24-hour Urinary Excretion Research Articles

Correlation of the Dietary Protein Intake between Those Estimated from a Short Protein Food-Recall Questionnaire and from 24-Hour Urinary Urea-Nitrogen Excretion in Stages 3-4 Chronic Kidney Disease Patients.

High protein intake may accelerate progression of chronic kidney disease (CKD). Estimation of dietary protein intake (DPI) is indispensable for management of CKD, but to achieve optimum DPI is quite challenging in routine clinical practice. We recently studied a beneficial effect of utilizing integrated care on the management of CKD at the rural community level. In that study, we created a short protein food-recall questionnaire (S-PFRQ) as a working tool to estimate DPI of the CKD patients during home visit by community health personnel. Herein, we reported the initial evaluation of the reliability of S-PFRQ from our previous study. We compared the amount of DPI obtained from S-PFRQ with that obtained from protein-equivalent of total nitrogen appearance (PNA). In the previous ESCORT-2 study, 914 patients with CKD stage 3 or 4, who were living in the rural area of Thailand, were prospectively followed while receiving integrated care for 36 consecutive months. During home visits by community nurses from subdistrict health centers, dietary food recall was made, recorded in S-PFRQ, and DPI was obtained. Among these, sixty patients were randomly selected, and 24-h urine was collected for urinary urea-N and estimation of PNA. A correlation was made between DPI obtained from S-PFRQ and PNA. The DPIs derived from S-PFRQ and PNA were 28.8 ± 14.8 and 39.26 ± 17.79 g/day, respectively. The mean difference and 95% CI between the 2 methods was -10.43 (-7.1 to -13.8) g/day, respectively (P < 0.001). Interclass correlation between these 2 methods was 0.24, P = 0.007. The difference between the 2 methods remained constant across different amounts of DPI. The DPI estimated from S-PFRQ significantly correlated to that from PNA. However, the S-PFRQ method yielded a DPI value which was about 10 g of protein or 25% less than the PNA method. Despite this amount of difference, this S-PFRQ is user-friendly and could be used during field work as an easy and simple tool for DPI estimation in resource-limiting condition.

Calcitriol reverses age-related hypertension via downregulating renal AP1/AT1R pathway through regulating mitochondrial function

ABSTRACT Background The vitamin D level in the blood is associated with the incidence of hypertension. The present study investigated whether or not calcitriol, an active form of vitamin D, reverses age-related hypertension. Methods Young (3-month-old) and aged (12-month-old) C57BL/6 male mice were administered with or without calcitriol at 150 ng/kg per day by oral gavage for 8 weeks. Blood pressure was measured by tail-cuff plethysmography and telemetry, and superoxide production in renal tissue was assessed by fluorescence imaging, and the protein expression of AP1/AT1R signaling pathway was examined by Western blot. Results We showed that 24-hour renal sodium excretion was impaired and blood pressure was increased in aged mice, which was related to the enhancement of renal AT1R expression and function. In addition, the expression of transcription factor AP1 (a dimer of c-Fos and c-Jun) and the binding of AP1 to the AT1R promoter region was significantly enhanced, accompanied by decreased nuclear translocation of Nrf2, abnormal mitochondrial function including decreased ATP production, NAD+/NADH ratio and mtDNA copy numbers, and increased reactive oxygen species. Calcitriol increased 24-hour urinary sodium excretion and reduced blood pressure in aged mice. Mechanically, calcitriol increased the nuclear translocation of Nrf2, improved mitochondrial function, reduced AP1 binding ability to AT1R promoter, which reversed enhanced AT1R expression and function, and lowered blood pressure in aged mice. Conclusions Our findings indicated that calcitriol reversed age-related hypertension via downregulating renal AP1/AT1R pathway through regulating mitochondrial function. Thus, calcitriol may be a valuable therapeutic strategy for age-related hypertension.

Abstract 11900: Potassium Magnesium Citrate is Superior to Potassium Chloride in Reversing Metabolic Side Effects of Chlorthalidone

Thiazide-type diuretics (TD) are the first-line treatment of hypertension in many guidelines because of its consistent benefit in lowering BP and cardiovascular risk. TD is also known to cause excess risk of diabetes mellitus (DM), which may limit its long-term use. Although hypokalemia was thought to be the main mechanism of TD-induced dysglycemia, potassium (K) supplementation alone does not consistently prevent TD-induced elevation in fasting plasma glucose (FPG). In addition to reducing serum K, TD triggers magnesium (Mg) depletion. However, it is unknown if Mg supplementation attenuates metabolic side effects of TD. Accordingly, we conducted a randomized double-blinded clinical trial in 60 hypertensive patients without DM to compare effects of KCl (40 meq daily) vs. KMgCitrate (Cit) powder containing identical amount of K, 20 meq of Mg, and 74 meq of Cit daily during chlorthalidone (CTD) treatment. Each patient received CTD alone (25 mg/day) for 3 weeks prior to randomization. The primary endpoint was the change in FPG after 4-month of treatment from baseline (CTD alone) after adjusting for baseline FPG as a covariate. The mean age of subjects was 59±11 years (45% Female, 30% Black participants). We found that CTD induced a significant rise in FPG, insulin, and a significant fall in serum K and 24-h urinary citrate excretion (all p &lt; 0.05). We found that KMgCit significantly increased serum K, 24-hour urinary Mg, and 24-hour urinary Cit excretion; and attenuated the rise in FPG which was not observed with KCl (Figure 1 A-C). There were no significant differences in liver fat by MRI or fasting plasma insulin between the 2 groups. In conclusion, our study showed beneficial effects of magnesium supplementation in maintaining serum K and reversing effects CTD on plasma glucose, which may improve safety profile and optimize long-term cardiovascular outcomes in hypertensive patients.

An Unusual Cause of Bilateral Adrenal Incidentaloma: A Case Report of Primary Adrenal Lymphoma

Primary adrenal lymphoma (PAL) is an extremely rare among the causes of adrenal incidentaloma. Most were diagnosed with adrenal insufficiency and B symptoms (unexplained weight loss, night sweats, fever). This article presented a 57-year-old woman who was investigated for bilateral adrenal masses found incidentally on computed tomography (CT). Physical examination and laboratory tests revealed no evidence of adrenal insufficiency or B symptoms. Only 24-hour urinary metanephrine and normetanephrine excretion were increased. Tumour F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET/CT) scan showed the greatest dimension was 14 cm in the left adrenal mass and the maximum standardized uptake value (SUV max) was 26.1 (relative to mean SUV in the normal liver parenchyma, which was 2). An adrenal biopsy was performed after taking adequate precautions against the possibility of a catecholamine crisis. Histopathology revealed high-grade B-cell lymphoma. Bone marrow involvement and brain metastasis were not observed. She received the R-EPOCH (rituximab, etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin) regimen and intrathecal methotrexate therapy as central nervous system prophylaxis. The patient responded well to treatment, and close clinical follow-up continues. PAL should always be considered when a bilateral adrenal mass is detected.

Genetic and clinical characterization of familial renal glucosuria.

Familial renal glucosuria (FRG) is a hereditary disorder caused by variants in SLC5A2 encoding sodium-glucose cotransporter 2 (SGLT2). In this study, we aimed to characterize proximal tubule solute transport, glucagon secretion and the genotype-phenotype relationship in FRG patients. We sequenced SLC5A2 and PDZK1IP1 in 21 FRG patients and measured the renal threshold of glucose (RTG) in 15 patients. We built an open-source online calculator of RTG, evaluated the proximal tubule transport of amino acid, uric acid and phosphate, and explored glucagon secretion after glucose ingestion in FRG patients. We identified 12 novel SLC5A2 variants (G484D, R564W, A212S, c.574+1G>C, W649*, S592Cfs*6, Q579*, Y339*, V39F, G491E, A464E and G360D) in our cohort and yielded 111 SLC5A2 variants from literature review. RTG in our cohort ranged from 1.0 to 9.2mmol/L. Patients with two SLC5A2 variants had lower RTG (3.9 vs 6.2mmol/L) and higher 24-h urinary glucose excretion (24hUG) than single-variant carriers (291.0 vs 40.0mmol/1.73 m2). Patients with homozygous missense or in-frame indels had mean 24hUG of 457.2mmol/1.73 m2, comparable to those with homozygous truncating variants (445.0mmol/1.73 m2) and significantly more than those with homozygous splicing variants (196.6mmol/1.73 m2). Patients with homozygous missense variants involving conservative residues (582.0mmol/1.73 m2) had more 24hUG than those with variants at non-conservative residues (257.6mmol/1.73 m2). Four out of 14 tested patients had mild aminoaciduria. The RTG of FRG patients had no significant correlation to phosphate reabsorption but a potential negative correlation to the fractional excretion of uric acid. Postprandial suppression of glucagon secretion was absent in most FRG patients. We built a comprehensive map showing the impact of SLC5A2 variant type and variant location on glucosuria severity. Our results highlighted the role of key residues in maintaining the transport function of SGLT2 and the functional link between glucosuria and reabsorption of amino acid and uric acid in FRG patients.

CORRELATION OF 24-HOUR URINARY PROTEIN TO SPOT URINARY PROTEIN TO CREATININE RATIO AT DIFFERENT TIMES OF THE DAY IN PATIENTS WITH CHRONIC KIDNEY DISEASE

Spot urine protein to creatinine ratio has become a conventional measure of daily protein excretion in patients with chronic kidney disease (CKD). It is easily obtained and is reproducible. However, the values may vary with the time of the day, and collecting the first-morning void is typical. Twenty-four hours of urinary protein has been the traditional gold standard test for estimating protein excretion. This test is still carried out in centers where spot measurements are unavailable. We conducted our study to determine the correlation between 24-hour urinary protein and spot urinary protein to creatinine ratio at different times of the day (early morning, afternoon, and night). Sixty-seven patients of CKD fulfilling the inclusion criteria were asked to provide 24-hour urine samples according to standard recommendations. According to protocol, small aliquots of urine samples (5 ml each) were taken from the 24-hour sample to be processed for spot urinary protein and creatinine. Data was analyzed on SPSS version 22 and is presented as numbers, means + SD (age, spot urinary protein to creatinine ratio for morning, afternoon, and night), and frequencies (gender, type of kidney disease). Pearson's 'r' was tested for a significant correlation between 24 hours of urine protein and all different samples of spot collections. In contrast, sensitivity and specificity for spot urine protein-to-creatinine ratio predicting 24-hour protein excretion of &lt;1, 1 – 3.5, and &gt;3.5 g/day were determined using receiver operating characteristic curves (ROC Curves). In our cohort of patients across all stages of chronic kidney disease, we observed that there was a strong correlation between all three protein-to-creatinine ratio samples with 24 hours of urinary protein excretion; however, nighttime protein creatinine ratio showed the strongest correlation with 24 hours of urinary protein excretion (Pearson's r: 0.797). Nighttime spot urine protein to creatinine ratio sample was also found to have the highest sensitivity across all 24-hour urinary protein excretion levels.A nighttime spot urinary protein to creatinine ratio sample may reliably predict 24 hours of urinary protein excretion.

Potassium Magnesium Citrate Is Superior to Potassium Chloride in Reversing Metabolic Side Effects of Chlorthalidone.

Thiazide diuretics (TD) are the first-line treatment of hypertension because of its consistent benefit in lowering blood pressure and cardiovascular risk. TD is also known to cause an excess risk of diabetes, which may limit long-term use. Although potassium (K) depletion was thought to be the main mechanism of TD-induced hyperglycemia, TD also triggers magnesium (Mg) depletion. However, the role of Mg supplementation in modulating metabolic side effects of TD has not been investigated. Therefore, we aim to determine the effect of potassium magnesium citrate (KMgCit) on fasting plasma glucose and liver fat by magnetic resonance imaging during TD therapy. Accordingly, we conducted a double-blinded RCT in 60 nondiabetic hypertension patients to compare the effects of KCl versus KMgCit during chlorthalidone treatment. Each patient received chlorthalidone alone for 3 weeks before randomization. Primary end point was the change in fasting plasma glucose after 16 weeks of KCl or KMgCit supplementation from chlorthalidone alone. The mean age of subjects was 59±11 years (30% Black participants). Chlorthalidone alone induced a significant rise in fasting plasma glucose, and a significant fall in serum K, serum Mg, and 24-hour urinary citrate excretion (all P<0.05). KMgCit attenuated the rise in fasting plasma glucose by 7.9 mg/dL versus KCl (P<0.05), which was not observed with KCl. There were no significant differences in liver fat between the 2 groups. KMgCit is superior to KCl, the common form of K supplement used in clinical practice, in preventing TD-induced hyperglycemia. This action may improve tolerability and cardiovascular safety in patients with hypertension treated with this drug class.

Ofatumumab in Rituximab-Resistant and Rituximab-Intolerant Patients With Primary Membranous Nephropathy: A Case Series

Rituximab is the first-choice therapy for patients with primary membranous nephropathy (MN) and nephrotic syndrome. However, approximately 30% of patients are treatment-resistant or become treatment-intolerant with hypersensitivity reactions upon repeated drug exposures. We aimed to assess whether ofatumumab, a fully human second-generation anti-CD20 antibody, could be a valuable alternative to rituximab in this population. Case series. 7 rituximab-intolerant and 10 rituximab-resistant patients with MN who consented to receive ofatumumab (50-300mg, single intravenous infusion) and were followed at the nephrology unit of Azienda Socio-Sanitaria Territoriale Papa Giovanni XXIII (Bergamo, Italy) between September 2015 and January2019. Over a median (IQR) follow-up of 5.0 (3.0-9.8) months, all 7 rituximab-intolerant and 3 of the 10 rituximab-resistant patients exhibited complete (proteinuria<0.3g/d) or partial (proteinuria<3.5g/d with≥50% reduction vs baseline) remission of nephrotic syndrome. Circulating B cells were similarly depleted in all patients by 1 week, and serum anti-phospholipase A2 receptor antibody concentrations decreased to<2.7 relative units/mL in 3 of 4 rituximab-intolerant and 4 of 8 rituximab-resistant patients with phospholipase A2 receptor-related disease. Ofatumumab significantly reduced 24-hour urinary protein and immunoglobulin G excretion and increased serum albumin and immunoglobulin G levels. These effects were greater in rituximab-intolerant than in rituximab-resistant patients. Measured glomerular filtration rate significantly increased by an average of 13.4% at 24 months compared with baseline (P=0.036) among all patients in the series. There were 14 nonserious infusion-related adverse events in 9 patients that recovered with temporary infusion interruption. Retrospective design, limited number of patients. Ofatumumab may represent an effective and safe treatment for rituximab-intolerant cases of MN. Larger prospective studies will be needed to validate these preliminary findings and explore the effectiveness of other second-generation anti-CD20 antibodies in this clinical setting. Primary membranous nephropathy (MN) is one of the most frequent causes of nephrotic syndrome (NS) in adults. In this case series, we explored the efficacy of ofatumumab, a fully human second-generation anti-CD20 antibody, in 17 patients with MN and NS who were intolerant or unresponsive to rituximab. All 7 rituximab-intolerant patients exhibited complete or partial clinical remission, compared with only 3 of the 10 rituximab-resistant patients. Autoantibody levels decreased in all patients with phospholipase A2 receptor-related disease. Ofatumumab achieved a significant reduction in urinary protein and immunoglobulin G excretion while increasing serum albumin and immunoglobulin G levels. Ofatumumab may be a promising option for patients with MN who are rituximab-intolerant. Further investigations are warranted to validate these preliminary findings.

Analysis of Clinical Characteristics of Patients with Different Types of Primary Hyperuricemia

Objective: This paper aims to study the clinical characteristics of patients with different types of primary hyperuricemia (HUA). Methods: Using a retrospective research method, 200 patients with primary HUA in the hospital from June 2020 to January 2023 were selected as the research objects. Patients were grouped according to the detection results of 24-hour urinary uric acid excretion (UUE) and fractional excretion of uric acid (FEUA) (renal insufficiency type, renal overload type, mixed type, and other types). The general information of patients in the four groups (gender, age, body mass index, living habits, etc.), underlying diseases (hypertension, diabetes), blood test results [uric acid (UA), creatinine (Cre)], urine test results (24-hour urine UA, 24-hour urine Cre) were summarized and the differences between the groups were analyzed. Results: The 200 cases of HUA patients were divided into 54.00% with renal insufficiency type, 38.50% with mixed type, 6.00% with renal overload type, and 1.50% with other types. The age of patients with mixed HUA was younger than that of patients with other types, renal overload type, and renal insufficiency type, and the difference was statistically significant (P &lt; 0.05). The UA level of patients with other types of HUA was lower than that of patients with mixed type HUA, and there was statistical significance (P &lt; 0.05). The Cre level of patients with mixed type HUA was lower than that of patients with renal insufficiency type and renal overload type, and the difference was statistically significant (P &lt; 0.05). The 24-hour urinary UA level in patients with renal insufficiency type HUA was lower than that in patients with renal overload type and mixed type HUA, and the difference was statistically significant (P &lt; 0.05). The 24-hour urinary Cre level of patients with other types of HUA was lower than that of patients with renal overload type and mixed HUA, the difference was statistically significant (P &lt; 0.05). The estimated glomerular filtration rate (eGFR) level of patients with other types of HUA was lower than that of patients with mixed type HUA, and the difference was statistically significant (P &lt; 0.05). There was no significant difference in the proportions of hypertension, diabetes, coronary heart disease, and urinary calculi among patients with renal insufficiency type, renal overload type, mixed type, and other types of HUA (P &gt; 0.05). Conclusion: The primary HUA patients are mainly of renal insufficiency type, followed by mixed type. There are significant differences in the clinical characteristics of patients with different types of HUA. Among them, patients with other types of HUA are the oldest and have the lowest uric acid levels. Patients with mixed HUA had the best renal function but the highest 24-hour urine creatinine level. This study can be used as a basis for rational selection of urate-lowering drugs for different HUA patients.

Comparison of Spot Urinary Protein Creatinine Ratio and 24 hour Urinary Protein Excretion in Children presenting with Nephrotic Syndrome in Tertiary Care Hospital of Eastern Nepal

Introduction: Nephrotic syndrome is an important chronic disorder in children and it’s one of the important diagnostic criteria is presence of heavy proteinuria (&gt; 40 mg/m2/hour). As 24-hour urinary protein estimation is cumbersome, inconvenient, time consuming and expensive, a more convenient and accurate method of urinary protein estimation is needed. 24-hour urinary protein estimation and urine protein/creatinine in a child with nephrotic syndrome correlates well but there are very few studies done in Nepal to prove this correlation. Hence, this study is undertaken with objective of evaluating usefulness of urine protein/creatinine (UP/UC) in random sample of urine as a rapid and reliable test for quantification of proteinuria and to know their correlation with 24hour urinary protein excretion. Objectives: Primary Objective: To evaluate accuracy of urine protein creatinine ratio (UP/UC) in early morning sample in comparison with 24 hours urinary protein excretion in children of nephrotic syndrome having normal Glomerular Filtration Rate. Secondary Objective: To evaluate usefulness of urine protein / creatinine ratio (UP/UC) in random sample of urine as rapid and reliable test for quantification of proteinuria. To evaluate biochemical and other laboratory abnormalities in children with nephrotic syndrome. To study varied clinical presentation of Pediatric nephrotic syndrome Methodology: This is a descriptive cross-sectional study conducted in pediatric unit, Nobel Medical College Teaching Hospital, Biratnagar for 12 months. In this study, 50 patients of both sexes, ranging from one to fifteen years of age were studied. The modes of presentation, laboratory investigation reports which included urine routine microscopy, 24-hour urine protein estimation, urine protein / creatinine in random sample of urine were documented and data was analyzed by linear regression. Results: Linear regression revealed that as timed 24-hour urine protein in gm/24 hour increased, Random urine/protein creatinine ratio mg/mg also increased linearly with correlation coefficient of r = 0.56 which was highly significant (p &lt; 0.001). Conclusion: This study concludes that UP/UC ratio in a spot urine reflects the amount of protein in 24-hour urine collection. UP/UC ratio &gt; 2 in patients with normal renal function represents nephrotic range proteinuria.

Reducing the Sodium Intake of Patients With Chronic Kidney Disease Through Education and Estimating Salt Excretion: A Propensity Score Matching Analysis.

Japanese people traditionally consume high quantities of salt. This study aimed to investigate the effects of educating patients with chronic kidney disease (CKD) on simple methods for reducing their daily dietary salt intake. This single-center, retrospective observational study included 115 outpatients with CKD at Kawashima Hospital (Tokushima, Japan). One physicianroutinely recommended that patients should reduce their salt intake and provided tips for salt restriction. The physician estimated the patients' daily salt intake using spot urine samples at each medical examination (education group; n = 61). The other physicians' outpatients only received dietary guidance on recommended salt intake (control group; n = 54). The estimated 24-hour urinary sodium excretion (24hUNaV) and 24-hour potassium excretion (24hUKV) were calculated using Tanaka's equation. Estimated 24hUNaV was positively correlated with body mass index (BMI), estimated 24hUKV, and urinary Na/K ratio. The patients in the education group were younger and had a lower BMI, higher estimated glomerular filtration rate, and lower systolic blood pressure (SBP). Using 38 pairs of patients obtained by propensity score matching with these variables, estimated 24hUNaV, estimated 24hUKV, and diastolic blood pressure (DBP) after one year were significantly reduced in the education group. A simple salt reduction education may reduce salt intake in outpatients with CKD.

Novel Diabetic Nephropathy-Based Hypertension Treatment for Type-2 Diabetes Mellitus and CKD Patients: A Mini Review

Diabetes mellitus is known to result in persistent renal impairment among individuals with the condition and is presently the primary aetiology of terminal-stage renal disease, with more than fifty percent of dialysis patients being affected. The prevalence of diabetes continues to rise, resulting in a decline in individuals' health status and imposing significant financial burdens on healthcare systems. Accurately distinguishing between the various types of diabetes is crucial in order to provide appropriate treatment that mitigates the severity of associated complications and their significant consequences. The co-occurrence of diabetes and renal disease has been found to be linked with a significant fourfold rise in both the frequency and fatality of cardiovascular disease. Pharmacological interventions aimed at reducing blood pressure have been a crucial component in the management of diabetic nephropathy for several decades. The past decade has witnessed a decline in the occurrence of end-stage renal disease, owing to enhanced care measures such as the administration of hypertension medication. It is assumed in clinical practice recommendations that angiotensin-converting enzyme inhibitors and angiotensin-receptor antagonists hold an equivalent status. The efficacy of low doses of ACEI and ARB in reducing proteinuria was found to be superior to that of high doses. The co-administration of angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) has been observed to elicit a more pronounced reduction in 24-hour proteinuria and urinary albumin excretion rate (UAER) in comparison to the singular administration of either ACEI or ARB.

Prognostic markers of recurrence in adrenocortical carcinoma patients after surgery

BACKGROUND: Adrenocortical carcinoma is a rare and aggressive disease. Tumor recurrence prevention is vital for increasing patients survival rate. Therefore, the identification of prognostic markers is of particular importance.&#x0D; AIM: To evaluate clinical, laboratory and chromatographic criteria for adrenocortical carcinoma recurrence using gas chromatography-mass spectrometry to optimize patients follow-up.&#x0D; MATERIALS AND METHODS: 40 patients [10 (25%) men and 30 (75%) women] with histologically confirmed adrenocortical carcinoma (according to the European Network for the Study of Adrenal Tumors stage I 3, II 29, III 8 patients at presentation) have been recruited. Measurement of 24-hour urinary steroid metabolite excretion has been carried out by gas chromatography-mass spectrometry (GCMS-ТQ8050, Shimadzu) in preoperative period. The survival distribution has been assessed according to the KaplanMeier method. Cox proportional hazards regression methods have been used to determine predictive factors on recurrence-free survival.&#x0D; RESULTS: The patients with early stages of disease (III versus III) had a significantly longer recurrence-free survival, overt hypercortisolism was associated with significantly shorter recurrence-free survival. A significant correlation between pregnenediol urinary excretion and tumor diameter, stage has been found. Increased urinary excretion of tetrahydro-11-deoxycortisol, pregnenediol was associated with a decreased recurrence-free survival in the patients with overt hypercortisolism. Increased urinary excretion of 16-OH-dehydroepiandrosterone was a marker of a shorter recurrence-free survival in the patients without Cushing syndrome. Increased urinary excretion of pregnenediol, pregnenetriol, 16-oxo-androstenediol in all the adrenocortical carcinoma patients was associated with a recurrence risk. In the multivariate analysis pregnenediol urinary excretion, stage and overt cortisol excess were significantly and independently associated with a shorter recurrence-free survival.&#x0D; CONCLUSIONS: Adrenocortical carcinoma recurrence prognostic markers have been found by gas chromatography-mass spectrometry. The application of these findings may improve patient-centered outcomes.

Pharmacokinetic and pharmacodynamic interaction of DWP16001, a sodium-glucose cotransporter-2 inhibitor, with phentermine in healthy subjects

ABSTRACT Background DWP16001, a sodium-glucose cotransporter-2 inhibitor, has shown promise for improving blood glucose control and facilitating weight loss. Co-administration with phentermine could enhance these effects. So, we aimed to evaluate the pharmacokinetic (PK) and pharmacodynamic (PD) interactions of DWP16001 and phentermine. Methods We conducted a randomized, open-label, 3-treatment, 6-sequence, 3-period crossover study involving 24 healthy adults. Participants received either DWP16001 (2 mg), phentermine (37.5 mg), or a combination of both once daily for 7 days. Blood samples, urine samples, and body weights were collected to evaluate the PK and PD. Results The PK of the combination was found to be similar to that of the monotherapy. The geometric mean ratio (GMR) of Cmax,ss, and AUCtau,ss were 0.98 and 1.00, respectively, for DWP16001, and 1.01 and 0.94, respectively, for phentermine. Co-administration did not significantly affect the 24-hour urinary glucose excretion compared to DWP16001 monotherapy, and the GMR was 0.90. Participants tended to experience greater weight loss in the combination therapy group, and all demonstrated good tolerance. Conclusions Our findings indicate that there were no significant interactions during co-administration. These results suggest that the combination of DWP16001 and phentermine may be safe and effective for the treatment of obesity and diabetes. Clinical trial registration NCT05321732

The effects of renal dopaminergic system on the development of hypertension with high salt diet and L-NNA administration

Objective: We aimed to investigate the intrarenal dopamine synthesis efficiency, blood pressure changes and the effects of this system on hypertension developed by NOS inhibition and high salt diet. Method: Wistar Albino male rats were administered water containing 50mg/L or 100mg/L concentrations of L-NNA, standard rat feed containing 0.8%salt, or 4%high salt alone or with L-NNA for 7days. Blood pressure measurements were made with the tail-cuff method. 24-hour water intake and urine volume were also measured. Results: Administration of L-NNA or high-salt diet alone for 7days did not cause a change in blood pressure, while their combined administration resulted in a significant increase in blood pressure. Blood pressures were found to be higher in the L-NNA100+HS group compared to the other groups. While the amount of water intake in 24hours did not change, the amount of 24-hour urine was reduced. 24-hour urinary sodium excretion, sodium clearance and GFR was decreased, and 24-hour urine dopamine concentrations were increased. Conclusion: Co-administration of nitric-oxide inhibitor and high-salt diet failed to prevent renal dopaminergic system blood pressure increase. Despite the increase in dopamine synthesis, intrarenal dopamine activity could not be realized by receptor interaction and it is thought that the increase in blood pressure is caused by the development of renal oxidative stress.

Application of selected biochemical parameters in prediction of acute kidney injury risk at the early stage of burn disease

Introduction and objectiveAcute kidney injury (AKI) is a common, severe complication of burn disease, developing in the first days after a massive thermal injury and worsening the prognosis of patients. Early diagnosis of AKI plays a crucial role in improving health of patients and therapeutic results. Detection of AKI based on the standard parameters of renal function is insufficient due to too late changes in their values. The aim of the study is to evaluate the relationship between the selected non-renal biochemical parameters and the risk of AKI in this group of patients.Material and methodsThe prospective study involved a group of 33 adult patients (22 men, 11 women) hospitalized after massive burns. The patients were intensively monitored for the first 7 days after the injury, daily assessing the parameters of renal function. The selected parameters were also measured: platelet count (PLT), sodium (Na), potassium (K), albumin (ALB), aspartate aminotransferase (AST), creatine kinase (CK), arterial blood pH, arterial blood bicarbonate (HCO3-), 24-hour urinary sodium excretion (24hUNa) and fractional excretion of sodium (FENa).ResultsAKI was diagnosed in 15 (45.5%) patients. Statistical differences in the obtained average values of selected parameters between the AKI and non-AKI groups were confirmed. A significant univariate relationship was found between CK, AST and ALB in the blood serum and an increased risk of developing AKI in the following days. However, after adjustment for The Abbreviated Burn Severity Index score, only CK remained significant.ConclusionsThe potential clinical benefit of monitoring AST and ALB in blood serum and especially CK was confirmed. The other routine parameters did not seem to be related to the risk of AKI and require further analysis.

Tissue Glucocorticoid Metabolism in Adrenal Insufficiency: A Prospective Study of Dual-release Hydrocortisone Therapy.

Patients with adrenal insufficiency (AI) require life-long glucocorticoid (GC) replacement therapy. Within tissues, cortisol (F) availability is under the control of the isozymes of 11β-hydroxysteroid dehydrogenase (11β-HSD). We hypothesize that corticosteroid metabolism is altered in patients with AI because of the nonphysiological pattern of current immediate release hydrocortisone (IR-HC) replacement therapy. The use of a once-daily dual-release hydrocortisone (DR-HC) preparation, (Plenadren®), offers a more physiological cortisol profile and may alter corticosteroid metabolism in vivo. Prospective crossover study assessing the impact of 12 weeks of DR-HC on systemic GC metabolism (urinary steroid metabolome profiling), cortisol activation in the liver (cortisone acetate challenge test), and subcutaneous adipose tissue (microdialysis, biopsy for gene expression analysis) in 51 patients with AI (primary and secondary) in comparison to IR-HC treatment and age- and BMI-matched controls. Patients with AI receiving IR-HC had a higher median 24-hour urinary excretion of cortisol compared with healthy controls (72.1 µg/24 hours [IQR 43.6-124.2] vs 51.9 µg/24 hours [35.5-72.3], P = .02), with lower global activity of 11β-HSD2 and higher 5-alpha reductase activity. Following the switch from IR-HC to DR-HC therapy, there was a significant reduction in urinary cortisol and total GC metabolite excretion, which was most significant in the evening. There was an increase in 11β-HSD2 activity. Hepatic 11β-HSD1 activity was not significantly altered after switching to DR-HC, but there was a significant reduction in the expression and activity of 11β-HSD1 in subcutaneous adipose tissue. Using comprehensive in vivo techniques, we have demonstrated abnormalities in corticosteroid metabolism in patients with primary and secondary AI receiving IR-HC. This dysregulation of pre-receptor glucocorticoid metabolism results in enhanced glucocorticoid activation in adipose tissue, which was ameliorated by treatment with DR-HC.

#4412 URINARY SODIUM-TO-POTASSIUM RATIO DOES NOT ACCURATELY REFLECT DIETARY SODIUM-TO-POTASSIUM RATIO

Abstract Background and Aims Low sodium intake is associated with a lower blood pressure and less proteinuria, which are important therapeutic targets in chronic kidney disease. In contrast, a low potassium intake has been associated with higher blood pressure and a higher incidence of chronic kidney disease and cardiovascular events. Counselling of patients regarding their sodium and potassium intake requires accurate estimation of their intake, but 24-hour urinary sodium and potassium excretion can deviate substantially from actual intake. Urinary sodium-to-potassium (Na/K) ratio is a promising alternative as it is less affected by incomplete urine collections and additionally captures both the effect of sodium and potassium. Our study aimed to assess whether the Na/K ratio in 24-hour urine reflects dietary intake more accurately than separate measurement of sodium or potassium in 24-hour urine. Method We performed a post-hoc analysis on data from the long-term sodium balance studies Mars105 and Mars520. Ten healthy participants consumed a diet with a known sodium and potassium content and collected 24-hour urine samples for 105 or 205 days. We calculated the log fold difference between dietary intake and urinary excretion of sodium, potassium and Na/K ratio. A mixed-effects model with a random intercept per subject was used to compare these estimates of accuracy. Subsequently, we performed a subgroup analysis per salt intake level (i.e. 6, 9 or 12 grams per day) and assessed the effect of increasing the number of 24-hour urine collections. Results Overall, the urinary Na/K ratio underestimated dietary Na/K ratio with a median difference of -0.21 (IQR -0.47 to 0.09). Estimation of dietary Na/K ratio intake using the urinary Na/K ratio was significantly less accurate compared to using urinary sodium or potassium measurement for estimation of sodium or potassium intake (Figure 1A). Only during a salt intake of 6 grams per day, the urinary Na/K ratio did not perform significantly worse than sodium measurements. Although increasing the number of 24-hour urine measurements to three or seven improved the accuracy of the urinary Na/K ratio, it remained inferior to separate assessment of urinary sodium and potassium excretion (Figure 1B). Conclusion The 24-hour urinary Na/K ratio is less accurate than 24-hour urinary sodium or potassium excretion for estimation of dietary intake in a controlled setting in healthy volunteers.

#4942 GENOTYPE-PHENOTYPE ANALYSIS IN FAMILIAL RENAL GLUCOSURIA PATIENTS: THE CRUCIAL ROLE OF CONSERVED RESIDUES

Abstract Background and Aims Familial renal glucosuria (FRG) is a hereditary disorder caused by mutations in SLC5A2, the gene encoding sodium-glucose cotransporter 2 (SGLT2) in proximal tubule cells. In this study, we aimed to characterize the genotype-phenotype relationship in FRG patients using data from our cohort and literature review. Method We sequenced SLC5A2 in a cohort of 21 FRG patients and measured the renal threshold of glucose (RTG) in 15 patients using urinary glucose excretion in a 4-hour oral glucose tolerance test (OGTT). We built an open-source online calculator to facilitate the calculation of RTG. Besides, we reviewed published literature and obtained information on SLC5A2 variants and 24-hour urinary glucose (24hUG) in FRG patients. Results We identified 27 rare SLC5A2 variants, including 13 novel variants (G484D, R564W, A212S, c.574+1G&amp;gt;C, W649*, S592Cfs*6, Q579*, A89T, Y339*, V39F, G491E, A464E, and G360D), in our cohort and yielded 107 SLC5A2 variants from literature review. RTG in our cohort ranged from 1.0 to 9.2mmol/L. Patients carrying two SLC5A2 variants had lower RTG (3.9 vs. 6.2 mmol/L, p = 0.057) and larger amounts of 24-hour urinary glucose excretion (24hUG) (52.39 vs. 7.20 g/1.73m2, p = 2.7*10−8) than those carrying a single variant. Patients with homozygous missense or in-frame indels had mean 24hUG of 82.30g/1.73m2, comparable to those with homozygous truncating variants (81.66g/1.73m2) and significantly more than those with homozygous splicing variants (35.38g/1.73m2, p = 0.026). Patients with homozygous missense variants involving conservative residues had more 24hUG (104.76g/1.73m2) than those with variants at non-conservative residues (46.37g/1.73m2, p = 0.0031). Conclusion We built a comprehensive map showing the impact of SLC5A2 variant type, variant location, and zygosity on glucosuria severity. Our results highlighted that conserved residues play an essential role in maintaining the transport function of SGLT2.

#4124 SEX AND CARDIOVASCULAR DISEASE IN STAGE G2-5 CKD PATIENTS

Abstract Background and Aims Male sex is considered a major risk factor for cardiovascular (CV) disease in the general population, but the role of this factor in the high risk for CV disease in the pre-dialysis CKD population is still debated. Methods We tested the relationship between sex and fatal and non-fatal major CV events (myocardial infarction, heart failure, arrhythmia, angina, stroke, transient ischemic attack, peripheral vascular disease, major arterial or venous thrombotic episodes and sudden death) in a cohort including 759 stage 2-5 CKD consecutively recruited from 22 Nephrology units in southern Italy between October 2005 and September 2008. After the initial assessment, patients were followed up for a median time of 36 months (range 0.3–48 months). Results Four hundred fifty-five patients were males (60%). The proportion of smokers was about 4 times higher in males (71.4%) than in females (17.4%). Males and females differed in the prevalence of diabetes (38.5% versus 29.6%) and the frequency of background CV comorbidities (35.6% versus 19.7%, P&amp;lt;0.001). Waist circumference (100.9±12.4 versus 96±14.1 cm), eGFR (37.5±13.4 versus 33±12.7 ml/min/1.73 m2), 24-hour urinary protein excretion (median: 0.7 g/24h, IQR: 0.2-1.6 g/24h versus 0.5, IQR: 0.2-1.2 g/24 h), and haemoglobin (13.4±1.9 versus 12.0±1.4 g/dL) were higher in males than in females. Serum phosphate (3.6±0.75 versus 3.9±0.75 mg/dL), hs-CRP (median; 2.2 mg/dl, IQR: 1-4.7mg/dl versus 2.8 mg/dl, IQR: 1.2-6.4 mg/dl) and total cholesterol (178.3±42.1 versus 198.8±45.6 mg/dl) were lower in males than in females. During follow-up, 42 patients died, and 118 had fatal and non-fatal CV events. On univariate Cox regression analyses, male gender failed to be associated with all-cause mortality but was strongly related to the incidence rate of fatal and non-fatal major CV events [HR 1.75, 95% CI: 1.18-2.60, P=0.006]. Data adjustment for a series of major potential confounders did not materially affect the strength of this relationship [HR:1.78, 95% CI: 1.03-3.09]. Further analysis testing the effect of age on major CV outcomes by gender showed an effect modification by this risk factor on the same outcome (P=0.037) because the hazard ratio of male versus female CV events increased progressively with ageing (Figure 1). Conclusion The excess risk for CV mortality by the male gender in the general population holds in stage G2-5 CKD patients. Age is a modifier for the excess risk for CV events in CKD patients because the risk excess of the male gender increases linearly across a wide age spectrum in CKD patients.