Uric Nephrolithiasis Research Articles

THE MULTIFUNCTIONAL ROLE OF HERBAL PRODUCTS IN THE MANAGEMENT OF GOUT (VATARAKTA): A COMPREHENSIVE REVIEW

Introduction: Vatarakta is a Vata Vyadhi that occurs due to exacerbated Vata and Rakta Dosha by their causa-tive factors. It can occur in the whole body but since joints of the hand and foot are more affected it resembles gouty arthritis as described in allopathic science. Gout is a disease described in conventional medicine that has similarities to the Vatarakta. It is a type of inflammatory arthritis that is triggered by the crystallization of uric acid within the joints and is often associated with hyperuricemia. Hyperuricemia can be caused by overproduc-tion of uric acid, or, more commonly by inefficient excretion by the kidneys. The clinical presentation of gout ranges from the typical episodic acute inflammation of the joint to chronic tophaceous gout, chronic polyarticular arthritis, urate nephrolithiasis, and interstitial nephropathies. Several herbal drugs are well known for their thera-peutic effects and lower toxicity and are important substances for new drug development. Objective: The objective of this systematic review was to explore and validate the efficacy of herbal medicines in the management of gout. This review aims to update some research findings regarding the biological activities of the herbal ingredients of Ayurvedic medicines used in gout and also to collect an adequate basis for the opti-mal integration of Ayurvedic medicines into the conventional health system (Allopath). Materials & Methods: Systematic literature searches were carried out and the available information on Vatarak-ta and gout was collected via electronic search and a library search for articles published in peer-reviewed jour-nals and locally available books. Literature searches were also carried out to find the biochemical effects of vari-ous herbs mentioned in the management of hyperuricemia and gout. Conclusion: It has been demonstrated that plant-derived biochemicals have a potential effect on gout. These ef-fects comprise XOD inhibitory action, uricosuric, anti-inflammatory, anti-oxidant effects, etc. During the analy-sis of the literature available in Ayurveda, Allopathy, and related other branches of health science it was found that integrative medicine would be the optimal strategy to develop more effective agents in the treatment of gout (Vatarakta) and a combination of therapies may be very effective in reducing both the effect and frequency of disease.

ИЗУЧЕНИЕ ЦИТОТОКСИЧНОСТИ ТРИПЕПТИДА LEU-ILE-LYS

Introduction. A comprehensive study of the toxicity of new pharmacologically active substances is a necessary step for their introduction into practical medicine. Earlier, studies of the Leu-Ile-Lys tripeptide, which showed an anti-lithogenic effect in experimental oxalate and urate nephrolithiasis, a nephroprotective effect in experimental type 2 diabetes mellitus, as a well as gastroprotective effect in experimental "indomethacin" gastropathy, were carried out at the Federal State Budgetary Educational Institution of the Ministry of Health of the Russian Federation. Currently, there is an active development of methods for investigating the effectiveness and safety of biologically active substances in vitro, which directly assess the direct effect of the substances under study on the vital activity of cell cultures. Objective. Study of the the cytotoxicity of Leu-Ile-Lys tripeptide in cell culture. Materials and methods. Cytotoxicity was studied on human lung adenocarcinoma cell culture A549. A control group and five experimental groups were identified. Solutions of Leu-Ile-Lys tripeptide were prepared in Dulbecco's Modified Eagle's Medium culture medium with concentrations of 0.5, 1, 2, 5 and 10 mg/ml. A monolayer of cells was prepared, followed by replacement of the culture medium with solutions of the test substance, followed by 24-hour incubation in carbon dioxide at 37° C. As part of the qualitative control, the morphology and density of the monolayer were studied. Quantitative control was carried out by counting the number of cells in the Goryaev chamber. Results. No significant changes in cell morphology, monolayer density, or cell count were detected in comparison to the control in all experimental groups. Conclusion. Thus, the revealed absence of cytotoxicity of the Leu-Ile-Lys tripeptide indicates the prospects for further research of this substance in order to develop new pharmacological agents based on it.

Сложности и ограничения в медикаментозной терапии пациента с рецидивирующим нефролитиазом и сопутствующими хроническими заболеваниями сердечно-сосудистой системы

Nowadays, under conditions of an aging population, the comorbidity problem is of utmost importance in all branches of clinical medicine. The greatest difficulties are caused by the case when drug therapy of one nosology contradict with drugs prescribed for the treatment of another. In modern cardiology, extensive groups of diuretics and antihypertensives are widely used for therapy. At the same time, doctors do not always take into account the negative impact of cardiotropic therapy on the kidney stone disease process, as well as the general principles of metaphylaxis of nephrolithiasis on the cardiovascular system state. The paper presents data that allows to recommend the prescription of thiazides and combined antihypertensives, which have such in their composition, if the form of nephrolithiasis is idiopathic (stiff restriction). Besides, in conditions of urate nephrolithiasis, it is desirable to replace acetylsalicylic acid with clopidogrel, losartan with another sartan or an angiotensin-converting enzyme inhibitor. It is worth prescribing citrate mixtures with caution in metaphylaxis and nephrolithiasis litholysis, if there is no complete confidence in compensated cardiovascular diseases. KEYWORDS: recurrent nephrolithiasis, thiazides, potassium-sparing diuretics, gliflozines, losartan, acetylsalicylic acid, furosemide, acetazolamide, natural diuretics, urine pH. FOR CITATION: Yarovoy S.K., Royuk R.V. Difficulties and limitations in drug therapy of a patient with recurrent nephrolithiasis and concomitant chronic cardiovascular diseases. Russian Medical Inquiry. 2024;8(4):235–239 (in Russ.). DOI: 10.32364/2587-6821-2024-8-4-8.

О воздействии терапии хронической сердечной недостаточности на литогенные свойства мочи.

Introduction. In cardiology practice, a considerable number of drugs, having evident metabolic effects, are used, including those that impact on the process of stone formation. The Research Aim. To study the effects of cardiotropic drugs that can affect the likelihood of recurrence of nephrolithiasis. Materials and Methods. The retrospective study was performed on 49 patients suffering from recurrent urate nephrolithiasis and drug-compensated chronic heart failure, who were treated in branch No. N.N. Burdenko” MO in 2018-2022. Two groups of patients were examined, according to the scheme of cardiotropic therapy: group I - losartan, bisoprolol, atorvastatin, clopidogrel, spironolactone, dapagliflozin (n=25); Group II - enalapril, bisoprolol, atorvastatin, acetylsalicylic acid, spironolactone (n=24). Duration of observation is 3 months. Results. When using the scheme based on losartan and dapagliflozin (Group I), a significant decrease in the serum concentration of uric acid and a simultaneous increase in its renal excretion against the background of increased diuresis and a decrease in urine acidity were revealed compared with patients who received the scheme based on enalapril (II group). There were no significant differences between the groups in terms of the risk of decompensation of chronic heart failure, recurrence of stone formation and the frequency of episodes of urinary tract infection. Conclusion. Сardiotropic therapy has a significant effect on the properties of urine in patients with nephrolithiasis. None of the approaches studied demonstrated either overwhelming advantages or disqualifying disadvantages. Both of them have the right to exist. Despite the uricosuric effect, the use of dapagliflozin for the treatment of chronic heart failure in patients with urate nephrolithiasis was not accompanied by an increase in the frequency of recurrence of stone formation.

Disorder of purine metabolism in the etiopathogenesis of urate nephrolithiasis

Urinary stone disease (USD) is a polyetiological urological disease caused by both exogenous and endogenous factors, including hereditary ones. It is characterized by the appearance of stones in the kidneys and urinary tract, and a tendency to relapse, often with a severe course. Almost 25 % of stones consist of uric acid (UA). The leading role in the pathogenesis of urate nephrolithiasis (UN) is played by disorders of purine metabolism, which are characterized by the development of hyperuricemia (HU) and hyperuricuria. The aim of the work is to review modern literary sources on the role of purine metabolism disorders in the etiopathogenesis of UN. Results. The development of UN depends on the constancy of the acidic urine pH, as well as on a decrease in diuresis, HU and hyperuricuria. UA is the final metabolite of purine metabolism and the main stone-forming substance in patients with UN. HU develops both due to uncompensated disorders of purine metabolism with a decrease in renal secretion and intestinal uricolysis (excretion pathway) and excessive intake of purine bases in the body and their increased synthesis in vivo (metabolic pathway). Citric acid, as one of the main metabolites of the tricarboxylic acid (TCA) cycle, is connected through the corresponding substrates to the formation of purines and the metabolite of amino acid metabolism, glutamine. TCA is connected to the cycles of urea, glyoxylate and purine bases through α-ketaglutaric acid. It is a substrate of citric acid, and it affects the synthesis of glutamate, which combines with ammonia to form glutamine, used in the cycle of purine synthesis. Conclusions. The role and diagnostic value of purine metabolism upsets, disorders of the TCA (citric acid), amino acid metabolism (glutamine), the activity of xanthine oxidase is a key enzyme in purine synthesis which passes through TCA with the participation of its metabolite α-ketaglutarate, have been established. TCA is bound to glutamine, rich in nitrogen, which is necessary for the synthesis of purine bases.

Effect of Carnosine on the Activity of Matrix Metalloproteinase-2 and Oxidative Stress in the Kidneys in Experimental Urate Nephrolithiasis.

The effect of carnosine on MMP-2 activity and oxidative stress in the kidneys in experimental urate nephrolithiasis was studied. Urate nephrolithiasis was modeled in Wistar rats by intragastric administration of a mixture of oxonic and uric acids. Carnosine was administered intragastrically through a tube in a dose of 15 mg/kg. In rats treated with carnosine, the concentration of MMP-2 in the urine decreased by 3.7 times, and the excretion of MMP-2 with urine decreased by 4.3 times. In the homogenate of the kidneys from rats treated with carnosine, the concentration of TBA-reactive substances decreased by 5 times and the concentration of MMP-2 decreased by 12.7%. After treatment with carnosine, the number of histologically confirmed cases of urate nephrolithiasis decreased by 2 times, while the mean size of urate deposits decreased by 2.7 times. Thus, carnosine inhibits MMP-2 and reduces the intensity of oxidative stress in the kidneys, which prevents the development of urate nephrolithiasis.

Лечение пациентов с хроническим калькулезным пиелонефритом.

Introduction. Frequent complications of kidney stone disease (KSD) are infectious and inflammatory processes in the organs of the genitourinary system, the most important of which is pyelonephritis. Adhering to a restrained tactic with small caliceal calculi, we observe a significant number of patients with chronic calculous non-obstructive pyelonephritis. Conservative treatment of these patients presents great practical difficulties, as it involves the mandatory parallel treatment of two diseases – pyelonephritis and KSD. The aim of this prospective study was to investigate the effectiveness of conservative therapy in patients with chronic calculous pyelonephritis. Materials and methods. The study included 100 patients with a verified diagnosis of chronic calculous pyelonephritis against the background of existing small caliceal calculi (up to 10 mm). Patients were divided into 2 groups, comparable in terms of the main evaluated criteria. Patients of the first (control) group (40 people) received etiotropic antibiotic course therapy in combination with antispasmodics and immunomodulators. Patients of the second (main) group (60 people) additionally for 3 months took the phytocomplex Onpelvicit 1 capsule 3 times a day under the control of urine pH. Results. At the control examination after 3 months in the group of patients treated with Onpelvicit the frequency of exacerbations of chronic pyelonephritis was significantly lower than in the control group of patients. In the main group, 50% of patients showed a decrease in the size of the calculus, in 15% of cases – complete litholysis. The noted positive effect in relation to chronic pyelonephritis is obviously associated with the phytocomponents of the drug. The effect on the size of the stones is largely due to the presence of sodium and potassium citrates in the complex. Citrate is one of the main inhibitors of crystallization. This effect is realized in both calcium oxalate and urate nephrolithiasis, although the mechanisms differ. Stabilization of the colloidal state of urine, normalization of the acidity index prevents the crystallization of salts and the growth of calculi. Conclusion. Chronic calculous pyelonephritis, which occurs against the background of small calyx calculi of the kidney, is a variant of a combined pathology that is widely encountered in urological practice. The dominant concept of management of this group of patients is to conduct conservative treatment. A pronounced acid reaction of urine in combination with crystalluria of one kind or another is a significant factor in the progression or recurrence of stone formation and the severe course of the inflammatory process. The present study shows that the correction of these disorders has a positive effect on the course of both diseases.

Features of the course urate nephrolithiasis, comorbid with the metabolic syndrome

The aim of the work is to study the peculiarities of the course of urate nephrolithiasis and urate nephrolithiasis comorbid with metabolic syndrome. Materials and methods. Clinical and laboratory data of 183 patients. The control group of patients with urate nephrolithiasis received traditional therapy. The patients of the main group with urate nephrolithiasis comorbid with metabolic syndrome took quertin and traditional therapy, as well as popular medical drugs that correct metabolic processes. Clinical laboratory, biochemical, ultrasound, radiological, radioisotope, immunoenzymatic, and physical-chemical methods were used. Results. The pain was more intense in patients with urate nephrolithiasis than in patients with urate nephrolithiasis comorbid with metabolic syndrome. Manifestations of the inflammatory process increased in patients with urate nephrolithiasis comorbid with metabolic syndrome, and concomitant diseases intensified the excretion of stone-forming compounds. Metaphylaxis with quertin against the background of commonly accepted drugs that correct metabolic processes had a positive effect on the course of urate nephrolithiasis comorbid with metabolic syndrome and contributed to the reduction of stone formation relapse. Conclusions. In-depth diagnosis of metabolic processes can help the doctor to correctly determine the differentiated tactics of examination and treatment, as well as to prevent possible complications in a timely manner.

Effect of quertine on electrolyte metabolism indicators in patients with urate nephrolithiasis comorbid with metabolic syndrome

The treatment of urate nephrolithiasis (UN) comorbid with metabolic syndrome (MS) is greatly interested in flavonoids, which are actively involved in purine, electrolyte, nitrogen, lipid, and carbohydrate metabolism. The aim of the study was to study the effect of quertine on electrolyte metabolism and excretion of stone-forming compounds in patients with UN comorbid with MS.The indicators of stone-forming compounds excretion were studied by the values of inorganic phosphorus, ionized calcium, magnesium, sodium, and potassium in blood serum and urine. Urine pH was determined by test indicator strips. Normalization of indicators of stone-forming compounds excretion under the influence of quertine, traditional therapy and drugs that correct metabolic processes, contributed to an increase of magnesium crystallization inhibitor in blood serum and urine. Besides, it is also important to increase daily diuresis and normalize urine pH, which contributed to the reduction of stone formation and recurrence of urolithiasis. It is important to prescribe quertine, traditional therapy and drugs that correct metabolic disorders, taking into account metabolic disorders, urinary pH and daily diuresis.

Assessment of the quality of life indicators in patients with urate nephrolithiasis comorbid with metabolic syndrome

Kidney stone disease (KSD) is one of the most common urological diseases; however, until recently, there was no specific tools for the study of the influence of urate nephrolithiasis (UN) on the patients’ quality of life. The use of WISQOL quality of life questionnaire enabled quantitative evaluation of the subjective notion and enhanced the insight on the condition of a patient with UN in general, for measuring the broad scope of functions of health perception. The aim of the research is to study quality of life indicators in patients with UN comorbid with metabolic syndrome. Materials and methods. The study included 65 patients with UN and UN comorbid with MS. In the control group, there were 21 patients with UN who received traditional therapy. The comparison group comprised 21 patients with UN comorbid with MS, who received both traditional therapy and drugs that correct metabolic disorders. The main group consisted of 23 patients with UN comorbid with MS, who took quertin against the background of the traditional therapy and drugs that correct metabolic disorders. To assess the quality of life, the WISQOL questionnaire was used, which included 4 domains: social impact (SI), emotional impact (EI), health impact (HI) and impact on life activity (ILA). The patients’ condition was assessed before treatment and after 1.5–6.0 months. Results. After the treatment, main group patients demonstrated an increase of EI indicator; comparison group patients demonstrated an increase in EI, ILA, and HI indicators. The efficacy of quertin was confirmed by an increase in ILA, SI, and HI indicators. Conclusions. The levels of SI and HI were decreasing before treatment in patients with UN comorbid with MS from the comparison and the main groups. The use of quertin against the background of the traditional therapy and drugs that correct metabolic processes, significantly increased EI and ILA levels.

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.

Efficacy of Leu-Ile-Lys tripeptide in the correction of experimental urate nephrolithiasis

Aim. To study the effect of the Leu-Ile-Lys (leucine-isoleucine-lysine) tripeptide on the course of experimental urate nephrolithiasis.
 Methods. The experiment was carried out on 23 male Wistar rats weighing 200220 grams that were divided into a control (n=8, modeling of urate nephrolithiasis) and an experimental (n=15, modeling of urate nephrolithiasis + administration of Leu-Ile-Lys tripeptide) groups. The tripeptide was administered intragastrically through a tube at a dose of 11.5 mg/kg. Daily urine was collected on a weekly basis, and the activity of lactate dehydrogenase and gamma-glutamyl transpeptidase was determined. After three weeks of the experiment, the animals were euthanized, and kidneys were removed to determine the parameters of free radical oxidation [concentration of thiobarbituric acid reactive substances (TARS), total pro-oxidant and total antioxidant activity, the activities of catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPX)] and conduct a morphological study in which the number and area of calculi and the condition of the renal tissues were determined. Statistical data processing was performed using the Statistica 12.0 software. We used the MannWhitney U test, the Wilcoxon signed rank test. The results are presented as median with the 25th and 75th percentiles. The differences were considered significant at p 0.05.
 Results. In the kidneys of the rats of the experimental group, the number of deposits decreased twofold, as compared with the control group (1.60.2 and 3.20.4, respectively, p=0.001). Lactate dehydrogenase activity in the urine of rats increased from 0.10 (0.06; 0.21) units/mg of creatinine per day initially to 0.75 (0.44; 1.07) units/mg creatinine per day on day 21 (p=0.012) in the control group, and from 0.10 (0.06; 0.12) units/mg creatinine per day to 0.45 (0.34; 0.71) units/mg creatinine per day on 21st day (p=0.003) in the experimental group. The concentration of thiobarbituric acid reactive substances in the experimental group was 1.2 times lower than that of the control group: 4.2 (3.9; 4.6) mol and 5.1 (4.7; 5.5) mol, respectively (p 0.001). In addition, in the kidneys of the rats of the experimental group, the total antioxidant activity was 1.3 times higher than in control: 70.4 (65.4; 74.1)% and 53.8 (33.3; 62.2)% respectively (p 0.001). Superoxide dismutase activity in the experimental group was 1.5 times higher than in the control group: 12.4 (11.0; 13.2)% against 8.1 (6.4; 13.1)% (p=0.016). Catalase activity in the experimental group was 1.2 times higher than in the control group: 31.1 (26.4; 36.1)% against 25.1 (20.3; 27.1)% (p=0.005).
 Conclusion. The Leu-Ile-Lys tripeptide has a litholytic effect, manifested in a statistically significant decrease in the activity of oxidative stress markers (p 0,001) and a twofold decrease in the average amount of uric acid kidney stones (p 0,001).

Effect of Carnosine on the Course of Experimental Urate Nephrolithiasis.

The prospect of using the antioxidant dipeptide carnosine for the treatment of urate nephrolithiasis was evaluated. Urate nephrolithiasis was modeled in rats by intragastric administration of a mixture of oxonic and uric acids. Carnosine was administered intragastrically through a tube in a dose of 15 mg/kg. In rats treated with carnosine, the concentration of TBA-reactive products decreased by 1.4 times, the total antioxidant activity increased by 1.4 times, and catalase activity increased by 1.3 times. By the end of the experiment, the lactate dehydrogenate level in experimental rats was 2-fold lower than in the control, and the number of urate deposits decreased by 1.6 times with a concomitant alleviation of the inflammatory processes. Thus, the use of direct peptide antioxidant carnosine attenuated the manifestations of urate nephrolithiasis.

Корекція квертином окисної модифікації білків у хворих на уратний нефролітіаз коморбідний з метаболічним синдромом

Key words: quertine, urate nephrolithiasis, metabolic syndrome, protein oxidative modification. The aim of the research was to study the effect of quertine on the processes of protein oxidative modification in patients with urate nephrolithiasis comorbid with metabolic syndrome. 118 patients, divided into three groups, were examined and treated. Group 1 (control) included patients with urate nephrolithiasis, who were prescribed traditional therapy. Group 2 (experimental) embraced patients with urate nephrolithiasis comorbid with metabolic syndrome, who were prescribed traditional therapy and generally recognized drugs that correct metabolic disorders. Group 3 (main) involved patients with urate nephrolithiasis comorbid with metabolic syndrome, who received traditional therapy and drugs that correct metabolic disorders. To study the state of protein peroxidation, the indicators of protein oxidative modifications were analysedwith the method designed by E.E. Dubininaet al. The study of indicators in the blood serum was performed before treatment and after 7 days, after 14 days, after 1.5-2 months, after 3-6 months. In patients with urate nephrolithiasis, prooxidant activation was observed in the course of traditional therapy: the level of neutral aldehyde and ketone derivatives as well as of alkaline aldehyde derivatives increased. Patients with urate nephrolithiasis and urate nephrolithiasis comorbid with metabolic syndrome demonstrated the development of oxidative stress, manifested by the accumulation of the content of products of protein oxidative modification. After the treatment with quertine, which contains the aglycone of various plant flavonoid glycosides, a more significant decrease in the indicators of protein oxidative modification was noted comparing to experimental group patients; this indicates the antioxidant properties of quertine. Thus, the use of quertine together with traditional therapy and drugs that affect metabolic disorders, differentiated between uricostatic and uricolytic agents, contributed to the normalization of the content of protein peroxidation products.

Влияние карнозина на течение экспериментального уратного нефролитиаза

Влияние карнозина на течение экспериментального уратного нефролитиаза

Risk Factors for Urolithiasis (Review)

Urolithiasis is still one of the most urgent problems of modern urology today. The incidence in the world is 5–10 %, with its annual increase. Frequent recurrence of the disease complicates the situation, significantly increasing the duration of disability, and the total number of patients with urolithiasis makes this pathology socially significant, given that in 65–70 % of cases it is diagnosed in the most able-bodied part of the population. There is no clear picture of urolithiasis etiology despite the considerable amount of scientific research in this field. Urolithiasis is considered a multifactorial disease. Molecular genetic studies have been actively pursued for many years to elucidate the relationship of urolithiasis with hereditary factors. To date, the close correlation of genetic disorders with clinical manifestations of urolithiasis has been sufficiently demonstrated. The majority of urolithiasis cases are related to pathologies with hereditary predisposition, but many syndromes with a monogenic inheritance nature are also described. Increasingly, there is a growing body of research in which the risk factors for urolithiasis are serious illnesses such as diabetes mellitus type 2, obesity, metabolic syndrome and more. There is a direct correlation between the incidence of urolithiasis and the degree of obesity in both men and women. The incidence of urinary calculi in patients with obesity is 4 times higher than in patients with normal body mass index. Too high frequency of urate nephrolithiasis was also observed in patients with DM type 2. Certain components of metabolic syndrom correlate with an increased risk of nephrolithiasis.The purpose of our work was to search, systematize, analyze existing publications regarding the role of various risk factors for the development of urolithiasis. The search for information was conducted using different databases (PubMed, electronic reference database of the National Scientific Library of Kyiv). Analysis of the scientific literature revealed that metabolic imbalance is significantly affected by the development of urolithiasis. Due to the increase in patients with diabetes mellitus, patients with obesity, metabolic syndrome, the development of urolithiasis under these conditions becomes an even greater problem and needs further research in terms of the etiology, pathogenesis, as well as serious risk factors in its occurrence. Thorough examination of metabolic disorders, local pathological changes of the urethro-renal complex, possible risk factors depend on the consequences of the disease and the frequency of relapse. The ability to identify risk factors for the formation of concrements will contribute to reducing the incidence of urolithiasis, its prevention and metaphilactic recurrence.

The state of purine exchange in patients with uratic nephrolithiasis comorbide with metabolic syndrome

The state of purine exchange in patients with uratic nephrolithiasis comorbide with metabolic syndrome

Improvement in urate nephrolithiasis with pegloticase in gout

Improvement in urate nephrolithiasis with pegloticase in gout

Renal and vaginal calculi in a free-ranging long-beaked common dolphin Delphinus capensis.

Bilateral nephrolithiasis with a concurrent vaginal calculus was identified in a stranded free-ranging long-beaked common dolphin Delphinus capensis. Necropsy and radiologic examinations of the sexually mature D. capensis revealed multiple small irregularly round nephroliths and a 6.4 × 4.1 × 9.2 cm vaginal calculus weighing 182 g. Nephroliths numbered 68 and 71 in the left and right kidneys, respectively, and ranged from 1.7 to 6.9 mm in diameter. Nephroliths were composed of 100% ammonium urate, which has been found in captive dolphin populations. However, the vaginolith consisted of struvite and calcium carbonate suggesting an alternate etiology. The composition of the vaginolith suggests that bacterial vaginitis could have served as the predisposing condition. Renal lesions included chronic tubulointerstitial nephritis with tubular degeneration and loss, likely secondary to the nephroliths. The pathogenesis of ammonium urate nephrolithiasis in managed care is suspected to be linked to diet and age but in this case may be due to metabolic disruption. However, if environmental changes cause a shift in prey species, the risk of nephrolithiasis in free-ranging cetaceans could increase. Careful surveillance for nephroliths in free-ranging populations should be considered by researchers.

Targeted renal knockdown of Na+/H+ exchanger regulatory factor Sip1 produces uric acid nephrolithiasis in Drosophila.

Nephrolithiasis is one of the most common kidney diseases, with poorly understood pathophysiology, but experimental study has been hindered by lack of experimentally tractable models. Drosophila melanogaster is a useful model organism for renal diseases because of genetic and functional similarities of Malpighian (renal) tubules with the human kidney. Here, we demonstrated function of the sex-determining region Y protein-interacting protein-1 (Sip1) gene, an ortholog of human Na+/H+ exchanger regulatory factor (NHERF1), in Drosophila Malpighian tubules and its impact on nephrolithiasis. Abundant birefringent calculi were observed in Sip1 mutant flies, and the phenotype was also observed in renal stellate cell-specific RNA interference Sip1 knockdown in otherwise normal flies, confirming a renal etiology. This phenotype was abolished in rosy mutant flies (which model human xanthinuria) and by the xanthine oxidase inhibitor allopurinol, suggesting that the calculi were of uric acid. This was confirmed by direct biochemical assay for urate. Stones rapidly dissolved when the tubule was bathed in alkaline media, suggesting that Sip1 knockdown was acidifying the tubule. SIP1 was shown to collocate with Na+/H+ exchanger isoform 2 (NHE2) and with moesin in stellate cells. Knockdown of NHE2 specifically to the stellate cells also increased renal uric acid stone formation, and so a model was developed in which SIP1 normally regulates NHE2 activity and luminal pH, ultimately leading to uric acid stone formation. Drosophila renal tubules may thus offer a useful model for urate nephrolithiasis.