Urinary angiotensin excretion during sodium restriction and diuretics

The urinary excretion rate and plasma concentration of angiotensin I (UAI, PAI) and angiotensin II (UAII, PAII), and plasma renin activity (PRA) were measured in seven healthy volunteers in the supine and upright position both on free and restricted sodium intakes. The same variables were measured before and after intravenous injection of furosemide, as well as before and during intravenous infusion of chlorothiazide. Assumption of the upright posture as well as sodium restriction increased PAI, PAII, and PRA, but UAI and UAII excretion were not altered by these manoeuvres. Furosemide injection resulted in increases of all variables, albeit that PAI and PAII were elevated to a lesser extent then PRA. Chlorothiazide infusion caused a reduction in PAI, PAII, and PRA, whereas UAI and UAII excretion increased modestly. The discrepancies between changes in plasma and urinary AI and AII may indicate that urinary angiotensin excretion provides information which is supplementary to that of plasma angiotensins.     

Urinary calcium and oxalate excretion in children

We have established normal values for calcium/creatinine (Ca/Cr) and oxalate/creatinine (Ox/Cr) ratios in 25 infants (aged 1–7 days) and 391 children (aged 1 month to 14.5 years) and compared these with values obtained in 137 children with post-glomerular haematuria and 27 with nephrolithiasis. Oxalate was measured by ion chromatography. Nomograms of Marshall and Robertson were used to calculate urine saturation to calcium oxalate. The Ca/Cr ratio was normally distributed whereas the Ox/Cr ratio had a log-normal distribution. The molar ratio of Ca/Cr was the lowest in the first days of life and the highest between 7 month and 1.5 years (mean±SD=0.39±0.28 mmol/mmol). Following a slight decrease it stabilised by the age of 6 years (0.34±0.19 mmol/mmol). The highest Ox/Cr values were measured during the 1st month of life [geometric mean 133 (range 61–280) mol/mmol], followed by a gradual decrease until 11 years of age [mean 24 (range 6–82) mol/mmol]. Thirty-six haematuric children had hypercalciuria (26%), 23 had absorptive hypercalciuria, 13 renal type. Children with absorptive hypercalciuria on a calcium-restricted diet had significantly higher oxalate excretion than those with renal hypercalciuria and the control group [38 (range 28–49) vs. 22 (range 16–29) and 23 (range 22–27) mol/mol respectively,P<0.01]. Calcium oxalate urine saturation of stone patients was higher than that of patients with haematuria and the normal population (1.18±0.05 vs. 1.06±0.03,P<0.03 and 0.84±0.03,P<0.001 respectively). The measurement of Ca/Cr and Ox/Cr in first-morning urine samples is suitable for screening for hypercalciuria and hyperoxaluria. Interpretation of the values requires age-specific reference values. Both calcium and oxalate determinations should be part of the evaluation of patients with haematuria, hypercalciuria or nephrolithiasis.     

Sodium excretion and hyperfiltration during glucose infusion in man

The relations between renal hemodynamics (Inutest, CPAH) and sodium excretion were studied in 7 nondiabetics in whom a similar expansion was induced (1) with a 3-hour 5% glucose infusion and (2) with a 0.9% saline load. With both infusions the body weight increased, hematocrit fell, and the plasma renin activity was suppressed. During glucose infusion, blood glucose rose from 3.9 mmol/l to a plateau of around 13 mmol/l; glycosuria was absent during the 1st h, then appeared and stabilized during the following 2h. Glucose infusion caused a progressive increase in glomerular filtration rate and in renal blood flow in both absence and presence of glycosuria, without significant changes in sodium excretion despite volume expansion and increase of filtered sodium load. When saline was infused, there was a sustained increase of fractional sodium excretion, and no hemodynamic modifications were observed. We suggest that a primary glucose-induced metabolic stimulation of sodium reabsorption may play a role in the genesis of glucose-induced hyperfiltration.     

Urinary oxalate and glycolate excretion in healthy infants and children

The molar ratios of oxalate and glycolate over creatinine were determined in single urine samples of 26 infants and 27 children aged 1–5 years. In 135 children aged 5–16 years, two urine specimens were collected, one before breakfast and one at noon. Oxalate was determined by oxalate oxidase, and glycolate was measured by a colorimetric method (improved chromatotropic acid-sulphuric acid assay after prior purification by cation and anion exchanger). Both ratios (expressed in mmol/mol creatinine and analysed on a log-normal basis) were highest in infants 0–6 months old [mean oxalate 147 (95% confidence interval: 60–360), mean glycolate 175 (72–425)]. The mean oxalate ratio was 72 mmol/mol (29–174) at the age of 7–24 months, 44 (19–101) at the age of 2–5 years and 22 (12–40) in adolescents aged 16 years. Molar glycolate ratios were higher, but disclosed the same pattern. Oxalate and glycolate ratios in fasting urines did not differ significantly from those in noon samples (except glycolate in the oldest age group). Oxalate ratios correlated well with glycolate ratios in children up to 5 years of age only. Random urine samples are thus suitable for screening. However, interpretation of data requires use of age-specific reference values that are based on comparable methods.     

Multiorgan crystal deposition following intravenous oxalate infusion in rat

Deposition of calcium oxalate is responsible for the pathologic manifestations of oxalosis and may contribute to multiorgan dysfunction in uremia and to the progression of renal damage after renal failure is established. We have developed a rat model of oxalosis using a single intravenous injection of sodium oxalate, 0.3 mmol./kg. body weight, in rats. Polarized light microscopy and section freeze-dry autoradiography were used to identify 14C-oxalate within the renal parenchyma and in extrarenal organs. 14C-oxalate crystals under three mu in length were identified within one min. of injection in proximal tubule lumens. Section freeze-dry autoradiography showed occasional minute crystals within glomeruli, heart, lung and liver at one hr. In contrast to concentrative cellular uptake demonstrated in rat renal cortical slices in vitro, intracellular accumulation of 14C-oxalate could not be detected in vivo. Within the first 24 hr., renal oxalate retention reached a maximum of 25 +/- 4 per cent of the injected dose/gm. kidney compared to a maximum of only 7 +/- 3 per cent/gm. kidney after intraperitoneal administration. Although less than one per cent dose/gm. kidney remained after one week, crystal fragments were scattered throughout the cortex and medulla, often surrounded by foci of interstitial nephritis. The retention of crystals in kidney and other body organs following i.v. oxalate provides a model of oxalosis which stimulates pathophysiologic events in a variety of clinical situations characterized by transiently or persistently elevated serum oxalate.     

Urinary excretion of urate in patients with calcium oxalate stone disease

Summary The diurnal variation in excretion and concentration of urinary urate was studied in 31 patients with calcium oxalate stone disease. Urate excretion was highest during the day-time, decreased in the evening and was low during the night. Meal-related peaks were observed. The concentration of urate reached the highest levels during the morning hours and, attributable to a low pH in morning urine, most samples were at this time super-saturated with respect to uric acid. In addition, many urines appeared to be at high risk of exceeding the uric acid formation product. Concerning the ion-activity product of sodium urate, supersaturated samples were frequently found, but the risk of exceeding the formation product for sodium urate at a normal urate excretion was apparently low.     

Urinary calcium excretion at extremes of sodium intake in normal man

To elucidate the relationship between the renal regulation of sodium and calcium excretion at extremes of sodium intake, we studied 6 normal men ingesting a fixed, 400 mg/day calcium intake and four levels of sodium intake from 10 to 1,500 mEq/day. Serum ionized calcium was not influenced by sodium intake. Blood pressure and cardiac index increased modestly. Urinary calcium excretion increased to 262 +/- 53 mg/day (mean +/- SE). Plasma norepinephrine concentration, serum PTH levels, hematocrit, total serum protein concentrations and CO2 content decreased with increasing sodium intake. Urinary cAMP increased as sodium intake was raised from 10 to 300 mEq/day, but subsequently decreased to basal values. Urinary calcium and sodium excretion were related (p less than 0.001) in a nonlinear fashion as were the fractional excretions of these cations (p less than 0.001). The filtered calcium load and the fractional calcium excretion were directly and linearly related (p less than 0.001). We conclude that the effect of sodium intake on urinary calcium excretion principally reflects changes in the filtered calcium load rather than changes in renal sodium handling. Calcium homeostasis at extremes of sodium intake does not appear to be critically dependent upon PTH-mediated mechanisms. The data suggest that the proximal tubule has a remarkable capacity to dissociate calcium resorption from that of sodium.     

Urinary oxalate excretion in female calcium oxalate stone formers with and without a history of recurrent urinary tract infections

Therapy with antibiotics in recurrent urinary tract infections may destroy colonies of Oxalobacter formigenes in the intestinal tract. A lack of oxalate degradation caused by the absence of this bacterium is suggested to contribute to the hyperabsorption of dietary oxalate and to the increase in urinary oxalate excretion. The present study was performed to evaluate the effect of recurrent urinary tract infections and subsequent changes induced in the urinary excretion profile in female calcium oxalate stone formers. Serum biochemical profiles, 24-h urinary parameters, and the personal characteristics of 57 female calcium oxalate stone patients with recurrent urinary tract infections (RUTI) were compared with 78 female calcium oxalate stone patients without a history of urinary tract infection. All subjects were recruited during the same period. In female patients with RUTI, urinary oxalate excretion was significantly higher (0.374 mmol/day) than in females without urinary tract infection (0.308 mmol/day) (P < 0.05). Moreover, the mean 24-h pH value and urinary sodium excretion were significantly higher in women with RUTI than in women without a history of urinary tract infection. The significantly higher urinary oxalate excretion in female calcium oxalate stone formers with recurrent urinary tract infections may be associated with the application of antibiotics and a subsequent temporary or permanent decolonization of Oxalobacter formigenes.     

Urinary excretion of minerals, oxalate, and uric acid in north Indian children

Urinary excretion of calcium, magnesium, phosphate, uric acid, oxalate, and creatinine was measured in 208 children (aged 8 – 15 years, 124 boys, 84 girls), living in a residential school near New Delhi. Levels were reduced compared with those reported from developed countries. The 95th percentile value of 24-h creatinine excretion was 33.4 mg/kg, calcium 2.2 mg/kg, magnesium 2.9 mg/kg, phosphate 9.4 mg/kg, uric acid 4.4 mg/kg, and oxalate 1.5 mg/kg. The 95th percentile value of the urine calcium/creatinine ratio was 0.15 and oxalate/creatinine 0.06. The dietary intake of proteins, calcium, and other nutrients in these children was less than recommended and explained the reduced urinary excretion observed. Physicians need to be aware of the regional patterns of normal urinary excretion of these constituents. Received November 30, 1995; received in revised form and accepted October 24, 1996     

Urinary albumin excretion rate during angiotensin II infusion in microalbuminuric patients with insulin and non-insulin-dependent diabetes mellitus

As angiotensin-converting enzyme inhibition is accompanied by a marked decrease in glomerular protein loss, the hypothesis was tested that an increase of the glomerular transcapillary hydraulic pressure difference by exogenous angiotensin II would increase microalbuminuria in patients with insulin (IDDM) and non-insulin-dependent diabetes mellitus (NIDDM). Acute effects of increasing doses of angiotensin II (1, 3 and 6 ng/kg/min) were studied on mean arterial pressure (MAP), glomerular filtration rate (GFR); effective renal plasma flow (ERPF), filtration fraction (FF), total renal vascuclar resistance (TRVR), and urinary albumin excretion rate (UAER) in 11 IDDM and 11 NIDDM microalbuminuric patients. Angiotensin II infusion changed MAP from 100±3 mmHg at baseline to 105±3, 111±3, and 116±3 mmHg (P <0.001), ERPF from 542±29 to 478±24, 429±23, and 382±19 ml/min (P <0.001), FF from 20.2±0.06 to 23.1±0.07, 27.1±1.1, and 29.8±1.2% (P <0.001), and TRVR from 9454±809 to 11 158±930, 13 310±1206, and 15 538±1362 dyne s cm^-5 (P <0.001). GFR and UAER, however, did not change significantly. Therefore, during angiotensin II infusion ERPF decreased, while FF and TRVR increased. As UAER and GFR remained unchanged, the presumed rise in intraglomerular capillary pressure by exogenous angiotensin II did not increase UAER. We suggest that during manipulation of the renin-angiotensin system, as in other renal diseases with proteinuria, factors other than glomerular transcapillary hydraulic pressure determine the degree of urinary albumin loss in microalbuminuric IDDM and NIDDM patients.     

Urinary phytate in calcium oxalate stone formers and healthy people--dietary effects on phytate excretion

The phytate urinary levels in a group of active calcium oxalate stone formers were studied and compared with those found in healthy people. Urinary phytate was significantly lower for stone formers. If deficit of the capacity to inhibit crystallization of calcium salts is considered an important factor related to calcium stone formation, the excretion of low phytate amounts could be an important risk factor in the development of this type of renal calculi. The influence of dietary phytate on urinary excretion was also studied. Clearly maintenance of a phytate-free diet significantly decreased the urinary excretion of phytate (about 50% after 36 h). This demonstrated the importance of dietary phytate in maintaining adequate urinary levels to permit effective crystallization inhibition of calcium salts and consequently preventing renal stone development.     

Urinary oxalic acid excretion differs after oral loading of rats with various oxalate salts

BACKGROUND: To compare urinary oxalate excretion after the oral administration of oxalic acid, disodium oxalate, or calcium oxalate in rats. METHODS: Male Wistar rats were divided into four groups of six rats each and were intravenously hydrated with normal saline, and then were administered normal saline (control group), 10 mg of oxalic acid, equimolar disodium oxalate, or equimolar calcium oxalate via a gastrostomy. Urine specimens were collected just before administration and at hourly intervals up to 5 h afterwards. The urinary oxalate, calcium, magnesium and phosphorus levels were measured. RESULTS: Urinary oxalate excretion peaked at 1-2 h after administration of oxalic acid or equimolar disodium oxalate, while administration of calcium oxalate only caused a small increase of urinary oxalate excretion. Cumulative urinary oxalate excretion during 5 h was 1.69 +/- 0.10 mg (mean +/- SD; 17%), 1.43 +/- 0.13 mg (13%), and 0.22 +/- 0.03 mg (2%) after the administration of oxalic acid, disodium oxalate, and calcium oxalate, respectively. Urinary calcium excretion showed a decrease in the oxalic acid and disodium oxalate groups, while urinary magnesium or phosphorus excretion did not change significantly. CONCLUSION: The upper gastrointestinal tract seems to be the major site of oxalic acid absorption and only free oxalate is absorbed irrespective of whether it is the sodium salt or not. After binding to calcium in the gut, oxalic acid absorption seems to be inhibited in the presence of calcium and this means that calcium oxalate is poorly absorbed (at least in the upper gastrointestinal tract).