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.

Actual possibilities of pathogenetic treatment of patients with with purine dismetabolism

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.

Development of medical nomenclature and algorithms for diagnosis and treatment of gout in outpatient settings

Gout is a chronic systemic disease characterized by the deposition of monosodium urate crystals in various tissues and inflammation. In Russia, time to diagnosis may be as long as 8 years. This leads to serious complications, such as urate nephropathy, and disability. Effective strategies are needed to improve the quality of medical care for gout patients. One of such strategies is creation of an expert system to aid the clinician in establishing the diagnosis and selecting adequate therapy. The cornerstone of an expert system is a knowledge base. The aim of this paper was to develop a medical nomenclature and algorithms for the diagnosis and treatment of gout that will be used to create an expert system in the future. A total of 1,174 entities were selected that laid the basis for 40 diagnostic and 50 treatment algorithms for gout patients. All informational models were verified by the expert panel.

Two cases of acute urate nephropathy in women with asymptomatic hyperuricemia

The article presents a description of two own observations of the development of acute urate nephropathy in women with asymptomatic hyperuricemia. Clinical data and the results of additional laboratory and instrumental studies are presented; in one of the observations, the morphological picture of intravital biopsy material against the background of prolonged use of diuretics is described. The second case characterizes tophus kidney damage (according to the pathological examination data) without characteristic clinical manifestations of gout in vivo. The authors draw attention to the need to study serum uric acid levels in all cases of acute kidney injury.

Urate Nephropathy from Tumor Lysis Syndrome in an Undiagnosed Case of Prostate Cancer

Prostate cancer can masquerade as just normocytic anemia and thrombocytopenia, thrombotic thrombocytopenic purpura (TTP), hemolytic uremic syndrome (HUS), or tumor lysis syndrome (TLS). We are reporting an intriguing case of metastatic prostate cancer which remained undiagnosed until the patient showed signs of tumor lysis syndrome (TLS), leading to urate nephropathy requiring urgent hemodialysis. Tumor lysis syndrome is an oncological emergency but an exceedingly rare complication in non-hematological malignancies, including prostate cancer. It is challenging to recognize features of TLS in a case such as this with an unknown diagnosis. In the case of an established diagnosis of malignancy, however, checking baseline renal function, uric acid, lactate dehydrogenase (LDH), potassium, and phosphate to monitor for TLS as well as considering urate lowering therapy can help prevent adverse outcomes.

Gouty (urate) nephropathy

Clinical variants of kidney damage in gout including asymptomatic disorders of uric acid metabolism are discussed. The risk factor for hyperuricemia and associated kidney damage, clinical variants of gouty nephropathy and approaches to its treatment are presented. Keywords: gout, urate nephropathy, hyperuricemia, uric acid For citation: Fomin VV. Gouty (urate) nephropathy. Consilium Medicum. 2021; 23 (1): 11–14. DOI: 10.26442/20751753.2021.1.200709

Association of Hyperuricemia With Acute Kidney Injury: Case Series Report Among Patients Hospitalized With General Tonic-Clonic Seizures

Background: Urate nephropathy is a rare cause of acute kidney injury. Although most risk factors are associated with chemotherapy, tumor lysis syndrome or rhabdomyolysis, occurrence following severe seizure has also been reported. Uric acid measurement following convulsion is rarely performed and, therefore, the incidence of hyperuricemia in this context is unknown. Objective: The objective is to present a case of urate nephropathy following generalized tonic-clonic seizure (GTCS) and to investigate the kinetics of serum uric acid and creatinine levels in a series of patients admitted for severe seizures. Design: Retrospective case report and prospective case series. Setting: Emergency room department and neurology unit of a tertiary care hospital. Patients: The study included 13 hospitalized patients for severe GTCS. Measurements: Type, timing, and duration of seizure episodes were documented. Demographic data, weight, hypouricemic therapy, and baseline serum creatinine were recorded. Blood samples (uric acid, creatinine, blood gas, lactate, and creatinine kinase) and urine samples (uric acid, creatinine, and dipstick) were prospectively collected at Day 0, 1, 2, and 3 following the GTCS episode. Methods: We identified and described one rare case of urate nephropathy following GTCS. Then, we presented the kinetic of uric acid and creatinine levels and the acute kidney injury incidence over the follow-up period. All analyses were using descriptive statistics. Results: During the study period, 13 patients with a median tonic-clonic seizure duration of 5.0 minutes (interquartile range [IQR], 2.0–12.5) were included. From day 0 to day 3, the median serum uric acid level decreased from 346.0 µmol/L (IQR, 155.0–377.5) to 178.0 µmol/L (IQR, 140.0–297.5) and median serum creatinine from 73.0 µmol/L (IQR, 51.0–80.0) to 57.0 µmol/L (IQR, 44.0–70.0). Acute kidney injury occurred in four patients. Limitations: This is a single-center observational study with small sample size, which does not allow us to demonstrate causality between the increase of uric acid levels observed and the occurrence of acute kidney injury. A delay between the first sampling and seizure episodes was observed and could explain the limited increase of uric acid levels captured. Conclusions: There is a signal for an acute increase of uric acid levels following a severe seizure before returning to baseline within 3 days. During that period, there might be an increased risk of acute kidney injury, although these changes seem to be usually mild and reversible. Our findings suggest that routine serum uric acid measurement in patients presenting with GTCS could help to identify those patients at risk of developing acute kidney injury as a result of acute hyperuricemia. Further larger studies are required to confirm the effectiveness of such screening in acute kidney injury prevention. Trial Registration: As an observational noninterventional study, no registration was required.

Chronic tubulointerstitial nephritis

Chronic tubulointerstitial nephritis is usually asymptomatic, presenting with slowly progressive renal impairment. Urinalysis may be normal or show low-grade proteinuria (<1.5 g/day) and/or pyuria. Diagnosis depends on renal biopsy, which reveals variable cellular infiltration of the interstitium, tubular atrophy, and fibrosis. There are many causes including sarcoidosis, drugs (prescribed and nonprescribed), irradiation, toxins, and metabolic disorders. Analgesic nephropathy—characterized by renal papillary necrosis and chronic interstitial nephritis and caused by the prolonged and excessive consumption of combinations of analgesics, mostly including phenacetin. Nonsteroidal anti-inflammatory drugs—the most frequent cause of permanent renal insufficiency after acute interstitial nephritis. Aristolochic acid nephropathy—(1) Chinese herb nephropathy—caused in most cases (but perhaps not all) by aristolochic acid, and is associated with a high incidence of urothelial malignancy. (2) Balkan endemic nephropathy—a chronic, familial, noninflammatory tubulointerstitial disease of the kidneys that is associated with a high frequency of urothelial atypia, occasionally culminating in tumours of the renal pelvis and urethra. 5-Aminosalicylic acid—used in the treatment of chronic inflammatory bowel disease and causes clinical nephrotoxicity in approximately 1 in 4000 patients/year. Chronic interstitial nephritis in agricultural communities (CINAC) —nonproteinuric chronic kidney disease that presents in young, agricultural workers in Central America and Sri Lanka in the absence of any clear aetiology. Lithium—the most common renal side effect is to cause nephrogenic diabetes insipidus. Radiation nephropathy—preventive shielding of the kidneys in patients receiving radiation therapy generally prevents radiation nephropathy, but total body irradiation preceding bone marrow transplantation leads 20% to develop chronic renal failure in the long term. Nephropathies induced by toxins (including lead and cadmium) or by metabolic disorders (chronic hypokalaemia and chronic urate nephropathy).