24-hour Urine Research Articles

Abstract P218: Resistant hypertension is associated with elevated 24-hour cortisol to cortisone ratios in black patients.

Background: RHTN is defined as blood pressure above goal despite using ≥3 antihypertensive medications. Patients with RHTN are at an increased risk for cardiovascular (CVD) compared to those with more easily controlled hypertension (HTN). Blacks With RHTN are at a specifically high risk for CVD. Mineralocorticoid receptor activation has been found as an important mechanism of RHTN. However, aldosterone levels are not different in blacks versus whites. The role of 24-hour cortisol-to-cortisone ratios in this group has not been investigated. Methods: We conducted a cross-sectional analysis of a large cohort of 2397 black and white patients with RHTN who were referred to the RHTN Clinic at the University of Alabama at Birmingham and who underwent 24-hour urine collection including cortisol and cortisone. Patients with HTN served as a control group. Results: Black patients with RHTN compared to whites had a trend to higher 24h cortisol levels (17.7±27.6 vs 16.9±14.9, p =0.70, significantly lower 24h cortisone levels (60.45±37.7 vs 75.3±40.0, p 0.000234), and significantly higher 24h cortisol-to-cortisone ratios (0.23±0.14 vs 0.20 ±0.10, p=0.027). They were younger (53.3±11.6 vs 59.4±12.9 years), more obese (BMI 34.9±7.6 vs 30.8±6.1 kg/m2, p<0.001), had earlier onset of HTN (35.6±12.5 vs 41.4±11.6 years of age, p<0.001), higher 24-hour urinary sodium excretion (188.2±92.5 vs 174.9±83.1 mmol, p=0.006) and lower potassium excretion (54.5 ±28.6 vs 65.5 ±30.5 mmol, p<0.001). Furthermore, they had a significantly higher rate of heart failure (p=0.000455) and diabetes (p=0.0006). Conclusion: Cortisol dysregulation and a higher cortisol-to-cortisone ratio as an index of 11beta HSD2 activity may play a role in black patients with RHTN and may be related to adverse outcomes in this population.

O39 IMPACT OF UROMODULIN CONCENTRATION ON RENAL AND HAEMODYNAMIC PARAMETERS IN A BLACK AFRICAN COMMUNITY WITH A HIGH PREVALENCE OF HYPERTENSION

Background and Objective: The burden of hypertension (HTN) and related comorbidities disproportionately affects developing countries like South Africa, particularly in urban populations of African ancestry. This demographic exhibits a volume-dependent form of HTN that is resistant to antihypertensive drugs that target the renin-angiotensin-aldosterone system. Renal fluid retention or abnormalities may cause HTN in this group, thus the need to investigate various nephron components for a better understanding. Uromodulin is a potential biomarker for renal function and tubular reserve. However, the relationship with renal function, haemodynamic parameters and HTN in a Black African population is unknown. Therefore, the aim of this study was to explore the relationship between urinary uromodulin concentration and renal as well as haemodynamic parameters in a Black African community with a high prevalence of volume-dependent HTN. Methods: Systemic haemodynamics (central pressures [SphygmoCor] and echocardiographic aortic velocity and diameter measurements in the outflow tract), urinary uromodulin concentrations (ELISA assay) and renal function (creatinine clearance from 24-hour urine collections [n=370]) were determined in a Black African community (n=397). Results: No relationships between urinary uromodulin concentrations and age, body mass index, blood pressure or hypertension were noted. However, urinary uromodulin concentrations were higher in females than males, even after adjusting for several confounders (p=0.0007). Although urinary uromodulin concentrations were unrelated to renal function, an inverse relationship with stroke volume (SV) was observed (p=0.0023). The inverse relationship between SV and urinary uromodulin concentration was independent of confounders and present in hypertensives (p=0.007) but not normotensives (p=0.43). The hypertensives were noted to have a higher SV than the normotensives (p=0.047). Conclusion: In a Black African community sample with a high prevalence of volume-dependent primary hypertension, urinary uromodulin was inversely related to SV, particularly in participants with hypertension. These data suggest the need to investigate the mechanisms linking urinary uromodulin to haemodynamic parameters to identify novel pathways to target for better treatment strategies in hypertension.

Development and validation of a prediction model for estimating 24-Hour Urinary Sodium Excretion using spot urine samples in adult patients

To assess whether 24-h urinary sodium excretion (24uNa) can be estimated from spot samples in adult patients who attend hospital clinics. Methods: A cross-sectional study with a development (284 patients) and a validation cohort (229 patients) was conducted at our hospital. A multivariate linear regression model was built which was compared with former models. Concordance analyses and comparison of the ability to correctly classify each patient against a prespecified uNa cut-off value of 130 mmol/24h were performed, assessed by the C-statistic. The model was well calibrated (slope [95%CI] in internal validation: 0.965 [0.947-0.987], showing good discrimination, and performed robustly in an external validation cohort (slope: 0.811 [0.675-0.946]). The mean bias between the measured and the estimated 24uNa by NaRYC was 24.85 mmol/24h [17.06-32.63]. The NaRYC had the highest values of Pearson coefficient (0.613 p<0.0001), accuracy (P30): 56.8%, and AUC-ROC: 0.822 [0.766-0.869] as compared to other seven equations. Although the mean bias of the results is quite acceptable, the variability observed in the 95%CI makes not recommend the general use of a spot as a substitute of the 24-hour urine in order to estimate the total urine excretion of Na in a single subject basis.

Abstract P420: Amino acid and organic acid signature in urine of prepubescents with higher cardiometabolic risk evaluated by waist-to-height ratio

The waist-to-height ratio (WHtR) is a valuable tool for assessing central obesity and cardiometabolic risk, even in non-obese individuals. Childhood obesity is linked to metabolic abnormalities underlying cardiovascular diseases. Amino acids are fundamental in several metabolic processes, such as synthesizing proteins, ATP, and neurotransmitters. Organic acids are products of the metabolism of amino acids, carbohydrates, and fats. We assessed the hypothesis that their levels can serve as biomarkers for exposure, disease progression, and susceptibility, aiding in early intervention strategies. This cross-sectional study assessed amino acids and organic acids profiles in urine from prepubescent children categorized by WHtR. The 110 Brazilian participants aged 9-10 were classified as higher (n=48) or normal (n=62) cardiovascular risk. LC-MS/MS analyzed 47 amino acids and 73 organic acids in 12-hour urine samples, concentration values were adjusted by urinary creatinine. Standard protocols were used to obtain biochemical profiles, cardiovascular and anthropometric parameters. A metabolic signature in the urine of prepubescents at higher cardiometabolic risk was characterized by increased levels of the aromatic amino acids [Tyr ( 131 vs 90, p &lt; 0.01 ), Trp ( 109 vs 95, p =0.02 ) and Phe ( 65 vs 46, p = 0.04 )], Lys ( 212 vs 160, p &lt; 0.01 ), α-aminoadipic acid (61 vs 49, p &lt; 0.01 ), and cystathionine ( 25 vs 21 nmol/mg of creatinine, p = 0.03 ) while the levels of the organic acids p-OH-phenyl lactic (4.82 vs 3.7 ug/mg of creatinine, p = 0.02 ), suberylglycine (0.37 vs 0.18 , p = 0.01 ), and benzoic acid (2.67 vs 1.77 , p = 0.01 ) were found to be reduced. These amino acids were correlated with increased anthropometric measurements, low HDL-C, and hypertriglyceridemia. Also, Lys and Tyr were positively associated with higher systolic blood pressure. The organic acids were negatively correlated with anthropometric measurements and benzoic acid showed a positive correlation with time of exclusive breastfeeding. Findings indicate that children at higher cardiometabolic risk present an amino acid and organic acid signature in urine, this amino acid signature is commonly reported in type 2 diabetes and adults with cardiovascular disease. The organic acid signature in the urine of children in the context of cardiometabolic risk is reported for the first time.

An Overview of Familial Hypocalciuric Hypercalcemia

Familial hypocalciuric hypercalcemia (FHH) is one of the rare reasons for hypercalcemia. FHH is an autosomal dominant disease that is inheritable. The most common calcium sensitive receptors (CaSR) develop because of the inactivation of. In addition, they also develop due to the function loss of AP2S1 and GNA11. The FHH sickness is characterized by hypercalcemia, hypocalciuria, the regular or increased level of the parathyroid hormone, and normal renal function. The symptoms of hypercalcemia are usually not observed. It is often diagnosed by calculating the calcium/creatine clearance ratio of a 24-hour urine sample, and then genetically looking at it. FHH is usually a benign disorder, and when symptomatic and rarely complications develop, calcimimetics are used or parathyroidectomy can be performed. In conclusion, FHH is a benign and genetically transmitted, moderate cause of hypercalcemia. It is rare and usually asymptomatic.

An aggressive Cushing's syndrome originating from a rare thymic neuroendocrine tumor, controlled successfully with fluconazole and octreotide therapy before surgery.

Cushing's syndromes (CSs) due to the thymic neuroendocrine tumors are rarely seen. Here, a case of ectopic CS originating from an atypical neuroendocrine tumor has been presented. A 49-year-old woman was hospitalized with symptoms of fatigue, chest pressure, dyspnea, muscle weakness, and resistant hypertension. There was marked hyperpigmentation in the whole-body surface suggestive of adrenocorticotropic hormone (ACTH) excess and there were physical features of CS. There was deep hypokalemia. Basal hormone profile, dexamethasone suppression tests, midnight cortisol, and 24-hour urine cortisol levels were suggestive of ectopic CS. The pituitary magnetic resonance imaging revealed a 5 mm cystic lesion and the patient refused inferior petrosal sinus sampling. Thorax computerized tomography showed an anterior mediastinal mass. A fluorodeoxyglucose-positron emission tomography showed the same mediastinal lesion (suvmax: 11.4), and no other tumor focus was detected. There was an aggressive cortisol excess causing acute respiratory distress syndrome, making it difficult to perform the surgery. We immediately started fluconazole and octreotide therapy and were successful in lowering the cortisol level. Then a complete resection of the tumor had been able to be surgically performed and tumor cells showed strong cytoplasmic immunopositivity with ACTH. A definitive diagnosis of "ACTH secreting atypical thymic carcinoid tumor" was rendered based on the histopathological and immunohistochemical features. There was only surrounding vessel invasion, and no lymphoid or other organ metastases were detected. As there were surrounding vessel invasions, a two-cycle regimen cisplatin-etoposide chemotherapy and radiotherapy were employed. After surgical and medical therapy, the cortisol and ACTH levels turned to normal. The patient is in biochemical and clinical remission and has no tumor recurrence yet. Ectopic ACTH-producing thymic carcinoids are rare but life-threatening tumors because of the underlying malignancy and severe hypercortisolemia. It is important to consider this disease and perform appropriate treatment at the right time. Today, surgery is the standard therapeutic modality if it is possible to perform, but there is not a clear and constant recommendation for nonsurgical therapeutic modalities. Further studies are needed for the optimal treatment strategies.

Long-Term Follow-up Results of Children with Urolithiasis Followed in Our Clinic

Title and Objective: Urolithiasis is a prevalent condition frequently observed in childhood within the Turkish population. The aim of this study was to evaluate the metabolic, radiological, and clinical features of pediatric patients with urolithiasis. Materials and Methods: Records of 158 children referred to the Pediatric Nephrology Department of Celal Bayar University between 2010 and 2020 with suspected urolithiasis and microlithiasis were retrospectively reviewed. The complaints and ages of the cases during hospital admission, their medical histories, and the location of the stones were determined. All patients underwent complete urine analysis, spot urine electrolytes, urine culture, serum electrolytes, kidney function tests, uric acid, albumin measurements, and urinary ultrasonography. 24-hour urine electrolytes were studied in patients capable of urine collection. Stone analysis using X-ray diffraction was performed on patients from whom stones were obtained. Results: Out of the individuals, 88 (55.7%) were male, and 70 (44.3%) were female, resulting in a male-to-female ratio of 1.25:1. The average age at the time of diagnosis was determined to be 89.82 ± 57.35 months. A family history of urolithiasis was reported in 108 (68.3%) patients, and 46 individuals (29%) were born from consanguineous marriages. At the time of diagnosis, 32 patients (20%) had a urinary tract infection. Stones were predominantly situated in the upper urinary system in 129 patients (81.6%), with 123 (77.8%) having unilateral stones and 35 (22.2%) having bilateral stones. Calcium oxalate stones were the most commonly observed (80%) in patients who underwent stone analysis. Hypercalciuria emerged as the most frequently identified urinary metabolic risk factor. At the end of the follow-up period, 14 patients experienced a recurrence, while 67 patients remained free of stones. Conclusion: Urolithiasis continues to be a significant concern among children in our nation. Due to the higher recurrence rate and more frequent underlying metabolic disorders in children with stone diseases compared to adults, metabolic assessment and stone analysis are recommended procedures, emphasizing the need for lifelong monitoring in these cases.

Reckoning of antiurolithiatic effect of Flemingia Strobilifera R. BR using ethylene glycol-induced urolithiatic animal model: demystifying traditional medicine

BackgroundUrolithiasis is a painful condition and current treatment doesn’t assure the prevention of recurrence. This research aims to demonstrate the scientific reliability of Chloroform leaf extract of Flemingia Strobilifera R.Br. (CEFS) for antiurolithiatic activity using ethylene glycol-induced urolithiasis model.ResultsEthylene glycol (EG) was used to induce hyperoxaluria in male Wistar rats. The rats were grouped into 7-groups containing six each. Group I and II served as negative and positive control, group III received standard treatment, whereas Group IV to VII served as testing groups. CEFS of 30 mg/kg body-weight and 60 mg/kg body-weight was used as a preventive and curative regimen. The urine biochemistry was analysed for the presence of calcium, magnesium, phosphate, and oxalate. The rats were sacrificed for histopathological examination and LDH detection. The 24-hours urine volume was increased in both EG-treated groups as well as CEFS-treated groups, indicating the diuretic activity of plant. CEFS dose-dependently inhibited urine excretion of phosphate, calcium, and oxalate compared to the positive-control group. The histopathological examination of CEFS-treated rats’ kidneys had reduced loss of renal structure and lessened deposition of calcium oxalate crystals.ConclusionCEFS exhibited significant antiurolithiatic activity by reducing supersaturation of urine and excretion of stone forming components.

Sestrin2 knockout exacerbates high-fat diet induced metabolic disorders and complications in female mice

BackgroundObesity and its associated complications raise significant public concern, revealing gender disparities in the susceptibility to metabolic disorders, with females often displaying greater resistance to obesity-related metabolic disorder than males. Sestrin2 is a crucial protein involved in metabolism and energy balance. This study seeks to explore whether Sesn2 knockout (KO) exacerbates high-fat diet (HFD) induced obesity in female mice.MethodsFemale mice with wild-type (WT) and Sesn2 KO were subjected to a 12-week regimen of normal diet or HFD. Using a Body Composition Analyzer, body composition was gauged. Biochemical assays encompassed glucose, lipid, and liver function measurements, alongside 24-hour urine albumin excretion. Echocardiographic evaluation assessed cardiac function. Histopathological analysis of key metabolic tissues (liver, kidney, and heart tissues) were conducted. Western blotting or qRT-PCR evaluated key proteins and genes linked to inflammation, mitochondrial, and lipid metabolism in adipose tissues.ResultsIn comparison to mice fed a regular diet, those on a HFD exhibited significant increases in body weight and fat mass. Notably, Sesn2 KO further aggravated obesity, showcasing the most pronounced metabolic anomalies: elevated body weight, fat mass, impaired glucose tolerance, and insulin sensitivity, alongside heightened levels of free fatty acids and triglycerides. Additionally, KO-HFD mice displayed exacerbated multi-tissue impairments, including elevated hepatic enzymes, increased urinary albumin excretion, compromised cardiac function, and accumulation of lipids in the liver, kidney, and heart. Moreover, adipose tissue showcased altered lipid dynamics and function, characterized by enhanced triglyceride breakdown and modified adipokine levels. Browning was diminished, along with decreased Pgc1α and Sirt1 in KO-HFD mice.ConclusionSesn2 KO exacerbates HFD-induced obesity and metabolic disorders in female mice. These findings underscore Sestrin2’s novel role as a regulator of obesity in female mice.

A Novel Machine-Learning Algorithm to Predict Stone Recurrence with 24-Hour Urine Data.

Objectives: The absence of predictive markers for kidney stone recurrence poses a challenge for the clinical management of stone disease. The unpredictability of stone events is also a significant limitation for clinical trials, where many patients must be enrolled to obtain sufficient stone events for analysis. In this study, we sought to use machine learning methods to identify a novel algorithm to predict stone recurrence. Subjects/Patients and Methods: Patients enrolled in the Registry for Stones of the Kidney and Ureter (ReSKU), a registry of nephrolithiasis patients collected between 2015-2020, with at least one prospectively collected 24-hour urine test (Litholink 24-hour urine test; Labcorp) were included in the training set. A validation set was obtained from chart review of stone patients not enrolled in ReSKU with 24-hour urine data. Stone events were defined as either an office visit where a patient reports symptomatic passage of stones or a surgical procedure for stone removal. Seven prediction classification methods were evaluated. Predictive analyses and receiver operator characteristics (ROC) curve generation were performed in R. Results: A training set of 423 kidney stone patients with stone event data and 24-hour urine samples were trained using the prediction classification methods. The highest performing prediction model was a Logistic Regression with ElasticNet machine learning model (area under curve [AUC] = 0.65). Restricting analysis to high confidence predictions significantly improved model accuracy (AUC = 0.82). The prediction model was validated on a validation set of 172 stone patients with stone event data and 24-hour urine samples. Prediction accuracy in the validation set demonstrated moderate discriminative ability (AUC = 0.64). Repeat modeling was performed with four of the highest scoring features, and ROC analyses demonstrated minimal loss in accuracy (AUC = 0.63). Conclusion: Machine-learning models based on 24-hour urine data can predict stone recurrences with a moderate degree of accuracy.

Primary Paraganglioma of the Prostate: A Systematic Review of the Literature for A Rare Entity.

Paragangliomas of the urinary tract are exceptionally uncommon, and sporadic case reports of primary paraganglioma of the prostate have been reported in the literature. Systematic research in PubMed/Medline and Scopus databases concerning primary prostatic paraganglioma was performed by two independent investigators. This analysis included 25 adult males, with a mean age of 49.8 ± 22.4 years. 32% of included patients had a history of hypertension. Problems during urination (52%), blood loss (44%), either as hematuria or hemospermia, and catecholamine-related symptoms (36%) comprised the most frequently reported clinical manifestations. Digital rectal examination found a palpable nodule in 36% of patients, while prostatic specific antigen (PSA) was normal in all tested patients. Abdominal ultrasound (44%), computed tomography (44%) and magnetic resonance imaging (28%) helped to identify the primary lesion. 24-hour urine epinephrine, norepinephrine and vanillylmandelic acid (VMA) levels were elevated in 90%, 80% and 90% of included patients. Open surgical excision of the mass was performed in 40%, transurethral resection in 8%, open radical prostatectomy in 24%, transurethral resection of the prostate in 16% and robot-assisted radical prostatectomy in 4% of included patients. Due to atypical clinical manifestation and scarcity of prostatic paraganglioma, urologists should be aware of this extremely rare entity.

Impaired Saltiness Perception Contributes to Higher Sodium Intake Among Patients With Chronic Kidney Disease: A Cross-Sectional Two-Center Study

Dietary sodium restriction is important in the prognosis of patients with chronic kidney disease (CKD). The association between saltiness perception and sodium intake among CKD patients is unclear, and the factors that influence saltiness are also not fully understood. We evaluated saltiness perception in CKD patients employing a cost-effective saltiness perception test using sodium solutions and evaluated the association between saltiness perception, sodium intake, and the influencing factors. CKD outpatients not undergoing dialysis were enrolled from two medical centers and underwent saltiness perception tests together with 24-hour urine collections to measure daily sodium intake. Participants who perceived saltiness using the test solution containing 25mM sodium were regarded to have "preserved" saltiness perception, while those unable to perceive saltiness were regarded as having "impaired" saltiness perception. Of the total 132 participants, the median daily sodium intake was 3.36g (range; 0.51-9.95g/day), and 43 (32.6%) were ex- or current smokers. When participants were divided into 3 groups (G) according to daily sodium intake level: low (G1; 0.51-2.61g/day), middle (G2; 2.62-3.99g/day), and high (G3; 4.06-9.95g/day), there was an obvious difference in impaired saltiness perception between three groups: 6.8% in G1, 50.0% in G2 and 86.4% in G3 (P value=8.035 × 10-14, Cochran-Armitage test). In a multiple regression analysis in which the saltiness perception was adopted as a subjective variable, smoking habit (ex- or current smoker) and nonadherence to dietary sodium restriction were identified as significant explanatory variables. We revealed the clear relationship between higher daily sodium intake and impaired saltiness perception that is related to nonadherence to dietary sodium restriction and smoking habit, both of which could be intervened by nutritional counseling and public health education.

Graded Organ Response and Progression Criteria for Kidney Immunoglobulin Light Chain Amyloidosis

Kidney light chain (AL) amyloidosis is associated with a risk of progression to kidney replacement therapy (KRT) and death. Several studies have shown that a greater reduction in proteinuria following successful anticlonal therapy is associated with improved outcomes. To validate graded kidney response criteria and their association with kidney and overall survival (OS). This retrospective, multicenter cohort was conducted at 10 referral centers for amyloidosis from 2010 to 2015 and included patients with kidney AL amyloidosis that was evaluable for kidney response and who achieved at least hematologic partial response within 12 months of diagnosis. The median follow-up was 69 (54-88) months. Data analysis was conducted in 2023. Four kidney response categories based on the reduction in pretreatment 24-hour urine protein (24-hour UP) levels: complete response (kidCR, 24-hour UP ≤200 mg), very good partial response (kidVGPR, >60% reduction in 24-hour UP), partial response (kidPR, 31%-60% reduction), and no response (kidNR, ≤30% reduction). Kidney response was assessed at landmark points (6, 12, and 24 months) and best kidney response. Cumulative incidence of progression to KRT and OS. Seven-hundred and thirty-two patients (335 women [45.8%]) were included, with a median (IQR) age of 63 (55-69) years. The median (IQR) baseline 24-hour proteinuria and estimated glomerular filtration rate was 5.3 (2.8-8.5) g per 24 hours and 72 (48-92) mL/min/1.73m2, respectively. In a competing-risk analysis, the 5-year cumulative incidence rates of progression to KRT decreased with deeper kidney responses as early as 6 months from therapy initiation (11%, 12%, 2.1%, and 0% for kidNR, kidPR, kidVGPR, and kidCR, respectively; P = .002) and were maintained at 12 months and 24 months and best kidney response. Patients able to achieve kidCR/kidVGPR by 24 months and at best response had significantly better OS compared with kidPR/kidNR. Kidney progression, defined as a 25% or greater decrease in estimated glomerular filtration rate, was associated with cumulative incidence of progression to KRT and OS. The results of this cohort study suggest that graded kidney response criteria offers clinically and prognostically meaningful information for treating patients with kidney AL amyloidosis. The response criteria potentially inform kidney survival based on the depth of reduction in 24-hour proteinuria levels and demonstrate an OS advantage for those able to achieve kidCR/kidVGPR compared with kidPR/kidNR. Taken together, achievement of at least kidVGPR by 12 months is needed to ultimately improve kidney and patient survival.

The Urine Output Response to Low-Dose Diuretic Challenge Predicts Tolerance to Negative Fluid Balance in Mechanically Ventilated, Critically Ill Patients.

Background and objective Although early diuretic use and negative fluid balance (NFB) have been associated with lower mortality in mechanically ventilated patients, some patients are not tolerant to NFB. Little is known about whether urine output response after the diuretic administration predicts NFB tolerance in mechanically ventilated patients. Hence, we conducted this study to look into this. Methods This was a single-center, prospective, observational study. We included mechanically ventilated patients who were hemodynamically stable with bilateral pulmonary opacities on chest radiography and planned to be diuresed per our fluid removal protocol. In the protocol, a low dose of furosemide adjusted to each patient's estimated glomerular filtration rate (eGFR) was administered, and then we started to measure urine outputs hourly for four hours. Tolerance to NFB was defined as "absence of hypotension, fluid resuscitation and vasopressors use, and acute kidney injury during fluid removal". We investigated whether the urine output predicts the tolerance to NFB during fluid removal treatment. Results A total of 60 mechanically ventilated patients were included. Notably, 80% (48/60) of the patients were tolerant to NFB. All hourly and cumulative urine output measurements during the first four hours after the first diuretic administration were significantly higher in the NFB-tolerant group than in the non-tolerant group. Among all hourly and cumulative urine output measurements, the first four-hour cumulative urine output showed the highest area under the receiver operating characteristic curve (AUC) of 0.83 for predicting the tolerance to NFB. Multivariate logistic regression analysis adjusted for the urine output two hours before the diuretic use showed that each 100-mL increase in the first four-hour cumulative urine output was significantly associated with an increased odds ratio (OR) of the tolerance to NFB [adjusted odds ratio (aOR): 1.53; 95% CI: 1.11-2.15]. Conclusions Based on our findings, the first four-hour cumulative urine output after the first low dose of diuretic administration might help predict tolerance to NFB during fluid removal treatment in mechanically ventilated, critically ill patients.

Early Anuria in Incident Peritoneal Dialysis Patients: Incidence, Risk Factors, and Associated Clinical Outcomes

Rationale & ObjectiveThe development of anuria was linked to worse clinical outcomes in patients undergoing peritoneal dialysis (PD). Our objective was to investigate the incidence, risk factors, and associated clinical outcomes of anuria within the first year after PD. Study DesignRetrospective Cohort Study. Setting & ParticipantsPatients who started continuous ambulatory peritoneal dialysis (CAPD) at our center between 2006 and 2020 were included and followed up until January 31, 2023. ExposureAge, gender, diabetes, temporary hemodialysis, angiotensin-converting enzyme inhibitors (ACEI)/angiotensin II receptor blockers (ARBs), diuretics, baseline urine volume, serum albumin, daily glucose exposure, peritonitis, and incremental PD. OutcomesThe primary outcome was early anuria, defined as 24-hour urine volume ≤ 100mL within the first year of PD initiation. Secondary outcomes included all-cause mortality, cardiovascular disease (CVD) mortality, technique failure, and peritonitis. Analytical ApproachCox proportional hazards model. ResultsA total of 2592 CAPD patients aged 46.7 ± 14.9 years were recruited. Among them, 58.9% were male, 24.0 % had diabetes. Within the first year of PD therapy, 159 (6.13%) patients developed anuria, with a median duration of 7.53 (interquartile range [IQR] 3.93-10.0) months. Higher baseline urine volume (hazard ratio [HR] 0.93, 95% confidence interval [CI] 0.90-0.97), higher serum albumin (HR 0.92, 95% CI 0.88-0.95), with diabetes before PD (HR 0.57, 95% CI 0.35-0.92), and prescribed incremental PD (HR 0.27, 95% CI 0.14-0.51) were associated with a reduced risk for early anuria, while a higher level of daily glucose exposure (HR 1.01, 95% CI 1.00-1.01) was identified as a risk factor for early anuria. Subgroup analyses showed that using ACEI/ARBs was linked to a lower risk of early anuria (HR 0.25, 95% CI 0.09-0.69) in diabetic patients. Treating early anuria as a time-dependent covariate, early anuria was associated with a higher risk for all-cause mortality (HR 1.69, 95% CI 1.23-2.32) and technique failure (HR 1.43, 95% CI 1.00-2.04) after adjusting for confounding factors. LimitationsSingle-center and observational study. ConclusionsThe incidence of early anuria in our center was 6.13%. Higher baseline urine volume, higher serum albumin, a history of diabetes, incremental PD start, and lower daily glucose exposure were associated with lower risks of early anuria. In patients with diabetes mellitus, non-use of ACEI/ARBs was associated with early anuria. Early anuria was related to a higher risk for all-cause mortality and technique failure.

Protein Intake and High Uric Acid Stone Risk

Rationale & ObjectiveWe evaluated the metabolic differences between pure and impure uric acid stone formers in this retrospective study of uric acid kidney stone formers diagnosed between 1996 and 2021. Study DesignDemographics and medical history were compared by chi-squared tests. 24-hour urine chemistries were compared using logistic regressions while controlling for demographics and comorbidities. Setting & ParticipantsPatients from Yale Urology and Nephrology Clinics with a documented kidney stone analysis containing uric acid were included. 4294 kidney stone formers had a stone analysis and 722 (16.8%) contained uric acid. Patients with all stone analyses ≥50% uric acid were allocated to the pure group, while patients with at least one stone analysis <50% uric acid were allocated to the impure group. ResultsAmong kidney stone formers, the prevalence of uric acid nephrolithiasis was 16.8%. Pure uric acid stone formers were more likely to be older, heavier, and were 1.5 times more likely to have chronic kidney disease. When controlling for age, sex, race, ethnicity, and body mass index, pure uric acid stone formers had lower urine pH and lower urine citrate normalized for creatinine. Additionally, they had a higher protein catabolic rate, urine urea nitrogen, and urine sulfur normalized for creatinine, all markers of dietary protein intake. These findings persisted after controlling for chronic kidney disease. LimitationsThis is a retrospective study from a single center. ConclusionsPure uric acid stone formation is more common with diminished kidney function; however, after controlling for kidney function, pure uric acid stone formation is associated with protein intake, suggesting that modifying protein intake may reduce risk.

Prognostic value of first 24-hour urine output in patients with acute myocardial infarction in intensive care units: a retrospective study based on the MIMIC-IV database.

To investigate the effect of first 24-hour (24-h) urine output (UO) on in-hospital and 1-year mortality in patients admitted to intensive care units due to acute myocardial infarction. This was a retrospective cohort study based on the medical information mart for intensive care IV database involving patients admitted to intensive care units due to acute myocardial infarction. Patients were classified as low UO (LUO), high UO (HUO), and middle UO with a first 24-h UO below 800ml, over 2500ml, or in between, respectively. The primary outcome was in-hospital mortality and the secondary outcome was 1-year mortality. A total of 4337 patients were involved. Taking middle UO group as reference, after adjusting for confounders including age, gender, height, weight, comorbidity, occurrence of cardiogenic shock, revascularization, blood pressure, creatinine, N-terminal pro-brain natriuretic peptide, and use of loop diuretics, LUO was independently associated with higher in-hospital mortality [odds ratio 4.05, 95% confidence interval (CI): 3.12-5.26], while HUO was an independent protective factor (odds ratio 0.52, 95% CI: 0.35-0.77). In the multivariant Cox regression model, LUO was an independent risk factor for 1-year mortality (hazard ratio 2.65, 95% CI: 2.16-3.26), while HUO did not show significant association. In patients admitted to intensive care units due to acute myocardial infarction, first 24-h UO <800ml was a strong predictor for higher in-hospital and 1-year mortality, while first 24-h UO over 2500ml was associated with lower in-hospital mortality but not long-term mortality.

Actinium-225 as an example for monitoring of internal exposure of occupational intakes of radionuclides in face of new nuclear-medical applications for short-lived alpha emitting particles

Monitoring of internal exposure to short-lived alpha-emitting radionuclides such as actinium-225 (225Ac), which are becoming increasingly important in nuclear medicine, plays an important role in the radiation protection of occupationally exposed persons. After having tested gamma spectrometry, liquid scintillation counting and alpha spectrometry for monitoring of internal exposure, the focus of the present study was on solid phase extraction of 225Ac from urine in combination with alpha spectrometry. The development of the method was based on recent findings from the literature on this topic. The method was used in a pilot phase to monitor internal exposure of four workers who were directly or indirectly involved in the manufacture and/or use of 225Ac. The monitoring protocol allowed a relatively short 24-hour urine sample analysis with excellent recovery of the internal standard, but it did not allow for a detection limit of less than 1 mBq nor a sufficient yield of 225Ac. Based on these results it is concluded that an in vitro excretion analysis alone is not appropriate for monitoring internal exposure to 225Ac. Instead, different radiation monitoring techniques have to be combined to ensure the radiation protection of employees.

A Urine pH-Ammonium Acid/Base Score and CKD Progression.

Acidosis is associated with exacerbated loss of kidney function in chronic kidney disease (CKD). Currently, acid/base status is assessed by plasma measures, although organ-damaging covert acidosis, subclinical acidosis, may be present before reflected in plasma. Low urine NH4+ excretion associates with poor kidney outcomes in CKD and is proposed as a marker for subclinical acidosis. However, low NH4+ excretion could result from either a low capacity or a low demand for acid excretion. We hypothesized that a urine acid/base-score reflecting both the demand and capacity for acid excretion would better predict CKD progression. 24-hour urine collections were included from three clinical studies of patients with CKD stage 3 and 4: A development cohort (n=82), a variation cohort (n=58), and a validation cohort (n=73). A urine acid/base-score was derived and calculated from urinary pH and [NH4+]. Subclinical acidosis was defined as an acid/base-score below the lower limit of the 95% prediction interval of healthy controls. Main outcomes were change in measured GFR after 18 months and CKD progression (defined as ≥50% decline in eGFR, initiation of long-term dialysis or kidney transplantation) during up to 10 years of follow-up. Subclinical acidosis was prevalent in all cohorts (n=54/82, 48/73, and 40/58, ∼67%). Subclinical acidosis was associated with an 18% (95% CI: 2-32) larger decrease of measured GFR after 18 months. During a median follow-up of 6 years, subclinical acidosis was associated with a markedly higher risk for CKD progression. Adjusted hazard ratios were 9.88 (95% CI 1.27-76.7) in the development cohort and 11.1 in the validation cohort (95% CI: 2.88-42.5). The acid/base-score had a higher predictive value for CKD progression than NH4+ excretion alone. Subclinical acidosis, defined by a new urine acid/base-score, was associated with a higher risk of CKD progression in patients with CKD stage 3 and 4.

Exploration on the protective effect of liraglutide on renal injury in diabetic nephropathy rats based on ROS-NLRP3 inflammasomes

Objective: To investigate the effect of liraglutide on diabetic nephropathy in rats and its regulatory mechanism. Methods: The diabetic nephropathy rat model was constructed with high-glucose-high-fat diet in combination with STZ, and was randomly divided into normal saline group and liraglutide group. The rats in liraglutide group were given sc 200 μg/kg of liraglutide, and the rats in normal saline group were given sc 20 mg/kg of normal saline twice a day for 4 weeks. The normal control group was not treated with any treatment. The biochemical indexes such as rat body weight, 24-hour urine total protein quantification (UTP), fasting blood glucose (FPG), triglyceride (TG), cholesterol (TC), blood urea nitrogen (BUN) and serum creatinine (Scr) were measured. HE staining, Masson staining and PAS staining were used to observe the pathologically morphological changes in renal tissues. Western-blot was used to detect the expression of NLRP3 inflammasome-related protein in renal tissues. Elisa was used to measure the serum levels of interleukin-18 (IL-18) and IL-1β. SPSS 26.0 statistical software and Graph Prism 9.0 software were used for analysis and mapping. The t-test was used for the comparison of measurement data between two groups, one-way ANOVA was used for the comparison among multiple groups, and Tukey’s test was used for the comparison in the same group. Results: Compared with the normal saline group, FBG, UTP, BUN, Scr, TC and TG in the liraglutide group were significantly decreased (p &lt; .01), the glomerular basement membrane was slightly thickened, with the tubular lumen slightly dilated and the lesion damage alleviated; the expression levels of NLRP3, ASC and caspase-1 inflammasome-related proteins were decreased (p &lt; .01), and the levels of IL-18 and IL-1β were decreased (p &lt; .01).Conclusion: Liraglutide can inhibit the activation of NLRP3 inflammasome mediated by oxidative stress in renal tissues through ROS-NLRP3 inflammasome pathway, thereby inhibiting the inflammation, and finally playing an anti-diabetic nephropathy renal injury role.