24-hr Urine Collection Research Articles

Greater urinary calcium excretion is associated with diminished bone accrual in youth with type 1 diabetes

Abstract Context The adverse skeletal effects of type 1 diabetes (T1D) include deficient bone accrual and lifelong increased fracture risk. The contributors to impaired bone accrual in people with T1D are incompletely understood. Objective To determine if urinary calcium excretion is associated with impaired bone accrual in youth with T1D and to characterize the contribution of glycemic control and markers of bone mineral metabolism to urinary calcium excretion. Design Observational study. Participants 50 participants with T1D aged 6-20 years completed a 12-month longitudinal study of bone accrual. A second cohort of 99 similarly aged participants with T1D completed cross-sectional 24-hr urine and blood collections. Main Outcome Measure Whole body less head bone mineral content (WBLH BMC) velocity Z-score and fractional excretion of calcium (FeCa). Results Participants in the bone accrual cohort had lower WBLH BMC velocity compared to a healthy reference dataset (Z-score −0.3 ± 1.0, p=0.03). FeCa was negatively associated with WBLH BMC velocity Z-score, ρ= −0.47, p=0.001. In the urinary calcium excretion cohort, intact parathyroid hormone (β= −0.4, p=0.01), beta c-telopeptide (β=0.35, p=0.007), and either hemoglobin A1c (HbA1c, β=0.08, p=0.03) or urine fractional glucose excretion (β=0.07, p=0.03) were associated with FeCa in multivariable regression models that included known determinants of urinary calcium excretion. Conclusions Urinary calcium excretion was negatively associated with bone accrual in this cohort of youth with T1D. Mechanistic studies are needed to determine if interventions to reduce urinary calcium excretion could increase bone accrual and reduce skeletal fragility in people with T1D.

Abstract P118: Effect of renal denervation on the blood pressure and progression of diabetic kidney disease in T2DN rats

Background: As a common complication of diabetes, diabetic kidney disease (DKD) is a chronic progressive disorder that can lead to kidney failure, and it is currently the leading cause of kidney replacement therapy in the USA and worldwide. Although renal denervation (RDNx) has recently been approved by the FDA to treat hypertension, contradictory findings have been reported on the effect of RDNx on the blood pressure and progression of DKD in type 2 diabetic mellitus. Here, we used type 2 diabetic nephropathy (T2DN) rats, a well-established non-obese model that displays similar renal abnormalities and hyperglycemic levels as seen in humans, to evaluate the effect of RNDx on the blood pressure and progression of DKD. Methods: Bilateral RDNx or sham surgeries were performed on male T2DN rats with mild and severe stages of DN (~20 or >35 weeks old). The blood pressure was monitored chronically using radio telemetry throughout the entire experiment. 24-hr urine collection, glucose tolerance test, and GFR measurement were performed at baseline and at the end of the experiments. Blood and urine electrolytes were measured using a blood gas analyzer. The amount of norepinephrine in the kidney was evaluated by ELISA. Results: Bilateral RNDx were successfully performed on T2DN rats with a significant reduction of norepinephrine in the kidneys of the RDNx group (244±13 vs. 8±1 pg/mg for >35 weeks old rats). The mean arterial pressure (MAP) and heart rate remain the same between the Sham and RDNx groups. The glucose tolerance test also indicates no difference between the two groups. While there is a significant decrease in the GFR in Sham group from baseline to week 3, the GFRs between Sham and RDNx groups are not different. Similarly, total body weight, kidney to total body weight ratio, heart to total body weight ratio, and blood and urine electrolytes are also not different between Sham and RDNx groups. Analysis of the younger group (~20 weeks old) is in progress. Conclusion: In summary, our data suggests that RDNx does not affect the blood pressure and progression of DKD in male T2ND rats, at least at the stage of severe kidney injury (>35 weeks old). Funding sources: National Institute of Health R01 DK135644 and R01 DK129227, Department of Veterans Affairs I01 BX004024 (to AS), and APS Postdoctoral fellowship (to BX).

#963 Discrepancy between actual and estimated urine creatinine excretion predicts mortality in chronic kidney disease: from the KNOW-CKD study

Abstract Background and Aims Urine creatinine excretion is a surrogate marker of muscle mass and low urine creatinine excretion is a predictor of poor clinical outcome. There are several methods to estimate urine creatinine excretion. However, little is known about the clinical implication of discrepancy between actual and estimated urine creatinine excretion in chronic kidney disease (CKD). The aim of this study is to investigate the association between actual and estimated urine creatinine excretion discrepancy and mortality in CKD. Method This study analysed 1805 participants from the KNOW-CKD cohort. They underwent 24-hr urine collection and measured urine creatinine excretion at baseline. Their estimated urine creatinine excretion was calculated by Joachim's method. Discrepancy between actual and estimated urine creatinine excretion (dUCr) was defined as actual urine creatinine excretion minus estimated urine creatinine excretion. Patients were divided into 3 groups according to their tertile of dUCr. The study endpoint was all-cause death. Results During a follow-up of 13 062 person-years (median 8.0 years), 151 patients (8.4%) died, with a corresponding death rate of 11.6 (95% CI 9.9-13.6) per 1000 patients-years. 86 (14.4%), 41 (6.8%) and 24 (3.4%) patients from each 1st to 3rd tertile of dUCr died (P < 0.001). In multivariate Cox proportional hazard analysis, there was a graded association of dUCr with all-cause mortality. The adjusted hazard ratios (95% CI) of 2nd and 3rd tertile were 0.58 (0.39-0.86) and 0.36 (0.22-0.58) compared with the 1st tertile. Conclusion Higher discrepancy between actual and estimated urine creatinine excretion is associated with lower risk of mortality in predialysis CKD patients. This association was independent of various conventional and CKD-related risk factors.

Prenatal perceived stress and urinary cortisol as risk factors for ASD and non-typical developmental outcomes in the MARBLES study

BackgroundFindings for prenatal stress, previously measured through stressful life event surveys items or biomarkers, in association with ASD are inconsistent. We prospectively examined prenatal perceived stress and prenatal urinary cortisol (PUC) in association with ASD and other non-typical developmental (Non-TD) outcomes in the child in a high familial likelihood cohort. MethodsThe Perceived Stress Scale questionnaire was used to measure perceived stress in the longitudinal Markers of Autism Risk in Babies: Learning Early Signs (MARBLES) Study. Cortisol was measured through 24-hr urine collections. At three years of age, an algorithm consisting of scores from the Autism Diagnostic Observation Schedule (ADOS) and Mullen Scales of Early Learning (MSEL) was used to classify children with ASD, Non-TD, or typically developing (TD) outcomes. Relative risk ratios (RRR) with TD as the reference were estimated using multinomial logistic regression. ResultsIncreased perceived stress was associated with Non-TD in trimester 1 (RRR 1.10; 95% CI: 1.00, 1.21) and ASD in trimesters 2 and 3 (RRR 1.08; 95% CI: 1.02, 1.14 and RRR 1.08; 95% CI: 1.03, 1.14, respectively). Results with PUC were non-significant but were in the direction consistent with previous findings suggesting that decreased cortisol levels are associated with higher likelihood of ASD. ConclusionsFindings support the hypothesis that higher perceived stress is associated with increased likelihood of ASD and possibly Non-TD, relative to TD. This suggests that stress reduction interventions during pregnancy could serve as preventative measures that help optimize the child’s long-term health. Larger studies are needed to replicate these findings.

Evaluation of kidney disease using e-GFR compared to measured creatinine clearance.

Measurement of renal function is required for diagnosis and stratification of kidney disease. GFR is considered as the best overall measure of kidney function for diagnosis and treatment of patients with CKD. Measuring GFR is time consuming and hence eGFR is calculated using equations with endogenous markers like SCr. Therefore, it is of interest to examine the accuracy of creatinine based estimates (CrCl and CG formula) of GFR among patients. Thus, 60 in-patients (30 men and 30 women) at the GVP hospital and 40 controls were enrolled in the study. SCr and 24 hrs urine creatinine are estimated using blood sample and same day 24-hr urine collection. SCr is estimated using the Kinetic Jaffe's method in Auto analyzer for serum and urine. eGFR is calculated using the CG formula for the SCr value. We evaluated the correlation between measured CrCl derived from 24-hr urine collection and calculated/predicted CrCl using the CG equations. A positive correlation was observed between measured GFR and e-GFR in case and control groups.

THU268 Hyperuricemia In Insulin Resistance Is Associated With Increased Synthesis And Not Decreased Renal Excretion Of Uric Acid In Humans

Abstract Disclosure: R. Haykal: None. A. Kinzer: None. B. Abel: None. M. Lightbourne: None. M.S. Startzell: None. E. Cochran: None. R.J. Brown: None. Title: Hyperuricemia in insulin resistance is associated with increased synthesis and not decreased renal excretion of uric acid in humans. Background: In obesity and lipodystrophy (LD), insulin resistance (IR) is “selective”, with lack of insulin signaling causing hyperglycemia, but enhanced insulin signaling causing dyslipidemia. Rare human conditions exist in which there is extreme, non-selective IR impairing all insulin signaling pathways (e.g. mutations of the insulin receptor, INSR), resulting in hyperglycemia without dyslipidemia. We previously found that patients with non-selective IR do not have the hyperuricemia observed in selective IR. Potential mechanisms of hyperuricemia in selective IR include altered expression of renal uric acid transporters leading to impaired uric acid excretion, and increased activity of xanthine oxidoreductase (XOR), causing increased uric acid synthesis. We thus hypothesized that enhanced insulin signaling in selective IR would result in decreased fractional excretion of uric acid (FEUA) and/or increased biomarkers of XOR activity compared to non-selective IR. Method: We conducted 2 cross-sectional analyses of patients with severe IR that was either selective (due to LD) or non-selective (due to INSR mutation). Analysis 1 compared fasting insulin, fasting serum uric acid, and FEUA from 24-hr urine collection in 46 patients with LD and 13 with INSR. Analysis 2 compared products of purine nucleotide catabolism and salvage pathways by untargeted metabolomics in serum of 30 subjects each with LD and INSR. Results: In analysis 1, fasting insulin was lower in LD vs INSR (median 37.5 [25th-75th percentile 23.1-87.0] vs 88.7 [41.9-458.6] mcU/mL; P=0.0097). Serum uric acid was higher in LD vs INSR (5.3±1.6 vs 3.3±1.0 mg/dL; P=0.04). FEUA was comparable in the 2 groups (9.0±5 vs 8.5±3.5%; P=0.75). In analysis 2, uric acid was 1.6 fold higher (P<0.0001) in LD vs INSR. Xanthine, hypoxanthine, and xanthine to hypoxanthine ratio were comparable in both groups, but uric acid to xanthine ratio was 1.5 fold higher (P=0.01) and AMP was 0.8 fold lower in LD vs INSR (P=0.0029). Conclusion: Patients with selective IR due to LD had elevated serum uric acid, consistent with the hyperuricemia seen in selective IR due to obesity. By contrast, patients with non-selective IR due to INSR had lower serum uric acid despite higher fasting insulin. However, FEUA did not differ in these groups, thus hyperuricemia in non-selective IR might not be related to decreased renal excretion of uric acid. Elevated uric acid to xanthine ratio and lower AMP in selective IR suggest increased irreversible conversion of xanthine to uric acid by XOR, precluding salvage of purine nucleotides to AMP. Direct measurement of XOR activity in selective vs non-selective IR is needed to this potential mechanism by which insulin may lead to hyperuricemia. Presentation: Thursday, June 15, 2023

Characterizing Hydration Practices in Healthy Young Recreationally Active Adults-Is There Utility in First Morning Urine Sampling?

First morning urine (FMU) assessment would be a practical and convenient solution for clinically acceptable detection of underhydration prior to competition/training, and for the general public. Thus, we thus sought to determine the diagnostic accuracy of FMU as a valid indicator of recent (previous 24hr, 5days average) hydration practices. For 5 consecutive days and one final morning, 67 healthy women (n = 38) and men (n = 29; age: 20 [1]years, body mass index: 25.9 [5.5]) completed 24-hr diet logs for total water intake (from beverages and foods, absolute and relative to body mass), 24-hr urine and FMU collection (last morning only) for osmolality(Osm), specific gravity(SG), and color(Col), and morning blood sampling for plasma osmolality and copeptin. Correlations determined significance and relationship strength among FMU and all other variables. Area under the receiver operating characteristic curves, sensitivity, specificity, and positive likelihood ratios were employed using previously reported values to indicate underhydration (total water intake < 30ml/kg, osmolality > 500, and >800mOsm/kg, specific gravity > 1.017, and copeptin > 6.93 pmol/L). FMU_Osm and FMU_SG were significantly correlated (p < .05) to all variables except the previous 5-day plasma osmolality. FMU_Col was only significantly correlated with other color time intervals and total water intake per gram. FMU_Osm held greatest utility (area under the receiver operating characteristic curve, sensitivity, and specificity >80%) overall, with the best outcome being FMU_Osm indicating a previous 24-hr osmolality threshold of 500mOsm/kg (FMU_Osm criterion >710mOsm/kg and positive likelihood ratio = 5.9). With less effort and cost restriction, FMU is a viable metric to assess underhydration.

#4321 ACTION3 PHASE 3 STUDY: EVALUATING A NOVEL THERAPEUTIC STRATEGY OF A CCR2 INHIBITOR (DMX-200) WITH ANGIOTENSIN RECEPTOR BLOCKADE IN FSGS

Abstract Background and Aims Focal segmental glomerulosclerosis (FSGS) is a disease of podocytes. Complications include nephrotic syndrome and progressive kidney failure. FSGS is a condition with high unmet need and there is no approved treatment. The angiotensin II receptor type 1 (AT1R) and chemokine receptor 2 (CCR2) are G protein coupled receptors that form functional heteromers. Simultaneous antagonism of these receptors suggested synergistic renoprotective effects in preclinical and early phase clinical studies of proteinuric kidney disease. DMX-200 (repagermanium) is a C-C chemokine receptor type 2 (CCR2) inhibitor that, when administered concurrently with an angiotensin II receptor blocker (ARB), is designed to inhibit recruitment of monocytes implicated in the inflammatory chemokine environment of chronic disease. In a Phase 2a open-label study of 27 patients with proteinuric chronic kidney disease, 25% of patients achieved &amp;gt; 50% reduction in uPCR with combined use of DMX-200 and irbesartan. A Phase 2a placebo-controlled cross-over study in 8 patients with primary FSGS receiving stable dose of irbesartan demonstrated evidence of promising efficacy with clinically relevant reduction in uPCR of 17% with DMX-200 compared with placebo. These encouraging data suggest that treatment with DMX-200 may result in clinically meaningful reduction in proteinuria when added to ARB in patients with glomerular diseases such as FSGS. Proteinuria reduction is a positive prognostic sign for preserving kidney function. The observations from earlier trials have led to the initiation of an international randomised double-blind, placebo-controlled Phase 3 clinical trial (ACTION3) to further evaluate the efficacy of DMX-200 in patients with FSGS receiving an ARB. Method Eligible patients are adults (18-80 years) with biopsy-proven primary FSGS, genetic FSGS or FSGS of undetermined cause (FSGS-UC), and uPCR of &amp;gt;1.5g/g based on 24hr urine collection and eGFR of ≥25 ml/min/1.73 m2. Blood pressure ≤160/100 mmHg and BMI ≤40kg/m2. Patients with secondary FSGS or those treated with strong immunomodulatory agents (other than corticosteroids) are excluded. All patients are required to receive concomitant ARB treatment at a dose of at least 50% of the maximum approved dose according to the relevant product label. Patients receiving ACE-inhibitors are required to switch to an ARB. Other background therapies such as SGLT-2 inhibitors and mineralocorticoid receptor antagonists are permitted if receiving a stable dose in the 3 months prior to screening. Patients are randomized in a 1:1 ratio to DMX-200 (120 mg twice daily) or placebo. The primary objective is to evaluate the efficacy of DMX-200 on reduction in PCR after 35 weeks of treatment and eGFR slope after 104 weeks of treatment. Secondary objectives are safety and tolerability of DMX-200 and to evaluate the effect of DMX-200 on response criteria and composite endpoint of worsening kidney function. Exploratory objectives include assessment of changes in inflammatory biomarkers such as MCP-1 and the pharmacokinetic profile of DMX-200. Two interim analyses (IA) are planned, first planned IA for futility will be performed by an Independent Data Monitoring Committee after the first ​72 randomized patients (36 patients per group) complete 35 weeks ​of treatment. A second IA will be performed once approximately​ 144 enrolled patients complete 35 weeks ​of treatment.​ The final analysis will be performed once approximately 286 patients complete 104 weeks of treatment. The study is currently open in 11 countries at approximately 75 investigational sites and will be expanded to include more countries and sites subject to a successful first interim analysis. Results ACTION3 is a trial in progress and is expected to be completed in 2026. Conclusion ACTION3 is a Phase 3 randomized, placebo-controlled efficacy and safety trial which evaluates the novel approach of combining an investigational CCR2 inhibitor, DMX-200, with angiotensin receptor blockade in patients with FSGS.

PS-R07-5: A CASE OF PRIMARY ALDOSTERONISM WITH DECLINED GLOMERULAR FILTRATION RATE AFTER ADRENALECTOMY

Background: Primary aldosteronism (PA) has been known to cause organ damage, such as renal and cardiovascular disorders more frequently than essential hypertension (EH), independently of blood pressure. Among renal disorders, albuminuria is more prevalent in patients with PA than EH, while GFR tends to be higher in PA due to glomerular hyperfiltration. Surgical and medical treatments for PA correct these effects of excess aldosterone, which sometimes uncover preexisting chronic kidney disease (CKD). Here we present a case of PA with CKD who manifested decline of glomerular filtration rate (GFR) and overt renal failure following resection of aldosterone-producing adenoma. Case report: A 53-year-old woman was diagnosed with hypertension at the age of 40. Her primary care physician started treatment with a calcium channel blocker (CCB). At the age of 49, she was diagnosed with Sjogren's syndrome (SS). Blood tests revealed severe hypokalemia and eGFR of 50 mL/min/1.73m2, while 24-hr urine collection showed urinary protein of 0.5 g per day. SS was suspected to underlie her renal disease. A renal biopsy was performed, and suggested nephrosclerosis and IgA nephropathy. On the other hand, a 11mm-sized tumor in the left adrenal gland was discovered during the investigation of secondary hypertension. PA was confirmed based on active renin concentration (ARC) of 4.3 pg/mL, plasma aldosterone concentration (PAC) of 342 pg/mL, an aldosterone-to-renin ratio of 79.5 (&gt; 40), and 24-hr urinary aldosterone levels of 15.9 μg per day under the adequate salt-loaded condition. Adrenal venous sampling yielded aldosterone hypersecretion from the left adrenal vein, which indicated aldosterone-producing adenoma. Laparoscopic partial left adrenalectomy was performed and fully normalized ARC, PAC, and urinary aldosterone levels, which indicated biochemical cure of PA. Consequently, blood pressure had been well controlled with a single CCB. However, while her preoperative serum creatine level ranged from 0.9 to 1.1 mg/dL and eGFR was around 40–50 mL/min/1.73m2, her postoperative serum creatine level increased to 1.4 to 1.9 mg/dL and eGFR decreased to 25 to 35 mL/min/1.73m2 on average. In contrast, urinary protein level improved to less than 0.1 g/day, suggesting that post-treatment increase in creatine level indicated unveiling CKD rather than deterioration of renal function. Conclusion: PA treatment may unmask CKD through improving glomerular hyperfiltration from aldosterone excess.

PS-R03-7: PARTIAL ADRENALECTOMY IN A PATIENT WITH ACTH-INDEPENDENT MACRONODULAR ADRENAL HYPERPLASIA: A CASE REPORT

Background: The standard treatment for ACTH-independent macronodular adrenal hyperplasia (AIMAH) with overt Cushing's syndrome is bilateral adrenalectomy. Here we show a case of AIMAH who underwent total adrenalectomy on one side and partial adrenalectomy on the other, resulting in the successful debulking of cortisol-secreting adrenal masses and improvement of Cushing's syndrome, yet not necessitating postoperative steroid replacement. Case presentation: A 74-year-old female patient with hypertension, type 2 diabetes and dyslipidemia developed edema of the legs. She visited her primary physician and was found to have lumbar vertebral compression fractures. The blood test and 24-hr urine collection revealed the plasma cortisol levels of 26.1 μg per dL, adrenocorticotropic hormone of 1.1 pg per mL, and urine free cortisol of 340 μg per day. Computed tomographic scan and adrenal scintigraphy confirmed bilateral adrenal nodules with notable tracer uptake. Diagnosis of AIMAH with Cushing's syndrome was made. Laparoscopic partial adrenalectomy, i.e., total removal of the left adrenal gland and partial removal of the right counterpart, was conducted aiming to avert from steroid replacement therapy. After the surgery, blood pressure and glycemic control were markedly improved and maintained for 4 years whilst adrenocortical functions were preserved. Conclusion: Partial adrenalectomy could be an effective therapy in selected cases of AIMAH.

Association of blood pressure after peritoneal dialysis initiation with the decline rate of residual kidney function in newly-initiated peritoneal dialysis patients.

BackgroundLower blood pressure (BP) levels are linked to a slower decline of kidney function in patients with chronic kidney disease (CKD) without kidney replacement therapy. However, there are limited data on this relation in peritoneal dialysis (PD) patients. Here we evaluated the association of BP levels with the decline of residual kidney function (RKF) in a retrospective cohort study.MethodsWe enrolled 228 patients whose PD was initiated between 1998 and 2014. RKF was measured as the average of creatinine and urea clearance in 24-hr urine collections. We calculated the annual decline rate of RKF by determining the regression line for individual patients. RKF is thought to decline exponentially, and thus we also calculated the annual decline rate of logarithmic scale of RKF (log RKF). We categorized the patients’ BP levels at 3 months after PD initiation (BP3M) into four groups (Optimal, Normal & High normal, Grade 1 hypertension, Grade 2 & 3 hypertension) according to the 2018 European Society of Cardiology and European Society of Hypertension Guidelines for the management of arterial hypertension.ResultsThe unadjusted, age- and sex-adjusted, and multivariable-adjusted decline rate of RKF and log RKF decreased significantly with higher BP3M levels (P for trend <0.01). Compared to those of the Optimal group, the multivariable-adjusted odds ratios (95% confidence interval) for the faster side of the median decline rate of RKF and log RKF were 4.04 (1.24–13.2) and 5.50 (1.58–19.2) in the Grade 2 and 3 hypertension group, respectively (p<0.05).ConclusionsHigher BP levels after PD initiation are associated with a faster decline in RKF among PD patients.

ADHERENCE DECREASES WITH HIGHER NUMBER OF MEDICATIONS IN CONTROLLED HYPERTENSIVE PATIENTS, CONTROLLED RESISTANT PATIENTS HAVE LOWER ADHERENCE THAN CONTROLLED NON-RESISTANT PATIENTS

Objective: Controlled hypertension in treated hypertensive patients is defined as controlled blood pressure (BP) in clinic (automated office BP [AOBP] &lt; 130/80 mmHg) and out-of-clinic by 24-hr ambulatory blood pressure monitoring (ABPM &lt; 125/75 mmHg). Uncontrolled resistant hypertension (RHTN) is defined as uncontrolled blood pressure (BP) on 3 or more medications, including a diuretic; BP controlled on 4 or more medications is defined as controlled RHTN. Controlled non-RHTN is BP controlled on 3 or less medications. Antihypertensive medication adherence is known to decrease with increase in number of antihypertensive medications, as well as medication adherence is lower in patients with uncontrolled RHTN. Unknown is the relative medication adherence in patients with controlled hypertension with number of antihypertensive medications and medication adherence in controlled RHTN versus controlled non-RHTN. Design and method: In this prospective evaluation patients were recruited from the Hypertension Clinic after having controlled BP readings at 3 or more clinic visits. All the patients were evaluated by in-clinic AOBP with use of the BpTRU device, out-of-clinic 24-hr ABPM monitoring and 24-hr urine collection to determine antihypertensive medication adherence by high-performance liquid chromatography-tandem mass spectrometry. After excluding patients with masked uncontrolled hypertension, 82 patients were controlled by AOBP and 24-hr ABPM. Of these, 40 patients had controlled RHTN and 42 patients had controlled non-RHTN. Results: Higher number of prescribed antihypertensive medications was associated with lower levels of medication adherence in patients with controlled hypertension. In addition, patients with controlled RHTN (72.7%) had significantly lower medication adherence than controlled non-RHTN (90.9%). Conclusions: Similar to uncontrolled hypertension, patients with controlled hypertension have less medication adherence with use of higher numbers of antihypertensive medications. In addition, similar to uncontrolled RHTN, patients with controlled RHTN have lower medication adherence than patients with controlled non-RHTN.

110 24hr and Random Spot Urine Collections Were Comparable in Assessing Oxalate Excretion and Response to Treatment in Primary Hyperoxaluria Type 1

110 24hr and Random Spot Urine Collections Were Comparable in Assessing Oxalate Excretion and Response to Treatment in Primary Hyperoxaluria Type 1

To evaluate and standardize the method of spot urine protein creatinine ratio for estimation of proteinuria

Background: Proteinuria is an independent risk factor for diabetic nephropathy and a predictor of end-stage renal disease. Measurement of protein excretion in a 24hr urine collection is the gold standard for the quantitative evaluation of proteinuria in diabetes. However, this is cumbersome, subjective to collection errors and required good compliance. Aims: To evaluate and standardize the method of spot urine protein creatinine ratio for estimation of Proteinuria. Materials and methods: We compared 24 hr urine protein estimation with urine spot protein creatinine ratio in type 2 diabetes mellitus patients with proteinuria. Results: In our study of 73 patients with type 2 diabetes mellitus and proteinuria, it was found that A maximum number of patients were noted in the age group 41-50 years. Males were more than females in the ratio of 2.04:1. The majority of patients had a duration of diabetes between 5 -10 yrs (52.05%). The mean duration of diabetes was 9.24+/- 6.1 yrs. Twenty-five patients (34.25%) had nephrotic range proteinuria. There was a good correlation between urine PCR and 24 hr urine protein at different levels of GFR. Maximum correlation between urine PCR and 24 hr urine protein was seen in the GFR >60 group. There was a good correlation between urine PCR and 24 hr urine protein at different ranges of proteinuria. A maximum correlation between urine PCR and 24 hr urine was seen in the proteinuria group

Nutriome-metabolome relationships provide insights into dietary intake and metabolism.

Dietary assessment traditionally relies on self-reported data which are often inaccurate and may result in erroneous diet-disease risk associations. We illustrate how urinary metabolic phenotyping can be used as alternative approach for obtaining information on dietary patterns. We used two multi-pass 24-hr dietary recalls, obtained on two occasions on average three weeks apart, paired with two 24-hr urine collections from 1,848 U.S. individuals; 67 nutrients influenced the urinary metabotype measured with 1H-NMR spectroscopy characterized by 46 structurally identified metabolites. We investigated the stability of each metabolite over time and showed that the urinary metabolic profile is more stable within individuals than reported dietary patterns. The 46 metabolites accurately predicted healthy and unhealthy dietary patterns in a free-living U.S. cohort and replicated in an independent U.K. cohort. We mapped these metabolites into a host-microbial metabolic network to identify key pathways and functions. These data can be used in future studies to evaluate how this set of diet-derived, stable, measurable bioanalytical markers are associated with disease risk. This knowledge may give new insights into biological pathways that characterize the shift from a healthy to unhealthy metabolic phenotype and hence give entry points for prevention and intervention strategies.

P1833HOW DO WE DEFINE HYPERCALCIURIA IN 24 HR URINE?

Abstract Background and Aims Hypercalciuria can clinically present itself as gross hematuria, microscopic hematuria, dysuria or abdominal pain without urinary lithiasis. It is also one of main metabolic causes of urinary lithiasis in children. In Nelson pediatrics, hypercalciuria is defined by a 24 -hour urine for calcium excretion&amp;gt;4mg/kg/day. A spot urine calcium creatinine ratio of &amp;gt;0.2, is considered abnormal in older children and adolescents. Both of them are not a standardized detect in children. Fasting and postprandial spot urinary calcium creatinine ratios may not detect hypercalciuria so accurately, that a 24-hour urine is preferred. In addition, 24hr urine collection is frequently under- or over-collected, which leads to an inadequate sampling hard to pick up which one the more accurate calculating methodology for the hypercalciuria detection with 24hr urine is. In this study, we evaluated the comparisons of 24 hr urine calcium creatinine ratio(Ca/Cr), 24hr urine calcium excretion(mg/kg)(Ca/Kg) and CCCR in school aged children. 24-hour urine for calcium excretion&amp;gt;4mg/kg/day 24-hour urine calcium creatinine ratio of &amp;gt;0.2 Calcium creatinine clearance ratio(CCCR); (24-hour U-calcium/P-total calcium) / (24-hour U-creatinine/P-creatinine), as known as fractional excretion of calcium(FeCa) Method We enrolled 250 normal kidney function patients who’s age is 7 to 18 year, was able to collect 24 hr urine in a single hospital unit. We conducted 24 hr urine collection, serum calcium creatinine levels on the same day from January 2007 to December 2019. We analyze of each values. We used SPSS. 25.0 Results

SAT-490 A Case of Unilateral Exophthalmos Due to Thyroid Orbitopathy and Its Association with Chronic Kidney Disease

Graves ophthalmopathy(GO)is the most common extra-thyroidal manifestation of Graves’ disease (GD). Most cases of GO are bilateral which may be asymmetric, whereas unilateral ophthalmopathy is less common and has been observed in 9-15% cases. Association between chronic kidney disease and unilateral Grave’s ophthalmopathy in a clinically euthyroid patient is rare. We report a case of a 24-year-old male with no previous history of any chronic medical illnesses who presented with protruded right eye for the past 6 months. He did not have any other visual symptoms or symptoms related to thyroid disease. Laboratory results revealed low TSH, normal free T3 and free T4. TSH receptor antibodies were positive. He also had elevated serum creatinine at 418 umol/L (normal levels 64 - 110 umol/L). US KUB showed bilateral small sized kidneys and increased parenchymal echogenicity suggestive of chronic kidney disease. MRI Head showed features suggestive of unilateral thyroid associated orbitopathy. Patient received 1-week course of oral prednisolone 10 mg per day after which his exophthalmos improved.Case report: A 24 year old male with no previous history of any chronic medical illnesses, presented to the clinic with protruded right eye for the past 6 months that was progressively getting worse. There was no eye pain, visual changes, ophthalmoplegia, dryness or discharge from eye. Patient did not report any other symptoms, Physical examination revealed a comfortable man with protruded right eye, lid retraction, normal eye movements and no signs of orbital cellulitis. Neck examination was significant for a mild diffuse goitre. Laboratory studies were significant for haemoglobin of 12.1 g/dl (normal 13-17 g/dl). He also had elevated serum creatinine at 418 umol/L (normal 64 - 110 umol/L). Serum electrolytes, liver function tests and lipid profile were within normal range. 24 hr urine collection showed 3.08 gm/24 hr proteinuria. Serum TSH was 0.04 mIU/L (normal 0.45 - 4.5 mIU/L), free T4 was 13.8 pmol/L (normal 9 - 20 pmol/L) and free T3 was 4.56 pmol/L (normal 2.89 - 4.88 pmol/L). Thyrotropin Receptor Ab titre was 4.69 IU/L (normal 0.00 - 1.75 IU/L). ANA, ANCA, C3, C4, Anti thyroid peroxidase and Anti GBM antibodies were negative. Screening for hepatitis B, C and HIV was negative US KUB showed bilateral small sized kidneys and increased parenchymal echogenicity suggestive of CKD. MRI Head was remarkable for proptosis of the right eye with increased retro-orbital fat, thickening and T2 hyper-intensity with sparing of the tendinous insertion involving the right inferior, medial, superior and lateral rectus muscles with crowding at the orbital apex. Features were suggestive of unilateral thyroid associated orbitopathy. Patient received 1-week course of oral prednisolone 10 mg per day after which his exophthalmos improved. An association between CKD and GO in a clinically euthyroid patient is rare.

Tryptophan Depletion through a Low Protein Diet Alters Renal Structure and Function in Young Male Mice

Low protein diets have been used in patients with chronic kidney disease to decrease uremic burden, but its use is controversial due to concerns about malnutrition. Long term use of a low‐protein diet may also impact bone health through reduction of the essential amino acid, tryptophan. We have previously shown that feeding a low‐protein diet with increased levels of its metabolite, kynurenine (a change that also occurs in aging) to adult mice leads to bone loss. The kidney regulates many important factors for bone health such as Vitamin D, and in conjunction with parathyroid hormone, phosphate and calcium. Since aging is known to also impact the kidney, we hypothesized that alterations in the normal ratio of tryptophan to kynurenine would impact kidney structure and function. We fed 3‐mo‐old male mice one of four diets [normal 18% protein (NP) or low 8% protein (LP) with or without kynurenine added] for 8 weeks. Mice were housed in metabolic cages for baseline measurements and again at the end of the feeding for 24‐hr urine collection. At sacrifice, kidneys were weighed to detect changes in renal mass, frozen for Western blotting or formalin‐fixed for histological analysis. As expected, we found decreased albuminuria with LP; however, there was a further reduction with KYN treatment in LP mice. There was significant diuresis (2.2±0.31 vs. 0.8±0.1 ml/day) in LP compared to NP mice that was attenuated in KYN mice (1.0±0.2ml/day); this effect may be due in part to a reduction in AQP2 levels. Natriuresis followed a similar trend but did not reach significance (0.12±0.01 vs. 0.08±0.01 mmol/day). Renal mass alone (0.17±0.00 vs. 0.20±0.01 g) and kidney weight/body weight (0.0055±0.0001 vs. 0.0059±0.0001) was decreased in LP mice with no further impact of KYN. Thus, while changes in the tryptophan to kynurenine ratio seem to impact the kidney, the changes vary with the renal parameter investigated.Support or Funding InformationAG036675

Development of objective indicators for quantitative analysis of sodium intake: the sodium to potassium ratio of second-void urine is correlated with 24-hour urinary sodium excretion.

BACKGROUND/OBJECTIVESTo date, sodium intake has been evaluated based on spot urine instead of 24-hour (hr) urine collection. Nevertheless, the optimal method for assessing daily sodium intake remains unclear.SUBJECTS/METHODSFifteen male (age 32.7 ± 6.5 years) participants were offered 3 meals with a total of 9–10 g salt over 24 hours, and 24-hr urine was collected from the second-void urine of the first day to the first-void urine of the second day. Twenty-four-hr urinary sodium (24UNa) was estimated using Tanaka's equation and the Korean formula, and spot urine Na, potassium (K), chloride (Cl), urea nitrogen (UN), creatinine (Cr), specific gravity (SG) and osmolality (Osm) were measured. The ratios of urinary Na to other parameters were calculated, and correlations with total measured 24UNa were identified.RESULTSAverage 24-hr urine volume was 1,403 ± 475 mL, and measured 24UNa was 143.9 ± 42.1 mEq (range, 87.1–239.4 mEq). Measured 24UNa was significantly correlated with urinary Na/UN (r = 0.560, P < 0.01), urinary Na/Osm (r = 0.510, P < 0.01), urinary Na/Cr (r = 0.392, P < 0.01), urinary Na/K (r = 0.290, P < 0.01), 24UNa estimated using Tanaka's equation (r = 0.452, P < 0.01) and the Korean formula (r = 0.414, P < 0.01), age (r = 0.548, P < 0.01), weight (r = 0.497, P < 0.01), and height (r = 0.393, P < 0.01) in all spot urine samples. Estimated 24UNa based on the second-void spot urine of the first day tended to be more closely correlated with measured 24UNa than were estimates from the other spot urine samples. The significant parameters correlated with the second-void urine of the first day were urinary Na/K (r = 0.647, P < 0.01), urinary Na/Cr (r = 0.558, P < 0.05), and estimated 24UNa using Tanaka's equation (r = 0.616, P < 0.05) and the Korean formula (r = 0.588, P < 0.05).CONCLUSIONSSecond-void urine is more reliable than first-void urine for estimating 24UNa. Urinary Na/K in the second-void urine on the first day is significantly correlated with 24UNa. Further studies are needed to establish the most reliable index and the optimal time of urine sampling for predicting 24UNa.

MASKED UNCONTROLLED HYPERTENSION IN TREATED HYPERTENSIVE PATIENTS IS NOT RELATED TO ANXIETY COMPARED TO TRUE CONTROLLED HYPERTENSION

Objective: Masked uncontrolled hypertension in treated hypertensive patients (MUCH) is defined as controlled blood pressure (BP) in clinic (Automated office BP [AOBP] < 135/85 mmHg) but uncontrolled BP out-of-clinic as measured by 24-hr ambulatory blood pressure monitoring (ABPM, daytime readings >= 135/85 mmHg). In- and out-of-clinic anxiety levels in patients with MUCH compared to patients with true controlled hypertension have not been previously compared. Design and method: In this prospective evaluation, 181 patients with controlled hypertension were recruited from the Hypertension Clinic. The patients were recruited after having controlled BP readings at 3 or more clinic visits. All the patients were evaluated by in-clinic AOBP with use of the BpTRU device, out-of-clinic ABPM, 24-hr urine collection to detect antihypertensive medication adherence by high-performance liquid chromatography-tandem mass spectrometry and state-trait anxiety inventory (STAI) to index self-reported anxiety both in- and out-of-clinic. Eighty patients had controlled hypertension in clinic and by daytime ABPM, indicating true controlled hypertension. The remaining 85 patients were controlled in clinic but uncontrolled by daytime ABPM, consistent with MUCH. Of these, 48 true controlled and 55 MUCH patients were fully adherent with prescribed antihypertensive medications. Results: Anxiety state levels were similar in patients with true controlled hypertension and MUCH both in-clinic (33.2 ± 11.6 vs 30.9 ± 11.8, p = 0.454) and out-of-clinic (32.4 ± 10.8 vs 32.2 ± 11.2, p = 0.943). In addition, anxiety trait levels were also similar in patients with true controlled hypertension and MUCH in-clinic (34.4 ± 12.2 vs 31.6 ± 10.7, p = 0.376) and out-of-clinic (33.6 ± 10.7 vs 33.7 ± 11.2, p = 0.972). Conclusions: Assessment of state and trait demonstrates a similar anxiety levels in both MUCH and true controlled hypertensive patients’ in- and out-of-clinic. This lack of difference in self-reported anxiety levels suggest that MUCH is not attributable to greater levels of anxiety.