Urine Collection Research Articles

#5924 LATE DIAGNOSIS OF IGA NEPHROPATHY IN LOWER SAXONY (GERMANY) – CLINICAL AND HISTOPATHOLOGICAL DATA FROM 246 PATIENTS AT TIME OF INITIAL RENAL BIOPSY

Abstract Background and Aims IgA Nephropathy (IgAN) is the most frequent glomerulonephritis and contributes significantly to the burden of dialysis dependence. If not detected in the context of screening health examinations e.g. for the military service, decline in renal function is usually unnoticed due to the lack of specific symptoms. After decades of limited pharmacological options, the advent of new therapies provides opportunities for early intervention. Age and renal function as well as proteinuria at the time of renal biopsy varies depending on healthcare systems but might influence the use of novel interventions. Publications from outside Germany report that eGFR at the time of first renal biopsy in IgAN varies between 73.8 and 94.9ml/min/1,73 m2. The age at the time of diagnosis is between 27 and 40 years. The aim of our study was to investigate renal function, degree of proteinuria as well as histological parameters at the time of first renal biopsy in patients with IgA nephropathy. Method This retrospective study evaluated data from two different tertiary care hospitals in Germany that that sent their renal biopsies to the Nephropathology Department at the Hannover Medical School from January 2012 – October 2022. Only initial biopsies from native kidneys were included. Histopathological parameters and clinical as well as laboratory parameters at the month of biopsy were obtained. eGFR was calculated according to the CKD-EPI formula. Results First time diagnosis of IgA nephropathy was made in 246 patients at a median age at of 45 (range 4–79) years, 76.8% were male. The median serum creatinine level was 1.44mg/dl, corresponding to a median eGFR of 43.0 (3.8–132) ml/min/1.73 m2. Surprisingly 49.5% of all patients were at CKD KDIGO GFR stage 3B or higher at the time of first biopsy (Figure 1). Median proteinuria was 1.84 (0.08 – 16.5) g/d in those patients where 24h urine collection was performed. 156 of 246 patients had microhematuria at the time of biopsy. Based on the Oxford classification >50% had hypercellularity. Endocapillary hypercellularity was present in 24%. Segmental glomerulosclerosis was almost evenly distributed (S0:116 | S1:112). Tubular atrophy and interstitial fibrosis were visible in most biopsies in 0-25% of cortical area (T0:153 | T1:59 | T2:16). In 27.2% the C-score was analyzed, showing cellular and/or fibrocellular crescent in 26.8% of those patients. Thrombosis and necrosis were rather uncommon in initial biopsies of IgA Nephropathy. Conclusion The study shows that an IgA Nephropathy shows severe renal impairment at the time of diagnosis i.e. first renal biopsy, suggesting that patients are referred rather late for this diagnostic procedure. These regional data have to be validated in larger cohorts. If confirmed, measures for earlier screening and referral should be implemented to allow timely intervention thus lowering need for renal replacement therapy.

#3741 A CASE OF PODOCYTIC INFOLDING GLOMERULOPATHY WITH DIABETES MELLITUS, NEPHROTIC RANGE PROTEINURIA AND POSITIVE ANTI-PLA2R IN SERUM

Abstract Background and Aims Podocytic infolding glomerulopathy (PIG) is a rare glomerular abnormality which was first proposed as a new disease entity in 2008. It is characterized by glomerular basement membrane (GBM) bubbling viewable by light microscopy, due to extensive trapping of podocytic cytoplasm fragments and cell membrane projections within the GBM. Electron microscopy reveals podocyte infolding and invagination into the glomerular basement membranes (GBMs). Most of the cases reported worldwide, indicate that PIG usually co-exists with autoimmune diseases. In this case we present a diabetic patient with no other autoimmune disease in his medical history, whose biopsy was characterized as PIG. Method A 60-year-old Caucasian man with a 5-year history of type II diabetes mellitus, hyperlipidemia, hypertension, hyperuricemia and benign colon polyps, was noted by his family physician to have proteinuria. He had been treated with an angiotensin II receptor blocker, statin, and allopurinol for 5 years and he was well regulated. At the point of admission, his 24-h urine collection showed 4,5gr of urine protein. His creatinine at the time was normal (0,89mg/dl), no hypoalbuminemia, no edema or deregulation of hyperlipidemia was noted. His fundoscopy at this point had no diabetic lesions. In the immunological work up, we found normal values of autoantibodies ANA, anti-dsDNA, anti-ENA, complement screening C3, C4, serum and urine protein electrophoresis - immunofixation. Everything was within normal limits except from serum autoantibodies to Phospholipase A2 Receptor of podocytes which was tested with ELISA and valued 35 RU/mL (<20RU/mL). In the following 9 months his proteinuria remained at the same levels. Due to the persistent nephrotic range proteinuria (>3.5gr/24h) a kidney biopsy was performed. Biopsy was evaluated under light microscope (histochemistry for Congo-Red and immunohistochemistry for C4d, PLA2R and DNAJB9 included), immunofluorescence and electron microscope. Results The renal biopsy included 8 glomeruli, 3 of them globally sclerosed (37.5%), the rest enlarged with mild to moderate mesangial matrix increase and thickening of the GBMs, without spikes, pin holes or reduplications. Immunohistochemistry for C4d, PLA2R and DNAJB9 was negative. Immunofluorescence revealed nothing noticeable (no staining of IgG, IgA, IgM, C3, C1q, C4, κ-λ chains) apart from a moderate linear albumin staining. Without electron microscopy the whole picture was rather reminiscent of mild to moderate lesions of diabetic nephropathy. On electron microscopy, no classical electron-dense deposits were found. Effacement of podocytes’ foot processes was multi-segmental. More importantly, podocytic cytoplasmic processes invaginating into the GBMs were observed, accompanied by scattered endomembranous, partially microspherular microstructures, sometimes with adjacent unclear small pyknotic areas. The biopsy report concluded that although light microscopy and immunofluorescence findings could indicate diabetic nephropathy, the electron microscopy lesions suggest the diagnosis of PIG. Conclusion To our knowledge, this is the first reported case with PIG and anti-PLA2R antibodies detected in the serum, without clear histological evidence of membranous nephropathy. Our patient was diabetic for five years with no diabetic lesions in fundoscopy. Although PIG has been reported mainly in the context of autoimmune diseases, the coexistence with diabetes or its possible role in PIG's pathogenesis has not been addressed. The treatment of this peculiar morphologically disease, still remains an open query for physicians.

#5807 FACTORS ASSOCIATED WITH KALEMIA IN RENAL DISEASE

Abstract Background and Aims International recommendations promote a strict potassium diet in order to avoid hyperkalemia in chronic kidney disease patients. However, efficiency of such a dietary counseling has never been demonstrated. The objectives of this study were to define the relationship between kalemia, dietary potassium intake estimated by kaliuresis and renal function and to define the factors associated with kalemia in patients using artificial intelligence. Method To this extent, data from patients followed in a nephrology unit, included in the UniverSel study and whose kalemia (measured on the day of urine collection; n = 367) were analyzed. The association between kalemia and thirty-four variables concerning the patients' characteristics, their biological work-up, their medications and their answers to the UniverSel dietary self-questionnaire on kalemia were assessed using a Bayesian network. Results The patients included had a wide range of estimated glomerular filtration rate, but few had stage 5 chronic kidney disease (CKD). Kalemia was negatively and linearly correlated to estimated glomerular filtration rate (p<0.001) but was not correlated to kaliuresis (p = 0.55). Kaliuresis was not correlated to estimated glomerular filtration rate (p = 0.08). Factors associated with kalemia were analyzed using a Bayesian network. The 5 variables most associated with kalemia were, in descending order, estimated glomerular filtration rate, original nephropathy, age, diabetes, and plasma bicarbonate level. RAS-blockers prescription was also associated to kalemia. Consumption of potassium rich food were poorly associated to kalemia. Conclusion Our results do not support a strict control of potassium intake in stage 1 to 4 CKD patients. Our results reinforce the interest of a multidimensional management including personalized therapy and strict correction of metabolic acidosis. Lightning dietary restrictions in potassium would improve the quality of life of patients with CKD who are often multi-pathological and already subject to multiple dietary constraints.

#6153 SODIUM-GLUCOSE COTRANSPORTER 2 INHIBITORS VERSUS DIPEPTIDYL PEPTIDASE 4 INHIBITORS AS STABILIZERS OF HIF PATHWAY IN DIABETIC NEPHROPATHY RATS

Abstract Background and Aims With the diabetes pandemic, chronic kidney disease is a burden, with diabetic nephropathy (DN) being the primary leading cause of end-stage renal disease. Antidiabetic drugs have shown renoprotective effects via different mechanisms, and among those are SGLT2 inhibitors and DPP-4 inhibitors. Hypoxia-inducible factor (HIF) pathway, a significant contributor to inflammation development in the kidneys, is a major pathway that regulates erythropoietin synthesis. Prolyl hydroxylase domain (PHD) decreases erythropoietin synthesis by inhibiting HIFs. PHD inhibitors are anticipated to have additional effects, such as protection against metabolic diseases, due to HIF's impact on many genes. The diabetic kidney is characterized by enhanced HIF-1α activation but decreased HIF-2α activity. These actions may significantly contribute to glomerular and renal tubular dysfunction, renal inflammation and fibrosis, and decreased erythropoietin synthesis observed in DN. This work aims to test the renoprotective effect of SGLT2 inhibitors and DPP-4 inhibitors by controlling the proinflammatory and anti-inflammatory domains of the HIF pathway. Method Type 1 DM rat model was induced in 24-hour-fasted Sprague Dawley rats by a single intraperitoneal injection of 45 mg/kg streptozotocin (STZ). DM was verified by measuring blood glucose seven days following STZ injection, and only animals with glucose levels of ≥15 mM were included (n = 24), randomly and equally distributed, then received either saline or vildagliptin (3 mg/Kg) or empagliflozin (30 mg/Kg) once daily by oral gavage for three months. An additional group was used as a non-diabetic control. At the end of the experiment, rats were placed in metabolic cages for 24-h urine collection, then sacrificed. Blood samples and kidney tissue were collected. Kidney function was assessed by measuring serum creatinine and urinary albumin: creatinine ratio. HIF1α, HIF2α, and PHD3 mRNA expression in kidney tissues were assessed using quantitative real-time PCR, and to indirectly assess HIF2α protein stability, immunohistochemical staining for PHD3 was also performed. Results Vildagliptin and empagliflozin could significantly ameliorate the diabetic disturbance of renal function, as demonstrated in serum creatinine (F = 23.518, p<0.001) with a non-significant difference between both treated groups, and in the significantly reduced albumin/creatinine ratio (F = 14.453, p<0.001), with a significantly lower ratio for empagliflozin (4.73±0.54) than vildagliptin-treated group (9.09±1.04). Regarding the HIF pathway as a potential mechanism, empagliflozin-treated groups showed a significantly higher HIF2α gene expression in kidney tissue samples (0.98±0.10) than the vildagliptin-treated group (0.58±0.05). For the expression of its regulator, PHD3, there was a significant difference between groups (F = 5.694, p = 0.005). However, the vildagliptin-treated group (0.65±0.06) didn′t differ significantly from the untreated group (0.60±0.03), in contrast to the empagliflozin-treated group (2.01±0.50), which showed a significantly higher expression than the other groups (Figure 1). Conclusion Empagliflozin significantly increased the level of HIF-2α in renal tissue. In addition, it nearly neutralizes the tubular expression of PHD3 compared to non-treated and vildagliptin-treated rats. SGLT2 inhibition is effective for correcting the proinflammatory/anti-inflammatory imbalance in DN.

#5527 ALDOSTERONE, CORTISOL AND URINE VOLUME CAN EXPLAIN DISCREPANCIES BETWEEN DIETARY AND URINARY NA/K RATIO

Abstract Background and Aims Increased urinary sodium-to-potassium (Na/K) ratio has been associated with chronic kidney disease. However, we demonstrated that urinary Na/K ratio does not accurately reflect dietary Na/K ratio. Rhythmic patterns of sodium storage and release from the skin interstitium are associated with aldosterone and cortisol levels and previous studies linked tissue sodium accumulation to water conservation. Therefore, we investigated whether the discrepancy between urinary and dietary Na/K ratio could be explained by these factors. Method For this post-hoc analysis, we used data from the long-term sodium balance studies Mars105 and Mars520. These studies collected 24-hour urine samples and controlled dietary salt intake for 105 (4 men) and 205 days (6 men) at levels of 6, 9 and 12 grams per day. We calculated the difference between urinary and dietary Na/K ratio. We tested whether this difference varied across salt intake levels in a linear mixed-effects model. Furthermore, we fitted two linear mixed-effect models to explain discrepancies between urinary and dietary Na/K ratio. In the first model, sodium intake, potassium intake, urinary aldosterone and urinary cortisol were fixed effects and for each factor random slopes per participant were allowed. In the second model, sodium intake, potassium intake and urine volume were fixed effects and for each factor random slopes per participant were allowed. Each salt intake level was assessed separately. Results The median difference between 24-hour urinary and dietary Na/K ratio was −0.21 (IQR −0.47 to 0.09). At higher salt intake levels the underestimation was significantly larger (mean difference −0.11, −0.22 and −0.36 for 6, 9 and 12 grams salt intake, respectively; P<0.001). At each salt intake level, higher urinary aldosterone was associated with underestimation of the dietary Na/K ratio (Figure 1A). In contrast, higher urinary cortisol and higher urine volume were associated with relative overestimation of the dietary Na/K ratio (Figure 1B and C, respectively). Conclusion The discrepancy between dietary and urinary Na/K ratio can be explained by sodium intake, aldosterone, cortisol and urine volume. This suggests that tissue sodium accumulation contributes to the inaccuracy of a single 24-hour urine collection for estimation of dietary sodium and potassium intake.

Obesity, Hyperfiltration, and Early Kidney Damage: A New Formula for the Estimation of Creatinine Clearance.

Glomerular hyperfiltration may represent a direct pathogenetic link between obesity and kidney disease. The most widely used methods to estimate creatine clearance such as Cockroft-Gault (CG), Modification of Diet in Renal Disease (MDRD), and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) have not been validated in subjects with obesity. The performance of prediction formulas was compared with measured creatinine clearance (mCrCl) in subjects with obesity. The study population included 342 patients with obesity (mean BMI 47.6 kg/m2) without primary kidney disease. A urine collection was performed over 24 hours for measurement of CrCl. mCrCl increased with body weight. The CG formula showed an overestimation at high CrCl, whereas an underestimation resulted from CKD-EPI and MDRD. To improve the accuracy of estimated CrCl (eCrCl), a new CG-based formula was developed:53+0.7×(140-Age)×Weight/(96xSCr)×(0.85iffemale)A cut-off point for BMI of 32 kg/m2 was identified, at which the new formula may be applied to improve eCrCl. In patients with obesity the glomerular filtration rate increases with body weight, and it is associated with the presence of albuminuria, suggesting an early kidney injury. We propose a novel formula that improves the accuracy of eCrCl to avoid missed diagnoses of hyperfiltration in patients with obesity.

Correlation of lactulose-to-mannitol ratios in plasma and urine for intestinal permeability assessment in pigs.

The lactulose-to-mannitol ratio test is a test to assess the disorders associated with gut permeability. The test requires an oral administration of the mixture of lactulose and mannitol and urine collection. The urinary ratio of lactulose to mannitol is an indicator of intestinal permeability. Due to the complexity of urine collection in animal studies, plasma exposure ratios of lactulose to mannitol compared to their urinary concentration ratios were evaluated following an oral administration of the sugar mixture in pigs. 10 pigs were orally dosed with a solution of lactulose and mannitol mixture. Plasma samples were collected at predose, 10 and 30 minutes and 2, 4, and 6 hours postdosing, and cumulated urinary samples were collected at 6 hours for liquid chromatography-mass spectrometry analysis. The ratios of pharmacokinetic parameters of lactulose to mannitol and the plasma sugar ratios at a single time point or the mean values of several time points were compared to their urinary sugar ratios. The results revealed that the lactulose-to-mannitol ratios of AUC0-6h, AUCextrap, and Cmax were correlated to the urinary sugar ratios, and the plasma sugar ratios of a single time point at 2, 4, or 6 hours and the mean values of those time points were also appropriate to replace their urinary ratios in pigs. Following an oral administration of lactulose and mannitol mixture, blood collection, and assay can be an option for assessing intestinal permeability, especially in animal studies.

Be aware of the sodium intake outside student canteens: development and validation of a sodium food frequency questionnaire in Chinese undergraduates

BackgroundChinese college students used to eat in student canteens, making dietary consumption outside the cafeterias the main reason for the difference in sodium intake. This study aims to develop and validate a food frequency questionnaire (Sodium-FFQ) targeting dietary sodium intake outside the canteens among undergraduates in China.MethodsThis cross-sectional study included 124 and 81 college students from comprehensive universities in the development and validation stage. A 24 h dietary recall and a food frequency questionnaire were used to develop the Sodium-FFQ. Food items were selected according to the foods that contributed more to the total sodium intake. Test–retest correlation coefficients with an interval of 14 days were employed to evaluate reproducibility. Validity was assessed against a single 24 h urine collection and a 3-day dietary record using correlation coefficients, Bland–Altman analyses, and cross-classification analysis of Kappa coefficients.ResultsThe Sodium-FFQ consists of 12 groups of foods with 48 items. The Spearman correlation coefficient of test–retest on sodium intake was 0.654 (p < 0.05), and that between the Sodium-FFQ, 3 × 24 h dietary record, and 24-h urinary sodium were 0.393 (p < 0.05) and 0.342 (p < 0.05), respectively. The Sodium-FFQ was correlated to 24 h urinary sodium-to-potassium ratio, with a Spearman coefficient of 0.370 (p < 0.05). The classification agreement of the Sodium-FFQ and 24 h urinary sodium was 68.4%, and the Kappa coefficient was 0.371 (p < 0.001).ConclusionThe Sodium-FFQ developed in this study presented an acceptable reproducibility, validity, and classification agreement. It indicates that the Sodium-FFQ could be a potential tool for promoting sodium restriction in college students.

An IoT-Based Automatic and Continuous Urine Measurement System

Urine output is an important indicator of renal function. In hospitals, urine is collected using a catheter connected to a urine collection bag that has volume gradation markings. This type of visual measurement has low levels of accuracy and is labor-intensive. This paper developed an Internet-of-Things enabled system that continuously monitors the urine volume collected via the urine collection system. The device is built utilizing a strain gauge load cell, an integrated circuit that contains an amplifier, analog-to-digital converter, and a WiFi-enabled microcontroller. The data is sent via wireless networking to a data collection and analysis server, which provides accurate analyses of urine output. A mobile application utilizing the Blynk.io system is used to display the data. This device and mobile application were built at a minimal cost of 26 USD. The device has been tested multiple times and reported urine output accurately, with minimal difference between actual versus measured volumes. In the future, further development of this device can provide hospitals and physicians worldwide with easy access to affordable, accurate, and real-time urine measurement, which would translate into better, life-saving medical care.

Estimation of 24-hour urinary creatinine excretion from patient variables: A novel approach to identify patients with low muscle mass and malnutrition and relationship to outcomes.

Low muscle mass has been correlated with adverse outcomes in patients who are critically ill. Methods to identify low muscularity such as computed tomography scans or bioelectrical impedance analyses are impractical for admission screening. Urinary creatinine excretion (UCE) and creatinine height index (CHI) are associated with muscularity and outcomes but require a 24-h urine collection. The estimation of UCE from patient variables avoids the need for a 24-h urine collection and may be clinically useful. Variables of age, height, weight, sex, plasma creatinine, blood urea nitrogen (BUN), glucose, sodium, potassium, chloride, and carbon dioxide from a deidentified data set of 967 patients who had UCE measured were used to develop models to predict UCE. The model identified with the best predictive ability was validated and then retrospectively applied to a separate sample of 120 veterans who were critically ill to examine if UCE and CHI predicted malnutrition or were associated with outcomes. A model was identified that included variables of plasma creatinine, BUN, age, and weight and was found to be highly correlated, moderately predictive of UCE, and statistically significant. Patients with model-estimated CHI 60% had significantly lower body weight, body mass index, plasma creatinine, and sera albumin and prealbumin levels; were 8.0 times more likely to be diagnosed with malnutrition; and were 2.6 times more likely to be readmitted in 6 months. A model that predicts UCE offers a novel method to identify patients with low muscularity and malnutrition on admission without the use of invasive tests.

HOW TO INTERPRET URINARY PROTEINURIA AS A MARKER OF HYPERTENSIVE NEPHROPATHY?

Objective: Proteinuria may be the first sign of underlying nephropathy. It is pathological when the value is higher than 0.15 g/24h. The gold standard of quantification is the determination of proteinuria on the collection of urine for 24 hours, however, in view of the errors related to the collection and storage, we adopted another mode of expression. The objective of our work is to evaluate the correlation between the results of the 24 hours proteinuria and the proteinuria calculated by ratio (proteinuria/creatinuria). Design and method: Our prospective comparative study was performed on 100 24-hour urine samples (100 patients). We recorded the 24h diuresis and we determined the proteinuria by the pyrogallol red method (Advia 1800) and the urinary creatinine by the compensated jaffa method (Cobas 6000). Statistical evaluation was performed using GraphPad Prism software7 Results: Our results show: the average proteinuria of 24 h is 309.7 mg/24H (the norms lower than 150 mg/24H) and the average proteinuria/creatinine ratio is 283.7 mg/g (the norms lower than 300 mg/g). Of the 100 samples, only 5 patients (5%) showed pathological 24-hour proteinuria with a proteinuria/creatinuria ratio within the norms, and one patient (1%) had 24-hour proteinuria within the norms and a high proteinuria/creatinuria ratio, 25 patients (25%) had a simultaneous increase in 24-hour proteinuria and in the proteinuria/creatinuria ratio The remaining 69 patients (69%) had 24-hour proteinuria and a proteinuria/creatinuria ratio within the physiological norms The comparative study found a significant difference p<0.0001 with a significant positive Pearson correlation R 2 = 0.92. The agreement of the 24 h proteinuria tests and the Proteinuria/creatinuria ratio is modelled by the Bland and Altman diagram which finds a bias of 1.02 and a Confidence interval 95%] 0.046-1.36 [. Conclusions: Therefore it is not necessary to carry out a 24-hour urine collection, preferring measurements on urine samples from the first morning micturition. In order to overcome the numerous false positives and negatives linked to the collection of 24-hour urine, this examination is a good alternative.

URINE SODIUM-TO-POTASSIUM RATIO DOES NOT ACCURATELY REFLECT DIETARY SODIUM-TO-POTASSIUM RATIO

Objective: High sodium intake is associated with an increased risk of cardiovascular disease, whereas a high potassium intake is associated with a reduced risk. Dietary counselling requires accurate estimation of sodium and potassium intake, but 24-hour urine sodium and potassium excretion demonstrated not to reflect actual intake. Urine sodium-to-potassium (Na/K) ratio is a promising alternative as it may be less affected by aldosterone-induced rhythmic changes in total body sodium and potassium content, is less influenced by incomplete urine collections, and incorporates both the effect of sodium and potassium. Our study assesses whether 24-hour urine Na/K ratio is superior in predicting dietary intake compared to 24-hour urine sodium or potassium excretion. Design and method: A post-hoc analysis was performed on data from the long-term sodium balance studies Mars105 and Mars520. Ten healthy participants received 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 urine content of sodium, potassium and Na/K ratio. We compared these estimates of accuracy using a mixed-effects model with a random intercept per subject. We analysed whether the accuracy differed among 6, 9 and 12 grams salt intake or was affected by the number of 24-hour urine collections. Results: Urine Na/K ratio underestimated dietary Na/K ratio with a median difference of -0.21 (IQR -0.47 to 0.09). Compared to sodium and potassium assessment, the Na/K ratio was significantly less accurate in predicting intake (Figure 1A). Only for the 6 gram salt phase the Na/K ratio did not perform significantly worse than sodium measurements. Increasing the number of 24-hour urine measurements to three or seven improved accuracy of the Na/K ratio, although it remained inferior to separate assessment of sodium and potassium excretion (Figure 1B). Conclusions: The 24-hour urine Na/K ratio is less accurate than 24-hour urine sodium excretion for estimation of dietary intake in a controlled setting.

DISCREPANCIES BETWEEN DIETARY AND URINE NA/K RATIO CAN BE EXPLAINED BY ALDOSTERONE, CORTISOL AND URINE VOLUME

Objective: Increased urine sodium-to-potassium (Na/K) ratio is associated with hypertension and cardiovascular disease. However, we demonstrated that urine Na/K ratio does not accurately reflect dietary Na/K ratio. As rhythmic patterns of sodium storage and release are associated with aldosterone and cortisol levels and previous studies linked tissue sodium accumulation to water conservation, we investigated whether the discrepancy between urine and dietary Na/K ratio could be explained by these factors. Design and method: We performed a post-hoc analysis of the long-term sodium balance studies Mars105 and Mars520. Ten healthy participants consumed a diet with known sodium and potassium content. For 105 or 205 days 24-hour urine samples were collected. We calculated the difference between urine and dietary Na/K ratio. A linear mixed-effect model was used to determine whether this difference varied across salt intake levels. Furthermore, we fitted two linear mixed-effect models to explain discrepancies between urine and dietary Na/K ratio. In the first, sodium intake, potassium intake, urine aldosterone and urine cortisol were fixed effects and for each factor random slopes per participant were allowed. In the second, sodium intake, potassium intake and urine volume were fixed effects and for each factor random slopes per participant were allowed. We analysed the salt intake levels 6, 9 and 12 grams separately. Results: Urine Na/K ratio underestimated dietary Na/K ratio (median difference -0.21, IQR -0.47 to 0.09). The discrepancy was significantly larger at higher salt intake levels (mean difference -0.11, -0.22 and -0.36 for 6, 9 and 12 grams salt intake, respectively, P < 0.001). At all salt intake levels, higher aldosterone levels were associated with underestimation of the dietary Na/K ratio (Figure 1A). In contrast, higher urine cortisol and higher urine volume were associated with overestimation of the dietary Na/K ratio (Figure 1B and C respectively). Conclusions: Sodium intake, aldosterone, cortisol and urine volume can explain the discrepancy between dietary and urine Na/K ratio. These data suggest that tissue sodium accumulation contributes to the inability to estimate dietary intake using the Na/K ratio in a single 24-hour urine collection.

Urinalysis in dogs and cats, part 1: physical and chemical urinalysis

The urinalysis of dogs and cats is an important part of the diagnostic evaluation of urinary tract diseases as well as for the identification of systemic diseases. A routine urinalysis consists of a physical and chemical examination of the urine as well as an examination of the urine sediment. Various urine collection methods (free-catch, catheterization, cystocentesis) are available. Each method has multiple advantages and disadvantages. The appropriate method must be chosen individually for each patient depending on the emphasis of the examination. The urine should ideally be examined within 30 minutes of collection as it is prone to change due to time and storage. Physical examination of the urine consists of the determination of urine color, clarity, and specific gravity which provides information regarding the concentration of the urine. The latter is determined by refractometry and needs to be interpreted in the context of the hydration status of the patient. Chemical examination of the urine consists of the determination of the pH value and the presence of blood/hemoglobin/myoglobin, protein, glucose, bilirubin, urobilinogen, nitrite, and ketones. The use of commercially available urine dipsticks is common. These must be stored and used according to the manufacturer's instructions and when interpreting the results, veterinary aspects need to be taken into consideration. The physical and chemical examinations of the urine represent rapid and readily performable methods that provide important information for the diagnosis or the exclusion of numerous diseases.

DIETARY SODIUM RESTRICTION REDUCES NOCTURNAL BLOOD PRESSURE IN PATIENTS WITH TREATMENT RESISTANT HYPERTENSION

Objective: Patients with treatment resistant hypertension (TRH) are characterised by lack of blood pressure (BP) control despite antihypertensive treatment. They are at particular risk of cardiovascular disease and more likely to experience BP increase as a response to sodium loading than other individuals. In this study, we aimed to analyse if self-performed dietary sodium restriction could be implemented in patients with TRH. Moreover, we aimed to analyse the effect of this on nocturnal and 24h BP, and how BP changes were correlated to changes in plasma levels of BNP, nitric oxide and body water content. Design and method: The study was conducted as an interventional cross-over study including patients with TRH from 20-70 years. Patients were screened with 24h ambulatory BP monitoring initiated after observed intake of usual antihypertensive medication. They were included if 24h systolic BP>130/80 mmHg. Study participation included two periods of 14 days; a standard period with usual diet and an interventional period with instructed dietary sodium restriction and handed-out sodium-free bread. At the end of each period, patients were examined with 24h BP monitoring, 24h urine collection (sodium excretion), blood samples (nitric oxide, BNP), and bioimpedance measurement (body water content). Results: Participation was completed by 15 patients with mean age 59 years and mean 24h BP 144/82 mmHg. Mean baseline urinary sodium excretion was 192(86) mmol/24h (11.2 grams of salt). As seen in Table 1, sodium excretion was reduced to 91 mmol/24h equalling 5.3 grams of salt. BP levels were reduced significantly. Plasma levels of nitric oxide increased significantly, and this was correlated to the change in 24h BP. Total body water content and plasma levels of BNP was reduced significantly. The changes in BP were not correlated to changes in sodium excretion, body water or BNP. Conclusions: Self-performed dietary sodium restriction could be implemented resulting in a significant reduction in BP levels. BP change was not related to changes in body water or sodium excretion. Increased levels of nitric oxide may be evidence of improved endothelial function and may be one of the involved mechanisms in BP decrease following sodium restriction

Assessing the impact of coexposure on the measurement of biomarkers of exposure to the pyrethroid lambda-cyhalothrin in agricultural workers.

There are few published data on the impact of combined exposure to multiple pesticides (coexposure) on levels of biomarkers of exposure in workers, which may alter their toxicokinetics and thus the interpretation of biomonitoring data. This study aimed to assess the impact of coexposure to two pesticides with shared metabolism pathways on levels of biomarkers of exposure to pyrethroid pesticides in agricultural workers. The pyrethroid lambda-cyhalothrin (LCT) and the fungicide captan were used as sentinel pesticides, since they are widely sprayed concomitantly in agricultural crops. Eighty-seven (87) workers assigned to different tasks (application, weeding, picking) were recruited. The recruited workers provided two-consecutive 24-h urine collections following an episode of lambda-cyhalothrin application alone or in combination with captan or following tasks in the treated fields, as well as a control collection. Concentrations of lambda-cyhalothrin metabolites - 3-(2-chloro-3,3,3-trifluoroprop-1-en-1-yl)-2,2-dimethyl-cyclopropanecarboxylic acid (CFMP) and 3-phenoxybenzoic acid (3-PBA) - were measured in the samples. Potential determinants of exposure established in a previous study, including the task performed and personal factors were documented by questionnaire. Multivariate analyses showed that coexposure did not have a statistically significant effect on the observed urinary levels of 3-PBA (Exp(β) (95% confidence interval (95% CI)): 0.94 (0.78-1.13)) and CFMP (1.10 (0.93-1.30). The repeated biological measurements ("time variable") - defined as the within-subjects variable - was a significant predictor of observed biological levels of 3-PBA and CFMP; the within-subjects variance (Exp(β) (95% (95% CI)) for 3-PBA and CFMP was 1.11 (1.09-3.49) and 1.25 (1.20-1.31). Only the main occupational task was associated with urinary levels of 3-PBA and CFMP. Compared to the weeding or picking task, the pesticide application task was associated with higher urinary 3-PBA and CFMP concentrations. In sum, coexposure to agricultural pesticides in the strawberry fields did not increase pyrethroid biomarker concentrations at the exposure levels observed in the studied workers. The study also confirmed previous data suggesting that applicators were more exposed than workers assigned to field tasks such as weeding and picking.

RANDOMIZED PILOT STUDY ON THE EFFECTS OF SARCOCORNIA AS A SALTSUBSTITUTE IN ARTERIAL BLOOD PRESSURE AND VASCULAR FUNCTION INHEALTHY YOUNG ADULTS

Objective: Previous studies have shown that excessive salt intake is strongly associated with highblood pressure (HT), vascular dysfunction, and the overall risk of cardiovascular diseases. The aimof this study was to evaluate Sarcocornia effectiveness as a salt substitute, addressing its effect oncardiovascular function in healthy young individuals. Design and method: Thirty healthy participants, aged 18 to 26 years,were randomized into two groups: the control group (CG) and the intervention group (IG). The IGused Sarcocornia powder as a salt substitute for cooking, and the CG used regular salt, during a periodof 1 month. A baseline evaluation was performed before the participants started the interventionphase, and was repeated after a 30-day intervention period. Each evaluation included blood pressure (BP) measurement, carotid-femoral pulse wave velocity (PWV), and carotid pulse wave analysis(PWA), and blood samples were also collected for analysis. Sodium excretion was measured atbaseline and after intervention through spot urine collection and analysis, a method suitable forthis population but with known limitations. Results: Baseline parameters were similar between groups and were within normal range. Sodium excretion remained unchanged in the two evaluations in the CG, but significantly decreased after intervention in the IG. The reduction in sodium excretion in the IG was followed by a significant reduction in brachial and aortic systolic (-7.0± 0.9 mmHg and -5.6 ± 1.0 mmHg, respectively; p<.001) and diastolic (-5.9 ± 1.0 mmHg; p<.001) blood pressure, with no differences observed in the CG. Also in the IG, PWV decreased from 6.0 ± 0.6 m/s at baseline to 5.7 ± 0.6 m/s after intervention (p = .042), with no significant changes in the CG. Conclusions: This preliminary study conveys positive results in favor of Sarcocornia as a dietary substitute for regular salt, providing added evidence on the negative cardiovascular effects of high salt intake in young and healthy adults. The overall nutritional value of Sarcocornia, also known for its high phenolic content, may also add to the observed benefits.

What US hospitals are doing to prevent common device-associated infections during the coronavirus disease 2019 (COVID-19) pandemic: Results from a national survey in the United States.

The ways that device-associated infection prevention practices changed during the coronavirus disease 2019 (COVID-19) pandemic remain unknown. We collected data mid-pandemic to assess the use of several infection prevention practices and for comparison with historical data. Repeated cross-sectional survey. US acute-care hospitals. Infection preventionists. We surveyed infection preventionists from a national random sample of 881 US acute-care hospitals in 2021 to estimate the current use of practices to prevent catheter-associated urinary tract infection (CAUTI), central line-associated bloodstream infection (CLABSI), and ventilator-associated events (VAE). We compared the 2021 results with those from surveys occurring every 4 years since 2005. The 2021 survey response rate was 47%; previous survey response rates ranged from 59% to 72%. Regular use of most practices to prevent CLABSI (chlorhexidine gluconate for site antisepsis, 99.0%, and maximum sterile barrier precautions, 98.7%) and VAE (semirecumbent positioning, 93.4%, and sedation vacation, 85.8%) continued to increase or plateaued in 2021. Conversely, use of several CAUTI prevention practices (portable bladder ultrasound scanner, 65.6%; catheter reminders or nurse-initiated discontinuation, 66.3%; and intermittent catheterization, 37.3%) was lower in 2021, with a significant decrease for some practices compared to 2017 (P ≤ .02 for all comparisons). In 2021, 42.1% of hospitals reported regular use of the newer external urinary collection devices for women. Although regular use of CLABSI and VAE preventive practices continued to increase (or plateaued), use of several CAUTI preventive practices decreased during the COVID-19 pandemic. Structural issues relating to care during the pandemic may have contributed to a decrease in device-associated infection prevention practices.

Associations between Net Gastrointestinal Alkali Absorption, 24-Hour Urine Lithogenic Factors, and Kidney Stones.

It is not clear whether kidney stone formers have an abnormal handling of alkali and acid precursors in the gut, which might affect urine composition and ultimately stone formation. In this study, we aimed to investigate the determinants of net gastrointestinal alkali absorption and its associations with key urinary parameters in a large group of stone formers and non-stone formers. Data were collected from three independent cohorts with at least one 24-hour urine collection. We explored potential determinants of net gastrointestinal alkali absorption and the association between net gastrointestinal alkali absorption, urinary parameters, and stone former status. Finally, we estimated the proportion of the association between urine parameters and stone former status explained by differences in net gastrointestinal alkali absorption. The analysis included 6067 participants (1102 men and 4965 women; 698 and 1804 of whom were stone formers, respectively). Average net gastrointestinal alkali absorption values were consistently lower in stone formers across the three cohorts (from -15.0 to -4.9 mEq/d). Age was directly associated with net gastrointestinal alkali absorption, whereas body mass index and net endogenous acid production were inversely associated. Net gastrointestinal alkali absorption was inversely associated with supersaturation for calcium oxalate, uric acid, and renal net acid excretion and directly associated with supersaturation for calcium phosphate, urine pH, and citrate. The odds of being a stone former was 15% (13%-17%) lower per 10 mEq/24 hours higher net gastrointestinal alkali absorption. Differences in net gastrointestinal alkali absorption explained a modest amount of the differences between stone formers and non-stone formers for supersaturation for calcium oxalate (6.3%) and a sizable amount for supersaturation for uric acid (15.2%), urine pH (38.3%), citrate (26.2%), and renal net acid excretion (63.4%). Kidney stone formers have lower net gastrointestinal alkali absorption, and this explains differences in urine composition and the likelihood of stone formation.

Development of 8‐h urine collections and an augmented renal clearance dosing program at an academic medical center

AbstractEnsuring appropriate dosing of medications is an essential practice of clinical pharmacists. Dose adjustments in the setting of decreased renal function are common but may also be warranted for patients with supraphysiologic or augmented renal clearance (ARC). Conventional estimates of creatinine clearance using only serum creatinine may not be accurate in the setting of ARC, thus a measured creatinine clearance using serum and urine creatinine measurements are preferred. We describe the development of an 8‐h urine collection and ARC dosing program at a large academic medical center initiated by critical care and infectious disease pharmacists. Using a Plan–Do–Study–Act approach, we implemented and updated the 8‐h collection program with the guidance of our clinical laboratories. Eight‐hour urine collections are useful for patients with suspected ARC and for other scenarios where accurate dose adjustments are needed to minimize toxicity in the absence of therapeutic drug monitoring.