Uric Acid Nephropathy Research Articles

Hyperuricaemia, gout and related adverse events associated with antihypertensive drugs: A real-world analysis using the FDA adverse event reporting system.

Background: The role of antihypertensive drugs in inducing hyperuricaemia and gout has been a long-term concern in clinical practice. However, clinical studies regarding this issue are limited in number and have yielded inconsistent results. We comprehensively evaluated the association between various antihypertensive drugs and the occurrences of hyperuricaemia, gout and related adverse events (AEs) using the FDA Adverse Event Reporting System (FAERS), aiming to guide the selection of antihypertensive drugs with a goal of minimizing the risk of hyperuricaemia, gout and related AEs. Methods: We used OpenVigil 2.1 to query the FAERS database. Hyperuricaemia, gout and related AEs were defined by 5 Preferred Terms: hyperuricaemia, gout, gouty arthritis, gouty tophus and urate nephropathy. Disproportionality analysis was performed, and a positive signal indicated an association between AEs and antihypertensive drugs. Results: The numbers of antihypertensive drugs with positive signals for hyperuricaemia, gout, gouty arthritis, gouty tophus and urate nephropathy were 46, 66, 27, 8 and 6, respectively. These drugs included diuretics, antihypertensive drugs with central action, α blockers, β blockers, α and β blockers, calcium channel blockers, angiotensin converting enzyme inhibitors, angiotensin II receptor blockers, renin inhibitors, vasodilators, and compound preparations. Furthermore, 42 antihypertensive drugs had positive signal for more than one AEs. Conclusion: Our study suggests that some potassium-sparing diuretics, calcium channel blockers and losartan may be associated with increased risk of hyperuricaemia, gout or related AEs, which is inconsistent with most previous studies. Moreover, Our study also suggests that some antihypertensive drugs with central action, α and β blockers, renin inhibitors and vasodilators may be associated with increased risk of hyperuricaemia, gout or related AEs, which has not been reported in previous studies. These findings complement real-world evidence on the potential risks of hyperuricaemia, gout and related AEs associated with antihypertensive drugs.

Mechanism of Xiezhuo Huayu Yiqi Tongluo Formula in the Treatment of Uric Acid Nephropathy Based on Network Pharmacology, Molecular Docking, and In Vivo Experiments.

Xiezhuo Huayu Yiqi Tongluo Formula (XHYTF) consists of 14 Chinese herbal medicines. In this study, we investigated the potential mechanism of XHYTF in the treatment of uric acid nephropathy (UAN) through network pharmacology, molecular docking, and in vivo methods. Using various pharmacological databases and analysis platforms, information on the active ingredients and targets of Chinese herbal medicine was collected, and UAN disease targets were retrieved using OMIM, Gene Cards, and NCBI. Then common target proteins were integrated. A Drug-Component-Target (D-C-T) map was constructed to screen core compounds and build a protein-protein interaction (PPI) network. Further, Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed for common targets, and a Drug-Component-Target-Pathway (D-C-T-P) network diagram was constructed. The molecular docking simulation was performed to verify the binding affinity between core components and hub targets. Subsequently, the UAN rat model was established, followed by the collection of serum and renal tissues. The expression levels of indicators in the serum were determined using an enzyme-linked immunosorbent assay. The pathological changes of renal tissues were detected using H & E staining and Masson staining. The expression of related proteins in renal tissue was detected by western blot. In the study, 216 active ingredients and 439 targets in XHYTF were screened, and 868 targets were identified as being related to UAN. Among them, 115 were common targets. Based on the D-C-T network, quercetin, luteolin, β-sitosterol, and stigmasterol were observed to be the key active ingredients of XHYTF that were effective against UAN. The analysis of the PPI network revealed TNF, IL6, AKT1, PPARG, and IL1β as the 5 key targets. GO enrichment analysis revealed that the pathways were mainly concentrated in cell killing, regulation of signaling receptor activity, and other activities. Subsequently, KEGG pathway analysis revealed that multiple signaling pathways, including the HIF-1, PI3K-Akt, IL-17, and other signaling pathways, were closely related to the action of XHYTF. All 5 key targets were confirmed to interact with all core active ingredients. In vivo experiments indicated that XHYTF significantly reduced blood uric acid and creatinine levels, alleviated inflammatory cell infiltration in kidney tissues, reduced the levels of serum inflammatory factors such as TNF-α and IL1β, and ameliorated renal fibrosis in rats with UAN. Finally, western blot revealed decreased levels of PI3K and AKT1 proteins in the kidney, which confirmed the hypothesis. Collectively, our observations demonstrated that XHYTF significantly protects kidney function, including alleviation of inflammation and renal fibrosis via multiple pathways. This study provided novel insights into the treatment of UAN using traditional Chinese medicines.

CiteSpace-based visualization of Chinese medicine for uric acid nephropathy

Objective: To analyze the research status and trend of Chinese medicine for the treatment of uric acid nephropathy in the past 30 years. Methods: The database of China Knowledge Network (CNKI) was searched, and CiteSpace analysis software was used to visualize and analyze the annual number of articles, authors, institutions, key words and emergent words. Results: A total of 767 relevant research papers were included. The number of annual publications showed a stable increasing trend; teams with close cooperation, such as Jiacai Hu's team, Dongdong Li's team, Nietao Guo's team and Fengxian Meng's team, were formed. A cluster of core research institutions including Beijing University of Traditional Chinese Medicine, Shuguang Hospital affiliated to Shanghai University of Traditional Chinese Medicine and Tianjin University of Traditional Chinese Medicine has been formed. Key words related mapping showed. Conclusion: Chinese medicine research on uric acid nephropathy is being developed and improved, and the combination of Chinese and Western medicine is highly valued. Basic experimental research on oxidative stress, inflammatory response, and disease prevention may be a hot spot for future research. Interdisciplinary, interdisciplinary and talent exchange and cooperation need to be strengthened, and further explored at the microscopic level through research in order to exploit the advantages of TCM in disease treatment.

Urate Nephropathy: A Rare Case Report

Acute hyperuricemia most commonly occurs in patients who experience tumor-lysis syndrome. Hyperuricemiaalong with other electrolyte abnormalities like hyperkalemia, hypocalcemia, and hyperphosphatemia leads to acutekidney injury (AKI) due to acute uric acid nephropathy which is associated with significant morbidity. High riskpatients are thus closely monitored for signs of these laboratory abnormalities. Extreme exercise, rhabdomyolysis,and seizures are rare causes of acute hyperuricemia. Serum uric acid level is not routinely monitored as a partof postictal labs. We report an unusual case of AKI in a young male and no associated rhabdomyolysis who wasfound to have acute uric acid nephropathy. Timely administration of Rasburicase prevented the need for dialysisin this patient and led to complete renal recovery. This case illustrates the importance of doing a urine microscopyand checking uric acid level in patients who develop unexplainable AKI, as timely management helps improveoutcome.

Uric acid accumulation in the kidney triggers mast cell degranulation and aggravates renal oxidative stress

The accumulation of uric acid (UA) in the body can lead to the occurrence of hyperuricemia or uric acid nephropathy. Mast cells (MCs) increase oxidative stress and release renin to promote the production of Ang II. The aim of this study was to investigate the effect of UA on MCs in rat kidneys and the association between MCs and renal injury. Our results show that UA accumulation in the kidney stimulated the degranulation of MCs and the release of renin to promote Ang II production, resulting in renal oxidative stress, mitochondrial structural damage, and microvascular system damage. The expression of urate-related transporters was regulated by the UA level and serum urinary toxins levels were substantially elevated in hyperuricemia. Administration of the MCs membrane stabilizer sodium cromoglycate (SCG) or the angiotensin receptor antagonist Valsartan decreased the production of renin and Ang II and relieved renal oxidative stress, mitigated mitochondrial structural damage and microvascular system damage, and promoted the excretion of UA and urinary toxins by increasing the expression of urate-related transporters. These results demonstrate that the accumulation of UA in the kidney can trigger the degranulation of MCs and promote the development of renal oxidative stress. Administration of SCG and Valsartan ameliorated UA-induced renal injury by inhibiting MCs degranulation and reducing renal oxidative stress by inhibiting renin and Ang II production and accelerating renal clearance of UA and uremic toxins.

A case of multiple myeloma with unusual presentation

Extramedullary plasmacytoma is a rare and unusual complication of multiple myeloma (MM). Some sites for the extramedullary involvement of MM are the liver, spleen, lymph node, lung, and skin. Renal failure is another complication of MM due to myeloma kidney, uric acid nephropathy, hemoconcentration, or light chain disease. This study reported a case of MM with unusual presentation. She was a 61-year-old woman who was admitted to the internal ward due to severe renal failure, anemia, mild proteinuria, hypertension, thrombocytopenia, and soft tissue mass in both lungs in the spiral computed tomography (CT) scan. In the skull X-ray, there was not any lytic lesion. Further, plasma cells greater than 30% were observed in serum protein electrophoresis pick of gamma region and in the bone marrow aspiration, so the final diagnosis of the patients was MM with extramedullary plasmacytoma.

Analysis of Correlation between Serum Uric Acid and Diabetes Nephropathy

Analysis of Correlation between Serum Uric Acid and Diabetes Nephropathy

Pseudohyperkalemia in Chronic Lymphocytic Leukemia: An Often Overlooked Clinical Entity.

Chronic lymphocytic leukemia (CLL) is the most common indolent leukemia in the United States (Bnaya et al., 2021). Metabolic complications (e.g., hyperkalemia, hyperuricemia, hypocalcemia) are particularly common in patients with unstable CLL and are caused by rapid cellular destruction (Higdon et al., 2018). Empirical reports emphasize that these derangements can lead to acute urate nephropathy, sudden cardiac arrest, and death, particularly with progressive disease or in those receiving active CLL-directed therapy (Higdon et al., 2018; Koehler et al., 2020).

Febuxostat Improves Uric Acid Levels and Renal Function in Patients with Chronic Kidney Disease and Hyperuricemia: A Meta-Analysis.

Background Uric acid nephropathy, also known as hyperuricemia nephropathy or gouty nephropathy, is characterized by uric acid crystal deposition and inflammatory cell infiltration. Herein, we aimed to demonstrate the role of febuxostat on uric acid levels and renal function in patients with chronic kidney disease and hyperuricemia. Methods Eight databases included were searched for clinical randomized controlled trials. Meanwhile, the confidence interval (CI) of either relative risk or mean difference was set to 95%. Besides, the heterogeneity of the research results is tested by I2. Results Ten studies were ultimately included in this meta-analysis. All of them were considered to be random controlled trials. 10 studies reported the serum uric acid of the test group and the control group, which was significantly lower (SMD: -146.44, 95% Cl: -195.96, -86.93, and P < 0.01) than the control group, EGFR (SMD: 3.21, 95% Cl: 1.17, 5.25, and P < 0.01), serum creatinine (SMD: -15.27, 95% Cl: -20.75, -9.79, and P < 0.01), serum urea nitrogen (SMD: -2.37, 95% Cl: -3.31, -1.61, and P < 0.01), and adverse reactions (OR: 0.74, 95% Cl: 0.32, 1.68, and P = 0.47). Conclusion The results of this study suggest that febuxostat may be effective in patients with CKD with HUA, as evidenced by serum uric acid, creatinine, urea nitrogen, and EGFR. However, large sample, multicenter, low risk of bias clinical studies, as well as basic medical research, are needed.

Novel insights into NOD-like receptors in renal diseases.

Nucleotide-binding oligomerization domain-like receptors (NLRs), including NLRAs, NLRBs (also known as NAIPs), NLRCs, and NLRPs, are a major subfamily of pattern recognition receptors (PRRs). Owing to a recent surge in research, NLRs have gained considerable attention due to their involvement in mediating the innate immune response and perpetuating inflammatory pathways, which is a central phenomenon in the pathogenesis of multiple diseases, including renal diseases. NLRs are expressed in different renal tissues during pathological conditions, which suggest that these receptors play roles in acute kidney injury, obstructive nephropathy, diabetic nephropathy, IgA nephropathy, lupus nephritis, crystal nephropathy, uric acid nephropathy, and renal cell carcinoma, among others. This review summarises recent progress on the functions of NLRs and their mechanisms in the pathophysiological processes of different types of renal diseases to help us better understand the role of NLRs in the kidney and provide a theoretical basis for NLR-targeted therapy for renal diseases.

Kidney and plasma metabolomics provide insights into the molecular mechanisms of urate nephropathy in a mouse model of hyperuricemia

Hyperuricemia (HUA) is closely associated with kidney damage and kidney diseases in humans; however, the underlying mechanisms of HUA-induced kidney diseases remain unknown. In the present study, we examined the kidney and plasma metabolic profiles in a HUA mouse model constructed by knocking out (Ko) the urate oxidase (Uox) gene. The Uox-Ko mice were characterized by an increase in uric acid, glycine, 3′-adenosine monophosphate, citrate, N-acetyl-l-glutamate, l-kynurenine, 5-hydroxyindoleacetate, xanthurenic acid, cortisol, and (−)-prostaglandin e2 together with a decrease of inosine in the kidneys. These altered metabolites confirmed disturbances of purine metabolism, amino acid biosynthesis, tryptophan metabolism, and neuroactive ligand-receptor interaction in Uox-Ko mice. Betaine and biotin were related to kidney function and identified as the potential plasma metabolic biomarker for predicting urate nephropathy (UN). Taken together, these results revealed the underlying pathogenic mechanisms of UN. Investigating these pathways might provide novel targets for the therapeutic intervention of UN and can potentially lead to new treatment strategies.

A Retrospective Case-Control Study on Late Failure of Arteriovenous Fistula in Hemodialysis Patients and Prediction of Risk Factors.

Objective A retrospective case-control study was conducted to explore the risk factors of late failure of arteriovenous fistula in hemodialysis patients. Methods A total of 95 hemodialysis patients treated in our hospital from January 2018 to January 2021 were included. The HE staining results of late failure of arteriovenous fistula in hemodialysis patients were observed. The general data and laboratory indexes of the patients were recorded by using a questionnaire survey, hospital case system, and hemodialysis record. According to the functional status of internal fistula, the patients were divided into two groups: failure group (n = 35) and patency group (n = 60). SPSS22.0 software was employed for statistical analysis, and the relevant data of the two groups were compared. The independent sample t-test was employed for the comparison of variance between groups, and the χ2 test was employed for counting data. Logistic multivariate regression was employed to analyze the risk factors of late loss of power in autologous arteriovenous fistula (AVF). Results (1) Late failure of arteriovenous fistula in hemodialysis patients: the results of HE staining showed the following: (1) histological changes of venous intima: 100% of the patients had varying degrees of intimal hyperplasia, mainly eccentric hyperplasia, resulting in luminal stenosis, and annular uniform intimal hyperplasia in some patients, and (2) histological changes of venous media: 81.6% of the patients had venous media lesions, which were mainly in two cases; one was media smooth muscle hyperplasia with fibrous tissue hyperplasia, and the other was smooth muscle compression when intimal hyperplasia was serious, resulting in smooth muscle fiber rupture, disarrangement, focal necrosis, atrophy, and thinning, and some smooth muscle stroma showed vitreous degeneration and myxoid degeneration. A few cases showed multifocal neutrophil, lymphocyte, and plasma cell infiltration. (2) First of all, we surveyed the general data, and there were significant differences in age, history of diabetes, history of hypertension, and uric acid nephropathy (P < 0.05). There was no significant difference in sex, body mass index, smoking history, polycystic kidney disease, chronic glomerulonephritis, and obstructive nephropathy between the two groups (P > 0.05). Secondly, we compared the levels of hemoglobin, eosinophils, platelet count, and hematocrit. The levels of hemoglobin, eosinophils, and hematocrit in the failure group were higher, and the platelet count was lower compared to that of the unobstructed group (P < 0.05). Furthermore, the calcium and phosphorus product and the level of C-reactive protein (CRP) in the failure group were higher, while the levels of fibrinogen and INR in the unobstructed group were lower. The levels of plasma protein, alkaline phosphatase, and cholesterol were higher in the failure group, while the level of triglyceride was lower in the failure group (P < 0.05). Finally, logistic regression analysis showed that age, hemoglobin, hematocrit, and calcium-phosphorus product were the risk factors for late failure of arteriovenous fistula in hemodialysis patients (P < 0.05). There exhibited no significant correlation between diabetes, hypertension, uric acid nephropathy, eosinophil, CRP, fibrinogen, INR, plasma protein, alkaline phosphatase, cholesterol, triglyceride, and late failure of arteriovenous fistula in hemodialysis patients. Conclusion Age, hemoglobin, hematocrit, and calcium-phosphorus product are independent risk factors for late failure of arteriovenous fistula in hemodialysis patients. The hemoglobin, eosinophil, platelet count, and hematocele in hemodialysis patients with late failure of arteriovenous fistula were higher. The indexes related to biochemistry, blood coagulation, and nutrition were significantly different from those without late failure of arteriovenous fistula. Thus, the risk of late failure of arteriovenous fistula can be predicted.

Alteration of Gut Microbiome and Correlated Amino Acid Metabolism Contribute to Hyperuricemia and Th17-Driven Inflammation in Uox-KO Mice.

Although gut dysbiosis had been demonstrated to be an important factor affecting hyperuricemia (HUA) and gout, little is known for its potential mechanistic connections. In this study, Uox-KO mice model that with spontaneously developed pronounced HUA and urate nephropathy was used to explore the pathophysiologic mechanism of microbiota alterations in HUA and gout with integrated multi-omics analysis. 16S rRNA gene sequencing was performed to characterize the characteristic bacteria, and untargeted LC/MS analysis was applied to reveal the featured metabolites. Our results showed there was a significant shift in gut microbiota composition and function in Uox-KO mice compared to WT mice and apparent metabolomics differences between the two groups. Among them, amino acids metabolism appears to play a critical role. Correlation analysis further revealed that the characteristic metabolites were strongly influenced by the discrepant bacterial genera. Furthermore, impairment of intestinal integrity and profound alterations in the profile of solute carrier family resulted in dysregulation of amino acids transportation, which subsequently impacted serum uric acid level and CD4+ Th17 driven inflammation. Together, these data indicate that gut dysbiosis promotes purine metabolism disorder and inflammation in Uox-KO mice. Remodeling the gut microbiota is a promising strategy to combat HUA and gout.

ГИПЕРУРИКЕМИЯ: КЛИНИЧЕСКИЕ ПОСЛЕДСТВИЯ, СЕРДЕЧНО-СОСУДИСТЫЙ РИСК, СОВРЕМЕННЫЙ ПОДХОД К ТЕРАПИИ

Introduction. In recent decades, increased attention has been paid to hyperuricemia due to the widespread prevalence of this pathology in the population (16.8%), the presence of a connection with the risk of developing cardiovascular diseases, as well as the variety of its clinical consequences. Aim. A review of current data on the causes of hyperuricemia, clinical aspects, the effect of hyperuricemia on cardiovascular risk, and the current view of therapy, including asymptomatic hyperuricemia. Material and methods. The review carried out topical medical publications in foreign and domestic literature on this issue, accumulated at the present time. Results and discussion. An increase in uric acid level can occur as a result of inaccuracies in the diet, taking certain medications, impaired excretion of uric acid due to impaired renal function and other reasons. Hyperuricemia is the main cause of gout, which can manifest itself as acute gouty arthritis, chronic topical arthritis, urate nephropathy, and other diseases. Modern research shows that an increase in serum uric acid concentration is associated with an increased cardiovascular risk. Acting as an independent predictor of arterial hypertension, coronary heart disease, chronic heart failure, chronic kidney disease. Treatment with xanthine oxidase inhibitors (allopurinol, febuxostat) can affect hyperuricemia, gout, and various forms of ischemic and vascular damage. As evidence of the efficacy of urate-lowering therapy remains controversial, these drugs are not currently indicated for routine prophylactic treatment in patients without gout symptoms. In 2018, specialists in the field of hyperuricemia proposed an algorithm for the management of patients with asymptomatic hyperuricemia. However, the algorithm is not recommended for everyday practice due to further research's need to verify it. Conclusion. Classic manifestations of hyperuricemia such as gout and kidney damage remain the main indications for urate-lowering therapy. At the same time, the increased cardiovascular risk in hyperuricemia, proven by numerous studies, requires special attention in treating patients with comorbid pathology. Diet and lifestyle changes remain an integral part of therapy. The final decision on the need for pharmacological treatment of patients with asymptomatic hyperuricemia with xanthine oxidase inhibitors is made individually. The development of algorithms and indications for the appointment of urate-lowering therapy continues. Recommendations for drug therapy for hyperuricemia are only possible after large, double-blind, placebo-controlled, randomized trials.

The Active Components of Sunflower (Helianthus annuus L.) Calathide and the Effects on Urate Nephropathy Based on COX-2/PGE2 Signaling Pathway and the Urate Transporter URAT1, ABCG2, and GLUT9.

The sunflower (Helianthus annuus L.) calathide is gradually used as an alternative treatment for hyperuricemia; nevertheless, evidence regarding its main components and therapeutic capacity for urate nephropathy is lacking. Identification of sunflower calathide aqueous extract (SCE) was rapidly done by UPLC-ESI-Q-Orbitrap, and 32 water-soluble compounds with a comprehensive score >80 were discovered. Besides, yeast extract was administrated to induce high UA levels and hyperuricemic renal injury. We found that SCE treatment not only decreased UA levels to a comparable degree as allopurinol and benzbromarone, but also reduced the BUN levels and participated in kidney injury repair induced by uric acid. Moreover, it regulated the expression of URAT1 and ABCG2, especially inhibiting the GLUT9 in the normal kidney. Results were multifacetedly evaluated with a view to suggesting a possible mechanism of action as compared with those of allopurinol and benzbromarone by western blotting, H&E staining, and immunohistochemistry. However, the H&E staining showed histological changes in model, benzbromarone, and allopurinol groups rather than SCE treatments, and at the same time, the uric acid was identified as a cause of renal damage. The antiinflammatory effects and the regulations of COX-2/PGE2 signaling pathway were revealed on the LPS-induced RAW264.7 cells, indicating that the SCE not only increased cellular proliferation but also downregulated the COX-2, PGE2, NO, and IFN-γ cytokines in the RAW264.7 cells. To conclude, the SCE acts on urate transporters and contributes to prevent urate nephropathy via alleviating inflammatory process involving COX-2/PGE2 signaling pathway. It is available to develop SCE as food supplemental applications for hyperuricemia and nephritic inflammation.

Bmk9 and Uricase Nanoparticle Complex for the Treatment of Gouty Arthritis and Uric Acid Nephropathy.

Uric acid is the final product of purine metabolism, and excessive serum uric acid can cause gouty arthritis and uric acid nephropathy. Therefore, lowering the uric acid level and alleviating inflammation in the body are the key points to treating these diseases. A stable nanosuspension of peptide BmK9 was prepared by the precipitation-ultrasonication method. By combining uricase on the surface of a positively charged carrier, a complex consisting of neutral rod-shaped BmK9 and uricase nanoparticles (Nplex) was formed to achieve the delivery of BmK9 and uricase, respectively. The formulation of Nplex has a diameter of 180 nm and drug loading up to 200%, which releases BmK9 and uricase slowly and steadily in drug release tests in vitro. There was significantly improved pharmacokinetic behavior of the two drugs because Nplex prolonged the half-life and increased tissue accumulation. Histological assessments showed that the dual drug Nplex can reduce the inflammation response in acute gouty arthritis and chronic uric acid nephropathy in vivo. In the macrophage system, there was lower toxicity and increased beneficial effect on inflammation with Nplex than free BmK9 or uricase. Collectively, this novel formulation provides a dual drug delivery system that can treat gouty arthritis and uric acid nephropathy.

Современные возможности патогенетического лечения пациентов с нарушениями пуринового обмена

Introduction. Purine dysmetabolism is occured by increased production of uric acid, which leads to hyperuricemia and hyperuricuria. The most common forms of purine metabolism disorders are the uratenephropathy, gout, and asymptomatic hyperuricemia. Purpose. To evaluate the data published from 1992 to 2021 on the prevalence, forms of purine metabolism disorders, diagnostics and methods of their treatment. Two hundred and seventy original publications were identified, of which 37 were selected and analyzed. Materials and methods. The search results in the scientific database PubMed, Web of Sciеnce, Sciеnce Direct were analyzed for the queries «urates», «gout», «uric acid», «purine metabolism», «hyperuricosuria», «treatment of urate nephrolithiasis», «luteolin; quercetin», «Smilax riparia». Results. Urates are formed as a result of the metabolism of purine bases, two-thirds of which are excreted with urine. The most common form of purine dysmetabolism is urate nephrolithiasis, which accounts for up to 10% of all forms of kidney stone disease. The main risk factors include low urinary pH, decreased urine output and hyperuricosuria. Treatment options for such stones depend on the size, chemical composition, location, and concomitant diseases. The main methods of treatment are conservative therapy and surgical interventions. Conclusions. Since the available conservative therapy may not be suitable for all patients, and surgical intervention carries certain risks, a unique herbal complex «Uralix®» was created to treat patients with urate stones in the kidneys and urinary tract. Its components luteolin, quercetin and sarsaparilla extract reduce uric acid levels and improve renal function in urate nephropathy.

"Acute Hyperuricemia Secondary to Epileptic Seizures Leading to Acute Urate Nephropathy: A Case report"

"Acute Hyperuricemia Secondary to Epileptic Seizures Leading to Acute Urate Nephropathy: A Case report"

Гіперурикемія — незалежний фактор прогресування хронічної хвороби нирок

Мета — вивчення ефективності комплексної гіпоурикемічної терапії в пацієнтів з гіперурикемією, уратною нефропатією на тлі супутньої патології (цукровий діабет 2-го типу, артеріальна гіпертензія) на підставі динаміки урикемії, урикозурії, функціонального стану нирок, мінімізації й усунення ризик-факторів прогресування хронічної хвороби нирок. У дослідженні брали участь 67 пацієнтів. Корекція гіперурикемії в пацієнтів з уратною нефропатією із супутньою патологією (цукровий діабет 2-го типу, артеріальна гіпертензія) із застосуванням фітодіуретика Уролесан® у комплексному лікуванні приводила до нормалізації процесів обміну сечової кислоти, покращення швидкості клубочкової фільтрації та зменшення рівня екскреції альбуміну.

The Rho kinase signaling pathway participates in tubular mitochondrial oxidative injury and apoptosis in uric acid nephropathy.

IntroductionOxidative stress is a pathologic feature of hyperuricemia that is highly prevalent and that contributes to kidney tubular interstitial fibrosis. Rho-kinase is closely related to mitochondrial-induced oxidative stress. Herein, we designed a study to explore the expression and role of Rho-kinase in hyperuricemia nephropathy. The secondary objective was to investigate whether the Rho-kinase signaling pathway regulates hyperuricemic tubular oxidative injury and apoptosis via the mitochondrial pathway in addition to the mechanisms that are involved.Materials and methodsHK-2 cells were divided into the following five groups: normal; uric acid (UA); UA+Fasudil; UA+ROCK1 si-RNA; and UA+sc-siRNA. Rho-kinase activity, mitochondrial oxidative injury, and apoptosis-related protein levels were measured in each group. A t-test was used to analyze the difference between groups.ResultsMyosin phosphatase target subunit 1 (MYPT1) overexpression was shown in HK-2 cells, which was caused by UA. High concentrations of UA also up-regulated Rho-kinase expression and mitochondrial and apoptosis-related protein expression, while treatment with fasudil and ROCK1 si-RNA significantly attenuated these responses.ConclusionThe Rho-kinase signaling pathway participates in tubular mitochondrial oxidative injury and apoptosis via regulating mitochondrial dyneins/biogenic genes in UA nephropathy, which suggests that the mitochondrial pathway might be a potential therapeutic target for hyperuricemia nephropathy.