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Background We aimed to describe the thiamine status in hospitalized hypervolemic heart failure (HF) and/or renal failure (RF) patients treated with furosemide and to investigate whether there was a difference in furosemide-related thiamine deficiency between patients with RF and HF. Methods Patients who were diagnosed as hypervolemia and treated with intravenous furosemide (at least 40 mg/day) were included in this prospective observational study. Whole blood thiamine concentrations were measured 3 times during hospital follow-up of patients. Results We evaluated 61 hospitalized hypervolemic patients, of which 22 (36%) were men and 39 (64%) were women, with a mean age of 69.00 ± 10.39 (45–90) years. The baseline and post–hospital admission days 2 and 4 mean thiamine levels were 51.71 ± 20.66 ng/ml, 47.64 ± 15.43 ng/ml and 43.78 ± 16.20 ng/ml, respectively. Thiamine levels of the hypervolemic patients decreased significantly during the hospital stay while furosemide treatment was continuing (p = 0.029). There was a significant decrease in thiamine levels in patients who had HF (p = 0.026) and also, thiamine was significantly lower in HF patients who had previously used oral furosemide before hospitalization. However, these findings were not present in patients with RF. Conclusions Thiamine substantially decreases in most hypervolemic patients receiving intravenous furosemide treatment during the hospital stay. Thiamine levels were significantly decreased with furosemide treatment in especially HF patients, but the decrease in thiamine levels did not detected at the same rate in RF patients. Diuretic-induced thiamine loss may be less likely in RF patients, probably due to a reduction in excretion.

The present study was carried out to evaluate the effect of dietary supplemental vitamin D3 on fibroblast growth factor 23 (FGF23) signals as well as phosphorus homeostasis and metabolism in laying hens. Fourteen 40-week-old Hy-Line Brown layers were randomly assigned into 2 treatments:1) vitamin D3 restriction group (n = 7) fed 0 IU/kg vitamin D3 diet, and 2) regular vitamin D3 group (n = 7) fed 1,600 IU/kg vitamin D3 diet. The study lasted for 21 d. Serum parameters, phosphorus and calcium excretion status, and tissue expressions of type II sodium-phosphate co-transporters (NPt2), FGF23 signals and vitamin D3 metabolic regulators were determined. Hens fed the vitamin D3 restricted diet had decreased serum phosphorus levels (by 31.3%, P = 0.028) when compared to those fed regular vitamin D3 diet. In response to the decreased serum phosphorus, the vitamin D3 restricted laying hens exhibited: 1) suppressed kidney expressions of 25-hydroxyvitamin D 1-α-hydroxylase (CYP27B1, by 52.8%, P = 0.036) and 1,25-dihydroxyvitamin D 24-hydroxylase (CYP24A1, by 99.4%, P = 0.032); 2) suppressed serum levels of FGF23 (by 14.6%, P = 0.048) and increased serum alkaline phosphatase level (by 414.1%, P = 0.012); 3) decreased calvaria mRNA expressions of fibroblast growth factor receptors (FGFR1, by 85.2%, P = 0.003, FGFR2, by 89.4%, P = 0.014, FGFR3, by 88.8%, P = 0.017, FGFR4, by 89.6%, P = 0.030); 4) decreased kidney mRNA expressions of FGFR1 (by 65.5%, P = 0.021), FGFR4 (by 66.0%, P = 0.050) and KLOTHO (by 68.8%, P = 0.038); 5) decreased kidney protein expression of type 2a sodium-phosphorus co-transporters (by 54.3%, P = 0.039); and 6) increased percent excreta calcium (by 26.9%, P = 0.002). In conclusion, the deprivation of dietary vitamin D3 decreased FGF23 signals in laying hens by reducing serum FGF23 level and suppressing calvaria and kidney mRNA expressions of FGF23 receptors.

Background: Vitexin is the main bioactive compound of hawthorn (Crataegus pinnatifida), a famous traditional Chinese medicine, and vitexin for injection is currently in phase I clinical trial in China. Objective: This investigation systematically evaluated the metabolism and toxicokinetics of vitexin in rats and dogs. Methods: Rats and beagle dogs were administrated different doses of vitexin, and then the plasma concentration, tissue distribution, excretion, metabolism, pharmacokinetics and plasma protein binding were investigated. Results : The elimination half-life (t1/2) values in rats after a single intravenous dose of 3, 15 and 75 mg/kg were estimated as 43.53±10.82, 22.86±4.23, and 21.17±8.64 min, and the values of the area under the plasma concentration-time curve (AUC0→∞) were 329.34±144.07, 974.79±177.27, and 5251.49±786.98 mg•min/L, respectively. The plasma protein binding rate in rats was determined as about 65% by equilibrium dialysis after 72 hr. After 24 hr of intravenous administration, 16.30%, 3.47% and 9.72% of the given dose were excreted in urine, feces and bile, respectively. The metabolites of the vitexin were hydrolyzed via deglycosylation. The pharmacokinetics of dogs after intravenous administration revealed t1/2, AUC0-∞ and mean residence time (MRT0-∞) values of 20.43±6.37 min, 227.96±26.68 mg•min/L and 17.12±4.33 min, respectively. The no-observed-adverse- effect level (NOAEL) was 50 mg/kg body weight/day. There was no significant accumulation effect at 8 or 20 mg/kg/day in dogs over 92 days of repeated administration. For the 50 mg/kg/- day dose group, the exposure (AUC, Cmax) decreased significantly with prolonged administration. This trend suggests that repeated administration accelerates vitexin metabolism. Conclusion: The absorption of vitexin following routine oral administration was very low. To improve the bioavailability of vitexin, the development of an injectable formulation would be a suitable alternative choice.

Polyuria is a common clinical condition characterized by a urine output that is inappropriately high (more than 3 L in 24 h) for the patient's blood pressure and plasma sodium levels. From a pathophysiological point of view, it is classified into two types: polyuria due to a greater excretion of solutes (urine osmolality300 mOsm/L) or due to an inability to increase solute concentration (urine osmolality150 mOsm/L). Sometimes both mechanisms can coexist (urine osmolality 150-300 mOsm/L). Polyuria is a diagnostic challenge and its proper treatment requires an evaluation of the medical record, determination of urine osmolality, estimation of free water clearance, use of water deprivation tests in aqueous polyuria, and measurement of electrolytes in blood and urine in the case of osmotic polyuria.

Introduction Hypouricemia may be caused by disorders leading to decreased UA production, oxidation of UA to allantoin by drugs or increased renal tubular loss of filtered UA, renal hypouricemia (RHUC). RHUC may be resulted from familial or acquired disorders. Familial RHUC cases are classified according to the gene affected as type 1 (SLC22A12 gene) and type 2 (SLC2A9). Clinical importance of RHUC entity is mainly determined by emerging of acute kidney injury (AKI) after strenuous exercise and urolithiasis. Case presentation Here, we report a case of RHUC with increased fractional excretion of uric acid value of more than 100%, serum uric acid level of nearly zero, and exercise-induced AKI episodes clinically and a new unpublished homozygous (biallelic) mutation of c.1419+2T>G (IVS11+2T>G) in the SLC2A9 gene genetically for the first time to our knowledge. Conclusion Clinicians should be aware of this rare entity defined as hereditary RHUC in order to provide long term renoprotection by advisements like simple precautions such as avoiding severe exercises.

In Morocco, the high consumption of dietary sodium increases the risk of non-communicable diseases (NCDs) and predisposes to cardiovascular diseases (CVDs) and hypertension. This study aims to assess the dietary sodium and potassium intake in a random sample of Moroccan adult students as a benchmark informing a national strategy for reducing salt intake. This cross-sectional study was conducted with 103 adults aged 18 to 25 years recruited in Casablanca. The 24-hour urinary excretion was used to measure the sodium and potassium. Creatinine excretion was used to validate the completeness of the urine collections. The average urinary sodium excretion was 3125.77 ± 121.99 mg/day, 13.5% consumed less than 5g/day, while 69% consumed more than 5 g/day of which 17.5% consumed more than twice the recommendations. For the average urinary potassium excretion was 1826.1 ± 61.2 mg/day, and more than 98% of the students consumed less than the adequate intake. The results of this pilot study show that the population studied has a high sodium intake and low potassium intake which does not meet World Health Organization (WHO) recommendations, which requires implementing an action plan to reduce salt.

Nalfurafine is a G-protein–biased KOR (kappa opioid receptor) agonist that produces analgesia and lacks central nervous system adverse effects. Here, we examined the cardiovascular and renal responses to intravenous and oral nalfurafine alone and in combination with furosemide, hydrochlorothiazide, or amiloride. We hypothesized that nalfurafine, given its distinct mechanism of vasopressin inhibition, would increase urine output to these diuretics and limit electrolyte loss. Following catheterization, conscious Sprague-Dawley rats received an isotonic saline infusion and were then administered an intravenous bolus of nalfurafine, a diuretic, or a combination. Mean arterial pressure, heart rate, and urine output were recorded for 90 minutes. In another study, rats were placed in metabolic cages and administered drug in an oral volume load. Hourly urine samples were then collected for 5 hours. Intravenous and oral nalfurafine produced a marked diuresis, antinatriuresis, antikaliuresis, and a decrease in mean arterial pressure. Compared with diuretic treatment alone, intravenous coadministration with nalfurafine significantly increased urine output to furosemide and hydrochlorothiazide and decreased sodium and potassium excretion. Notably, mean arterial pressure was reduced with nalfurafine/diuretic combination therapy compared to diuretics alone. Similarly, oral coadministration of nalfurafine significantly increased urine output to hydrochlorothiazide and decreased sodium and potassium excretion, whereas combination with furosemide only limited the amount of sodium excreted. Further, both intravenous and oral coadministration of nalfurafine enhanced the diuresis to amiloride and decreased sodium excretion. Together, these findings demonstrate that nalfurafine enhances the diuresis to standard-of-care diuretics without causing an excessive loss of electrolytes, offering a new approach to treat several cardiovascular conditions.

Potassium (K+) is the predominant intracellular cation in the body. The intracellular [K+] is 140–150 mEq/L; in blood it is 3.5–5 mEq/L. Serum contains a slightly higher concentration of K+ than plasma because K+ is released from red blood cells during clot formation. Maintenance of a high cellular concentration of K+ is necessary for several cellular functions, including growth, nucleic acid and protein synthesis, and regulation of cell volume, as well as pH and enzyme activation. In addition, a high intracellular concentration of K+ is essential to the maintenance of the resting membrane potential for cellular excitability and contraction. The high intracellular K+ concentration is maintained by the Na/K-ATPase located in the cell membranes of all animal cells. The activity of this enzyme is influenced by a variety of hormones. The kidney is the primary route for K+ excretion. In general, K+ excretion in the urine, called kaliuresis, parallels dietary intake. The other route for K+ excretion is the colon. Under conditions of decreased renal function, K+ excretion by the colon is enhanced.

Purpose In a search for potentially modifiable factors to improve long-term outcome among kidney transplant recipients (KTR), we hypothesized that boron exposure is associated with improved long-term outcome in KTR. Methods We determined 24 h urinary boron excretion using inductively coupled plasma mass spectrometry as a measure of boron exposure in 693 stable KTR (57% male, mean age 53y), enrolled in the TransplantLines Food and Nutrition Biobank and Cohort Study. Dietary intake was assessed using validated food-frequency questionnaires. Results Linear regression analyses showed that dietary intake of fruit, wine and nuts were key determinants of boron excretion. In addition, boron excretion was negatively correlated with homocysteine and inflammatory parameters. In total, 73 (32%), 47 (20%) and 30 (13%) KTR died among the lowest, middle and highest tertiles of 24 h urinary boron excretion, respectively (Plog-rank P Conclusion Boron may be an overlooked target to improve long-term survival among KTR and potentially other patients, likely through pathways other than inflammation or the methionine-homocysteine cycle that were previously suggested. Interventional trials are warranted to confirm the potential of dietary boron supplementation in KTR and other patient populations.

OBJECTIVE This study evaluated urinary angiotensinogen in preeclampsia. METHODS Normal pregnant (n = 57) and preeclamptic patients (n = 31); Normal pregnant (n = 10) and preeclamptic rats (n = 10) were studied. Urinary angiotensinogen and plasma angiotensin II were assayed by enzyme-linked immunosorbent assay (ELISA). RESULTS Urinary angiotensinogen in preeclampsia patients (2.0 ± 1.1 ng/mg creatinine) was suppressed (*p

Objectives The present study was designed to determine the effect of dietary phosphorus restriction, independent of protein intake, on the urinary protein excretion in patients with proteinuria. Methods Seventy-one patients with proteinuria were enrolled in a parallel randomized controlled trial study. The patients were randomly allocated to receive either a recommended phosphorus-restricted diet (n = 36) or a recommended control diet (n = 35), for 8 weeks. A diet was designed and recommended to participants in a way that both trial groups would receive the same amount of energy and protein and the only significant difference between them was the amount of phosphorus intake. The study outcomes included the changes in spot urine protein-to-creatinine ratio, the changes in serum and urine levels of phosphorus, as well as the changes in estimated glomerular filtration rate (eGFR). Results The mean ± standard deviation of age, body mass index, and eGFR of the participants were 59 ± 14 years, 29 ± 5.5 kg/m2, and 56.1 ± 21.7 mL/min/1.73 m2, respectively. The amount of phosphorus intake decreased significantly in the phosphorus-restricted group compared to the control one (−709 vs. −369 mg/day; P Conclusions Although adherence to a phosphorus-restricted diet by patients with proteinuria led to a significant decrease in urinary protein excretion, this change was not significantly different from that of the control diet. Further studies with larger sample sizes and different designs will reveal more evidence for a link between phosphorus intake and proteinuria.

Background: While 25% of adult women in the world are hypertensive, the percentage of women, who cannot achieve blood pressure control despite taking medication, is 55.9 ± 1.5%. The aim of this study was to determine the prevalence and control rate of hypertension and to detect the factors affecting this situation in women in the 15-49 age group. Material and Methods: 700 women in the 15-49 age group were selected and a questionnaire was applied. Height, weight, and blood pressure were measured and spot urines were collected on the same day. 24-hour sodium excretion and daily salt intake were calculated using the Kawasaki method. Results: While 14.3% of the women were hypertensive, only 19% of them were able to achieve blood pressure control. Fifty eight percent of the hypertensive women use more than 15 g / day of salt and the estimated 24-hour urinary sodium excretion of these women was 311.6 ± 39.5 mmol / l. Hypertensive women using less than 5 g / day of salt were 0.3%. Salty foods consumed by the hypertensive women were pickles (55.6%), cheese (92.6%), olives (88.8%), vine leaves (71.6%), sujuk and Turkish pastrami (47.6%), and tomato paste (100%). Conclusions: In our study, participants were consuming large amounts of salt and there was a positive correlation between salt intake and blood pressure. Therefore, all efforts for sodium restriction are very important in the management of hypertension.

Tungsten is a naturally occurring transition element used in a broad range of applications. As a result of its extensive use, we are increasingly exposed to tungsten from our environment, including potable water, since tungsten can become bioaccessible in ground sources. The kidneys are particularly susceptible to tungsten exposure as this is the main site for tungsten excretion. In this study, we investigated the prolonged effects of tungsten on the kidneys and how this may impact injury and function. When mice were exposed to tungsten in their drinking water for 1 mo, kidney function had not significantly changed. Following 3-mo exposure, mice were presented with deterioration in kidney function as determined by serum and urine creatinine levels. During 3 mo of tungsten exposure, murine kidneys demonstrated significant increases in the myofibroblast marker α-smooth muscle actin (αSMA) and extracellular matrix products: fibronectin, collagen, and matricellular proteins. In addition, Masson’s trichrome and hematoxylin-eosin (H&E) staining revealed an increase in fibrotic tissue and vacuolization of tubular epithelial cells, respectively, from kidneys of tungsten-treated mice, indicative of renal injury. In vitro treatment of kidney fibroblasts with tungsten led to increased proliferation and upregulation of transforming growth factor β1 (TGFβ1), which was consistent with the appearance of fibroblast-to-myofibroblast transition (FMT) markers. Our data suggest that continuous exposure to tungsten impairs kidney function that may lead to the development of chronic kidney disease (CKD).

Context No consensus exists about the optimal duration of the low-iodine diet (LID) in the preparation of 131I therapy in differentiated thyroid cancer (DTC) patients. Objective This work aimed to investigate if a LID of 4 days is enough to achieve adequate iodine depletion in preparation for 131I therapy. In addition, the nutritional status of the LID was evaluated. Methods In this prospective study, 65 DTC patients treated at 2 university medical centers were included between 2018 and 2021. The patients collected 24-hour urine on days 4 and 7 of the LID and kept a food diary before and during the LID. The primary outcome was the difference between the 24-hour urinary iodine excretion (UIE) on both days. Results The median 24-hour UIE on days 4 and 7 of the LID were not significantly different (36.1 mcg [interquartile range, 25.4-51.2 mcg] and 36.5 mcg [interquartile range, 23.9-47.7 mcg], respectively, P = .43). On day 4 of the LID, 72.1% of the DTC patients were adequately prepared (24-hour UIE Conclusion The 24-hour UIE on day 4 of the LID did not differ from day 7, and therefore shortening the LID from 7 to 4 days seems justified to prepare DTC patients for 131I therapy in areas with sufficient iodine intake and may be beneficial to maintain a sufficient nutritional intake during DTC treatment.

1. The metabolism and excretion of cetagliptin were investigated in healthy male subjects after a single oral dose of 100mg/50μCi [14C] cetagliptin.2. The mean concentration-time profile of cetagliptin was similar to that of total radioactivity in plasma after oral administration of [14C] cetagliptin in healthy male subjects. Cetagliptin was rapidly absorbed after oral administration. Unchanged cetagliptin was the most abundant radioactive component in all matrices investigated. Approximately 53.13% of plasma AUC of total radioactivity was accounted for by cetagliptin. Each metabolite plasma AUC was not higher than 2.93% of plasma AUC of total radioactivity. By 336 h after administration, 91.68% of the administered radioactivity was excreted, and the cumulative excretion in the urine and feces was 72.88% and 18.81%, respectively. The primary route of excretion of radioactivity was via the kidneys.3. Four metabolites were detected at trace levels, and it involved hydroxylated (M436-1 and M436-3), N- sulfate (M500), and N-carbamoyl glucuronic acid conjugates (M640B) of cetagliptin. These metabolites were detected also in plasma, urine, and feces at low levels, except that metabolite M640B was not detected in feces. All metabolites were observed with < 10% of parent compound systemic exposure after oral administration.

Space travel burdens health by imposing considerable environmental stress associated with radioactivity and microgravity. In particular, gravity change predominantly impacts blood pressure and bone homeostasis, both of which are controlled mainly by the kidneys. Nuclear factor erythroid-2-related transcription factor 2 (Nrf2) plays essential roles in protecting the kidneys from various environmental stresses and injuries. To elucidate the effects of space travel on mammals in preparation for the upcoming space era, our study investigated the contribution of Nrf2 to kidney function in mice two days after their return from a 31-day stay in the International Space Station using Nrf2 knockout mice. Meaningfully, expression levels of genes regulating bone mineralization, blood pressure and lipid metabolism were found to be significantly altered in the kidneys after space travel in an Nrf2-independent manner. In particular, uridine diphosphate-glucuronosyltransferase 1A (Ugt1a) isoform genes were found to be expressed in an Nrf2-dependent manner and induced exclusively in the kidneys after return to Earth. Since spaceflight elevated the concentrations of fatty acids in the mouse plasma, we suggest that Ugt1a isoform expression in the kidneys was induced to promote glucuronidation of excessively accumulated lipids and excrete them into urine after the return from space. Thus, the kidneys were proven to play central roles in adaptation to gravity changes caused by going to and returning from space by controlling blood pressure and bone mineralization. Additionally, kidney Ugt1a isoform induction after space travel implies a significant role of the kidneys for space travelers in the excretion of excessive lipids.

Excretion of [14C]HR011303-derived radioactivity showed significant species difference. Urine (81.50% of dose) was the main excretion route in healthy male subjects, whereas feces (87.16% of dose) was the main excretion route in rats. To further elucidate the underlying cause for excretion species differences of HR011303, studies were conducted to uncover its metabolism and excretion mechanism. M5, a glucuronide metabolite of HR011303, is the main metabolite in humans and rats. Results of rat microsomes incubation study suggested that HR011303 was metabolized to M5 in the rat liver. According to previous studies, M5 is produced in both human liver and kidney microsomes. We found M5 in human liver can be transported to the blood by multidrug resistance-associated protein (MRP) 3 and then the majority of M5 can be hydrolyzed to HR011303. HR011303 enters the human kidney or liver through passive diffusion, whereas M5 is taken up through organic anion transporter (OAT) 3, organic anion-transporting polypeptide (OATP) 1B1, and OATP1B3. When HR011303 alone was present, it can be metabolized to M5 in both sandwich-cultured rat hepatocytes (SCRH) and sandwich-cultured human hepatocytes (SCHH) and excreted into bile as M5 in SCRH. Using transporter inhibitors in sandwich-cultured model and membrane vesicles that expressing MRP2 or Mrp2, we found M5 was substance of MRP2/Mrp2 and the bile efflux of M5 mainly mediated by MRP2/Mrp2. Considering the significant role of MRP3/Mrp3 and MRP2/Mrp2 in the excretion of glucuronides, the competition between them for M5 was possibly the determinant for the different excretion routes in humans and rats. Significance Statement Animal experiments are necessary to predict dosage and safety of candidate drugs prior to clinical trials. However, extrapolation results often differ from actual situation. For HR011303, excretory pathways exhibited a complete reversal, through urine in humans and feces in rats. Such phenomena have been observed in several drugs, but no in-depth studies have been conducted to date. In the present study, the excretion species differences of HR011303 can be explained by the competition for M5 between MRP2/Mrp2 and MRP3/Mrp3.

Western-style high-fat/high-sucrose diet (HFHSD) changes gut microbiota and bile acid (BA) profiles. Because gut microbiota and BAs could influence each other, the mechanism of changes in both by HFHSD is complicated and remains unclear. We first aimed to clarify the roles of BAs in the HFHSD-induced change of gut microbiota. Then, we studied the effects of the changed gut microbiota on BA composition and liver function. Male wild-type (WT) and human-like Cyp2a12/Cyp2c70 double knockout (DKO) mice derived from C57BL/6J were fed with normal chow or HFHSD for 4 weeks. Gut microbiomes were analyzed by fecal 16S ribosomal RNA gene sequencing, and BA composition was determined by liquid chromatography-tandem mass spectrometry. The DKO mice exhibited significantly reduced fecal BA concentration, lacked muricholic acids, and increased proportions of chenodeoxycholic and lithocholic acids. Despite the marked difference in the fecal BA composition, the profiles of gut microbiota in the two mouse models were quite similar. An HFHSD resulted in a significant increase in the BA pool and fecal BA excretion in WT mice but not in DKO mice. However, microbial composition in the two mouse models was drastically but similarly changed by the HFHSD. In addition, the HFHSD-induced change of gut microbiota inhibited BA deconjugation and 7α-dehydroxylation in both types of mice, which improved chronic liver injury observed in DKO mice. Conclusion: The HFHSD itself causes the change of gut microbiota due to HFHSD, and the altered composition or concentration of BAs by HFHSD is not the primary factor. On the contrary, the gut microbiota formed by HFHSD affects BA composition and ameliorates liver injury in the mouse model with human-like hydrophobic BA composition.

Background: Measurement of the 24-h urinary iodine concentration or urinary iodine excretion (UIE) is the gold standard to determine iodine status; however, this method is inconvenient. The use of salivary iodine could be a possible alternative since salivary glands express the sodium-iodine symporter.Objectives: We aimed to establish the correlation between the salivary iodine secretion and UIE, to evaluate the clinical applicability of the iodine saliva measurement.Methods: We collected 24-h urine and saliva samples from 40 participants >= 18 y: 20 healthy volunteers with no specific diet (group 1), 10 patients with differentiated thyroid cancer with a low dietary intake (

Epidemiological studies related to androgens and prostate cancer (PC) have focused on serum determination of testosterone, androstenedione (A4), and DHEA, with inconsistent results. Herein, we hypothesized that differences in androgen biosynthetic and metabolic pathways, rather than differences in specific androgen concentrations, are associated with prostatic carcinogenesis. Therefore, spot urine samples from 111 incident PC cases with Gleason score at diagnosis and 227 healthy population controls, were analyzed. Urinary androgen concentrations (nanograms/milligrams of creatinine) were determined by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS). Using a factor analysis, we identified three androgen urinary excretion patterns. In a subsample, we evaluated a modification effect of the androgen receptor (AR) CAG polymorphism. Pattern I, characterized by A4 and testosterone hydroxylated metabolites (11β-OHT; 2β-OHT; 15β-OHT; 2α-OHT; 6β-OHT), was associated with high PC odds among carriers of AR gene (CAG)>19 repeats (OR: 3.67 95% CI: 1.23–11.0; P for interaction= 0.009). Conversely, higher testosterone excretion (pattern III), was marginally associated with lower (OR: 0.35 95% CI: 0.12–1.00, P for trend= 0.08) poorly differentiated PC (Gleason ≥8). No clear association was observed with pattern II (DHEA; 16α and 16β-OHT). Our results were consistent with the previous evidence which suggests that the C11-oxy backdoor pathway is important for prostatic carcinogenesis. Androgen urine excretion analysis could be useful for PC diagnosis, treatment, and prognosis; however, further studies with a larger number of samples and the urinary determination of 11-ketoandrogens are necessary.

The increasing burden of heart failure (HF) and emerging knowledge regarding chloride as a prognostic marker in HF have increased the interest in the pathophysiology and interactions of chloride abnormalities with HF-related factors and treatments. Chloride is among the major electrolytes that play a unique role in fluid homeostasis and is associated with cardiorenal and neurohormonal systems. This review elucidates the role of chloride in the pathophysiology of HF, evaluates the effects of treatment on chloride (eg, diuretic agents cause higher urinary chloride excretion and consequently serum hypochloremia), and discusses recent evidence for the association between chloride levels and mortality.

Background: Acute Kidney Injury (AKI), a common disease of the urinary system, can be induced by high doses of gentamicin (GM). The renin-angiotensin system exerts a key role in the progression of the AKI since elevated intrarenal levels of Ang II, and ACE activity is found in this condition. However, it is unknown whether oral administration of angiotensin (Ang)-(1-7), a heptapeptide that evokes opposite effects of Ang II, may attenuate the renal injuries induced by gentamicin. Objectives: To evaluate the effects of Ang-(1-7) on GM-induced renal dysfunction in rats. Methods: AKI was induced by subcutaneous administration of GM (80 mg/Kg) for 5 days. Simultaneously, Ang-(1-7) included in hydroxypropyl β-cyclodextrin (HPβCD) was administered by gavage [46 μg/kg HPβCD + 30 μg/kg Ang-(1-7)]. At the end of the treatment period (sixth day), the rats were housed in metabolic cages for renal function evaluation. Thereafter, blood and kidney samples were collected. Results: Ang-(1-7) attenuated the increase of the plasmatic creatinine and proteinuria caused by GM but did not change the glomerular filtration rate nor tubular necrosis. Ang-(1-7) attenuated the increased urinary flow and the fractional excretion of H2O and potassium observed in GM rats but intensified the elevated excretion of sodium in these animals. Morphological analysis showed that Ang-(1-7) also reduced the tubular vacuolization in kidneys from GM rats. Conclusion: Ang-(1-7) promotes selective beneficial effects in renal injuries induced by GM.

Excess salt intake is viewed as a major contributor to hypertension and cardiovascular disease, and dietary salt restriction is broadly recommended by public health guidelines. However, individuals can have widely varying physiological responses to salt intake, and a tailored approach to evaluation and intervention may be needed. The traditional sodium related concepts are challenging to assess clinically for two reasons: (1) spot and 24‐hour urine sodium are frequently used to evaluate salt intake, but are more suitable for population study, and (2) some adverse effects of salt may be blood pressure‐independent. In recent years, previously unknown mechanisms of sodium absorption and storage have been discovered. This review will outline the limitations of current methods to assess sodium balance and discuss new potential evaluation methods and treatment targets.

Hyperoxaluria, one of the major risk factors for calcium oxalate urolithiasis and nephrocalcinosis, causes significant morbidity and mortality and should therefore be detected and treated as soon as possible. An early, consequent and adequate evaluation, but also a distinction between primary (PH) and secondary hyperoxaluria (SH) is therefore essential. We evaluated the usefulness of three consecutive 24-h urine collections under different diets [usual diet, (A), low oxalate diet, (B), high oxalate diet, (C)] to prove SH, or to find evidence of PH by changes in urinary oxalate excretion (Uox). We retrospectively analyzed results from 96 pediatric patients (47 females and 49 males, age 3–18 years) who presented with a history of nephrolithiasis, nephrocalcinosis and/or persistent hematuria in whom hyperoxaluria was found in an initial urine sample. The typical pattern of SH was found in 34 patients (mean Uox (A) 0.85 ± 0.29, (B) 0.54 ± 0.15 and (C) 0.95 ± 0.28 mmol/1.73m2/d). PH was suspected in 13 patients [(A) 1.21 ± 0.75; (B) 1.47 ± 0.51 and (C) 1.60 ± 0.82 mmol/1.73m2/d], but genetically proven only in 1/5 patients examined. No hyperoxaluria was found in 16 patients. Data were inconclusive in 33 patients. Urine collection under different diets is helpful to diagnose secondary hyperoxaluria and may provide evidence, that urinary oxalate excretion is normal. We have now established this procedure as our first diagnostic step before further, more extensive and more expensive evaluations are performed.

Cystinuria is the most common genetic cause of nephrolithiasis in children. It is considered a heritable aminoaciduria as the genetic defect affects the reabsorption of cystine and three other amino acids (ornithine, lysine, and arginine) in the renal proximal tubule. Patients affected by this condition have elevated excretion of cystine in the urine, and because of this amino acid's low solubility at normal urine pH, patients tend to form cystine calculi. To date, two genes have been identified as disease-causative: SLC3A1 and SLC7A9, encoding for the two subunits of the heterodimeric transporter. The clinical features of this condition are solely related to nephrolithiasis. The diagnosis is usually made during infancy or adolescence, but cases of late diagnosis are common. The goal of therapy is to reduce excretion and increase the solubility of cystine, through both modifications of dietary habits and pharmacological treatment. However, therapeutic interventions are not always sufficient, and patients often have to undergo several surgical procedures during their lives to treat recurrent nephrolithiasis. The goal of this literature review is to synthesize the available evidence on diagnosis and management of patients affected by cystinuria in order to provide physicians with a practical tool that can be used in daily clinical practice. This review also aims to shed some light on new therapy directions with the aim of ameliorating kidney outcomes while improving adherence to treatment and quality of life of cystinuric patients.

At the onset of entrance into hibernation in many mammals, there is a reduction in the respiratory exchange ratio (RER) thought to result in a retention of CO2 that contributes to the ensuing metabolic suppression. In steady-state hibernation, the relative hypercapnic ventilatory response (HCVR; the % change in ventilation to CO2 exposure) is elevated. These two observations, paradoxically, suggest a transient decrease in CO2 sensitivity at the onset of entrance into hibernation, allowing the retention of CO2, then a subsequent increase in CO2 sensitivity giving rise to the elevated HCVR in steady-state hibernation. We examined the time course of the changes in ventilation, O2 consumption rates ([Formula: see text]o2), CO2 excretion rates, body temperature, and hence the RER and ACR (air convection ratio, ventilation/[Formula: see text]o2) and the HCVR throughout entrance and arousal into and out of hibernation in 13-lined ground squirrels to confirm this. We observed a significant drop (entrance) and rise (arousal) in the RER produced by hypo- and hyperventilation, respectively. CO2 chemo-sensitivity while the RER was reduced on entrance was blunted and rose late in entrance. On arousal, CO2 chemo-sensitivity was elevated when the RER was elevated and fell immediately after RER returned to normal values. At any given Tb, the HCVR was lower during entrance compared to arousal producing a significant hysteresis. The HCVR, however, was the same at any given [Formula: see text]o2 during entrance and arousal. These data suggest that both the changes in [Formula: see text]o2 and in the HCVR are associated with changes in central regulation of the effector limbs establishing steady-state hibernation.

La etiología de diversos tipos de cáncer, además de patologías relacionadas con el sistema cardiovascular y respiratorio, reside en el consumo de tabaco. Hoy en día, los nuevos estudios apuntan a que el tabaco produce un daño renal que puede degenerar en insuficiencia renal crónica a largo plazo. No obstante, los parámetros utilizados en clínica para la detección del daño renal, como la creatinina plasmática, no son útiles para evidenciar la disfunción. Por ello, los métodos de diagnóstico más innovadores incluyen los biomarcadores urinarios de daño renal temprano, que permitirían prevenir la evolución de la enfermedad renal. Por otra parte, basándonos en estudios previos de nuestro laboratorio, se ha desarrollado el concepto de predisposición adquirida al daño renal, así como la existencia de biomarcadores urinarios asociados a esta condición. Nuestro objetivo es estudiar si determinados biomarcadores de predisposición son capaces de detectar entre los pacientes fumadores a aquellos que están predispuestos a sufrir daño renal. Nuestros resultados demuestran que algunos de estos biomarcadores se excretan en orina de un modo significativamente superior en individuos fumadores respecto a no fumadores. La mayor excreción de dichos biomarcadores podría estar relacionada con una predisposición de los individuos fumadores a sufrir disfunción renal, aspecto clave a tener en cuenta en clínica.

The metabolic fate of a newly developed herbicide, epyrifenacil, (ethyl[(3-{2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-3,6-dihydropyrimidin-1(2H)-yl]phenoxy}pyridin-2-yl)oxy]acetate, S-3100), in rats was determined using 14C-labeled epyrifenacil. When it was administered orally to rats at 1 mg/kg, around 73-74% of the dose was absorbed, metabolized, and mainly excreted into feces within 48 h. The elimination of radioactivity in plasma and tissues was rapid, suggesting that exposure of epyrifenacil and metabolites is small. Metabolite analysis revealed that epyrifenacil was rapidly ester-cleaved to M1 and then mainly excreted into bile or further metabolized. No parent was detected in plasma, tissues, and urine. Remarkably, M1 was mainly distributed in the liver (at a concentration of 70-112 times higher than in plasma at a low dose). Furthermore, a significant sex-related difference was observed in urinary excretion of M1. Considering the above observations with those in the literature, the organic anion-transporting polypeptide (OATP) likely plays a role on the active transport of M1 in the liver and kidney.

Hypertriglyceridemia, a symptom of elevated triglyceride level in the blood, is a potent risk factor for cardiovascular and metabolic disorders. Among the numerous treatments to regulate circulating triglyceride levels, fibrates are widely used to treat hypertriglyceridemia, although they also have side effects such as hepatotoxicity and gallstone formation. In the present study, we aimed to investigate the blood triglyceride-lowering effects of a naturally fermented green tea extract (NFGT) and the underlying mechanisms on hypertriglyceridemia in vitro and in vivo models. NFGT suppressed the expression of lipogenic genes, while augmented expression of fatty acid oxidation-related genes in cultured cells, leading to the significant decrease of intracellular triglyceride content. NFGT treated group in fructose-induced hypertriglyceridemic rat model significantly decreased plasma and hepatic triglyceride, which was accompanied by an increase in excretion of fecal fat. Taken together, we propose that NFGT could be potentially a novel functional ingredient to prevent or treat hypertriglyceridemia.

Arginine (Arg) and lysine (Lys) moieties of proteins undergo various post-translational modifications (PTM) including enzymatic NG- and Nε-methylation and non-enzymatic NG- and Nε-glycation. In a large cohort of stable kidney transplant recipients (KTR, n = 686), high plasma and low urinary concentrations of asymmetric dimethylarginine (ADMA), an abundant PTM metabolite of Arg, were associated with cardiovascular and all-cause mortality. Thus, the prediction of the same biomarker regarding mortality may depend on the biological sample. In another large cohort of stable KTR (n = 555), higher plasma concentrations of Nε-carboxymethyl-lysine (CML) and Nε-carboxyethyl-lysine (CEL), two advanced glycation end-products (AGEs) of Lys, were associated with higher cardiovascular mortality. Yet, the associations of urinary AGEs with mortality are unknown. In the present study, we measured 24 h urinary excretion of Lys, CML, and furosine in 630 KTR and 41 healthy kidney donors before and after donation. Our result indicate that lower urinary CML and lower furosine excretion rates are associated with higher mortality in KTR, thus resembling the associations of ADMA. Lower furosine excretion rates were also associated with higher cardiovascular mortality. The 24 h urinary excretion rate of amino acids and their metabolites decreased post-donation (varying as little as − 24% for CEL, and as much as − 62% for ADMA). For most amino acids, the excretion rate was lower in KTR than in donors pre-donation [except for S-(1-carboxyethyl)-l-cysteine (CEC) and NG-carboxyethylarginine (CEA)]. Simultaneous GC–MS measurement of free amino acids, their PTM metabolites and AGEs in urine is a non-invasive approach in kidney transplantation.

Introduction. Catabolic syndrome is typical for most critical illness situations. A long progressive course of hypercatabolism is considered by a number of authors as a prognostic criterion for negative clinical outcome of the disease. Objective. Evaluation of the prognostic value of some indicators of the severity of catabolic syndrome in ICU patients with COVID-19. Materials and methods. A prospective cohort study was conducted in 55 patients of the intensive care unit in the period from May 2020 to March 2021. The severity of hypercatabolism was determined by the dynamics of serum albumin and daily urinary nitrogen excretion within 14 days from admission to the ICU. Comparative analysis of nonparametric quantitative data was carried out using the Mann–Whitney test. To determine the predictive value of the diagnostic test, we plotted using the curves of operating characteristics (ROC, Receiver Operating Characteristics) with the subsequent determination of the sensitivity and specificity at the separation point. Results. ROC analysis revealed moderate sensitivity (75.9 %) and low specificity (58.1 %) of the daily urinary nitrogen excretion during the first 14 days of treatment in the ICU in patients with severe SARSCoV-2. It was also shown that the dynamics of serum albumin has a low predictive value for negative clinical outcome. It should be noted that in the group of survived patients a significant increase in daily urinary nitrogen excretion was observed on days 4–7 (p = 0.022) and 8–14 (p = 0.01) of intensive therapy. Conclusion. Nitrogen urinary excretion is a more accurate prognostic marker of poor clinical outcome than serum albumin in ICU patients with severe COVID-19. The main feature of the catabolic syndrome in patients with positive clinical outcome is a progressive increase in the rate of urinary nitrogen excretion from 4 to 14 days after admission to ICU.

CASE PRESENTATION A two-year-old boy visited the doctor for hypokalemia and metabolic alkalosis. Laboratory examination revealed that urinary potassium excretion and serum aldosterone level were increased, with hyperthyroidism and thyroid-related antibodies positive at the same time. Genetic testing showed that there was a complex heterozygous mutation in the SLC12A3 gene, c.1077C>G (p.N359K) and c.1567G>A (p.A523?); the final diagnosis was Gitelman syndrome and autoimmune hyperthyroidism. BACKGROUND Gitelman syndrome is an autosomal recessive genetic disease caused by the inactivation of mutation of the SLC12A3 gene. The onset age is more than 6 years old; it is mainly manifested as low blood potassium, low blood sodium, low blood chlorine, metabolic alkalosis, increased urine potassium and urine chlorine excretion, and low urine calcium. Autoimmune hyperthyroidism manifests due to autoimmune disorders. The highest incidence rate in children is of Graves' disease, followed by chronic lymphocytic thyroiditis. CONCLUSION Several cases of Gitelman syndrome with autoimmune hyperthyroidism have been reported, most of which were Asian adults, and the case we identified is the first reported case in children under 14 years with both Gitelman syndrome and autoimmune hyperthyroidism. At the same time, we carried out a high-precision clinical exosome analysis of the gene of this case and further explored the relationship between Gitelman syndrome and autoimmune hyperthyroidism from the perspective of the gene.This case suggests that even children under 6 years with hyperthyroidism and hypokalemia should be suspected of Gitelman syndrome to avoid misdiagnosis.

The aim of this study was to determine whether carbohydrate antigen 72–4 (CA72–4) is elevated in diabetic kidney disease (DKD), and examine the association between urinary albumin-to-creatinine ratio (UACR) and CA72–4 in patients with type 2 diabetes mellitus (T2DM). Non-dialysis patients with T2DM (n=296) and 90 healthy controls were recruited in this study. CA72–4 level was measured by electrochemiluminescence immunoassay. DKD was defined as UACR≥ 30 mg/g in the absence of a urinary infection or other renal diseases. We found that patients with DKD had significantly higher serum CA72–4 levels compared to those with normoalbuminuria and healthy controls. Positive rates of CA72–4 increased gradually and markedly from normoalbuminuria to microalbuminuria and to macroalbuminuria in diabetic patients (7.5, 11.2, and 17.4%, respectively; P for trend< 0.05). CA72–4 also showed a positive correlation with UACR (r=0.288, P< 0.01). Logistic regression analysis revealed the association of increased UACR with an increased odds ratio of elevation of CA72–4 levels (P for trend< 0.05) after multivariable adjustment. In conclusion, serum levels of CA72–4 increase abnormally with the increase in urinary albumin excretion, which affects the specificity of diagnosis of malignancies. An appropriate interpretation of CA72–4 is essential to prevent unnecessary and even hazardous diagnostic procedures in patients with T2DM.

Urinary progranulin is an inflammatory marker that may indicate renal damage at an early stage of diabetic nephropathy. To determine urinary level of progranulin in patients with type 2 diabetic nephropathy and to ascertain its correlation with renal function. This was a cross-sectional comparative study that was carried out at Jawaharlal Institute of Postgraduate Medical Education & Research (JIPMER), Pondicherry, India. Thirty-three control subjects and 99 diabetic patients (divided into 3 equal groups based on urinary albumin excretion) were included. Albuminuria was detected by dipstick method in a spot urine sample for all subjects. Urinary albumin level was estimated by nephelometry for diabetic subjects who had trace or no albuminuria by dipstick method. Urinary progranulin was estimated by ELISA technique for all study subjects. eGFR (estimated glomerular filtration rate) was calculated by chronic kidney disease epidemiology collaboration (CKD-EPI) formula for all study subjects. Urinary progranulin levels were found to be significantly elevated in diabetic patients as compared to the control subjects (p

Few studies have reported the roles of the complement system in concomitant idiopathic membranous nephropathy and IgA nephropathy (IMN-IgAN). Complement factor B (CFB) is a crucial factor that involved in the alternative complement pathway. We aimed to evaluate the association between disease activity (eGFR, anti-PLA2R antibody levels and 24 h urinary protein excretion), progression and serum CFB levels of IMN-IgAN patients. In total, 39 IMN-IgAN patients (median follow-up, 46.6 months), 99 IMN patients and 92 IgAN patients participated in this study. The disease progression event was defined as end-stage renal disease (ESRD) or a 30% decline in estimated glomerular filtration rate (eGFR). The serum CFB concentration was measured by enzyme-linked immunosorbent assay. Serum CFB levels were lower in IMN-IgAN patients than in patients with IgAN only (P

Suppression of hepatic gluconeogenesis is thought to largely underlie the antidiabetes action of metformin. However, this drug also exerts various effects on the gut, one of which is the enhancement of the uptake of 18F-labeled fluorodeoxyglucose (FDG), a nonmetabolizable glucose derivative, during [18F]FDG positron emission tomography (PET)–computed tomography (CT). Whereas the relevance of this effect to the glucose-lowering action of metformin remains unclear, it is of special interest because it was discovered in humans. Cessation of metformin treatment for several days is required to normalize [18F]FDG uptake in the intestine, suggesting that the enhanced uptake is not a direct effect of the drug in the circulation but rather a prolonged secondary effect. A recent study with state-of-the-art PET–magnetic resonance imaging (MRI), which provides better tissue registration and soft-tissue contrast compared with PET-CT, revealed that metformin-induced accumulation of [18F]FDG occurs primarily in the lumen of the intestine, indicating that the drug promotes excretion of glucose from the circulation into this space. This phenomenon does not necessarily imply that metformin stimulates the removal of glucose from the body in the stool. Instead, it might be related to changes in the abundance and metabolism of the gut microbiota induced by metformin. Further studies of this effect of metformin might shed light on the unanswered questions that still remain concerning the clinical action of this old drug.

Актуальність. Після встановлення діагнозу пієлонефриту в дитини одним із провідних завдань є безпосередня оцінка того, якою мірою запальний процес призвів до склерозування тканини нирок та формування хронічної хвороби нирок. Провідне місце відводиться маркерам недиференційованої дисплазії сполучної тканини та склерозування гломерулярної частини нефронів у дітей, якими є показник вмісту оксипроліну, рівень креатиніну та глікозаміногліканів у добовій сечі. Мета дослідження: рання діагностика нефросклерозу в дітей до 3 років, хворих на гострий неускладнений пієлонефрит, без анатомічних природжених вад розвитку органів сечовидільної системи у періоді його повної ремісії. Матеріали та методи. Обстежено 65 дітей раннього віку з гострим пієлонефритом у періоді повної ремісії, у яких після нефроурологічного обстеження не було виявлено анатомічних вад розвитку органів сечовидільної системи. Дітям проводилося загальноклінічне обстеження, визначались маркери функціонального стану тубулярного епітелію та гломерулярної частини нефронів, оксипролін у сечі, виконувались тести уринолізису. Результати та обговорення. Тести уринолізису вказують на більшу частоту екскреції всіх показників у сечі дітей основної групи порівняно із здоровими дітьми. Рівень креатиніну в сечі дітей з пієлонефритом був зниженим у 21,5 % обстежених порівняно з 2,5 % здорових дітей. У 9,2 % дітей з пієлонефритом у сечі відмічалось підвищення рівня оксипроліну, що є маркером дисфункції сполучної тканини в паренхімі нирок. Аналіз екскреції глікозаміногліканів показує, що в дітей з пієлонефритом усіх вікових груп вона не була вірогідно підвищена. Висновки. З метою прогнозування формування та ранньої діагностики нефросклерозу в дітей раннього віку з пієлонефритом рекомендовано використовувати такі маркери, як результати тестів урінолізису, рівень екскреції креатиніну та оксипроліну в добовій сечі. Рекомендовано застосування методів корекції виявлених змін.

Актуальность. Изучение проблемы уролитиаза в последние годы вышло на качественно новый уровень в связи с использованием мультидисциплинарного подхода и принципов доказательной медицины. В отечественной литературе имеются единичные сообщения о значении и методах коррекции метаболических нарушений при мочекаменной болезни. До сих пор нет единого мнения по поводу целесообразности и эффективности профилактических методов после удаления конкрементов. Цель исследования:. оценка влияния фитотерапии (препарата Уролесан®)) на метаболический статус и микробиоту мочи у пациентов с мочекаменной болезнью — оксалатно-кальциевым нефролитиазом после проведения ударно-волновой литотрипсии. Материалы и методы. У 50 больных с оксалатно-кальциевым нефролитиазом после проведения ударно-волновой литотрипсии в возрасте от 18 до 65 лет (средний возраст — 41,1 ± 1,6 года) изучали влияние препарата Уролесан® на метаболический статус пациентов (влияние на рН мочи, уровень экскреции оксалатов, кальция, мочевой кислоты, показатели биохимического исследования крови), особенности микробиоты мочи и предупреждение рецидивного образования конкрементов. Результаты. Анализ динамики уровня рН мочи, измерямого на 2, 5, 10, 20 и 30-е сутки лечения Уролесаном®, показал, что пациенты при контрольном обследовании имели постепенное повышение уровня рН мочи с 5,80 ± 0,04 до 6,13 ± 0,04 на 5-е сутки (р

Background. In recent decades, more and more attention of practitioners is attracted to the role of pathology of various organs and systems of the human body associated with connective tissue dysplasia, which leads to chronicity and relapse of the pathological process in the kidneys. The purpose of the research: to clarify the role of undifferentiated connective tissue disease in the severity of pyelonephritis in children and to search for possible molecular genetic markers associated with violations of fibrillogenesis in children with different clinical course of pyelonephritis. Materials and methods. There were examined 60 children with pyelonephritis aged 3–18 years. According to the results of follow-up, they were divided in 2 groups: І — 30 patients with chronic pyelonephritis, whose follow-up was characterized by 3 and more pyelonephritis relapses during 2 years, ІІ — 30 children with pyelonephritis, who didn’t have relapses within 2 years. The control group consisted of 42 somatically healthy children of the same age. All children underwent the routine comprehensive clinical and laboratory examination, clinical and laboratory markers of fibrillogenesis disorders were evaluated. There was conducted the molecular and genetic investigation of polymorphic locі rs605143 of collagen gene COL4A1 and rs565470 of collagen gene COL4A2. Results. In children with chronic pyelonephritis, phenotypic signs of undifferentiated connective tissue dysplasia were significantly more common as compared to that of children, who had only one episode of pyelonephritis a year. Virtually in all examined children with chronic pyelonephritis, the values of free and bound fractions of hydroxyproline in the blood plasma were significantly increased (47.14 ± 0.03 μmol/l and 40.08 ± 0.03 μmol/l, respectively) indicating an increased collagen exchange, and differed reliably from those in patients with acute pyelonephritis (17.65 ± 0.01 μmol/l and 17.22 ± 0.02 μmol/l), whose hydroxyproline fractions were elevated only by 12.0 and 16.0 %, respectively. In 97.0 % of children with chronic pyelonephritis, elevated levels of urinary hydroxyproline were detected indicating an increase in the breakdown and excretion of collagen metabolism products, which significantly exceeds the rate of excretion of hydroxyproline in patients with acute pyelonephritis (10 %). The frequency of the wild AA genotype rs605143 of the COL4A1 collagen gene in children with recurrent chronic pyelonephritis was found to be higher than that of control group (21.4 vs. 4.8 %, p < 0.05). The presence in a child of AA genotype of the polymorphic rs605143 locus of the COL4A1 collagen gene five times increases the risk of chronic pyelonephritis recurrence (odds ratio (OR) 5.105, 95% confidence interval (CI) 0.12–0.87). On the contrary, as our studies have shown, the presence of TT genotype of the polymorphic locus rs565470 of the COL4A2 collagen gene reduces the risk of pyelonephritis recurrence (OR 0.14, 95% CI 0.02–1.19). Conclusions. The presence of undifferentiated connective tissue dysplasia in a child plays an important role in the course of chronic pyelonephritis. In order to predict genetically determined propensity to pyelonephritis relapse, it is recommended to carry out a molecular genetic testing of AA and AG genotypes of the polymorphic locus rs605143 of COL4A1 collagen gene, and TT and TS the genotypes of the rs565470 polymorphic locus of the COL4A2 collagen gene.

Purpose of the work: to substantiate the choice and eva­luate the effectiveness of the use of a metabolic therapeutic complex (vitamin E and L-carnitine) aimed at reducing tissue hypoxia and improving metabolic processes in the renal parenchyma du­ring the treatment of acute pyelonephritis against the background of vesicoureteral reflux (VUR) as visceral manifestation of undifferentiated connective tissue dysplasia (UCTD) in young children. Materials and methods. Sixty-seven children aged 3 months to 3 years with pyelonephritis and VUR associated with UCTD were examined. The control group consisted of 65 young children with acute pyelonephritis, who after examination did not reveal VUR and signs of UCTD. The second control group included 40 somatically healthy children of the same age. In order to diagnose the presence of undifferentiated connective tissue dysplasia, all children with remission of the inflammatory process underwent a hydroxyproline urine test. Markers of renal parenchymal hypoxia were determined ­using a test for anticrystallization function of urine and daily urinary salt excretion according to the method of Yu.Ye. Veltyshchev and Ye.O. Yurieva. The markers of the morphofunctional state of the renal epithelial cytomembranes were studied by means of a test for calcification — the presence of polar lipids in urine, and a test for the presence of lipid peroxidation products (LPР) in urine. For young children with pyelonephritis, VUR and UCTD in whose urine a high excretion of hydroxyproline was detected, in addition to protocol treatment in the period of remission of the inflammatory process, it was recommended to take for a month medications that have antihypoxant properties and are able to improve metabo­lic processes in the renal parenchyma — vitamin E and L-carnitine in age-related doses. Results. The high frequency of detection of phenotypic signs of undifferentiated connective tissue dysplasia and significant urinary excretion of hydroxyproline (86.6 %) in children with pyelonephritis against the background of vesicoureteral reflux reliably indicate the presence of undifferentiated connective tissue dysplasia as a result of fibrillogenesis disorders. In young children with pyelonephritis against the background of vesicoureteral reflux, the presence of renal parenchymal hypoxia and nephrothelial membrane destruction was revealed, as indicated by a decrease in the anticrystallization function of urine, daily excretion of phosphates and a high excretion of lipid peroxidation products from urine and polar lipids. In children in whom the association of the pathological process with UCTD was detected, these changes were more significant. This is indicated by a more pronounce decrease, compared to children in whom no association with UCTD was found, in the anticrystallization function of urine, an increase in the oxalate excretion and a decrease in the daily urinary excretion of phosphates and urates, which was accompanied by a significant intensification of lipid peroxidation processes and the appearance of polar lipids in daily urine. After metabolic therapy with antihypoxant and membrane-protective action, the exa­mined children showed a significant positive dyna­mics of the studied markers of tissue hypoxia and membrane destruction of the renal parenchyma. Conclusions. A positive effect of a metabolic complex (vitamin E and L-carnitine) during remission of the inflammatory process in the kidneys was revealed, which was expressed in a decrease in the degree of tissue hypoxia and membrane destruction, which confirms the possibility of reducing tissue hypoxia in children with pyelonephritis and vesicoureteral reflux associated with undifferentiated dysplasia connective tissue using vitamin E and L-carnitine in age-related doses for a month and allows you to recommend metabolite therapy to these children.

Increased levels of uric acid (UA), which is mainly excreted through the kidneys, are independently associated with higher mortality in end-stage renal disease (ESRD) patients. The uricolysis of gut microbiota plays an important role in extrarenal excretion of UA. This study aimed to examine the effect of inulin-type prebiotics (a type of fermentable dietary fiber) on intestinal microbiota modulation and serum UA levels in ESRD patients. Continuous ambulatory peritoneal dialysis (CAPD) patients were recruited to a randomized, double-blind, placebo-controlled crossover trial of 12-week inulin-type prebiotics. Participants were visited before and after treatment with prebiotics or placebo. Serum UA levels, dietary purine intake, serum xanthine oxidase (XO) activity, daily “renal excretion” of UA, and fecal UA degradation capability were measured at each visit. Fecal metagenomic analysis was conducted to assess microbial composition and function. Sixteen participants (mean age = 37 y; 10 men and 6 women) completed the trial, and 64 specimens were analyzed. The average concentration of serum UA decreased by approximately 10% in the prebiotic intervention group in comparison to the placebo group (p = 0.047) without an increase in daily “renal excretion” of UA via urine and dialysate. There were no significant changes in purine intake or activity of XO. Notably, enhanced fecal UA degradation was observed after prebiotic intervention (p = 0.041), and the ratio of Firmicutes/Bacteroidetes, which was positively associated with fecal UA degradation, increased in the prebiotic period (p = 0.032). Furthermore, prebiotics enriched purine-degrading species in the gut microbiota, including unclassified_o_Clostridiales, Clostridium sp. CAG:7, Clostridium sp. FS41, Clostridium citroniae, Anaerostipes caccae, and Clostridium botulinum. Inulin-type prebiotics is a promising therapeutic candidate to reduce serum UA levels in renal failure patients, and this urate-lowering effect could possibly be attributed to intestinal microbial degradation of UA. This study was registered at the Chinese Clinical Trials Registry ( http://www.chictr.org.cn/ ), registration ID: ChiCTR-INR-17013739, registration date: 6th Dec 2017.

The kidney is an extremely important organ, whose main activity is blood filtration, being responsible for the excretion of undesirable substances in the body. Whenever there is a failure or injury in this organ either due to infections and/ or pathologies, loss of functional capacity may occur, requiring hemodialysis. In more severe cases, transplantation is prioritized. The most common type of graft is allogeneic performed between individuals of the same species, and although there is partial compatibility between the recipient and the donor, there are risks and cases of rejection; so the use of immunosuppressants is essential, involving the use of both conventional and biological therapies. Thus, biological therapies are becoming an alternative treatment for several patients, and the use of monoclonal antibodies is promising, with possible reduction in the dose of immunosuppressant, and reduction of severe side effects. On the market, Muromonab, Basiliximab and Alentuzumab are currently used as therapy in kidney transplanted recipients. The significant decrease in rejection in kidney transplant recipients is partly associated with these biological treatments.

The article presents an analysis of the literature data on the connection of chronic pancreatitis of biliary genesis and obesity. The obesity is associated with hormonal disorders with excessive production of hormones with anti-inflammatory action, and reduction of pro-inflammatory hormones. It is accompanied by maintenance and enhancement of the chronic inflammatory process in pancreas as well as increases the risk of further complications. Obesity reduces the pancreatic exocrine function due to fatty degeneration of the acinar cells; it also leads to atherosclerosis of vessels with further deterioration of pantreatic trophism. The obesity is associated with enhanced synthesis and excretion of cholesterol with bile following concurrent increase of its lithogenicity as well as appearance of biliary sludge and concretion.

BACKGROUND Octreotide is widely used for the treatment of acromegaly, neuroendocrine tumors, and secretory diarrhea. However, long-term octreotide treatment can increase the incidence of gallstones. Vicarious contrast medium excretion (VCME) through the hepatobiliary system is well known. However, few studies have reported octreotide-induced acute gallstones following VCME. CASE SUMMARY A 69-year-old man presented with left lower back pain and hematuria caused by a fall. The patient had a history of polycystic kidney disease. VCME occurred following renal artery embolization for a ruptured polycystic kidney. After 5 d of treatment with octreotide, the patient developed acute gallstones and intrahepatic cholestasis which further induced pancreatitis and cholangitis. He was discharged after hemodialysis, antibiotics, and supportive treatments. CONCLUSION For patients with a high-risk of VCME, octreotide should be cautiously administered and carefully monitored.

BACKGROUND Irritable bowel syndrome (IBS) patients often experience meal-associated symptoms. However, the underlying mechanisms are unclear. AIM To determine small intestinal mechanisms of lipid-induced symptoms and rectal hypersensitivity in IBS METHODS: We recruited 26 IBS patients (12 IBS-C, 14 IBS-D) and 15 healthy volunteers (HV). In vivo permeability was assessed using saccharide excretion assay. Rectal sensitivity was assessed using a barostat before and after small bowel lipid infusion; symptoms were assessed throughout. Next, an extended upper endoscopy with probe-based confocal laser endomicroscopy (pCLE) was performed with changes induced by lipids. Duodenal and jejunal mucosal biopsies were obtained for transcriptomics. RESULTS Following lipid infusion, a higher proportion of HV than IBS patients reported no pain, no nausea, no fullness and no urgency (P

Objective This study aimed to evaluate the effect of swimming training (T) on the renal system and body composition parameters in young animals treated with a high sucrose diet (SUD) during 12 weeks. Results The SUD impaired the physical performance, increased the body adiposity index (BAI), Lee index (LI) and retroperitoneal adipose tissue (RAT) weight, plasma creatinine and number renal cells nuclei, decreased urinary volume and urinary creatinine excretion besides creatinine clearance. The T reversed the increased the BAI, LI, RAT weight, plasma and urinary creatinine, creatinine clearance and number renal cells nuclei in addition to promoting decrease in urinary protein excretion. This study found that eight weeks of swimming physical training protected renal function and restored normal glomerular filtration rate (GFR) values. Swimming training also contributed to prevention of the onset of a renal inflammatory process and caused a decrease in the risk of development of obesity promoted by SUD decreasing the body composition parameters (BAI, LI, and RAT weight).

To reduce nitrogen excretion and lower feeding costs, low crude protein (CP) diets are sometimes proposed, however, a great reduction of dietary CP concentration (>4% reduction vs. recommended concentration), even supplemented with essential and nonessential amino acids (AA) can detrimentally affect small intestinal barrier function and immunity, possibly due to the excessive lack of peptides. Here we hypothesize that with an extremely low CP concentration diet, protein-derived peptides, rather than AA supplementation, can improve intestinal barrier development and health. To test this hypothesis, 21 growing pigs (19.90 ± 1.00 kg body weight) were randomly assigned to 3 treatments with control diet (16% CP), or low CP diets (13% CP) supplemented with AA (LCPA) or casein hydrolysate (LCPC) for 28 days. In comparison with the control diet, the LCPA diet decreased the protein expression level of jejunal barrier factor zonula occludens-1 (ZO-1) and stem cell proliferation factor leucine-rich repeat-containing G-protein-coupled receptor-5, whereas the LCPC diet enhanced intestinal barrier function by increasing the protein expression level of jejunal occludin and ZO-1 and ileal mucin-2. The LCPA diet reduced Lactobacillus counts, whereas the LCPC diet increased Lactobacillus counts and reduced Escherichia coli counts in the ileum. The LCPA diet also increased protein expression levels of pro-inflammatory cytokine interleukin-6 (IL-6) and IL-22, whereas the LCPC diet decreased protein expression levels of pro-inflammatory IL-1β, IL-17A and tumor necrosis factor-α in the ileum. Collectively, the casein hydrolysate supplementation of low CP diets showed beneficial effects on the small intestinal barrier, bacterial community, and immunity in pigs, pointing to the important role of protein-derived peptides in small intestinal health in cases of low crude protein diets.

Objective: Non-adherence to antihypertensive agents leads to reduced blood pressure (BP) control. Data supporting the correlation of adherence with arterial stiffness (AS) are few. Furthermore, the causal relationship between AS and cognitive dysfunction (CO/DY) has not been clearly established. It is suggested that angiotensin II receptor blockers (ARBs) exhibit the lowest discontinuation rate among antihypertensive drugs. Design and Methods: We followed up with patients receiving monotherapy with irbesartan. CO/DY was assessed with the Mini-Mental State Examination (MΜSE) and other tests. Results: Patients [n=77; mean age: 56±11 years; 39 men (50.6%)] were followed-up for 16.1±10.9 months. At the end of follow up, significant reductions were observed in mean peripheral systolic BP (135±117 vs 153±11 mmHg; p : AS indices [carotid-femoral pulse wave velocity and augmentation index] also improved significantly: 7.7±1.4 vs 8.2±1.4 m/sec (p : At the end of the study, a significant improvement was observed in the MMSE test (29.7±0.7 vs. 29.2±0.9; p : The level of adherence was high in 60/77 (77.9%), medium in 9/77 (11.6%) and low in 8/77 (10.38%) patients. Conclusions: Hypertensive patients receiving mono-therapy with an ARB showed reduced AS, cognitive improvement, significant reductions in BP (peripheral and central) and decreased 24h urinary albumin excretion.

Faxuan Wang,1,2,&ast; Binxia Wang,3,&ast; Xiyuan Chen,1,2 Wanlu Liu,1,2 Guoqi Wang,1,2 Xiaoxia Li,1,2 Xiuying Liu,1,2 Nan Li,1,2 Jiaxing Zhang,1,2 Ting Yin,1,2 Jinyun Jing,1,2 Xiaoyu Chang,4 Yanan Jin,5 Yuhong Zhang,1,2 Yi Zhao1 1School of Public Health and Management, Ningxia Medical University, Yinchuan, Ningxia, People’s Republic of China; 2Key Laboratory of Environmental Factors and Chronic Disease Control, Yinchuan, Ningxia, People’s Republic of China; 3Second People’s Hospital of Gansu Province, Lanzhou, Gansu, People’s Republic of China; 4Editorial Department of the Journal of Ningxia Medical University, Ningxia Medical University, Yinchuan, Ningxia, People’s Republic of China; 5Centers for Disease Control and Prevention in Ningxia, Yinchuan, Ningxia, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yi ZhaoSchool of Public Health and Management, Ningxia Medical University Tel +86 139 9501 1690Fax +86 951-6980144Email zhaoyi751114@hotmail.comBackground: Recently, the association between lifestyle-related diseases and free amino acids in the blood plasma—especially branched-chain amino acids (BCAAs) and aromatic amino acids (AAAs)—has been highlighted. However, few studies have been carried out on 24-hour urine samples. Therefore, we aimed to explore the relationships between 24-hour urinary BCAAs and AAAs excretion rate and blood pressure (BP) in elderly patients with hypertension.Methods and Results: Each of the 322 elderly patients with hypertension completed an in-person questionnaire interview, underwent a physical examination, and provided a 24-hour urine specimen. We measured their BCAAs and AAAs excretion rate, and used multiple linear regression analysis with variable selection to construct models describing the relationships between their BCAAs and AAAs excretion rate and BP. After adjusted for age, gender, height, and weight, valine was inversely associated with both systolic blood pressure (SBP) (β: − 0.232, 95% CI: − 0.16, − 0.006) and diastolic blood pressure (DBP) (β: − 0.144, 95% CI: − 0.089, − 0.005). These findings were invariant even following adjustment for urine volume and drugs history, and Ile was positively associated with DBP (β: 0.170, 95% CI: 0.001, 0.066).Conclusion: The data revealed that the excretion rate of 24-hour urinary BCAAs was closely related to BP in elderly hypertension patients, and these findings will provide new insights into the association between BACC metabolism and BP.Keywords: hypertension, branched-chain amino acid, aromatic amino acid, association

Diabetes, obesity and metabolism 23(12), 2814-2818 (2021). doi:10.1111/dom.14517, Published by Wiley-Blackwell, Oxford [u.a.]