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BACKGROUND: Motivation for the study. Apical periodontitis (AP) can trigger immune responses that affect other organs. Main findings. This animal study examined the effects of AP on renal tissue, finding significant changes in parameters such as renal corpuscle area and Bowman's space, which may have implications for chronic kidney disease. Implications. Future research will provide insight into how dental conditions may affect renal health. If confirmed, regular dental checkups would not only be critical to improve the overall health of patients with kidney disease, but could also serve as a preventive measure. OBJECTIVES.: To evaluate the effect of apical periodontitis (AP) induced in Wistar rats on histologically examined renal tissue. MATERIALS AND METHODS.: Fourteen 12-week-old male Wistar rats weighing an average of 250 grams were used. AP was induced with pulp exposure of the upper and lower first molars using a #1011 HL spherical bur in high rotation. The lesions were left exposed to the oral environment for a period of 7 weeks. Blood pressure was measured by the tail-cuff plethysmography method from the fourth week. The kidney was dissected for histological analysis (H&E). Mann-Whitney and Student's t-test were used for non-parametric and parametric data, respectively, with a significance level of 5%. RESULTS.: A statistically significant increase in both Bowman's space area and renal corpuscle area was found in the AP group (p<0.05). The AP group had a higher percentage of renal tissue with inflammatory infiltrate, but without significant difference. Blood pressure did change during the experimental period and no difference was identified between the groups. CONCLUSIONS.: Induction of AP in Wistar rats resulted in significant changes of certain renal histological parameters, suggesting a possible interaction between AP and renal tissue that requires further research.

OBJETIVOS.: Evaluar el efecto de la periodontitis apical (PA) inducida en ratas Wistar sobre el tejido renal examinado histológicamente. MATERIALES Y MÉTODOS.: Fueron utilizadas 14 ratas Wistar macho, de 12 semanas y 250 gramos promedio. La PA fue inducida con la exposición pulpar de los primeros molares superiores e inferiores utilizando una fresa esférica #1011 HL en alta rotación. Las lesiones se dejaron expuestas al medio bucal por un periodo de 7 semanas. La presión arterial fue medida mediante el método de pletismografía del manguito de la cola a partir de la cuarta semana. Fue realizada la disección del riñón para análisis histológico (H&E). Fue utilizada la prueba de Mann-Whitney y t de Student para datos no paramétricos y paramétricos, respectivamente, con un nivel de significancia del 5%. RESULTADOS.: Se observó un aumento estadísticamente significativo tanto en el área del espacio de Bowman como en el área del corpúsculo renal en el grupo PA (p<0,05). El grupo con PA presentó mayor porcentaje de tejido renal con infiltrado inflamatorio, pero sin diferencia significativa. La presión arterial no sufrió modificaciones durante el periodo experimental y no fue identificada diferencia entre los grupos. CONCLUSIONES.: La inducción de PA en ratas Wistar resultó en modificaciones significativas de ciertos parámetros histológicos renales, sugiriendo una posible interacción entre la PA y el tejido renal que requiere de investigaciones adicionales.

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Sirtuins (SIRTs) are key regulators of cellular metabolism, involved in a wide range of physiological and pathological processes. However, there is scarce knowledge about the effect of sugar consumption and physical activity on SIRTs in kidney disorders. Here, we evaluated the impact of prolonged consumption of an isocaloric high-sugar diet (HSD) and physical training on the modulation of renal Sirts and the link between these alterations and possible obesity-associated kidney damage. Newly weaned male Wistar rats were fed a standard chow diet (STD) or HSD ad libitum and then subjected or not to regular workload swimming training for 18 weeks. Morphometric and biochemical parameters were analyzed, and the kidneys were removed for lipid quantification, histological analysis, and for Sirts1-7 expression. HSD led to the development of obesity, increased serum triglyceride levels, and glucose intolerance, regardless of higher caloric consumption. However, training was able to partially inhibit the HSD-induced obesogenic effect. No changes were identified in kidney mass, lipid content, histology, and creatinine clearance among the groups; these results were associated with a decrease in the renal expression of Sirt2-3 and Sirt7; however, training was able to reverse this modulation. The interaction between HSD and training led to an increase in Sirt4-7. However, Sirt1 remained constant among experimental groups. In conclusion, our results indicated that the transcriptional modulation of Sirts precedes HSD-induced damage and loss of kidney function, as well as a possible protective adaptive response of physical exercise on long-term Sirts expression.

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BACKGROUND: Kidney biopsy registries are valuable tools for guiding clinical practice and developing health policies. In 2021, the Brazilian Society of Nephrology (SBN) created the Brazilian Kidney Biopsy Registry (BKBR). This is the first BKBR report, presenting patient data from 2021. METHODS: BKBR is a web-based platform hosted on the BSN website, which contains patient demographics, clinical data, frequency, and distribution of histologic diagnosis of Brazilian adult native kidney biopsies. RESULTS: Of the 1012 cases registered in 2021, 954 cases were evaluated after excluding pediatric and kidney transplant cases. Twenty-one centers enrolled patients, with representation from all Brazilian regions. There was a slight predominance of females (52.6%), a mean age of 44.7 ± 16 years, and 13.6% of patients were >65 years old. The main indication for kidney biopsy was renal dysfunction (56%) and nephrotic syndrome (41.4%), respectively. At the time of the biopsy, 47.9% of the patients were hypertensive and 15.2% were diabetic. Although 66.2% of patients had eGFR ≤60ml/min/1.73m2 upon biopsy, the majority (60.2%) had mild interstitial fibrosis and tubular atrophy. The most frequent diagnosis in the BKBR was glomerular disease (74.8%). Lupus nephritis was the most frequent diagnosis of glomerular disease (22.6%), followed by IgA nephropathy (13%) and focal segmental glomerulosclerosis (12.2%). CONCLUSION: This is the first report of a Nationwide registry of kidney biopsies in Brazil. This data provides pivotal information about the kidney disease profile in this country with continental dimensions.

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BACKGROUND: COVID-19 became a pandemic disease in 2020, with multisystem involvement and high renal morbidity during the acute phase. Some affected patients began to present new or persistent symptoms in a condition known as Long COVID. The study aimed to evaluate renal function using clinical and laboratory findings, and to establish the frequency and staging of renal function decline in Long COVID patients, as well as the associated factors. METHODS: This is a cross-sectional observational study that selected participants from a Long COVID clinical care program between 2020 and 2022. RESULTS: A total of 246 patients were selected for this study, and renal function decline was found in 83 (33.7%). Patients over 60 years (29.6%) and those who developed glycaemic alterations (41.8%) exhibited a higher prevalence of renal outcomes in long COVID. Some laboratory test as LDH levels and glycated hemoglobin seems to have a statistic relation with a decrease in renal function (p < 0.05). CONCLUSION: A decline in renal function was common in patients with Long COVID in this study, and older age and glycaemic alterations were relevant to this condition. Some laboratory markers can be used to predict this outcome.

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This study analyzes the morphology of melanomacrophage centers (MMCs) in the kidney, liver, and spleen of Gymnotus carapo across two different environmental settings with varying degrees of anthropogenic impact, aiming to link habitat conditions to fish health and validate MMCs as bioindicators for environmental monitoring. A total of 28 specimens, captured and humanely sacrificed under anesthesia, were processed using conventional histological techniques. Morphometric measurements were recorded, and tissue samples were examined on an Olympus BX 41 microscope, selecting 10 random 10x fields per organ to count MMCs. Macroscopic and histological examination of the liver, kidney, and spleen highlighted MMCs distribution patterns and notable differences across sex and age groups. Adult and juvenile males showed major MMCs counts in the kidney and spleen compared to females, while liver samples from both sexes contained only pigmented cells without significant MMCs formation. Differences in MMCs quantity and structure were also observed between environments: natural habitats displayed lower MMCs counts in both sexes compared to samples from locations with higher anthropogenic impact, where MMCs frequency and pigmentation intensity were notably elevated. These findings suggest that MMCs variations in G. carapo may reflect environmental conditions and stressors, supporting the potential application of MMCs as health indicators for aquatic organisms and ecosystem monitoring. This work provides comprehensive morphometric and histological data on MMCs distribution in G. carapo, emphasizing its potential as a bioindicator species, particularly valuable in regions with varying pollution levels.

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PURPOSE OF REVIEW: This review highlights the latest findings regarding hypocitraturia in autosomal dominant polycystic kidney disease (ADPKD), from both experimental and clinical studies, exploring the underlying pathophysiology and potential therapeutic approach. RECENT FINDINGS: Experimental studies have shown that the lodging of microcrystals in the tubules can trigger cyst formation and growth in polycystic kidney disease (PKD). ADPKD patients are prone to developing hypocitraturia in early stages, which could predispose to calcium microcrystal formation. Low urinary citrate excretion has been associated with a more rapid decline in eGFR and poorer renal survival in ADPKD patients. Animal studies employing citrate supplementation have shown promising effects on preserving the decline in estimated glomerular filtration rate (eGFR) and cyst growth. SUMMARY: Current knowledge suggests that urinary citrate could be incorporated into existing prognostic markers for disease progression and potential adjuvant therapy in ADPKD, but further clinical studies to support such hypothesis must be undertaken.

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Partial stenosis of the renal artery causes renovascular hypertension (RVH) and is accompanied by chronic renal ischemia, resulting in irreversible kidney damage. Revascularization constitutes the most efficient therapy for normalizing blood pressure (BP) and has significant benefits for renal function; however, the tissue damage caused by chronic hypoxia is not fully reversed. Mesenchymal stem cells (MSCs) have produced discrete results in minimizing RVH and renal tissue and functional improvements since the obstruction persists. This study aimed to evaluate the effects of administration of MSCs in combination with renal artery revascularization in rats subjected to RVH. The following groups were evaluated: control (SHAM), hypertensive (2K-1C), hypertensive treated with MSCs (MSC), hypertensive subjected to revascularization (REV), and hypertensive subjected to revascularization and treatment with MSCs (REV + MSC). The animals were followed up for 10 weeks. The animals in the MSC group received cell infusions at the 3rd, 5th, 7th and 9th weeks. In the REV and REV + MSC groups, the clip was removed by the 6th week (revascularization), and in the REV + MSC group, MSCs infusion was performed at the 6th and 8th weeks. Tail systolic blood pressure (SBP) was measured weekly, and histological parameters and renal function were evaluated at the end of the protocol. The clipped animals developed RVH, deterioration of total renal function (50% decrease in creatinine clearance), and significant proteinuria (15x increase). Treatment with MSCs had no detectable beneficial effects on kidney function or SBP. REV resulted in normalization of BP and a significant but partial reduction in proteinuria (80% vs. 2K-1C), but areas with renal fibrosis persisted. The combination of the two treatments was effective at normalizing all renal parameters as well as reversing proteinuria, reducing the number of ischemic glomeruli and atrophic tubules, indicating an improvement of the renal parenchyma. The results suggest that therapy with MSCs associated with revascularization can potentially help in the full recovery of renal function in the long term in patients with RVH.

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Serum creatinine levels are the most used clinical marker to estimate renal function as the glomerular function rate because it is simple, fast, and inexpensive. However, creatinine has limitations, as its levels can be influenced by factors such as advanced age, physical activity, protein-rich diets, male gender, medications, and ethnicity. Serum cystatin C and its combination with serum creatinine may serve as an alternative since these factors do not affect it. Most creatinine synthesis occurs in the muscles, making it a valuable marker for assessing lean body mass within body composition. This measurement is crucial for evaluating and monitoring nutritional status in patients with chronic kidney disease. This review aimed to discuss the literature on creatinine metabolism, its advantages and disadvantages in assessing renal function, and its utility in measuring lean body mass. The variability in the creatinine generation rate among individuals should be considered when assessing the glomerular function rate.

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BACKGROUND: Obesity is a significant risk factor for chronic kidney disease (CKD), with metabolic bariatric surgery offering potential renal benefits. However, there is limited comparative data on the impact of Roux-en-Y gastric bypass (RYGB) versus laparoscopic sleeve gastrectomy (LSG) on renal function in individuals with obesity without end-stage renal disease (ESRD). The objective of this study was to compare renal function outcomes following RYGB and LSG in patients with obesity, focusing on estimated glomerular filtration rate (eGFR), serum creatinine, albumin-creatinine ratio (ACR), and serum cystatin C. METHODS: A systematic review and meta-analysis were conducted following Cochrane and PRISMA guidelines. Data from 17 observational studies (n = 3339) were analyzed. Primary outcomes included changes in eGFR, ACR, serum creatinine, and cystatin C. Secondary outcomes included excess weight loss (%EWL) and total weight loss (%TWL). Statistical analysis involved fixed and random-effects models based on heterogeneity levels. RESULTS: RYGB demonstrated significant improvements in eGFR (SMD = - 0.71; 95% CI - 0.89 to - 0.52, p < 0.00001) and serum cystatin C (MD = - 0.10; 95% CI - 0.17 to - 0.03, p = 0.004) compared to LSG. No significant differences were found for serum creatinine (MD = - 1.06; 95% CI - 4.42 to 2.30, p = 0.54) or ACR (MD = 1.95; 95% CI - 0.39 to 4.29, p = 0.10). RYGB also showed greater long-term weight loss, particularly at 5 years (%EWL: MD = 22.00; 95% CI 6.56 to 37.44, p = 0.005). CONCLUSIONS: RYGB offers similar renal improvements with superior weight loss compared to LSG in individuals with obesity without ESRD. These findings emphasize the need for personalized treatment approaches and further research to validate these outcomes.

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BACKGROUND AND OBJECTIVE: The aim of this retrospective observational case-control study was to examine the significance of different renal Doppler marker variations within the initial 24-hour period as potential predictors of Acute Kidney Injury (AKI) in patients with sepsis. METHODS: A total of 198 sepsis patients were enrolled and categorized into two groups: the AKI group (n = 136) and the non-AKI group (n = 62). Three renal Doppler indices, Renal Resistive Index (RRI), Power Doppler Ultrasound (PDU) score and Renal Venous Stasis Index (RVSI), were measured within 6h (T0) and at 24h (T1) after ICU admission. RESULTS: The AKI group had more hypertension patients than the non-AKI group (p = 0.047). The cases of the AKI group showed higher levels of CRP (p = 0.001), PCT (p < 0.001), lactate (p < 0.001), AST (p = 0.003), ALT (p = 0.049), total bilirubin (p = 0.034), BNP (p = 0.019) and cTnI (p = 0.012). The RRI at T1 was significantly higher in the AKI group (p = 0.037). AKI group exhibited a lower incidence of reduced RRI at T1 compared with non-AKI group (p < 0.001). After controlling for age, sex, and BMI through partial correlation analysis, the results indicated significant associations between SA-AKI and CVP (r = -0.473), SOFA score (r = 0.425), lactate (r = 0.378), and RRI reduction (r = -0.344) in sepsis patients. The multivariate logistic regression analysis showed that variables including CVP, SOFA score, CRP, lactate, VIS, and RRI not reduced following 24h of ICU treatment were predictive indicators for early detection of SA-AKI in sepsis patients. CONCLUSION: CVP, SOFA score, CRP, lactate, VIS, and RRI not reduction following 24h of ICU treatment can be utilized as predictive indicators for early detection of SA-AKI in sepsis patients.

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OBJECTIVE: The present study evaluated urinary oxidative stress (OxS) biomarkers to explain the extrapulmonary effect of renal function decline due to subchronic inhalation exposure to particles smaller than 2.5 µm, as well as the correlation of the biomarkers with the particles' endotoxin content. MATERIALS AND METHODS: Adult male Sprague-Dawley rats were exposed to subchronic inhalation of particles smaller than 2.5 µm (8 weeks, 4 days/week, 5 h/day). The control group was exposed to filtered air. MiniVol and HiVol samplers were used to estimate the concentration and collected particles, respectively. Biomarkers were assessed in weekly urine samples harvested by the metabolic cage. The OxS biomarkers assessed were methylglyoxal, non-esterified fatty acids, malondialdehyde, advanced oxidative protein products, arginase, myeloperoxidase, glutathione S-transferase, and gamma-glutamyl transferase, all of which were evaluated by colorimetric assays. Creatinine was evaluated by the Jaffe reaction, and cystatin-C (Cys-C) and neutrophil gelatinase-associated lipocalin-2 were quantified using Luminex technology. Endotoxin content was analyzed with the Limulus Amebocyte Lysate Pyrochrome Chromogenic Test Kit. RESULTS AND DISCUSSION: Subchronic exposure to PM2.5 increased OxS biomarkers in urine. Endotoxin content showed a positive correlation with the urinary OxS biomarkers evaluated. Additionally, urinary OxS biomarkers correlated with creatinine and the early kidney damage biomarkers Cys-C and neutrophil gelatinase-associated lipocalin-2, where the strongest and positive correlations were observed with the latter two biomarkers. CONCLUSIONS: Inhalation of environmental airborne particles smaller than 2.5 µm increased urinary OxS biomarkers, correlated with endotoxin content and early kidney damage biomarkers. This finding corroborates the extrapulmonary nephrotoxic effect of inhaled particles.

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Environmental stressors, such as air particulate matter (PM) and nutrient deficiencies, can significantly impact crucial organs involved in detoxifying xenobiotics, including lungs, liver, and kidneys, especially in vulnerable populations like children. This study investigated the effect of 4-week exposure to Residual Oil Fly Ash (ROFA) on these organs in young rats under growth-restricted nutrition (NGR). We assessed histological, histomorphometric and biochemical parameters. ROFA exposure induced histological changes and inflammation in all three organs when compared to control (C) animals. Specifically, in lungs ROFA caused a significant reduction in alveolar airspace (C: 55.8 ± 1.8% vs. ROFA: 38.7 ± 3.0%, p < 0.01) and alveolar number along with changes in alveolar size distribution, and disruption of the smooth muscle layer which may impaired respiratory function. In the liver, ROFA increased binucleated cells, macro and microvesicles and both AST and ALT serum biomarkers (AST: C = 77.7 ± 1.3 vs. ROFA = 81.6 ± 1.3, p < 0.05; ALT: C = 44.5 ± 0.9 vs. ROFA = 49.4 ± 1.3, p < 0.05). In the kidneys, a reduced Bowman's space (C: 2.15 ± 0.2 mm2 vs. ROFA: 1.74 ± 0.2 mm2, p < 0.05) was observed, indicative of glomerular filtration failure. NGR alone reduced Bowman's space (C: 2.15 ± 0.2 mm2 vs. NGR: 1.06 ± 0.1 mm2, p < 0.001). In lung and liver NGR showed higher levels of proinflammatory cytokine IL-6 (p < 0.01 and p < 0.001, respectively) when compared to C. In conclusion, both stressors negatively affected lung and excretory organs in young rats, with nutritional status further modulating the physiological response to ROFA. These findings highlight the compounded risks posed by environmental pollutants and poor nutrition in vulnerable populations.

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We evaluated both environmental (workplace) and biological (urine) exposure to the anesthetic isoflurane concerning the effects of such exposure on the hematological, hepatic, and renal parameters in veterinarians. Samples were collected from exposed and nonexposed (volunteers) groups to assess hematological and several biochemical markers, and isoflurane was measured in the workplace air and veterinarian's urine. Isoflurane was detected at high levels in the air and urine. No differences were observed in hematological parameters between the groups, although the number of monocytes increased among veterinarians, values were within the normal range. No significant differences were found in the hepatic enzymes or renal parameters between the groups, and all marker levels were within the normal range. In conclusion, urinary isoflurane is a suitable internal biomarker for monitoring occupational exposure and is associated with veterinary workplace measurements, and that occupational exposure is not associated with abnormal hematological or biochemical changes in veterinarians.

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BACKGROUND: Congenital anomalies of the kidney and urinary tract (CAKUT) are a common cause of kidney failure in childhood. Renal transplantation is the modality of treatment used for kidney failure that promotes improved quality of life for pediatric patients. It is believed that patients with CAKUT are more predisposed to developing graft reflux in the post-transplant period, but its influence on graft survival is poorly understood. A comparative analysis between patients with and without VUR in the graft was made to determine the impact of reflux on graft function and survival in pediatric CAKUT patients. METHODS: A retrospective case-control study of patients undergoing first renal transplantation between April 2008 and October 2021 was done. The study included CAKUT individuals who underwent voiding cystourethrogram after transplantation. Patients were stratified into a group without reflux in the transplanted kidney (controls) and a group with reflux (cases). Six-year graft and patient survivals were calculated and compared using Kaplan-Meier curves and the log-rank test. RESULTS: A total of 257 CAKUT patients were studied. Of this group, 63 (24%) underwent voiding cystourethrogram after transplantation, and 48 (76%) had reflux in the transplanted kidney. Estimated six-year survival of the graft was 72% in the control group versus 96% in the case group (log-rank 0.889). The median follow-up time after transplantation in years was 7.6 in controls and 6.6 in cases (p = 0.383). CONCLUSIONS: Pediatric patients with CAKUT who presented reflux in transplanted kidneys had similar graft and patient survivals compared to patients without reflux.

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OBJECTIVE: The expansion of human activities in northern Colombia has increased human-snake encounters, particularly with venomous Porthidium lansbergii lansbergii. Given the limited knowledge of systemic envenomation effects and previous studies focusing only on early murine symptoms, this investigation aimed to describe the time-course physiopathology of P. lansbergii lansbergii envenomation following intramuscular injection in vivo. METHODS: Venom was inoculated in the gastrocnemius muscles of Swiss Webster mice, and blood, urine, and tissue samples were taken at different times to evaluate lethality and biochemical markers of renal function and oxidative stress. RESULTS: This study reports the first intramuscular LD50 for P. lansbergii lansbergii venom at 24.83 mg/Kg. Administering 80% of this LD50 induced early signs of renal injury, evidenced by urinary biomarkers over 24 h. The antioxidant activity was found at low levels in kidney tissue throughout the evaluated time post-envenomation. Malondialdehyde activity increased at the earliest point, while proinflammatory activity increased later. Urine metabolomics revealed elevated taurine and allantoin in the envenomed groups. DISCUSSION: Compensatory mechanisms in response to oxidative stress and tissue damage induced by the venom were evident in the envenomed mice over the evaluated time. However, histological analysis revealed evidence of pro-inflammatory processes occurring only at early times. Metabolomic analyses of urine samples identified taurine as a potential early biomarker of elevated oxidative stress and protein and creatinine levels. CONCLUSIONS: P. lansbergii lansbergii venom induces alterations in murine renal tissue, affecting urinary biomarkers of kidney function within hours post-envenomation. Delayed proinflammatory effects may suggest an antioxidant imbalance in the envenomed mice, with unknown long-term effects. Further research on the role of oxidative stress and inflammation in renal structure and function following envenomation is necessary, emphasizing the need for prompt clinical management.

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BACKGROUND: Most studies regarding kidney outcomes in patients with Shiga toxin-producing Escherichia coli-hemolytic uremic syndrome (STEC-HUS) focus on kidney status at last assessment. We aimed to describe patterns of changes in kidney function during follow-up and investigate associations between kidney function at 1st, 5th, and 10th year after onset and long-term kidney outcomes. METHODS: Data of patients with STEC-HUS followed for at least 15 years were analyzed. Kidney function patterns were constructed considering kidney status at 1st, 5th, 10th, and ≥ 15 years and defined as (1) progressive, if patients changed from complete recovery to any chronic kidney disease (CKD) stage or if CKD worsened; (2) improvement, if they shifted from any CKD stage to complete recovery or to a milder stage; and (3) stable, if remained unchanged. RESULTS: Of 152 patients included, after 1 year of follow-up, 47% had complete recovery, 22% CKD1, and 32% CKD2-5. At last assessment, 46% had complete recovery, 34% CKD1, and 19% CKD2-5. Despite percentages seeming similar, patients differed: 48% were stable, 27% improved, and 25% worsened. Further, 62% of patients with CKD2-4 in the 1st year normalized their glomerular filtration rate (GFR) thereafter. Comparison of kidney function between 1st, 5th, and 10th year to last assessment shows a stable pattern in 48, 59, and 69% respectively. CONCLUSIONS: Changes in kidney function showed a dynamic and complex behavior, with patients moving from one group to another. Consistently, kidney function neither at the 1st, 5th, or 10th year was representative of final outcome. Unexpectedly, two-thirds of patients with CKD2-4 after 1 year achieved normal eGFR later during follow-up.

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Page kidney (Page phenomenon) is a rare and treatable cause of hypertension which can occur if a haematoma, leading to extrinsic compression, occurs after renal transplant biopsy. The renin-angiotensin-aldosterone system is activated leading to hypertension. This case report is that of a male in his 70s who had a renal transplant biopsy of his transplanted kidney and subsequently developed Page phenomenon as a result of an expanding haematoma. He developed elevated blood pressure (BP) along with a decrease in his renal function. Surgical intervention was used to salvage his transplanted kidney. The index case highlights the importance of being aware of the signs of Page kidney to ensure early recognition and intervention. To our knowledge, this is the first case of a Page kidney in a renal allograft documented in the Caribbean region.

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Chronic hyperglycemia results in morphological and functional alterations of the kidney and microvascular damage, leading to diabetic nephropathy (DN). Since DN progresses to irreversible renal damage, it is important to elucidate a pharmacological strategy aimed for treating DN in the early stage. Here, we used the type 2 diabetic rat model to induce DN and show a nephroprotective effect following the stimulation of PPAR-α, which stabilized renal tight junction components claudin-2, claudin-5, and claudin-16. At 14 weeks old, streptozotocin-induced DN, evidenced by elevated creatinine clearance, proteinuria, and electrolyte excretion, was followed by an elevation in oxidative stress and increasing MMP activities affecting the integrity of claudin-2 and claudin-5. Treatment with a PPAR-α agonists decreased glucose levels in diabetic rats. In addition, we found that the expressions of CLDN-5 in glomeruli, CLDN-2 in proximal tubules, and CLDN-16 in the thick ascending limb of the loop of Henle were increased after treatment. As a result, renal function improved, while the oxidative stress and enzymatic activity of MMP-2 and MMP-9 decreased. In conclusion, PPAR-α stimulation prevented the decrease in claudins through a mechanism involving a correction of hyperglycemia, decreasing it in kidney oxidative stress and MMP-2 and MMP-9 activities, showing a promising nephroprotective action in the early stage of DN.

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Diabetic nephropathy (DN) is one of the most relevant and prevalent microvascular complications associated with Diabetes Mellitus. In recent years, hyperbaric oxygen therapy (HBO) has been used to mitigate tissue damage caused by hypoxia, thereby attenuating inflammatory processes. This study aimed to explore morphological aspects associated with DN in rats subjected to HBO. Forty-eight Wistar rats were divided into the following groups: C (normoglycemic animals), n = 12; C + HBO (normoglycemic animals submitted to HBO), n = 12; D (diabetic animals) n = 12; D + HBO (diabetic animals submitted to HBO), n = 12. The C + HBO and D + HBO groups were daily treated with HBO at 2.5 atmospheres absolute pressure (ATA) for 60 min, 5 days a week, for 5 weeks. Kidneys were collected for assessment of structural changes in the tissue parenchyma, assessment of renal fibrosis and renal protein expression of tumor necrosis factor-α (TNF-α) and transforming growth factor-ß1 (TGF-ß1). Our results showed that group D had hyperglycemia and weight loss, and that there was also an increase in the renal corpuscle, Bowman's space, and distal tubular epithelium, as well as accumulation of collagen. HBO administration effectively prevented glomerular hypertrophy and attenuated the expression of TNF-α and TGF-ß1. It also positively affected renal tubules, inhibiting the development of tubular atrophy. These findings suggest that HBO was effective in attenuating the initial alterations observed in DN.

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GLP1 receptor agonists (GLP1-RAs) are drugs that mimic the effects of the incretin hormone GLP1 and were initially introduced in medicine for the treatment of diabetes in 2005 and for obesity in 2014. Over time, data from secondary and exploratory objectives of large randomized controlled-trials suggested that GLP1-RAs could also exert renal action by slowing the progression of kidney disease in patients with and without diabetes. Based on this rationale, the Flow study (1 mg semaglutide vs placebo) was designed and recruitment began in 2019 until May 2021. The recently published results confirmed the effect of semaglutide in reducing the composite renal outcome. However, similar to SGLT2 inhibitors, the potential mechanisms behind the renal effects of GLP1-RAs still need to be elucidated. The aim of this review is to address the different physiological mechanisms of GLP1-RAs at the renal level, using evidence from experimental studies and current scientific literature.