OBJECTIVES: To analyze the differentially expressed exosomal miRNAs in patients with chronic heart failure (CHF) complicated by hyperuricemia (HUA) and explore their potential as novel diagnostic molecular markers and their target genes. METHODS: This study was conducted among 30 CHF patients with HUA (observation group) and 30 healthy volunteers (control group) enrolled between September, 2020 and September, 2023. Peripheral blood samples were collected from 6 CHF patients with HUA for analyzing exosomal miRNAs by high-throughput sequencing, and the results were validated in the remaining 24 patients using qRT-PCR. GO and KEGG enrichment analyses were performed to predict the the target genes of the identified differential miRNAs. We also validated the differentially expressed miRNAs by animal experiment. RESULTS: A total of 42 differentially expressed exosomal miRNAs were detected in observation group by high-throughput sequencing; among them, miR-27a-5p was significantly upregulated (P=0.000179), and miR-139-3p was significantly downregulated (P=0.000058). In the 24 patients with both CHF and PUA, qRT-PCR validated significant upregulation of miR-27a-5p (P=0.004) and downregulation of miR-139-3p (P=0.005) in serum exosomes. When combined, miR-27a-5p and miR-139-3p had a maximum area under the curve (AUC) of 0.899 (95% CI: 0812-0.987) for predicting CHF complicated by HUA. GO and KEGG enrichment analyses suggested that the differential expressions of miR-27a-5p and miR-139-3p was associated with the activation of the AMPK-mTOR signaling pathway to activate the autophagic response. We obtained the same conclusion from animal experiment. CONCLUSIONS Upregulated exosomal miR-27a-5p combined with downregulated exosomal miR-139-3p expression can serve as a novel molecular marker for diagnosis of CHF complicated by HUA, and their differential expression may promote autophagy in cardiomyocytes by activating the AMPK-mTOR signaling pathway.
Humans ; Hyperuricemia/diagnosis* ; Heart Failure/genetics* ; MicroRNAs/metabolism* ; Exosomes/metabolism* ; Chronic Disease ; Male ; Female ; Middle Aged ; Animals

BACKGROUND: Hyperuricemia is associated with the development and progression of chronic kidney disease (CKD) as well as cardiovascular diseases. However, there is no consistent recommendation regarding the treatment of asymptomatic hyperuricemia (AHU) in CKD patients. Here, we surveyed Korean physicians’ perceptions regarding the diagnosis and management of AHU in CKD patients. METHODS: Questionnaires on the management of AHU in CKD patients were emailed to regular members registered with the Korean Society of Nephrology. RESULTS: A total of 158 members answered the questionnaire. Among the respondents, 49.4%/41.1% were considered hyperuricemic in male CKD patients whereas 36.7%/20.9% were considered hyperuricemic in female CKD patients when defined by serum uric acid level over 7.0/8.0 mg/dL, respectively. A total of 80.4% reported treating AHU in CKD patients. The most important reasons to treat AHU in CKD patients were renal function preservation followed by cerebro-cardiac protection. Majority of respondents (59.5%) thought that uric acid-lowering agents (ULAs) were the most effective method for controlling serum uric acid levels. Approximately 80% chose febuxostat as the preferred medication. A total of 32.3% and 31.0%, respectively, initiated ULA treatment if the serum uric acid level was more than 8.0 or 9.0 mg/dL, respectively. In addition, 39.2% and 30.4% answered that target serum uric acid levels of less than 6.0 or 7.0 mg/dL, respectively, were appropriate. The two major hurdles to prescribing ULAs were concerns of adverse reactions and the existing lack of evidence (i.e., the absence of Korean guidelines). CONCLUSION: Most Korean physicians treat AHU in CKD patients to prevent CKD progression and cerebro-cardiovascular complications.
Cardiovascular Diseases ; Diagnosis ; Electronic Mail ; Febuxostat ; Female ; Humans ; Hyperuricemia ; Male ; Methods ; Nephrology ; Renal Insufficiency, Chronic ; Surveys and Questionnaires ; Uric Acid

Gout is a chronic systemic metabolic disease characterized by recurrent attacks of inflammatory arthritis resulting from the precipitation of monosodium urate crystals, which has various clinical and pathological manifestations. The disease is associated with multiple comorbidities, an impaired quality of life, and a heavy economic burden. The incidence and prevalence of gout is increasing in many developed and developing countries, as in Korea. Gout is diagnosed by confirming monosodium urate crystals in the synovial fluid or affected tissue. If crystal documentation is unavailable, new gout classification criteria presented by the American College of Rheumatology and European League Against Rheumatism (ACR/EULAR) in 2015 can be applied. There are many guidelines for managing gout published in the United States, Japan, and Europe. However, there are no guidelines for the tailored management of gout for Korean patients. This review describes a new classification for the diagnosis of gout and management guidelines.
Arthritis ; Classification* ; Comorbidity ; Developing Countries ; Diagnosis ; Europe ; Gout* ; Humans ; Hyperuricemia ; Incidence ; Japan ; Korea ; Metabolic Diseases ; Prevalence ; Quality of Life ; Rheumatic Diseases ; Rheumatology ; Synovial Fluid ; United States ; Uric Acid

Adult ; Genetic Background ; Gout ; diagnosis ; genetics ; urine ; Humans ; Hyperuricemia ; diagnosis ; genetics ; urine ; Kidney Diseases ; diagnosis ; genetics ; urine ; Male ; Uric Acid ; urine ; Young Adult

Gout is an inflammatory arthritis characterized by deposition of monosodium urate crystals in joints. Though gout frequently involves the big toe or other extremities, it rarely occurs in the spinal canal. A 35-year-old man presented with left L5 radiculopathy. He had leg pain for 8 months and received several epidural steroid injections. Magnetic resonance imaging revealed a 1.7×1.1-cm ovoid contrast-enhancing mass, causing pressure erosion of the left L5 pedicle. Microscopic laminotomy was performed at the left L5 lamina. White chalky materials, identified at the left lateral recess of the spinal canal, were removed in a piecemeal manner. The histopathologic diagnosis was tophaceous gout. Although the patient's radiating pain did not resolve postoperatively, it was dramatically relieved with uric acid-lowering medications. If a mass effect is suspected, surgical removal of gouty tophi might aid in symptom release and definite diagnosis. Medical treatment after rheumatology consultation is crucial.
Adult ; Arthritis ; Arthritis, Gouty ; Diagnosis ; Extremities ; Gout* ; Hallux ; Humans ; Hyperuricemia ; Joints ; Laminectomy ; Leg ; Magnetic Resonance Imaging ; Radiculopathy ; Rheumatology ; Spinal Canal* ; Uric Acid ; Zygapophyseal Joint

Gout, which is caused by the deposition of monosodium urate crystals in synovial fluid and other tissues, is the most common inflammatory rheumatic disease in men, at least in the Western world, and is increasing in prevalence worldwide. In addition to extremely painful recurrent acute and chronic arthritis, gout is associated with chronic kidney diseases and metabolic syndrome, including dyslipidemia, hypertension, hyperglycemia, and obesity. Thus it has an impact on morbidity and premature mortality. For the proper management of gout, definite diagnosis should come first. Management plans for the treatment of gout have to be designed to meet the requirements of each individual patient and to control both gout and its associated disorders. The goals of treatment for gout are fast pain relief and the prevention of future gout attacks and long-term complications, such as joint destruction and other comorbidities. In this article, recent advanced non-pharmacologic and pharmacologic management strategies for gout and hyperuricemia will be described.
Arthritis ; Comorbidity ; Diagnosis ; Dyslipidemias ; Gout* ; Humans ; Hyperglycemia ; Hypertension ; Hyperuricemia ; Joints ; Male ; Mortality, Premature ; Obesity ; Prevalence ; Renal Insufficiency, Chronic ; Rheumatic Diseases ; Synovial Fluid ; Uric Acid ; Western World

Tumor lysis syndrome (TLS) is an oncologic emergency due to the rapid lysis of tumor cells and subsequent release of large amounts of intracellular potassium, phosphate, and uric acid into the bloodstream. Precipitation of uric acid and/or calcium phosphate crystals in the renal tubules can result in acute kidney injury. TLS is frequently observed in children with malignancy, which has high tumor burden, rapid cell turnover or high chemosensitivity (particularly, Burkitt's lymphoma and acute lymphoblastic leukemia), following the initiation of cytotoxic therapy. The current recommendations for prophylaxis and management are based on the TLS risk stratification. It is essential to administer adequate fluid and hypouricemic agents (allopurinol and/or rasburicase) to prevent acute kidney injury. In children susceptible to TLS, prompt diagnosis and aggressive treatment, such as renal replacement therapy, should be performed through close monitoring.
Acute Kidney Injury ; Burkitt Lymphoma ; Calcium ; Child ; Diagnosis ; Emergencies ; Humans ; Hyperkalemia ; Hyperphosphatemia ; Hyperuricemia ; Hypocalcemia ; Monitoring, Physiologic ; Potassium ; Primary Prevention ; Renal Replacement Therapy ; Tumor Burden ; Tumor Lysis Syndrome* ; Uric Acid

To explore the correlation between hyperuricemia and renal damage in patients with lupus nephritis (LN).
 Methods: The data for clinical features, laboratory and renal pathological examination were collected from 177 renal biopsy-proven LN patients with or without hyperuricemia and were retrospectively analyzed to determine the correlation between serum uric acid and renal damage.
 Results: LN patients with hyperuricemia group had higher rate of hypertension and higher level of blood urea nitrogen and serum creatinine while lower estimated glomerular filtration rate (eGFR) and lower positive rate of anti-U1RNP antibody (P<0.05). In the LN patients with hyperuricemia group, renal pathological scores, including acitive index, chronic index and tubulointerstitial lesions, were higher than those in the LN patients without hyperuricemia group (P<0.05). The level of serum uric acid was positively correlated with serum creatinine, renal pathological classification and renal pathological scores while negatively correlated with eGFR (P<0.05).
 Conclusion: LN patients with hyperuricemia are associated with more serious renal damage. Hyperuricemia is an important predictor for poor prognosis in patients with LN.
Blood Urea Nitrogen ; Creatinine ; blood ; Female ; Glomerular Filtration Rate ; physiology ; Humans ; Hypertension ; Hypertension, Renal ; Hyperuricemia ; epidemiology ; Kidney ; pathology ; Lupus Nephritis ; complications ; diagnosis ; Male ; Prognosis ; Retrospective Studies ; Ribonucleoprotein, U1 Small Nuclear ; blood ; Risk Factors ; Uric Acid ; blood

Sorafenib is indicated for the treatment of advanced hepatocellular carcinoma (HCC), but although rare, tumor lysis syndrome (TLS) can be fatal in HCC patients with a large tumor burden. The authors describe the case of a 55-year-old hepatitis B carrier who visited our clinic with progressive dyspnea for 3 weeks. Chest and abdominal computed tomography revealed a huge HCC in the left lobe of the liver with invasion of the inferior vena cava, right atrium, and pulmonary arteries. After 8 days of sorafenib administration, TLS was diagnosed based on the characteristic findings of hyperuricemia, hyperkalemia, and acute kidney injury with massive tumor necrosis by follow-up imaging. Despite discontinuation of sorafenib and supportive care, the patient's clinical course rapidly deteriorated. The authors describe a rare but fatal complication that occurred soon after sorafenib initiation for HCC. Careful follow-up is required after commencing sorafenib therapy for the early diagnosis and management of TLS.
Acute Kidney Injury ; Carcinoma, Hepatocellular* ; Dyspnea ; Early Diagnosis ; Follow-Up Studies ; Heart Atria ; Hepatitis B ; Humans ; Hyperkalemia ; Hyperuricemia ; Liver ; Middle Aged ; Necrosis ; Pulmonary Artery ; Thorax ; Tumor Burden ; Tumor Lysis Syndrome* ; Vena Cava, Inferior

BACKGROUND/AIMS: Allopurinol is a urate-lowering agent that is commonly used to prevent chemotherapy-related hyperuricemia. Allopurinol hypersensitivity syndrome (AHS) is a disorder involving multiple organs, which may be accompanied by cutaneous adverse reactions. We identified the characteristics and clinical outcomes of chemotherapy-associated AHS in patients with hematological malignancies. METHODS: This retrospective single-center study included 26 AHS patients (11 with and 15 without hematological malignancies) admitted to Seoul St. Mary's Hospital. AHS was defined using the criteria of Singer and Wallace. Comparisons were made using the Mann-Whitney U test and Fisher exact test as appropriate. RESULTS: In patients with a hematological malignancy and AHS, statistically significant differences were observed in terms of younger age at onset; shorter duration of exposure; higher starting and maintenance doses of allopurinol; lower incidence of eosinophilia, leukocytosis, and underlying renal insufficiency; and more frequent occurrence of fever compared to AHS patients without a hematological malignancy. Two AHS patients with a hematological malignancy were examined for human leukocyte antigen (HLA)-B typing, but neither patient harbored the HLA-B*5801 allele. All of the patients ceased allopurinol treatment, with most patients making a full recovery. Two patients in the study died; however, these deaths were unrelated to AHS. One patient developed serious sequelae of AHS that required hemodialysis. CONCLUSIONS: Physicians who prescribe allopurinol for the prevention of chemotherapy-related hyperuricemia should be aware of the unique risk of AHS, even in patients with hematological malignancies who do not have known risk factors for AHS. Novel urate-lowering agents should be considered alternative treatments.
Adolescent ; Adult ; Age Factors ; Aged ; Allopurinol/*adverse effects ; Antineoplastic Agents/*adverse effects ; Comorbidity ; Dose-Response Relationship, Drug ; Drug Hypersensitivity Syndrome/diagnosis/drug therapy/*etiology ; Female ; Glucocorticoids/therapeutic use ; Gout Suppressants/*adverse effects ; Hematologic Neoplasms/*drug therapy ; Humans ; Hyperuricemia/chemically induced/diagnosis/*prevention & control ; Male ; Medical Records ; Middle Aged ; Republic of Korea ; Retrospective Studies ; Risk Factors ; Treatment Outcome ; Young Adult