante 2018 y 2019 en Cartagena. La muestra son 163 pacientes que cumplen con los criterios de elegibilidad. La fuente de información para el estudio es una fuente mixta que se obtuvo por un instrumento semiestructurado y la revisión de la historia clínica de pacientes en los servicios de consulta externa y cirugía. Se realizaron análisis univariado y bivariados con los cálculos de riesgo para el caso de la recurrencia de esta patología.Resultados: En la población de estudio 44,6 % presentó litiasis por primer episodio, 38,9 % evidencia recurrencia de este evento en segundo episodio y 16,6 % recurrencia en tercer episodio. Las variables asociadas a recurrencias de litiasis renal son sobrepeso, hipertensión, consumo de café y lácteos como la leche. El consumo de medicamentos para el dolor y jugos cítricos estuvieron presentes en este grupo de pacientes.Conclusiones: El sobrepeso y la hipertensión arterial constituyen factores de riesgo tanto para un primer episodio, como para la recurrencia de la litiasis renal; esta recurrencia se ve aumentada por hábitos alimenticios como el consumo de cítricos, lácteos y el abuso de fármacos.

Introduction: Tacrolimus, an immunosuppressive drug prescribed to a majority of organ transplant recipients is nephrotoxic, through still unclear mechanisms. This study on a lineage of proximal tubular cells using a multi-omics approach aims to detect off-target pathways modulated by tacrolimus that can explain its nephrotoxicity. Methods: LLC-PK1 cells were exposed to 5 µM of tacrolimus for 24 h in order to saturate its therapeutic target FKBP12 and other high-affine FKBPs and favour its binding to less affine targets. Intracellular proteins and metabolites, and extracellular metabolites were extracted and analysed by LC-MS/MS. The transcriptional expression of the dysregulated proteins PCK-1, as well as of the other gluconeogenesis-limiting enzymes FBP1 and FBP2, was measured using RT-qPCR. Cell viability with this concentration of tacrolimus was further checked until 72 h. Results: In our cell model of acute exposure to a high concentration of tacrolimus, different metabolic pathways were impacted including those of arginine (e.g., citrulline, ornithine) (p < 0.0001), amino acids (e.g., valine, isoleucine, aspartic acid) (p < 0.0001) and pyrimidine (p < 0.01). In addition, it induced oxidative stress (p < 0.01) as shown by a decrease in total cell glutathione quantity. It impacted cell energy through an increase in Krebs cycle intermediates (e.g., citrate, aconitate, fumarate) (p < 0.01) and down-regulation of PCK-1 (p < 0.05) and FPB1 (p < 0.01), which are key enzymes in gluconeogenesis and acid-base balance control. Discussion: The variations found using a multi-omics pharmacological approach clearly point towards a dysregulation of energy production and decreased gluconeogenesis, a hallmark of chronic kidney disease which may also be an important toxicity pathway of tacrolimus.

This thesis focused on the fabrication of kidney proximal tubule models. A coaxial printing system allowed the robust and straightforward fabrication of coiled perfusable microfibers, replicating the kidney proximal convoluted tubules. The formed alginate-gelatin microfibers offer a complex tubular shape in which the cells exhibit mature markers, such as functional transporters and polarized monolayers. Moreover, this model has proven to support both healthy and cystinotic proximal tubule cell lines and allows for mechanistically studying tubulopathies. Though distinctive 3D-printing strategies offer opportunities to mimic the structure of the convoluted proximal tubule, printing resolution remains restricted for soft hydrogel materials. Therefore, a unique method was studied, whereby post-printing treatment induced resolution enhancement of methacrylated hyaluronic acid / gelatin methacryloyl (HAMA/GelMA) based hydrogels. This shrinking technique opens a wide application to create higher resolutions for 3D printing. However, we also found that the polycationic shrinking reagents used were relatively toxic for our cells of interest. Therefore, more research is needed to prevent the direct exposure of cells to the shrinking reagents. Using melt electrowriting, scaffolds were fabricated that are self-supportive, yet small-sized and highly porous. These scaffolds enable direct access to the basolateral and luminal cell sides to facilitate solute exchange with vasculature in immediate proximity, which is critical for functional proximal tubule constructs. The polymer applied, polycaprolactone, is used to prepare biomaterials that generally show good biocompatibility and is compatible with implantation in the future. Kidney proximal tubule cells and glomerular endothelial cells form polarized monolayers in our tubules, form their own extracellular matrix, and show functionality for important kidney transporters. In our preliminary results we showed initial work with indu

Kidney organoids generated from induced pluripotent stem cells (iPSC) have proven valuable for studies of kidney development, disease, and therapeutic screening. However, specific applications have been hampered by limited expansion capacity, immaturity, off-target cells, and inability to access the apical side. Here, we apply recently developed tubuloid protocols to purify and propagate kidney epithelium from d7+18 (post nephrogenesis) iPSC-derived organoids. The resulting ‘iPSC organoid-derived (iPSCod)’ tubuloids can be exponentially expanded for at least 2.5 mo, while retaining expression of important tubular transporters and segment-specific markers. This approach allows for selective propagation of the mature tubular epithelium, as immature cells, stroma, and undesirable off-target cells rapidly disappeared. iPSCod tubuloids provide easy apical access, which enabled functional evaluation and demonstration of essential secretion and electrolyte reabsorption processes. In conclusion, iPSCod tubuloids provide a different, complementary human kidney model that unlocks opportunities for functional characterization, disease modeling, and regenerative nephrology.

Introduction: Developmental programming predisposes theindividual to suffer from diseases during adulthood. Low birth weight(LBW) is one of the markers of the adverse intrauterine environment.Studies indicate that adverse intrauterine and immediate postnatalinfluences can generate structural and functional alterations in someorgans, which will manifest themselves in later stages of life. Amongthese diseases is high blood pressure, in which the role of the kidney isdemonstrated.Objective: To systematize studies that assess the changes that occurin kidney morphology and function in individuals with low birth weight.Material and Methods: A systematic review was carried out fromMay to September 2022. The Virtual Regional Health Library and thePubMed and SciELO Cuba databases were consulted.Results: A total of 114 articles were recovered, of which 16 wereselected taking into account the inclusion and exclusion criteria.Morphometric variables of the kidney were evaluated in 13 articles, andrenal function was evaluated in 7 of them. The articles reviewed deal withresearch carried out under very varied experimental conditions. In most ofthem, it has been demonstrated that LBW causes renal morphofunctionalchanges.Conclusions: The number of nephrons was found to be reduced.The intensity of glomerular filtration was not found to be different forthe entire renal mass, but it was increased for the isolated nephron. Earlyextrauterine nutrition is important. It is evident that the cause and natureof the disturbance of the maternal-fetal environment must be taken intoaccount., Introducción: La programación del desarrollo predispone al individuo a padecer enfermedades durante la adultez El bajo peso al nacer (BPN) es uno de los marcadores del ambiente adverso intrauterino. Estudios señalan que influencias intrauterinas y postnatales inmediatas adversas, pueden generar alteraciones estructurales y funcionales en algunos órganos; las cuales se manifestarán en etapas tardías de la vida. Dentro de estas enfermedades se encuentra la hipertensión arterial, en la cual el papel del riñón está demostrado.Objetivo: sistematizar los estudios que valoran los cambios que se producen en la morfología y la función renal en individuos con bajo peso al nacer.Material y métodos: Se realizó una revisión sistemática de mayo a septiembre de 2022. Se consultaron la Biblioteca virtual en salud regional y las bases de datos PubMed y SciELO Cuba.Resultados: Se recuperaron 114 artículos de los cuales 16 fueron seleccionados teniendo en cuenta los criterios de inclusión y exclusión. En 13 se evaluaban variables morfométricas del riñón y en 7 función renal. Los artículos revisados tratan de investigaciones realizadas en condiciones experimentales muy variadas. En la mayor parte de ellos, queda demostrado que el BPN provoca modificaciones en la morfofunción renal.Conclusiones: Se encontró reducido el número de nefronas. La intensidad de filtrado glomerular no se encontró diferente para la totalidad de la masa renal, pero sí se encuentra aumentada para la nefrona aislada. Es importante la nutrición extrauterina temprana. Se evidencia que debe ser tenido en cuenta la causa la naturaleza de la perturbación del ambiente maternofetal.