Butylparaben induced zebrafish (Danio rerio) kidney injury by down-regulating the PI3K-AKT pathway.

Butylparaben, a common endocrine disruptor in the environment, is known to be toxic to the reproductive system, heart, and intestines, but its nephrotoxicity has rarely been reported. In order to study the nephrotoxicity and mechanism of butylparaben, we examined the acute and chronic effects on human embryonic kidney cells (HEK293T) and zebrafish. Additionally, we assessed the potential remedial effects of salidroside against butylparaben-induced nephrotoxicity. Our in vitro findings demonstrated oxidative stress and cytotoxicity to HEK293T cells caused by butylparaben. In the zebrafish model, the concentration of butylparaben exposure ranged from 0.5 to 15 µM. An assortment of experimental techniques was employed, including the assessment of kidney tissue morphology using Hematoxylin-Eosin staining, kidney function analysis via fluorescent dextran injection, and gene expression studies related to kidney injury, development, and function. Additionally, butylparaben caused lipid peroxidation in the kidney, thereby damaging glomeruli and renal tubules, which resulted from the downregulation of the PI3K-AKT signaling pathway. Furthermore, salidroside ameliorated butylparaben-induced nephrotoxicity through the PI3K-AKT signaling pathway. This study reveals the seldom-reported kidney toxicity of butylparaben and the protective effect of salidroside against toxicological reactions related to nephrotoxicity. It offers valuable insights into the risks to kidney health posed by environmental toxins.

Acute kidney failure reveals primary renal non-Hodgkin lymphoma.

A male patient in his 60s was admitted to our hospital with symptoms of dyspnoea, asthenia, diaphoresis and acute kidney failure. No tumour or infection was detected in initial screening. However, laboratory examination suggested that the acute kidney failure was due to an intrarenal cause, exhibiting a tubular injury pattern and indications of tumour lysis syndrome. Initial hydration therapy, paired with intravenous rasburicase, rapidly improved the kidney function. Unfortunately, the kidney function deteriorated once again, prompting a kidney biopsy that revealed an aggressive diffuse large B-cell non-Hodgkin lymphoma of the kidney. The chemotherapy, comprised of R-CHOP scheme, led to a full recovery of the kidney function and complete remission of the lymphoma. Primary renal non-Hodgkin lymphoma without nodal manifestation is rare, and its pathophysiology is poorly understood. Therapy schemes can vary significantly between cases, relying primarily on non-renal-specific haemato-oncological guidelines. Therefore, further studies are needed to develop the best therapeutic approaches.

Spilanthes filicaulis (Schumach. & Thonn.) C.D. Adams leaves protects against streptozotocin-induced diabetic nephropathy.

BACKGROUND AND OBJECTIVE: Diabetic neuropathy (DN) is a complex type of diabetes. The underlying cause of diabetic nephropathy remains unclear and may be due to a variety of pathological conditions resulting in kidney failure. This study examines the protective effect of the methanolic extract of Spilanthes filicaulis leaves (MESFL) in fructose-fed streptozotocin (STZ)-induced diabetic nephropathy and the associated pathway. METHODS: Twenty-five rats were equally divided randomly into five categories: Control (C), diabetic control, diabetic + metformin (100 mg/kg), diabetic + MESFL 150 mg/kg bw, and diabetic + MESFL 300 mg/kg bw. After 15 days, the rats were evaluated for fasting blood glucose (FBG), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), urea, uric acid, serum creatinine, reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), and lipid peroxidation (MDA). Gene expression levels of cyclic adenosine monophosphate (cAMP), protein kinase A (PKA), cAMP response element-binding (CREB), cFOS and the antiapoptotic protein Bcl-2 were examined. RESULTS: We observed that MESFL at 150 and 300 mg/kg bw significantly downregulated the protein expression of cAMP, PKA, CREB, and cFOS and upregulated the Bcl-2 gene, suggesting that the nephroprotective action of MESFL is due to the suppression of the cAMP/PKA/CREB/cFOS signaling pathway. In addition, MESFL increases SOD and CAT activities and GSH levels, reduces MDA levels, and reduces renal functional indices (ALP, urea, uric acid, and creatinine). CONCLUSION: Therefore, our results indicate that MESFL alleviates the development of diabetic nephropathy via suppression of the cAMP/PKA/CREB/cFOS pathways.

When Waldenström macroglobulinemia hits the kidney: Description of a case series and management of a "rare in rare" scenario.

BACKGROUND: Renal injury related to Waldenström macroglobulinemia (WM) occurs in approximately 3% of patients. Kidney biopsy is crucial to discriminate between distinct histopathological entities such as glomerular (amyloidotic and non-amyloidotic), tubulo-interstitial and non-paraprotein mediated renal damage. In this context, disease characterization, management, relationship between renal, and hematological response have been poorly explored. We collected clinical, genetic and laboratory data of seven cases of biopsy-proven renal involvement by WM managed at our academic center and focused on three cases we judged paradigmatic discussing their histopathological patterns, clinical features, and therapeutic options. CASE: In this illustrative case series, we confirm that serum creatinine levels and 24 h proteinuria are parameters that when altered should prompt the clinical suspicion of WM-related renal involvement, even if at present there are not precise cut-off levels recommending the execution of a renal biopsy. In our series AL Amyloidosis (n = 3/7) and tubulo-interstitial infiltration by lymphoma cells (n = 3/7) were the two more represented entities. BTKi did not seem to improve renal function (Case 1), while bortezomib-based regimens demonstrated a beneficial activity on the hematological and organ response, even when used as second-line therapy after chemoimmunotherapy (Case 3) and also with coexistence of anti-MAG neuropathy (Case 2). In case of poor response to bortezomib, standard chemoimmunotherapy (CIT), such as rituximab-bendamustine, represents an effective option (Case 1, 6, and 7). In our series, CIT generates durable responses more frequently in cases with amyloidogenic renal damage (Case 1, 5, and 7). CONCLUSION: In this illustrative case series, we confirm that serum creatinine levels and 24 h proteinuria are parameters that when altered should prompt the clinical suspicion of WM-related renal involvement, even if at present there are not precise cut-off levels recommending the execution of a renal biopsy. Studies with higher numerosity are needed to better clarify the pathological and clinical features of renal involvement during WM and to determine the potential benefit of different therapeutic regimens according to the histopathological subtypes.

Extracellular vesicles as potential diagnostic markers for kidney allograft rejection.

Kidney transplantation is a highly effective treatment for end-stage kidney disease. However, allograft rejection remains a significant clinical challenge in kidney transplant patients. Although kidney allograft biopsy is the gold-standard diagnostic method, it is an invasive procedure. Since the current monitoring methods, including screening of serum creatinine and urinary protein, are not of sufficient sensitivity, there is a need for effective post-transplant monitoring to detect allograft rejection at an early stage. Extracellular vesicles are vesicles with a lipid bilayer that originate from different cell types in pathological and physiological conditions. The content of extracellular vesicles reflects the status of cells at the time of their production. This review comprehensively summarizes clinical, in vivo, and in vitro reports that highlight the potential of extracellular vesicles as diagnostic biomarkers for kidney allograft rejection. Clarification would facilitate differentiation between rejection and non-rejection and identification of the mechanisms involved in the allograft rejection. Despite increasing evidence, further research is necessary to establish the clinical utility of extracellular vesicles in the diagnosis and monitoring of allograft rejection in kidney transplant recipients. Using extracellular vesicles as non-invasive biomarkers for diagnosis of kidney allograft rejection could have tremendous benefits in improving patient outcomes and reduce the need for invasive procedures.

Identifying and validating MMP family members (MMP2, MMP9, MMP12, and MMP16) as therapeutic targets and biomarkers in kidney renal clear cell carcinoma (KIRC).

Kidney Renal Clear Cell Carcinoma (KIRC) is a malignant tumor that carries a substantial risk of morbidity and mortality. The MMP family assumes a crucial role in tumor invasion and metastasis. This study aimed to uncover the mechanistic relevance of the MMP gene family as a therapeutic target and diagnostic biomarker in Kidney Renal Clear Cell Carcinoma (KIRC) through a comprehensive approach encompassing both computational and molecular analyses. STRING, Cytoscape, UALCAN, GEPIA, OncoDB, HPA, cBioPortal, GSEA, TIMER, ENCORI, DrugBank, targeted bisulfite sequencing (bisulfite-seq), conventional PCR, Sanger sequencing, and RT-qPCR based analyses were used in the present study to analyze MMP gene family members to accurately determine a few hub genes that can be utilized as both therapeutic targets and diagnostic biomarkers for KIRC. By performing STRING and Cytohubba analyses of the 24 MMP gene family members, MMP2 (matrix metallopeptidase 2), MMP9 (matrix metallopeptidase 9), MMP12 (matrix metallopeptidase 12), and MMP16 (matrix metallopeptidase 16) genes were denoted as hub genes having highest degree scores. After analyzing MMP2, MMP9, MMP12, and MMP16 via various TCGA databases and RT-qPCR technique across clinical samples and KIRC cell lines, interestingly, all these hub genes were found significantly overexpressed at mRNA and protein levels in KIRC samples relative to controls. The notable effect of the up-regulated MMP2, MMP9, MMP12, and MMP16 was also documented on the overall survival (OS) of the KIRC patients. Moreover, targeted bisulfite-sequencing (bisulfite-seq) analysis revealed that promoter hypomethylation pattern was associated with up-regulation of hub genes (MMP2, MMP9, MMP12, and MMP16). In addition to this, hub genes were involved in various diverse oncogenic pathways. The MMP gene family members (MMP2, MMP9, MMP12, and MMP16) may serve as therapeutic targets and prognostic biomarkers in KIRC.

Effects of adenosine triphosphate, Lacidipine, and Benidipine on 5-fluorouracil-induced kidney damage in rats.

OBJECTIVE: In the present study, the protective effects of adenosine triphosphate (ATP), Benidipine, and Lacidipine on potential kidney damage induced by 5-fluorouracil (5-FU) were investigated in rats. MATERIALS AND METHODS: Totally 48 rats were divided into 8 groups: healthy (HG), 5-FU (FUG), ATP+5-FU (AFU), Benidipine+5-FU (BFU), Lacidipine+5-FU (LFU), ATP+Benidipine+5-FU (ABFU), ATP+Lacidipine+5-FU (ALFU) and Benidipine+Lacidipine+5-FU (BLFU). In a 10-day period, ATP (4 mg/kg) was administered intraperitoneally, and Benidipine (4 mg/kg) and Lacidipine (4 mg/kg) were administered orally once a day. On days 1, 3, and 5, 5-FU (100 mg/kg) was administered intraperitoneally one hour after the drug was administered. Afterward, the rats were euthanized, and kidney tissues were removed. An analysis of malondialdehyde, total glutathione, superoxide dismutase, and catalase was performed on tissues, as well as a histopathological examination. A creatinine and blood urea nitrogen analysis were performed on blood samples. RESULTS: It was revealed that 5-FU decreased the amount of total glutathione, superoxide dismutase, and catalase activities in rat kidney tissues and increased malondialdehyde. Further, increased serum creatinine and blood urea nitrogen levels, as well as histopathological examination of kidney tissues, were found in the 5-FU group. ATP+Benidipine and ATP treatments were the most effective in preventing both biochemical and histopathological changes induced by 5-FU. A treatment with Benidipine improved biochemical and histopathologic data, but not to the same extent as a treatment with ATP+Benidipine and ATP. As a result of Lacidipine+ATP combination, 5-FU-induced biochemical changes in kidney tissue were partially inhibited, but the degree of histopathologic damage remained unchanged. Neither Benidipine+Lacidipine nor Lacidipine showed a protective effect on both biochemical changes and histopathologic damage. CONCLUSIONS: It may be possible to prevent nephrotoxicity by adding ATP + Benidipine or ATP to 5-FU treatment.

Determinants and impact of calcium oxalate crystal deposition on renal outcomes in acute kidney injury patients.

OBJECTIVES: Calcium oxalate (CaOx) crystal deposition in acute kidney injury (AKI) patients is under recognized but impacts renal outcomes. This study investigates its determinants and effects. METHODS: We studied 814 AKI patients with native kidney biopsies from 2011 to 2020, identifying CaOx crystal deposition severity (mild: <5, moderate: 5-10, severe: >10 crystals per section). We assessed factors like urinary oxalate, citrate, urate, electrolytes, pH, tubular calcification index, and SLC26A6 expression, comparing them with creatinine-matched AKI controls without oxalosis. We analyzed how these factors relate to CaOx severity and their impact on renal recovery (eGFR < 15 mL/min/1.73 m2 at 3-month follow-up). RESULTS: CaOx crystal deposition was found in 3.9% of the AKI cohort (32 cases), with 72% due to nephrotoxic medication-induced tubulointerstitial nephritis. Diuretic use, higher urinary oxalate-to-citrate ratio induced by hypocitraturia, and tubular calcification index were significant contributors to moderate and/or severe CaOx deposition. Poor baseline renal function, low urinary chloride, high uric acid and urea nitrogen, tubular SLC26A6 overexpression, and glomerular sclerosis were also associated with moderate-to-severe CaOx deposition. Kidney recovery was delayed, with 43.8%, 31.2%, and 18.8% of patients having eGFR < 15 mL/min/1.73 m2 at 4, 12, and 24-week post-injury. Poor outcomes were linked to high urinary α1-microglobulin-to-creatinine (α1-MG/C) ratios and active tubular injury scores. Univariate analysis showed a strong link between this ratio and poor renal outcomes, independent of oxalosis severity. CONCLUSIONS: In AKI, CaOx deposition is common despite declining GFR. Factors worsening tubular injury, not just oxalate-to-citrate ratios, are key to understanding impaired renal recovery.

Myofibroblast-derived exosomes enhance macrophages to myofibroblasts transition and kidney fibrosis.

A critical event in the pathogenesis of kidney fibrosis is the transition of macrophages into myofibroblasts (MMT). Exosomes play an important role in crosstalk among cells in the kidney and the development of renal fibrosis. However, the role of myofibroblast-derived exosomes in the process of MMT and renal fibrosis progression remains unknown. Here, we examined the role of myofibroblast-derived exosomes in MMT and kidney fibrogenesis. In vitro, transforming growth factor-ß1 stimulated the differentiation of kidney fibroblasts into myofibroblasts and promoted exosome release from myofibroblasts. RAW264.7 cells were treated with exosomes derived from myofibroblasts. We found purified exosomes from myofibroblasts trigger the MMT. By contrast, inhibition of exosome production with GW4869 or exosome depletion from the conditioned media abolished the ability of myofibroblasts to induce MMT. Mice treatment with myofibroblast-derived exosomes (Myo-Exo) exhibited severe fibrotic lesion and more abundant MMT cells in kidneys with folic acid (FA) injury, which was negated by TANK-banding kinase-1 inhibitor. Furthermore, suppression of exosome production reduced collagen deposition, extracellular matrix protein accumulation, and MMT in FA nephropathy. Collectively, Myo-Exo enhances the MMT and kidney fibrosis. Blockade of exosomes mediated myofibroblasts-macrophages communication may provide a novel therapeutic target for kidney fibrosis.

Subcutaneous injection of adipose stromal cell-secretome improves renal function and reduces inflammation in established acute kidney injury.

BACKGROUND: Adipose stromal cells (ASC) are a form of mesenchymal stromal cells that elicit effects primarily via secreted factors, which may have advantages for the treatment of injury or disease. Several previous studies have demonstrated a protective role for MSC/ASC on mitigating acute kidney injury but whether ASC derived factors could hasten recovery from established injury has not been evaluated. METHODS: We generated a concentrated secretome (CS) of human ASC under well-defined conditions and evaluated its ability to improve the recovery of renal function in a preclinical model of acute kidney injury (AKI) in rats. 24 h following bilateral ischemia/reperfusion (I/R), rats were randomized following determination of plasma creatinine into groups receiving vehicle -control or ASC-CS treatment by subcutaneous injection (2 mg protein/kg) and monitored for evaluation of renal function, structure and inflammation. RESULTS: Renal function, assessed by plasma creatinine levels, recovered faster in ASC-CS treated rats vs vehicle. The most prominent difference between the ASC-CS treated vs vehicle was observed in rats with the most severe degree of initial injury (Pcr > 3.0 mg/dl 24 h post I/R), whereas rats with less severe injury (Pcr < 2.9 mg/dl) recovered quickly regardless of treatment. The quicker recovery of ASC-treated rats with severe injury was associated with less tissue damage, inflammation, and lower plasma angiopoietin 2. In vitro, ASC-CS attenuated the activation of the Th17 phenotype in lymphocytes isolated from injured kidneys. CONCLUSIONS: Taken together, these data suggest that ASC-CS represents a potent therapeutic option to improve established AKI.

Attenuating Renal Interstitial Fibrosis by Shenqi Pill via Reducing Inflammation Response Regulated by NF-κB Pathway In Vitro and In Vivo.

INTRODUCTION: One of the most significant clinical features of chronic  kidney disease is renal interstitial fibrosis (RIF). This study aimed  to investigate the role and mechanism of Shenqi Pill (SQP) on RIF. METHODS: RIF model was established by conducting unilateral  ureteral obstruction (UUO) surgery on rat or stimulating human  kidney-2 (HK-2) cell with transforming growth factor ß1 (TGFß1).  After modeling, the rats in the SQP low dose group (SQP-L), SQP  middle dose group (SQP-M) and SQP high dose group (SQP-H)  were treated with SQP at 1.5, 3 or 6 g/kg/d, and the cells in the  TGFß1+SQP-L/M/H were treated with 2.5%, 5%, 10% SQP-containing  serum. In in vivo assays, serum creatinine (SCr) and blood urea  nitrogen (BUN) content were measured, kidney histopathology  was evaluated., and α-smooth muscle actin (α-SMA) expression  was detected by immunohistochemistry. Interleukin-1ß (IL-1ß),  interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) content,  inhibitor of kappa B alpha (IKBα) and P65 phosphorylation were  assessed. Meanwhile, cell viability, inflammatory cytokines content,  α-SMA expression, IKBα and P65 phosphorylation were detected  in vitro experiment.  Results. SQP exhibited reno-protective effect by decreasing SCr  and BUN content, improving renal interstitial damage, blunting  fibronectin (FN) and α-SMA expression in RIF rats. Similarly, after  the treatment with SQP-containing serum, viability and α-SMA  expression were remarkably decreased in TGFß1-stimulated HK-2  cell. Furthermore, SQP markedly down-regulated IL-1ß, IL-6, and  TNF-α content, IKBα and RelA (P65) phosphorylation both in vivo and in vitro.  Conclusion. SQP has a reno-protective effect against RIF in vivo and in vitro, and the effect is partly linked to nuclear factor-kappa  B (NF-κB) pathway related inflammatory response, which indicates  that SQP may be a candidate drug for RIF. DOI: 10.52547/ijkd.7546.

Case of IgG4-related Disease with Crescentic Glomerulonephritis: An Unusual Presentation of the Disease.

IgG4-related disease (IgG4-RD) is a chronic systemic inflammatory  disease, characterized by tissue infiltration of lymphocytes and  IgG4-secreting plasma cells, presenting by fibrosis of different  tissues, which is usually responsive only to oral steroids therapy.  Kidneys are the most commonly involved organs, exhibiting renal  insufficiency, tubulointerstitial nephritis, and glomerulonephritis.  Here, we describe a patient with acute renal insufficiency who  was presented with edema, weakness, anemia and multiple  lymphadenopathies. Kidney and lymph node biopsy showed  crescentic glomerulonephritis in kidneys and lymphoplasmacytic  infiltration in lymph nodes. After a course of treatment with an  intravenous pulse of corticosteroid and cyclophosphamide, the  patient's symptoms subsided, and kidney function improved. DOI: 10.52547/ijkd.7788.

Microvesicles from Mesenchymal Stem Cells Overexpressing MiR-34a Ameliorate Renal Fibrosis In Vivo.

INTRODUCTION: We recently discovered that microvesicles (MVs)  derived from mesenchymal stem cells (MSCs) overexpressing  miRNA-34a can alleviate experimental kidney injury in mice. In  this study, we further explored the effects of miR34a-MV on renal  fibrosis in the unilateral ureteral obstruction (UUO) models.  Methods. Bone marrow MSCs were modified by lentiviruses  overexpressing miR-34a, and MVs were collected from the  supernatants of MSCs. C57BL6/J mice were divided into control,  unilateral ureteral obstruction (UUO), UUO + MV, UUO + miR-34aMV and UUO + miR-34a-inhibitor-MV groups. MVs were injected  to mice after surgery. The mice were then euthanized on day 7  and 14 of modeling, and renal tissues were collected for further  analyses by Hematoxylin and eosin, Masson's trichrome,  and Immunohistochemical (IHC) staining.  Results. The UUO + MV group exhibited a significantly reduced  degree of renal interstitial fibrosis with inflammatory cell infiltration,  tubular epithelial cell atrophy, and vacuole degeneration compared  with the UUO group. Surprisingly, overexpressing miR-34a enhanced  these effects of MSC-MV on the UUO mice.  Conclusion. Our study demonstrates that miR34a further enhances  the effects of MSC-MV on renal fibrosis in mice through the  regulation of epithelial-to-mesenchymal transition (EMT) and  Notch pathway. miR-34a may be a candidate molecular therapeutic  target for the treatment of renal fibrosis. DOI: 10.52547/ijkd.7673.

Atypical anti-glomerular basement membrane disease with membranous hyperplasia: diagnostic challenges and treatment variability.

This case report presents a detailed analysis of a 31-year-old male patient who presented with a complex array of clinical symptoms, including proteinuria, hematuria, edema, and kidney insufficiency. Despite undergoing multiple tests, the results for anti-glomerular basement membrane antibodies yielded negative findings. Subsequently, kidney biopsy pathology revealed a distinct diagnosis of atypical anti-glomerular basement membrane (anti-GBM) disease with membrane hyperplasia. Treatment was initiated with a comprehensive approach involving high doses of corticosteroids therapy and cyclophosphamide (CTX). However, contrary to expectations, the patient's kidney function exhibited rapid deterioration following this therapeutic regimen. The culmination of these complications necessitated a pivotal transition to maintenance hemodialysis. This case underscores the intricate challenges associated with diagnosing and managing rare and atypical presentations of kidney disorders. The negative anti-GBM antibody results and subsequent identification of atypical anti-GBM nephropathy highlight the need for tailored diagnostic strategies to discern subtle nuances within complex clinical scenarios. Additionally, the unexpected response to the treatment regimen emphasizes the potential variability in individual patient responses, underlining the necessity for vigilant monitoring and adaptable treatment strategies. This case report contributes to the evolving understanding of atypical kidney pathologies and the complexities involved in their management.

Antibody-mediated rejection in pediatric kidney transplant recipients: A report from the Pediatric Nephrology Research Consortium.

BACKGROUND: Antibody-mediated rejection (AMR) is a major cause of kidney allograft loss. There is a paucity of large-scale pediatric-specific data regarding AMR treatment outcomes. METHODS: Data were obtained from 14 centers within the Pediatric Nephrology Research Consortium. Kidney transplant recipients aged 1-18 years at transplant with biopsy-proven AMR between 2009 and 2019 and at least 12 months of follow-up were included. The primary outcome was graft failure or an eGFR <20 mL/min/1.73 m2 at 12 months following AMR treatment. AMR treatment choice, histopathology, and DSA class were also examined. RESULTS: We reviewed 123 AMR episodes. Median age at diagnosis was 15 years at a median 22 months post-transplant. The primary outcome developed in 27.6%. eGFR <30 m/min/1.73 m2 at AMR diagnosis was associated with a 5.6-fold higher risk of reaching the composite outcome. There were no significant differences in outcome by treatment modality. Histopathology scores and DSA class at time of AMR diagnosis were not significantly associated with the primary outcome. CONCLUSIONS: In this large cohort of pediatric kidney transplant recipients with AMR, nearly one-third of patients experienced graft failure or significant graft dysfunction within 12 months of diagnosis. Poor graft function at time of diagnosis was associated with higher odds of graft failure.

Mechanism of dexmedetomidine protection against cisplatin induced acute kidney injury in rats.

OBJECTIVE: This study explored the molecular mechanisms by which dexmedetomidine (Dex) alleviates cisplatin (CP)-induced acute kidney injury (AKI) in rats. METHODS: CP-induced AKI models were established, and Dex was intraperitoneally injected at different concentrations into rats in the model groups. Subsequently, rats were assigned to the control, CP, CP + Dex 10 µg/kg, and CP + Dex 25 µg/kg groups. After weighing the kidneys of the rats, the kidney arterial resistive index was calculated, and CP-induced AKI was evaluated. In addition, four serum biochemical indices were measured: histopathological damage in rat kidneys was detected; levels of inflammatory factors, interleukin (IL)-1ß, IL-18, IL-6, and tumor necrosis factor alpha, in kidney tissue homogenate of rats were assessed through enzyme-linked immunosorbent assay (ELISA); and levels of NLRP-3, caspase-1, cleaved caspase-1, gasdermin D (GSDMD), and GSDMD-N in kidney tissues of rats were determined via western blotting. RESULTS: Dex treatment reduced nephromegaly and serum clinical marker upregulation caused by CP-induced AKI. In addition, hematoxylin and eosin staining revealed that Dex treatment relieved CP-induced kidney tissue injury in AKI rats. ELISA analyses demonstrated that Dex treatment reduced the upregulated levels of proinflammatory cytokines in the kidney tissue of AKI rats induced by CP, thereby alleviating kidney tissue injury. Western blotting indicated that Dex alleviated CP-induced AKI by inhibiting pyroptosis mediated by NLRP-3 and caspase-1. CONCLUSION: Dex protected rats from CP-induced AKI, and the mechanism may be related to NLRP-3/Caspase-1-mediated pyroptosis.

Nlrp2 deletion ameliorates kidney damage in a mouse model of cystinosis.

Cystinosis is a rare autosomal recessive disorder caused by mutations in the CTNS gene that encodes cystinosin, a ubiquitous lysosomal cystine/H+ antiporter. The hallmark of the disease is progressive accumulation of cystine and cystine crystals in virtually all tissues. At the kidney level, human cystinosis is characterized by the development of renal Fanconi syndrome and progressive glomerular and interstitial damage leading to end-stage kidney disease in the second or third decade of life. The exact molecular mechanisms involved in the pathogenesis of renal disease in cystinosis are incompletely elucidated. We have previously shown upregulation of NLRP2 in human cystinotic proximal tubular epithelial cells and its role in promoting inflammatory and profibrotic responses. Herein, we have investigated the role of NLRP2 in vivo using a mouse model of cystinosis in which we have confirmed upregulation of Nlrp2 in the renal parenchyma. Our studies show that double knock out Ctns-/- Nlrp2-/- animals exhibit delayed development of Fanconi syndrome and kidney tissue damage. Specifically, we observed at 4-6 months of age that animals had less glucosuria and calciuria and markedly preserved renal tissue, as assessed by significantly lower levels of inflammatory cell infiltration, tubular atrophy, and interstitial fibrosis. Also, the mRNA expression of some inflammatory mediators (Cxcl1 and Saa1) and the rate of apoptosis were significantly decreased in 4-6-month old kidneys harvested from Ctns-/- Nlrp2-/- mice compared to those obtained from Ctns-/-mice. At 12-14 months of age, renal histological was markedly altered in both genetic models, although double KO animals had lower degree of polyuria and low molecular weight proteinuria and decreased mRNA expression levels of Il6 and Mcp1. Altogether, these data indicate that Nlrp2 is a potential pharmacological target for delaying progression of kidney disease in cystinosis.

Percutaneous kidney biopsies in children: a 24-year review in a tertiary center in northern Portugal.

INTRODUCTION: Percutaneous kidney biopsy (KB) is crucial to the diagnosis and management of several renal pathologies. National data on native KB in pediatric patients are scarce. We aimed to review the demographic and clinical characteristics and histopathological patterns in children who underwent native percutaneous KB over 24 years. METHODS: Retrospective observational study of patients undergoing native percutaneous KB in a pediatric nephrology unit between 1998 and 2021, comparing 3 periods: period 1 (1998-2005), period 2 (2006-2013), and period 3 (2014-2021). RESULTS: We found that 228 KB were performed, 78 (34.2%) in period 1, 91 (39.9%) in period 2, and 59 (25.9%) in period 3. The median age at KB was 11 (7-14) years. The main indications for KB were nephrotic syndrome (NS) (42.9%), hematuria and/or non-nephrotic proteinuria (35.5%), and acute kidney injury (13.2%). Primary glomerulopathies were more frequent (67.1%), particularly minimal change disease (MCD) (25.4%), IgA nephropathy (12.7%), and mesangioproliferative glomerulonephritis (GN) (8.8%). Of the secondary glomerulopathies, lupus nephritis (LN) was the most prevalent (11.8%). In group 1, hematuria and/or non-nephrotic proteinuria were the main reasons for KB, as opposed to NS in groups 2 and 3 (p < 0.01). LN showed an increasing trend (period 1-3: 2.6%-5.3%) and focal segmental glomerular sclerosis (FSGS) showed a slight decreasing trend (period 1-3: 3.1%-1.8%), without statistical significance. CONCLUSIONS: The main indication for KB was NS, which increased over time, justifying the finding of MCD as main histological diagnosis. LN showed an increase in incidence over time, while FSGS cases did not increase.