24-hour Urinary Phosphorus Excretion Research Articles

#2971 LONG-TERM EFFECTS OF THE NEW NORDIC RENAL DIET ON PHOSPHOROUS HOMEOSTASIS IN PATIENTS WITH CHRONIC KIDNEY DISEASE STAGE 3 AND 4

Abstract Background and Aims Chronic kidney disease (CKD) causes severe disturbances in phosphate metabolism. The New Nordic Renal Diet (NNRD) is a whole food approach designed by our group, with low dietary phosphorus content (850 mg/day). In a 1-week study, NNRD had positive effects on phosphorus homeostasis in patients with CKD stage 3-4 [1]. The aim of the present study was to examine the long-term health effects of a dietary intervention with NNRD in patients with CKD stage 3-4 [2]. Method A 26-week randomized, controlled, non-blinded trial comparing the effect of NNRD vs. non-restricted habitual diet. Patients in the NNRD group received weekly home delivery of fresh food items (free of charge) and recipes for five days of the week, and on the remaining two days they were instructed to prepare meals according to the NNRD food principles. The study was designed with seven follow-up visits in the outpatient clinic where fasting blood samples and 24-hour urine collection were delivered. Linear mixed-effects models were used to assess the effects of the intervention, time, and the potential interaction between intervention and time. The primary endpoint was the difference in 24-hour urine phosphorus excretion between the two study groups. Secondary endpoints included fractional phosphorus excretion and plasma fibroblast growth factor 23 (p-FGF23). Results Sixty patients (mean age 54 years, 31 women) with mean eGFR of 34 ml/min/1.73 m2 were included. Two patients were withdrawn due to dialysis initiation. In the NNRD-group (n = 29), mean 24-hour urine phosphorus excretion during the intervention period was 651 mg (SD, 35 mg) vs. 930 mg (SD, 84 mg) in the control group (n = 29), between-group difference 279 (95% CI; -372, -91; P < 0.001) (Figure 1). Mean fractional phosphorus excretion was 11% (SD, 5%) in the NNRD-group and 14% (SD, 7%) in the control group, between-group difference 3% (95% CI; -6.4, -0.8; P = 0.01). Mean p-FGF23 was 162 pg/ml (SD, 130 pg/ml) in the NNRD-group and 215 pg/ml (SD, 230 pg/ml) in the control group, between-group difference 52 pg/ml (95% CI; -100, 73; P = 0.03). P-urea was 3.4 mmol/L lower in the NNRD group (95% CI; -5.3, -0.2, P = 0.03). P-albumin was 1.1 g/L higher in the NNRD group (95% CI; 0.02, 2.4; P = 0.04) and 24-h urine bicarbonate excretion was 4.1 mmol higher in the NNRD group (95% CI; 0.7, 7.5, P = 0.01). There was no difference between study groups in p-phosphorous, p-creatinine, p-potassium, p-calcium, p-lipids, or proteinuria. Conclusion NNRD intervention in the context of fresh food delivery and recipes was feasible and had a major beneficial effect on phosphorous parameters in patients with CKD 3-4.

Changes and Influencing Factors of Urinary Phosphorus Excretion in Patients with Different Stages of Chronic Kidney Disease.

The aim of the study was to explore the changes and the possible influencing factors of phosphorus excretion in chronic kidney disease (CKD) patients. A database with 204 patients who met the CKD diagnostic criteria was established. Clinical data, including 24-hour urine phosphorus excretion (24-hour UPE), were collected. The demographic and clinical characteristics of CKD patients in different stages and the changes in serum phosphorus (P) and 24-hour UPE with renal function were studied. After exploring the factors influencing 24-hour UPE by multiple linear regression analysis, the effects of gender on 24-hour UPE was assessed. Among 204 patients, there were significant differences in serum calcium (Ca), P, 24-hour UPE, intact parathyroid hormone (iPTH), and 25-hydroxyvitamin D [25(OH)-VD] among different CKD stages. Twenty-four-hour UPE fluctuated greatly, but serum P was relatively stable, which was > 1.46 mmol/L at an estimated glomerular filtration rate (eGFR) < 10 mL/minute/1.73 m2. Male gender (β = 3.42, p < 0.00) and eGFR (β = 0.06, p < 0.00) were related to 24-hour UPE, while age, body weight, albumin (ALB), iPTH, and serum P were not related to 24-hour UPE according to regression analysis. There were significant differences in 24-hour UPE and serum P between males and females. Urinary phosphorus excretion decreased with decreasing renal function in CKD patients. Urinary phosphorus excretion might be affected by eGFR and gender.

274 Determination of phosphorus requirement of lactating sows based on 24-hour urinary phosphorus excretion

Abstract The objective was to determine phosphorus (P) requirement of lactating sows using 24-hour urinary P excretion as the response criteria. The underlying assumption was that urinary P remains low and constant until the requirements are met then increases as P consumption increases. Thirty-six crossbred PIC Camborough sows (parity 3 to 7) were randomly assigned to 1 of 6 corn-soybean-meal diets with increasing dietary total P (tP) levels (0.40, 0.48, 0.56, 0.64, 0.72, and 0.80%) and a constant calcium (Ca) to tP ratio (1.25:1). Diets were fed from breeding until the end of lactation. Urine and blood samples were collected on days 4 and 18 of lactation and analyzed for P and Ca concentrations. Data were analyzed using MIXED and NLIN procedures of SAS. Phosphorus requirements were estimated using a broken-line regression model. Plasma Ca (ranging from 12.1 to 10.3 mg/dL) was not affected by dietary treatments, and was maintained within the normal physiological range on day 4 and 18 of lactation. Plasma P (ranging from 2.9 to 6.4 mg/dL) linearly increased (P &amp;lt; 0.05) with increasing dietary tP levels on day 4 and 18 of lactation. Only sows fed the 0.40% tP diet failed to maintain plasma P concentrations within the normal physiological range. Clinical signs of P and Ca deficiencies were not observed. Differences in sow and litter performance among treatments were not detected. A nonlinear response of urinary P excretion to dietary P intake was observed. Based on a broken-line linear model fit to 24-hour urinary P excretion, minimum tP requirements of sows at day 4 and 18 of lactation were 0.47 and 0.54%, respectively. In conclusion, 24-hour urine P excretion provided sensitive criteria for estimates of tP requirements in lactating sows. Efforts to adjust heteroscedasticity for animals fed dietary P above the estimated requirement need further evaluation.

Urinary Phosphate Excretion and Microvascular Function in a Population-Based Cohort

Urinary Phosphate Excretion and Microvascular Function in a Population-Based Cohort

Acid Load and Phosphorus Homeostasis in CKD

The kidneys maintain acid-base homeostasis through excretion of acid as either ammonium or as titratable acids that primarily use phosphate as a buffer. In chronic kidney disease (CKD), ammoniagenesis is impaired, promoting metabolic acidosis. Metabolic acidosis stimulates phosphaturic hormones, parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF-23) invitro, possibly to increase urine titratable acid buffers, but this has not been confirmed in humans. We hypothesized that higher acid load and acidosis would associate with altered phosphorus homeostasis, including higher urinary phosphorus excretion and serum PTH and FGF-23. Cross-sectional. 980 participants with CKD enrolled in the Chronic Renal Insufficiency Cohort (CRIC) Study. Net acid excretion as measured in 24-hour urine, potential renal acid load (PRAL) estimatedfrom food frequency questionnaire responses, and serum bicarbonate concentration< 22 mEq/L. 24-hour urine phosphorus and calcium excretion and serum phosphorus, FGF-23, and PTH concentrations. Using linear and log-linear regression adjusted for demographics, kidney function, comorbid conditions, body mass index, diuretic use, and 24-hour urine creatinine excretion, we found that 24-hour urine phosphorus excretion was higher at higher net acid excretion, higher PRAL, and lower serum bicarbonate concentration (each P<0.05). Serum phosphorus concentration was also higherwith higher net acid excretion and lower serum bicarbonate concentration (each P=0.001). Only higher net acid excretion associated with higher 24-hour urine calcium excretion (P<0.001). Neither net acid excretion nor PRAL was associated with FGF-23 or PTH concentrations. PTH, but notFGF-23, concentration (P=0.2) was 26% (95% CI, 13%-40%) higher in participants with a serumbicarbonate concentration<22 versus≥22 mEq/L (P<0.001). Primary results were similar if stratified by estimated glomerular filtration rate categories or adjusted for iothalamate glomerular filtration rate (n=359), total energy intake, dietary phosphorus, or urine urea nitrogen excretion, when available. Possible residual confounding by kidney function or nutrition; urine phosphorus excretion was included in calculation of the titratable acid component of net acid excretion. In CKD, higher acid load and acidosis associate independently with increased circulating phosphorus concentration and augmented phosphaturia, but not consistently with FGF-23 or PTH concentrations. This may be an adaptation that increases titratable acid excretion and thus helps maintain acid-base homeostasis in CKD. Understanding whether administration of base can lower phosphorus concentrations requires testing in interventional trials.

Sclerostin and bone metabolism markers in hyperthyroidism before treatment and interrelations between them.

Sclerostin, which is a glycoprotein produced by osteocytes, reduces the formation of bones by inhibiting the Wnt signal pathway. Thyroid hormones are related with Wnt signal pathway and it has been reported that increased thyroid hormones in hyperthyroidism fasten epiphysis maturation in childhood, and increase the risk of bone fractures by stimulating the bone loss in adults. The aim of this study was to examine the sclerostin serum levels, the relation between sclerostin and thyroid hormones as well as the biochemical markers of the bone metabolism in patients with hyperthyroidism (including multinodular goiter and Graves' disease), whose treatments have not started yet. No difference was found in the serum sclerostin levels between the hyperthyroidism group (n=24) and the control group (n=24) (p=0.452). The serum osteocalcin levels and 24-hour urinary phosphorus excretion were found to be higher in the hyperthyroid group than in the control group (p<0.001, p=0.009). A positive correlation was determined between the sclerostin and bone alkaline phosphatase levels (p<0.001); a negative correlation between the osteocalcin and thyroid stimulating hormone (TSH) (p<0.05); a positive correlation between the osteocalcin and thyroid hormones (FT3,FT4) (p<0.001); and a positive correlation between the deoxypyridinoline and hydroxyproline (p<0.001). No correlation was determined between sclerostin and TSH,FT3,FT4 (p>0.05). Therefore, we consider that a long-term study that covers the pre-post treatment stages of hyperthyroidism, including both the destruction and construction of the skeleton would be more enlightening. Moreover, the assessment of the synthesis of sclerostin in the bone tissue and in the serum level might show differences.

Phosphorus Additives and Albuminuria in Early Stages of CKD: A Randomized Controlled Trial

Little is known about the effects of phosphorus additives on patients with kidney disease. Randomized, double-blind, crossover trial. 31 adults with early stages of presumed chronic kidney disease (estimated glomerular filtration rate≥ 45mL/min/1.73m2; urine albumin-creatinine ratio sex-specific cutoff points: men≥ 17mg/g, women≥ 25mg/g). Higher versus lower phosphorus intake for 3 weeks. Higher phosphorus intake was achieved by the addition of commercially available diet beverages and breakfast bars to diet. Change in 24-hour urine albumin excretion and plasma fibroblast growth factor 23 level. Two 24-hour urine collections and a single fasting blood draw at the end of each period. Mean baseline values for phosphorus intake, 24-hour urine phosphorus excretion, and estimated glomerular filtration rate were 1,113±549 (SD) mg/d, 688±300mg/d, and 74.6±22.0mL/min/1.73m2. Median urine albumin excretion of 82.7 (IQR, 39.6-174.1) mg/d. Although phosphorus intake from study products increased by 993mg/d (P<0.001) during the higher compared to lower phosphorus additive period, background phosphorus intake decreased by 151mg/d (P=0.004). Higher phosphorus additive consumption increased 24-hour urine phosphorus excretion by 505 (95% CI, 381 to 629) mg/d (P<0.001), but did not significantly increase albuminuria (higher vs lower: 14.3%; 95% CI,-2.5% to 34.0%; P=0.1) or fibroblast growth factor 23 level (higher vs lower: 3.4%; 95% CI,-5.9% to 13.6%; P=0.4). Small sample size, short duration of intervention, changes in background diet during the intervention. A 3-week consumption of higher phosphorus food additives did not significantly increase albuminuria. Further studies are needed to confirm these results.

Abstract P145: The Effects of Phosphorus Additives on Albuminuria and Fibroblast Growth Factor-23

Background: Phosphorus-based additives are prevalent in processed foods. Their effects on cardiovascular and renal health are unknown. Methods: We conducted a randomized, double-blind, cross-over study to examine the effects of phosphorus additives on albuminuria and fibroblast growth factor-23 (FGF-23) in adults with microalbuminuria and estimated glomerular filtration rate (eGFR) ≥ 45 ml/min/1.73m2. Participants (n=31) received unaltered beverages and breakfast bars (with or without phosphorus additives; 941 mg/d contrast in phosphorus) for 3 week periods, separated by a 2-4 week washout period. Diet was assessed by 24-hour recalls bi-weekly. Primary outcomes were albuminuria and FGF-23 assessed by two 24-hour urine collections and a single fasting blood draw at the end of each period. Results: We included 31 participants (32% female, 90% black, 87% hypertension, 48% diabetes) with mean age, eGFR, and 24-hour urine albumin excretion of 66 years, 68 ml/min/1.73m2, and 74.4 mg/d, respectively. Mean self-reported phosphorus intake and 24-hour urine phosphorus excretion was 1113 mg/d and 687.9 mg/d at baseline. Self-reported phosphorus intake (excluding intervention products) decreased by 151 mg/d (p=0.004) during the phosphorus additive period compared to the non-phosphorus additive period as did protein intake (8.0 g/d lower, p=0.02). In unadjusted analyses, consumption of phosphorus additives increased 24-hour urine phosphorus excretion by a mean of 505 mg/d, non-significantly increased albuminuria by 14.3% (95% CI: -2.5% to 34.0%, p=0.1), but had no effect on FGF-23 (3.0%, 95% CI: -9.3% to 16.8%). After adjustment for changes in weight and self-reported dietary intake (sodium, phosphorus, and protein intake), consumption of phosphorus additives increased albuminuria by 22.5% (95% CI: 3.1% to 45.6%, p=0.02). In unadjusted analysis excluding two patients non-compliant with the intervention, consumption of phosphorus additives increased albuminuria by 17.3% (95% CI: 0.08% to 37.5%, p=0.049). Neither sensitivity analysis showed an effect on FGF-23. Conclusion: High consumption of phosphorus-based additives may increase albuminuria. Further studies are needed to confirm this finding and determine the long-term effects on cardiovascular and renal health.

Association of a Reduction in Central Obesity and Phosphorus Intake With Changes in Urinary Albumin Excretion: The PREMIER Study

Excess adiposity and dietary factors may be important determinants of urinary albumin excretion (UAE). Observational analysis of PREMIER, a randomized trial designed to lower blood pressure using behavioral interventions (counseling on weight loss, healthy diet, and exercise). 481 participants with normal kidney function who provided adequate 24-hour urine collections at baseline and 6 months. Change in waist circumference; 24-hour urine sodium, potassium, and phosphorus excretion; and protein intake estimated from urea nitrogen. The primary outcome was change in log-transformed 24-hour UAE over 6 months. After 6 months, the proportion of individuals with UAE ≥10 mg/d decreased from 18.7% to 12.7% (P < 0.001). Changes in mean waist circumference (-4.2 ± 6.6 [SD] cm), 24-hour excretion of sodium (-28.2 ± 71.7 mmol/d), potassium (+8.4 ± 27.8 mmol/d), phosphorus (-27.7 ± 314.1 mg/d), and protein intake (-1.7 ± 19.4 g/d) were observed. After adjustment for relevant covariates, the following variables were associated significantly with reduction in ln(UAE) in separate models: decrease in waist circumference (P = 0.001), decrease in 24-hour urine phosphorus excretion (P < 0.001), and decrease in protein intake (P = 0.01). In a multivariable model including these 3 predictors, decreases in waist circumference (P = 0.002) and 24-hour urine phosphorus excretion (P = 0.03), but not change in protein intake (P = 0.5), remained associated significantly with reduction in ln(UAE). These associations remained significant even after adjustment for changes in blood pressure and insulin resistance. Baseline UAE and metabolic syndrome modified the relationship of waist circumference with ln(UAE); specifically, individuals with higher UAE and baseline metabolic syndrome experienced greater reductions in ln(UAE) from decreases in waist circumference. Observational study with potential for confounding. In adults with normal kidney function, decreases in waist circumference and 24-hour urine phosphorus excretion are associated with reductions in UAE. These findings support the rationale for clinical trials to determine whether reducing dietary phosphorus intake or waist circumference could prevent chronic kidney disease or slow its progression.

AB1057 Osteoporosis in calcium pyrophosphate deposition disease

ObjectivesTo study the frequency of osteoporosis (OP) in patients with calcium pyrophosphate deposition disease (CPPD).Methods85 pts with crystal-proven diagnosis of CPPD and chondrocalcinosis phenomena, confirmed either by conventional radiography (Rg)...

24-Hour Urine Phosphorus Excretion and Mortality and Cardiovascular Events

Higher morning serum phosphorus has been associated with cardiovascular disease (CVD) in patients with or without CKD. In patients with CKD and a phosphorous level >4.6 mg/dl, the Kidney Disease Improving Global Outcomes guidelines recommend dietary phosphorus restriction. However, whether phosphorus restriction influences serum phosphorus concentrations and whether dietary phosphorus is itself associated with CVD or death are uncertain. Among 880 patients with stable CVD and normal kidney function to moderate CKD, 24-hour urine phosphorus excretion (UPE) and serum phosphorus were measured at baseline. Participants were followed for a median of 7.4 years for CVD events and all-cause mortality. Mean ± SD age was 67±11 years, estimated GFR (eGFR) was 71±22 ml/min per 1.73 m(2), and serum phosphorus was 3.7±0.6 mg/dl. Median UPE was 632 (interquartile range, 439, 853) mg/d. In models adjusted for demographic characteristics and eGFR, UPE was weakly and nonsignificantly associated with serum phosphorus (0.03 mg/dl higher phosphorus per 300 mg higher UPE; P=0.07). When adjusted for demographics, eGFR, and CVD risk factors, each 300-mg higher UPE was associated with 17% lower risk of CVD events. The association of UPE with all-cause mortality was not statistically significant (hazard ratio, 0.93; 95% confidence interval, 0.82 to 1.05). Results were similar irrespective of CKD status (P interactions > 0.87). Among outpatients with stable CVD, the magnitude of the association of UPE with morning serum phosphorus is modest. Greater UPE is associated with lower risk for CVD events. The association was similar for all-cause mortality but was not statistically significant.

Evidence in Favor of a Severely Impaired Net Intestinal Calcium Absorption in Patients with (Early-Stage) Chronic Kidney Disease

Introduction: Calcium and phosphorus are essential to many vital physiological processes. Little is known about the net and fractional intestinal absorption of calcium and phosphorus in patients with chronic kidney disease (CKD) and their clinical and hormonal determinants. Methods: Blood and 24-hour urine samples were collected in 20 healthy volunteers (HV) and 72 stable CKD stage 1–4 patients and analyzed for parameters of mineral metabolism including calcidiol, calcitriol, and parathyroid hormone (PTH). Dietary intake was assessed by dietary history. Results: The 24-hour urinary calcium excretion, as opposed to the phosphorus excretion, showed a stepwise decrease across CKD stages (median of 219, 84, 40, and 22 mg/day in HV and patients with CKD stages 1–2, 3 and 4, respectively). Younger age, high serum calcitriol, and high estimated GFR were associated with a high 24-hour urinary calcium excretion. High serum calcitriol levels and dietary phosphorus intake were associated with a high 24-hour urinary phosphorus excretion. The fractional intestinal calcium absorption, as estimated by the urinary-to-ingested calcium ratio, decreased across CKD stages. Conclusions: The 24-hour urinary excretion of calcium, as opposed to phosphorus, is markedly decreased in CKD, even in early-stage disease. This is partly explained by low calcitriol levels and older age. Assuming a neutral calcium balance at the time of urine collection, we infer that net intestinal calcium absorption may be severely impaired in CKD.

Elevated Fibroblast Growth Factor 23 in a Patient With Metastatic Prostate Cancer and Hypophosphatemia

Elevated Fibroblast Growth Factor 23 in a Patient With Metastatic Prostate Cancer and Hypophosphatemia

Metabolic and Skeletal Effects of Low and High Doses of Calcium Acetate in Patients with Preterminal Chronic Renal Failure

Background: Secondary hyperparathyroidism commonly evolves, as the glomerular filtration rate falls. The metabolic and skeletal effects of a possible remedy, calcium acetate, have not been studied in patients with preterminal chronic renal failure. Methods: Men with a mean creatinine clearance of approximately 30 ml/min took calcium acetate for 24 weeks at doses which provided 507 or 1,521 mg calcium/day with meals. Metabolic determinations were made at intervals of 4–8 weeks, and the bone mineral density (BMD) was measured at the beginning and at the end of the trial. Results: The low-dose regimen produced no metabolic or skeletal effect. In subjects prescribed the high-dose regimen, the 24-hour urine phosphorus excretion fell from 0.53 mg/mg creatinine to values ranging from 0.34 to 0.41 mg/mg creatinine. The theoretical phosphorus threshold concentration rose by a maximum of 38.6%, and the serum phosphorus concentration did not change. The mean serum calcium concentration rose by a maximum of 7.2%. The mean fractional changes in parathyroid hormone and 1,25-dihydroxyvitamin D concentrations ranged from –27.0 to –39.6% and from –5.0 to –20.3%, respectively. The BMD increased at L1, L3, and L4. Conclusion: Calcium acetate prescribed to deliver 1,521 mg calcium/day with meals reduced parathyroid hormone and 1,25-dihydroxyvitamin D concentrations and increased lumbar BMD in men with preterminal chronic renal failure.

Serial changes in serum calcium and phosphorus concentration and in urinary phosphorus excretion after parathyroid surgery: further evidence for a dual effect of parathyroid hormone.

ABSTRACT. Determinations of serum calcium and phosphorus concentrations, 24-hour urinary phosphorus excretion, and phosphorus and creatinine clearances were performed serially before and following corrective surgery in 8 patients with primary hyperpara thyroidism. Similar studies were carried out in a euparathyroid patient following inadvertent total parathyroidectomy. Thus the effects of an acute change in both elevated and normal levels of endogenous parathyroid hormone could be studied. An immediate reduction in urinary phosphorus excretion and a return of the elevated serum calcium concentration to normal, without a concomitant elevation in the serum phosphorus level or a consistent alteration in the glomerular filtration rate, followed the removal of a functioning parathyroid adenoma in each hyperparathyroid patient. These changes, correlated with a similar sequence of events in the euparathyroid patient subjected to total parathyroidectomy, are unequivocal evidence for a direct phosphaturic action o...