Kidney & blood pressure research最新文献

Introduction: Diabetic nephropathy (DN) is a serious complication of diabetes. In this study, we aimed to develop a diagnostic model for DN based on PANoptosis-related genes.

Methods: PANoptosis-related differentially expressed gene (DEGs) associated with DN were identified in the GSE96804 and GSE142025 datasets. Pairwise correlations among these genes were assessed via Pearson correlation analysis. Immune cell abundance in DN patients versus controls was compared in GSE96804. Feature genes for DN prediction were selected with machine learning, and a diagnostic model was constructed using LASSO regression. High-risk and low-risk groups were established based on risk scores, with GSEA used to explore enriched biological processes and pathways. The association between risk scores and immune cell infiltration was examined using CIBERSORT. Potential therapeutic drugs were investigated via the DGIdb database.

Results: Six PANoptosis-related DEGs were found. Immune cell analysis showed significant differences in dendritic cells, macrophages, mast cells, and neutrophils between DN patients and controls. A diagnostic model using three genes (PDK4, YWHAH, PRKX) achieved high accuracy (area under the curve = 0.8-1.0) across datasets, with a reliable nomogram for DN prediction. Risk stratification linked higher risk scores to distinct immune infiltration patterns and enriched cellular transport and metabolic pathways in high-risk DN patients. Protein-protein interaction network and correlation analyses revealed complex gene interactions. Potential therapeutic targets (PRKX, PDK4) and drugs were identified, and quantitative PCR validated YWHAH upregulation in patient plasma samples.

Conclusion: The integration of PANoptosis-related genes PDK4, YWHAH, and PRKX offers a promising diagnostic model for DN, with YWHAH potentially involved in the pathological progression of DN.

Background: Kidney transplantation was an effective method for treating chronic kidney failure via transplanting a healthy kidney from a donor to a patient with the loss of kidney function. However, clinical studies revealed that the posttransplantation status of patients was associated with a substantial aggregation of risk factors contributing to metabolic syndrome.

Summary: This article provided a comprehensive review of the current researches on metabolic syndrome after kidney transplantation, and the latest advances in the interaction between metabolism and immune cells were also covered.

Key messages: Our aim was to identify and intervene high-risk recipients in time and thus improving the prognosis of recipients.

Introduction: Kidney stone caused by calcium oxalate (CaOx) is a chronic kidney disease. Acyl-coenzyme A thioesterases (ACOTs) serve as the key regulators of fatty acid metabolism. However, ACOTs' effect on CaOx kidney stone formation remains to be explored. Here, we aimed to investigate the effect of ACOTs on CaOx kidney stone formation.

Methods: HK-2 and M-1 cells were cultured in DMEM/F12 medium supplemented with 10% FBS. Cells were treated with varying concentrations of calcium oxalate (CaOx) and transfected with siRNA or plasmid vectors targeting ACOT4 and ACOT6 using Lipofectamine RNAiMAX or Lipofectamine 3000. RT-qPCR and Western blotting were used to analyze gene and protein expression. Cell viability was assessed with CCK-8, and cell apoptosis was measured by flow cytometry. Crystal adhesion was visualized under a microscope. Lactate dehydrogenase (LDH) release was measured using a cytotoxicity assay kit. A kidney stone mouse model was established by injecting glyoxylic acid to induce kidney stones, and tissues were analyzed by Western blotting.

Results: The mRNA and protein levels of several ACOT family members were upregulated in HK-2 cells treated with CaOx (inducing cell injury). Knockdown of ACOT4 and ACOT6 significantly suppressed the activity of CaOx-pretreated HK-2 and M-1 cells, and promoted the crystal formation and LDH release, whereas overexpression of ACOT4 and ACOT6 reduced CaOx crystal-induced kidney cell injury. Furthermore, the levels of p-AKT and p-S6 decreased after ACOT4 and ACOT6 knockdown and increased following ACOT4 and ACOT6 overexpression, suggesting that both ACOT4 and ACOT6 activated Akt/mTOR signaling pathway in HK-2 cells. We also observed that knockdown of ACOT4 and ACOT6 induced the apoptosis of HK-2 cells after CaOx treatment. Inhibition of apoptosis using Z-VAD-FMK reversed the enhanced cell injury caused by CaOx treatment and ACOT4/6 knockdown, suggesting that knockdown of ACOT4 and ACOT6 promoted cell injury via inducing cell apoptosis.

Conclusions: ACOT4 and ACOT6 could be protecting factors for kidney cell injury induced by CaOx via reducing apoptosis and activating Akt/mTOR signaling pathway. The study of the role of ACOT4 and ACOT6 in kidney cell injury provides a new insight into the cause of CaOx kidney stone formation. Its in-depth study may provide new targets for stone treatment.

Introduction: IgA nephropathy (IgAN) is characterized by hematuria but can present with different clinical presentations. Proteinuria has been reported as the most important risk factor for the progression of IgAN and it may be related to podocyte injury.

Methods: The kidney biopsy samples from patients with IgAN were analyzed using immunohistochemistry for WT1 to determine podocyte density and transmission electron microscopy to assess ultrastructural changes in podocytes and adjacent structures. A comparative group of patients diagnosed with minimal change disease (MCD) and a control group of autopsy samples without kidney disease were included.

Results: Slit diaphragm density was lower in IgAN cases compared to controls but higher than in MCD cases. Podocyte density was significantly lower in the IgAN and MCD groups compared to controls, with the MCD group showing even lower density than the IgAN group. Podocyte density was lower in cases with nephrotic proteinuria both in MCD and IgAN. A significant negative correlation was detected between podocyte density and proteinuria in both conditions. A significantly lower proportion of detached podocytes was observed in cases with isolated autophagy and cases with autophagy showed a lower frequency of hematuria and a higher percentage of T0.

Conclusion: We demonstrated that podocyte alterations in IgAN correlate with clinical parameters, including nephrotic proteinuria, hematuria, and interstitial fibrosis. Podocyte loss was associated with necrosis and mitotic catastrophe, while autophagy was prevalent but not apoptosis. Autophagy appears to protect against podocyte detachment. These findings highlight pathophysiological mechanisms relevant to diagnostic and clinical practice.

Background: The pathogenesis of systemic lupus erythematosus (SLE) remains complex, and studies have found that abnormal lipid metabolism may be involved in the disease. Therefore, we aim to investigate the dyslipidemia in SLE patients and analyze the relationship between lipid metabolism and the disease activity.

Methods: A total of 174 patients diagnosed with SLE were enrolled in Henan Provincial People's Hospital from December 2016 to September 2022. Clinical data and laboratory indicators were collected, and SLE patients were grouped according to the levels of serum lipid. SPSS 26.0 statistical software was used for comparative analysis of SLE patients.

Results: The prevalence of dyslipidemia was about 92.53% (161/174), mainly with decreased high-density lipoprotein cholesterol (HDL; 125/174, 77.64%) and increased triglyceride (TG; 86/174, 53.42%). The lipids were positively correlated with inflammatory indexes, such as white blood cell (WBC), neutrophil, systemic immune-inflammation index (SII), neutrophil-to-lymphocyte ratio, lymphocyte-to-monocyte ratio, and so on. Furthermore, the blood lipid levels were significantly correlated with SLEDAI-2K, erythrocyte sedimentation rate, C3, C4, blood urea nitrogen (BUN), serum creatinine (Scr), and 24-h urine protein (p < 0.05). With the increasing types of dyslipidemia, the value of inflammatory indicators such as WBC and SII were higher, as well as the rate of kidney involvement. This is manifested by the elevation of renal function parameters such as BUN, Scr, eGFR and 24-h urine protein levels, while the levels of IgG, total protein and albumin decrease accordingly. The area under the curve (AUC) values of total cholesterol (TC), TG and low-density lipoprotein cholesterol (LDL) predicting lupus nephritis were 0.759, 0.713, and 0.729, which provided 69.6%, 81.4% and 63.7% sensitivity, and 76.4%, 56.9% and 73.6% specificity, respectively. With an AUC of 0.771, the combined detection of TC, TG, HDL, and LDL exhibited a greater potential for discrimination than any separate measurements.

Conclusions: Dyslipidemia is prevalent among SLE patients, and the levels of lipid can be informative in predicting renal involvement in SLE. It is crucial to monitor lipid levels and inflammation indexes and take lipid-lowering therapy along the discourse of SLE.

Introduction: Primary hyperoxaluria type 1 (PH1) is a rare autosomal recessive disorder caused by a deficiency of the hepatic peroxisomal enzyme alanine-glyoxylate aminotransferase, which catalyzes the conversion of glyoxylate to glycine, resulting in increased oxalate production. The clinical consequences of the progressive buildup of oxalates include nephrocalcinosis, nephrolithiasis, chronic kidney disease, and ultimately, renal failure with extra-renal involvement. The diagnosis of PH1 is challenging due to the non-specific nature of its symptoms and the need for costly genetic testing. For many years, the management of PH1 was mainly supportive care. Currently, we have access to novel RNA interference (RNAi) therapeutics, such as lumasiran and nedosiran, which reduce hepatic oxalate production; however, they are prohibitively expensive in most countries. The only curative treatment is liver transplantation, and in cases that progress to end-stage kidney disease (ESKD), simultaneous dual kidney and liver transplantation is usually indicated.

Case presentation: We present a case of a 46-year-old woman admitted to our clinic on the eighth day of post-kidney transplantation for evaluating the causes of delayed graft function. During the diagnostic work-up, PH1 was diagnosed. A biopsy of the transplanted kidney also revealed microvascular inflammation (MVI). The patient was treated with fluid therapy, a restrictive diet, pyridoxine, and initially, intensive hemodialysis. Given the identification of a genetic variant of the disease that responds well to pyridoxine treatment, and considering the exceedingly high cost of lumasiran therapy, this medication was not utilized. In addition, it was decided to administer methylprednisolone pulses, plasmapheresis, and immunoglobulin infusions in response to MVI. This treatment resulted in improvements in both clinical and laboratory parameters.

Conclusions: PH1 is a rare cause of calcium oxalate nephrolithiasis and nephrocalcinosis and should be considered in the differential diagnosis of patients with progressive renal failure. This case highlights the importance of early diagnosis, which allows optimal supportive and/or RNAi therapy and appropriate qualification for kidney transplantation in cases of ESKD. This is particularly important as isolated kidney transplantation (without concomitant liver transplantation) can lead to rapid loss of graft function and may ultimately prove futile.

Background: Pheochromocytomas and paragangliomas are rare chromaffin cell-derived tumors characterized by catecholamine-secreting activity. Pheochromocytomas account for 1.7% of pediatric hypertension cases. Surgical resection, the definitive pheochromocytoma treatment, carries risks of hemodynamic instability and cardiovascular complications. Nevertheless, mortality rates decreased significantly in the latter half of the 20th century due to effective perioperative blood pressure (BP) management. The literature on BP management tailored to pediatric pheochromocytoma is limited, while the sustained hypertension rate in this population is high (up to 90%) and related to a high risk of intraoperative complications. In this narrative review, we provide up-to-date recommendations regarding BP management to minimize perioperative comorbidities in children with pheochromocytoma.

Summary: Antihypertensive agents, primarily alpha (α)-blockers, should be promptly administered for suspected pheochromocytoma. Beta (β)-blockers may be introduced thereafter to counteract reflex tachycardia. The patient must be salt- and water-replete preoperation. Intraoperatively, stable hemodynamics should be ensured during anesthesia and surgery, and short-acting intravenous medications and resuscitation fluid should be supplied. Postoperatively, patients should be admitted to the pediatric intensive care unit for close monitoring for at least 24-48 h. Genetic testing is recommended for all pheochromocytoma patients. Identifying underlying mutations, like in succinate dehydrogenase subunit B, which is linked to a higher risk of multifocality and metastasis, is imperative for tailoring treatment strategies and prognostication.

Key messages: Achieving optimal outcomes in pediatric pheochromocytoma relies on preoperative BP optimization with appropriate antihypertensive agents, intraoperative hemodynamic stability, and postoperative routine long-term follow-up to monitor for complications, recurrence, and metastasis. Future research should prioritize well-designed prospective multicenter studies with adequate sample sizes and, where feasible, randomized controlled trials with standardized protocols and appropriate endpoints. These studies should focus on the efficacy and safety of preoperative nonselective versus selective α-blockers, whether as monotherapy or combined with other medications (e.g., calcium channel blockers and/or β-blockers), or treatment without preoperative anti-hypertensives.

Background: Renal fibrosis is a key driver of chronic kidney disease, often leading to end-stage renal disease (ESRD). Secreted phosphoprotein 1 (Spp1) is implicated in fibrotic processes, but its specific role in renal fibrosis, particularly associated with hydronephrosis, remains underexplored. This study investigates Spp1's involvement using transcriptomic analysis, machine learning, and clinical data integration.

Methods: Renal tissues from sham-operated mice with unilateral ureteral obstruction for 7 days were analyzed via transcriptome sequencing to identify differentially expressed genes (DEGs). Hub genes were identified through Weighted Gene Co-Expression Network Analysis and pathway enrichment. LASSO regression pinpointed potential biomarkers, with Spp1 validated in mouse and human samples through RT-PCR and immunohistochemistry. Clinical correlations were drawn from hydronephrosis patient data.

Results: Transcriptomic analysis revealed 5,219 DEGs, highlighting key pathways including IL-17, TNF, and PI3K/AKT. Spp1 emerged as a significant biomarker, strongly associated with tubular injury and fibrosis markers such as neutrophil gelatinase-associated lipocalin. Logistic regression and receiver operating characteristic (ROC) analysis confirmed Spp1 and urinary transferrin (U-TRF) as predictors of severe hydronephrosis, with high diagnostic accuracy (area under the ROC curve: 0.898 for Spp1; 0.938 for U-TRF).

Conclusions: Spp1 is a critical mediator in renal fibrosis and a promising biomarker for assessing hydronephrosis severity. Its diagnostic value, particularly when combined with U-TRF, underscores the need for further research into Spp1-targeted therapies in renal fibrosis.

Introduction: Acute kidney injury (AKI) is a rapid and often reversible decline in renal excretory function. Acetaminophen (APAP) overdose causes AKI. APAP nephrotoxicity is mostly due to the overproduction of reactive oxygen species (ROS). As no effective treatment for AKI is available, researchers are looking for natural and safe alternatives using plants. In this study, they aimed to evaluate the nephroprotective effects of Moringa oleifera (Mor), Mucuna pruriens (Muc), or milk thistle (MT) at the biochemical and molecular levels in an APAP-induced AKI mouse model.

Methods: AKI was induced in mice with a single intraperitoneal dose of APAP (1,000 mg/kg). The aqueous extracts of the three plants were given orally at 350 mg/kg daily for 21 days pre-AKI induction. Creatinine and BUN levels were measured in serum to assess kidney function. The oxidative stress and inflammatory indicators SOD, CAT, MDA, IL-6, and TNF-α were determined using colorimetric and ELISA kits, respectively. SIRT1 protein levels were determined by Western blot.

Results: Pretreatment with the three plant extracts significantly decreased the kidney biomarkers. SOD and CAT activities were enhanced with a decrease in MDA levels. IL-6 and TNF-α were also significantly lowered. A significant increase in SIRT1 expression was observed.

Conclusion: Pretreatment with Mor, Muc, and MT has a nephroprotective effect against APAP-induced kidney injury, regulating oxidative stress and inflammatory response.

Background: Genetic diseases collectively affect more than 300 million individuals worldwide, posing a significant health burden, as diagnosis is often challenging and therapeutic options are limited. Recent genetic technological advancements are improving the management of many inherited disorders, including genetic kidney disorders (GKDs), the leading cause of early-onset chronic kidney disease (CKD) and the cause of 10-15% of kidney replacement therapy in adults.

Summary: GKDs fall into different clinical categories, including cystic and fibro-cystic diseases in the setting of ciliopathies, rare conditions caused by the dysfunction of the primary cilium, typically characterized by multiorgan dysfunction. CKD is a significant cause of morbidity and mortality in these patients and a correct diagnosis is crucial for patient's management.

Key message: The present review analyzes whether advances in genomic technologies have provided benefit in the ciliopathy field, in both modeling renal diseases and improving patient's care.