Urinary Solute Excretion Research Articles

Normonatremic Transient Renal Salt Wasting (TRSW) Is Not Rare in a Department of Internal Medicine.

We previously reported that for around 5% of patients hospitalized with hyponatremia, it was related to what is called "transient renal salt wasting" (TRSW). In the present study we ask whether TRSW can also be observed in patients without hyponatremia. In this observational retrospective study we analyze the urine solute excretion of 200 consecutive normonatremic patients with normal kidney function and admitted in our department over one year. Patients were selected for analyses of FE.K, UCa/UCr and FE.PO4 if FE.Na was higher than 2% (N < 1.6%) before any treatment, and only if they were not taking diuretics. Eleven normonatremic patients presented with transient high FE.Na > 2% on admission (2.9 ± 0.6% with a high FE.K of 28 ± 6.4%; a high UCa/UCr of 0.37 ± 0.13 and a high FE.PO4 of 23.2 ± 9.6%). All of these patients were elderly. Seven were female and four were male. Neurological disorders were observed in six patients (three strokes, one transient ischemic attack, one syncope and one epileptic attack). Heart problems were observed in three patients (all angina pectoris, two of which also had HBP). One patient presented with rectal bleeding with HBP, and another presented COPD with a pneumothorax. One patient with angina pectoris showed a transient relapse after four days of hospitalization (FE.Na 3.6%). The urine electrolyte excretion in these patients are similar to those observed after furosemide intake. Normonatremic TRSW is not a rare observation, particularly in patients with neurological or cardiac problems.

Evaluation of nocturnal blood pressure changes and urinary electrolyte excretion in children with enuresis.

Monosymptomatic nocturnal enuresis (MNE) is defined as involuntary nighttime urination of children over five years of age without any congenital or acquired defect in the central nervous system. Many factors, mainly nocturnal polyuria, sleep disorders, decreased bladder capacity, and bladder dysfunctions play a role in the etiology of MNE. Eighty-three children diagnosed with MNE were included in the study. Complete blood cell count, blood biochemistry, renin, and aldosterone levels of all children were obtained. Twenty-four-hour urine samples were collected separately daytime and nighttime and urinary electrolytes were evaluated. Also, 24-hour ambulatory blood pressure monitoring (ABPM) was performed for each patient. The results were evaluated by comparing both enuretic children vs. control group and enuretic children with polyuria vs. without polyuria. When we compared the enuretic children and the control group in terms of urinary electrolytes, the fractional excretion of sodium (FENa) and fractional excretion of potassium (FEK) values of the enuretic group were higher than the control. The evaluation of the 24-hour ABPM findings revealed no significant difference in terms of the mean arterial pressure (MAP) and diastolic blood pressure (DBP) during the daytime and nighttime measurements. The daytime systolic blood pressure (SBP), however, was significantly lower in the enuretic group. When enuretic children with and without polyuria and the control group were compared, the nighttime, FENa, FEK, as well as nighttime urinary excretion of calcium and protein were significantly higher in enuretic children with polyuria. No difference was detected on the MAP, SBP, or DBP values. In conclusion, the nighttime urinary solute excretion of enuretic children was found to be higher and this condition may especially be associated with pathogenesis of nighttime polyuria. In enuretic children, nighttime blood pressure changes were not influential in the etiopathogenesis in all patient groups and multiple mechanisms may play a role in the pathogenesis of enuresis.

Renal lithiasis in pediatric patients: correlation of methods that depend on 24-h collections with simpler methods that do not require timed urine

IntroductionDaily practice requires quick, simple and accessible methods to appropriately assess the urinary excretion of solutes in diagnostic or follow-up evaluations of children with renal lithiasis. ObjectivesThe objective of this study was to correlate urine elimination of substances related to renal lithiasis that depend on the volume of excreted urine in a unit of time with other parameters that are calculated by measuring the concentration of these substances in blood and urine, such as urinary ratios, fractional excretions and excretion rates. Materials and methodsThe study included 401 healthy children aged 3–14 years (187 boys and 214 girls), mean age 8,78 ± 3,40 years. The analysis was carried out by Pearson’s correlation coefficient. ResultsThere was significant correlation between the elimination of sodium, potassium and chlorine in 24-h urine sample and the urinary ratios and fractional excretions of these ions.Urinary ratios and rates of excretion of calcium, uric acid, phosphate, magnesium, citrate and oxalate were highly correlated with the determinations of these substances in 24-h collections. ConclusionsThese equations provide relevant information for the study of the etiology of renal lithiasis in children, as well as about compliance to dietary treatment. They also assess the effectiveness of the various treatments used in these patients, without having to resort to 24-h collections, which pose a considerable challenge in the pediatric age group.

Litiasis en pediatría: correlación de métodos que dependen de la recogida de orina de 24 horas con otros más sencillos que no requieren orina minutada

IntroductionDaily practice requires quick, simple and accessible methods to appropriately assess the urinary excretion of solutes in diagnostic or follow-up evaluations of children with renal lithiasis. ObjectivesThe objective of this study was to correlate urine elimination of substances related to renal lithiasis that depend on the volume of excreted urine in a unit of time with other parameters that are calculated by measuring the concentration of these substances in blood and urine, such as urinary ratios, fractional excretions and excretion rates. Materials and methodsThe study included 401 healthy children aged 3-14 years (187 boys and 214 girls), mean age 8.78±3.40 years. The analysis was carried out by Pearson's correlation coefficient. ResultsThere was significant correlation between the elimination of sodium, potassium and chlorine in 24-hour urine sample and the urinary ratios and fractional excretions of these ions.Urinary ratios and rates of excretion of calcium, uric acid, phosphate, magnesium, citrate and oxalate were highly correlated with the determinations of these substances in 24-hour collections. ConclusionsThese equations provide relevant information for the study of the etiology of renal lithiasis in children, as well as about compliance to dietary treatment. They also assess the effectiveness of the various treatments used in these patients, without having to resort to 24-hour collections, which pose a considerable challenge in the pediatric age group.

Sex differences in solute transport along the nephrons: effects of Na+ transport inhibition.

Each day, ~1.7 kg of NaCl and 180 liters of water are reabsorbed by nephron segments in humans, with urinary excretion fine tuned to meet homeostatic requirements. These tasks are coordinated by a spectrum of renal Na+ transporters and channels. The goal of the present study was to investigate the extent to which inhibitors of transepithelial Na+ transport (TNa) along the nephron alter urinary solute excretion and how those effects may vary between male and female subjects. To accomplish that goal, we developed sex-specific multinephron models that represent detailed transcellular and paracellular transport processes along the nephrons of male and female rat kidneys. We simulated inhibition of Na+/H+ exchanger 3 (NHE3), bumetanide-sensitive Na+-K+-2Cl- cotransporter (NKCC2), Na+-Cl- cotransporter (NCC), and amiloride-sensitive epithelial Na+ channel (ENaC). NHE3 inhibition simulations predicted a substantially reduced proximal tubule TNa, and NKCC2 inhibition substantially reduced thick ascending limb TNa. Both gave rise to diuresis, natriuresis, and kaliuresis, with those effects stronger in female rats. While NCC inhibition was predicted to have only minor impact on renal TNa, it nonetheless had a notable effect of enhancing excretion of Na+, K+, and Cl-, particularly in female rats. Inhibition of ENaC was predicted to have opposite effects on the excretion of Na+ (increased) and K+ (decreased) and to have only a minor impact on whole kidney TNa. Unlike inhibition of other transporters, ENaC inhibition induced stronger natriuresis and diuresis in male rats than female rats. Overall, model predictions agreed well with measured changes in Na+ and K+ excretion in response to diuretics and Na+ transporter mutations.

Mediterranean diet adherence and risk of incident kidney stones

Diet plays an important role in kidney stone formation. Several individual components have been associated with the risk of kidney stone formation, but there is limited evidence regarding the role of healthful dietary patterns. To prospectively study the association between adherence to the Mediterranean diet and the risk of incident kidney stones. We conducted a longitudinal study using 3 different cohorts: the Health Professionals Follow-up Study (n=42,902 men), the Nurses' Health Study I (n=59,994 women), and the Nurses' Health Study II (n=90,631 women). We assessed diet every 4 y using an FFQ and calculated adherence to a Mediterranean diet using the alternate Mediterranean diet score (aMED). A subgroup of 6077 participants provided ≥1 24-h urine sample, and urinary solute excretion was analyzed. We used Cox proportional hazards regression to examine the independent association between the aMED and incidence of kidney stones, adjusting for potential confounders. We used adjusted linear regression models to study the relation between aMED and urine composition. During 3,316,633 person-years of follow-up, 6576 cases of incident kidney stones were identified. For participants in the highest aMED score category, the risk of developing a kidney stone was between 13% and 41% lower compared with participants in the lowest score (pooled HR: 0.72, 95% CI: 0.59, 0.87; P value for trend<0.001). A higher aMED score was associated with higher urinary citrate, magnesium, oxalate, phosphate, uric acid, volume, and pH, and lower urinary sodium, resulting in lower supersaturation for calcium oxalate, calcium phosphate, and uric acid. Adherence to a Mediterranean diet is associated with a lower risk of developing a kidney stone.

Diffusion modelling of percutaneous absorption kinetics. Predicting urinary excretion from in vitro skin permeation tests (IVPT) for an infinite dose

In this work, we developed a number of generalised skin diffusion based pharmacokinetic models to relate published in vivo urinary excretion data to matching experimentally generated in vitro human skin permeation test (IVPT) data for a series of topically applied salicylate esters. A simplified linear in vivo model was found to inadequately describe the time course of urinary excretion over the entire sampling period. We represented the skin barrier as both a one layer (stratum corneum) and a two-layer (stratum corneum with viable epidermis) diffusion model and convoluted their Laplace solutions with that for a single exponential disposition phase to describe the urinary excretion profiles in the Laplace domain. We also derived asymptotic approximations for the model and estimated the conditions under which they could be used. We then sought to develop in vitro - in vivo relationships (IVIVR) for topically applied methyl, ethyl and glycol salicylates using our experimental IVPT data and the literature urinary excretion data. Good linear IVIVRs for ethyl and glycol salicylates were obtained, but the IVIVR for methyl salicylate was poor, perhaps because of topical stimulation of local skin blood flow by methyl salicylate. The ratio of the hydrated to dehydrated skin permeation for all salicylate esters was the same in both the IVPT and in vivo studies. A diffusion based one compartment pharmacokinetic model was also developed to describe the urinary excretion of solutes after removal of topical products and to compare the methyl salicylate skin permeation for five different body sites. The work presented here is consistent with the development of skin IVIVRs, but suggests that different skin conditions, application sites and local skin effects may affect model predictions.

A computational model of epithelial solute and water transport along a human nephron.

We have developed the first computational model of solute and water transport from Bowman space to the papillary tip of the nephron of a human kidney. The nephron is represented as a tubule lined by a layer of epithelial cells, with apical and basolateral transporters that vary according to cell type. The model is formulated for steady state, and consists of a large system of coupled ordinary differential equations and algebraic equations. Model solution describes luminal fluid flow, hydrostatic pressure, luminal fluid solute concentrations, cytosolic solute concentrations, epithelial membrane potential, and transcellular and paracellular fluxes. We found that if we assume that the transporter density and permeabilities are taken to be the same between the human and rat nephrons (with the exception of a glucose transporter along the proximal tubule and the H+-pump along the collecting duct), the model yields segmental deliveries and urinary excretion of volume and key solutes that are consistent with human data. The model predicted that the human nephron exhibits glomerulotubular balance, such that proximal tubular Na+ reabsorption varies proportionally to the single-nephron glomerular filtration rate. To simulate the action of a novel diabetic treatment, we inhibited the Na+-glucose cotransporter 2 (SGLT2) along the proximal convoluted tubule. Simulation results predicted that the segment’s Na+ reabsorption decreased significantly, resulting in natriuresis and osmotic diuresis.

Solute transport and oxygen consumption along the nephrons: effects of Na+ transport inhibitors.

Sodium and its associated anions are the major determinant of extracellular fluid volume, and the reabsorption of Na+ by the kidney plays a crucial role in long-term blood pressure control. The goal of this study was to investigate the extent to which inhibitors of transepithelial Na+ transport (TNa) along the nephron alter urinary solute excretion and TNa efficiency and how those effects may vary along different nephron segments. To accomplish that goal, we used the multinephron model developed in the companion study (28). That model represents detailed transcellular and paracellular transport processes along the nephrons of a rat kidney. We simulated the inhibition of the Na+/H+ exchanger (NHE3), the bumetanide-sensitive Na+-K+-2Cl- transporter (NKCC2), the Na+-Cl- cotransporter (NCC), and the amiloride-sensitive Na+ channel (ENaC). Under baseline conditions, NHE3, NKCC2, NCC, and ENaC reabsorb 36, 22, 4, and 7%, respectively, of filtered Na+ The model predicted that inhibition of NHE3 substantially reduced proximal tubule TNa and oxygen consumption (QO2 ). Whole-kidney TNa efficiency, as reflected by the number of moles of Na+ reabsorbed per moles of O2 consumed (denoted by the ratio TNa/QO2 ), decreased by ∼20% with 80% inhibition of NHE3. NKCC2 inhibition simulations predicted a substantial reduction in thick ascending limb TNa and QO2 ; however, the effect on whole-kidney TNa/QO2 was minor. Tubular K+ transport was also substantially impaired, resulting in elevated urinary K+ excretion. The most notable effect of NCC inhibition was to increase the excretion of Na+, K+, and Cl-; its impact on whole-kidney TNa and its efficiency was minor. Inhibition of ENaC was predicted to have opposite effects on the excretion of Na+ (increased) and K+ (decreased) and to have only a minor impact on whole-kidney TNa and TNa/QO2 Overall, model predictions agree well with measured changes in Na+ and K+ excretion in response to diuretics and Na+ transporter mutations.

Short-Term Tolvaptan Increases Water Intake and Effectively Decreases Urinary Calcium Oxalate, Calcium Phosphate and Uric Acid Supersaturations

Some patients cannot effectively increase water intake and urine volume to prevent urinary stones. Tolvaptan, a V2 receptor antagonist, blocks water reabsorption in the collecting duct and should decrease urinary supersaturation of stone forming solutes, although this action has never been proved. We conducted a double-blind, randomized, placebo controlled, crossover study of 21 calcium urinary stone formers stratified into majority calcium oxalate (10 patients) and calcium phosphate (11) groups. Patients received 45 mg tolvaptan per day or placebo for 1 week, followed by a washout week and crossover to tolvaptan or placebo for week 3. A 24-hour urine sample was collected at the end of weeks 1 and 3. Tolvaptan vs placebo decreased urinary osmolality (mean ± SD 204 ± 96 vs 529 ± 213 mOsm/kg, p <0.001) and increased urinary volume (4.8 ± 2.9 vs 1.8 ± 0.9 L, p <0.001). The majority of urinary solute excretion rates, including sodium and calcium, did not change significantly, although oxalate secretion increased slightly (from mean ± SD 15 ± 8 to 23 ± 8 mg per 24 hours, p = 0.009). Mean ± SD urinary calcium oxalate supersaturation (-0.01 ± 1.14 vs 0.95 ± 0.87 dG, p <0.001), calcium phosphate supersaturation (-1.66 ± 1.17 vs -0.13 ± 1.02 dG, p <0.001) and uric acid supersaturation (-2.05 ± 4.05 vs -5.24 ± 3.12 dG, p=0.04) all dramatically decreased. Effects did not differ between the calcium oxalate and calcium phosphate groups (p >0.05 for all interactions). Tolvaptan increases urine volume and decreases urinary supersaturation in calcium stone formers. Further study is needed to determine if long-term use of V2 receptor antagonists results in fewer stone events.

The kidney and uremic toxin removal: glomerulus or tubule?

Chronic kidney disease (CKD) is a condition that affects approximately 10% of the adult population in developed countries. In patients with CKD adequate renal clearance is compromised, resulting in the accumulation of a plethora of uremic solutes. These uremic retention solutes, also known as uremic toxins, are a heterogeneous group of organic compounds, many are too large to be filtered (middle molecules) or are protein-bound. Tubular secretion shifts the binding and allows for active secretion of such solutes. To mediate urinary solute excretion, renal proximal tubules are equipped with a range of transporters that cooperate in basolateral uptake and luminal excretion. These putative uremic toxins are poorly filtered across dialysis membranes because they are protein bound and current dialysis therapy does not correct the full spectrum of uremic toxicity. Residual renal function, which may represent an important contribution of solutes secreted by the proximal tubule rather than unreabsorbed filtrate, is an important predictor of survival of CKD patients. Many of the transporters that mediate the renal excretion of uremic retention solutes were first recognized as mediators of drug trafficking and drug-drug interactions, and a considerable amount of literature concerning the actions of these transporters antedates the recognition of their importance in the proximal renal tubular transport of uremic retention solutes. These transporters include members belonging to the organic cation/anion/zwitterion solute carrier family, such as the organic anion transporters (OAT)1, OAT3, and OATP4C1, and to the adenosine triphosphate binding cassette superfamily of transmembrane transporters, including the multidrug resistance proteins and breast cancer resistance protein. This article draws on this body of information to describe the renal tubular clearance mechanisms for uremic toxins, as well as the intracellular events associated with their accumulation, involving activation of the aryl hydrocarbon receptor, disturbance of mitochondrial functioning, and competition with metabolizing enzymes.

The Changing Epidemiology of Urolithiasis in Pediatric Patients

The etiology of kidney stones is divided in three broad categories: (i) Metabolic abnormalities that lead to excessive urinary excretion of solutes those are susceptible to crystallization or reduced excretion of inhibitors of crystallization (ii) Anatomic defects that cause disturbances in voiding or urinary stasis (iii) Idiopathic. The laboratory assessment has focused on 24-hour urine collections to measure excretion of calcium, oxalate, citrate, cystine, uric acid, magnesium, and creatinine, selective blood tests, and imaging studies to determine renal structure and function. This article reviews recent data suggesting that the incidence of kidney stones is rising in children and adolescents.

Effect of nebivolol, a novel beta 1-selective adrenoceptor antagonist with vasodilating properties, on kidney function.

Nebivolol (CAS 99200-09-6) is a novel beta 1-selective adrenoceptor antagonist which possesses vasodilating properties and lowers systemic vascular resistance in dogs and humans, presumably by a nitric oxide-related mechanism. In the present study, clearance techniques were applied to anaesthetized male Sprague Dawley rats, and the effects of nebivolol on renal hemodynamics (glomerular filtration rate and renal plasma flow), on urinary excretion of sodium, chloride and potassium, on renal NO-excretion, and on plasma renin activity were studied. Nebivolol doses ranging from 0.1 to 2 mg/kg i.v. were tested. The results revealed that nebivolol dose-dependently increased glomerular filtration rate, urine flow and urinary excretion of sodium and chloride. Potassium excretion was only inconsistently increased and showed no dose dependency. At a dose of 1 mg/kg, the drug also significantly increased renal plasma flow measured as 3H-PAH (p-aminohippurate) clearance. The effect of nebivolol on the glomerular filtration rate could be abolished by L-NMMA (N6-monomethyl-L-arginine) (1 mg/kg), a non-selective inhibitor of NO-synthase and by iminoethyllysine (1 mg/kg), a relatively selective inhibitor of the inducible NO-synthase, but not by 7-nitroindazole (1 mg/kg), a relatively selective inhibitor of the neuronal NO-synthase isoform. The saluretic effect of nebivolol was diminished by all of the three NO-synthase inhibitors, but could not be completely reversed. At a dose of 2 mg/kg, nebivolol increased renal NO-excretion by 70.7%. This effect could be completely abolished by L-NMMA (1 mg/kg). Plasma renin activity was lowered by nebivolol (2 mg/kg) from 14.6 +/- 1.49 to 6.5 +/- 1.66 ng angiotensin I/ml/h (p < 0.01). The results demonstrate that, in anaesthetized rats, nebivolol exerts significant renal vasodilating effects and increases urinary excretion of fluid and solutes. The actions of nebivolol on renal hemodynamics are assumed to be mediated by a stimulation of the NO-synthase, probably the inducible isoform. Since none of the NO-synthase inhibitors could completely abolish the saluretic effect of nebivolol, an additional mechanism, not related to NO, may be involved in the tubular action of this drug.

Diagnostic Value of Urinary Sodium, Chloride, Urea, and Flow

Up to 30% of hospitalized critically ill patients may have a rise in serum creatinine concentration. In addition to history and physical examination, there is diagnostic value in assessing urinary electrolytes, solute excretion, and urine flow in these patients. The correct interpretation of these urinary parameters can avoid unnecessary volume overload and mechanical ventilation, risk factors for increased mortality in patients with rising serum creatinine. The present article also discusses the role of arterial underfilling in causing prerenal azotemia in the presence of an increase in total body sodium and extracellular fluid expansion. As with extracellular fluid volume depletion, arterial underfilling secondary to impaired cardiac function or primary arterial vasodilation can delay or prevent recovery from ischemic or toxic acute tubular necrosis. The present brief review discusses the various aspects of the correct interpretation of urinary electrolytes, solute excretion, and urine flow in the setting of a rising serum creatinine concentration.

Update on nephrolithiasis: beyond symptomatic urinary tract obstruction

Nephrolithiasis research and care have been focused on biochemical changes in urinary solute excretion leading to stone formation, but abnormalities in urine chemistry alone do not explain many aspects of the condition of patients with kidney stone disease. Evidence exists of an association with metabolic syndrome, obesity, diabetes and hypertension, and of enhanced risk of chronic kidney disease and metabolic bone disease. Very recently also a higher risk of cardiovascular events and damage has been reported in kidney stone formers when compared with non-stone formers. It is time to view nephrolithiasis as a condition predictive of chronic kidney disease and cardiovascular damage, which deserves full metabolic evaluation together with an early prevention care strategy, mainly consisting of dietary and lifestyle changes, in a multidisciplinary approach. Kidney stone disease should be considered as a systemic disorder with clinical relevance beyond symptomatic urinary tract obstruction.

Carnitine Deficiency and Oxidative Stress Provoke Cardiotoxicity in an Ifosfamide‐Induced Fanconi Syndrome Rat Model

In addition to hemorrhagic cystitis, Fanconi Syndrome is a serious clinical side effect during ifosfamide (IFO) therapy. Fanconi syndrome is a generalized dysfunction of the proximal tubule which is characterized by excessive urinary excretion of glucose, phosphate, bicarbonate, amino acids and other solutes excreted by this segment of the nephron including L-carnitine. Carnitine is essential cofactor for β-oxidation of long-chain fatty acids in the myocardium. IFO therapy is associated with increased urinary carnitine excretion with subsequent secondary deficiency of the molecule. Cardiac abnormalities in IFO-treated cancer patients were reported as isolated clinical cases. This study examined whether carnitine deficiency and oxidative stress, secondary to Fanconi Syndrome, provoke IFO-induced cardiomyopathy as well as exploring if carnitine supplementation using Propionyl-L-carnitine (PLC) could offer protection against this toxicity. In the current study, an animal model of carnitine deficiency was developed in rats by D-carnitine-mildronate treatment Adult male Wistar albino rats were assigned to one of six treatment groups: the first three groups were injected intraperitoneally with normal saline, D-carnitine (DC, 250 mg/kg/day) combined with mildronate (MD, 200 mg/kg/day) and PLC (250 mg/kg/day), respectively, for 10 successive days. The 4th, 5th and 6th groups were injected with the same doses of normal saline, DC-MD and PLC, respectively for 5 successive days before and 5 days concomitant with IFO (50 mg/kg/day). IFO significantly increased serum creatinine, blood urea nitrogen (BUN), urinary carnitine excretion and clearance, creatine phosphokinase isoenzyme (CK-MB), lactate dehydrogenase (LDH), intramitochondrial acetyl-CoA/CoA-SH and thiobarbituric acid reactive substances (TBARS) in cardiac tissues and significantly decreased adenosine triphosphate (ATP) and total carnitine and reduced glutathione (GSH) content in cardiac tissues. In carnitine-depleted rats, IFO induced dramatic increase in serum creatinine, BUN, CK-MB, LDH, carnitine clearance and intramitochondrial acetyl-CoA/CoA-SH, as well as progressive reduction in total carnitine and ATP in cardiac tissues. Interestingly, PLC supplementation completely reversed the biochemical changes-induced by IFO to the control values. In conclusion, data from the present study suggest that: Carnitine deficiency and oxidative stress, secondary to Fanconi Syndrome, constitute risk factors and should be viewed as mechanisms during development of IFO-induced cardiotoxicity. Carnitine supplementation, using PLC, prevents the development of IFO-induced cardiotoxicity through antioxidant signalling and improving mitochondrial function.

Spot Urine Osmolality/Creatinine Ratio in Healthy Humans

Background: Spot urine albumin/creatinine ratio is a reliable estimate of 24-hour urine albumin excretion. In a pilot study, we observed that the spot urine osmolality/creatinine ratio (U_osm/U_cr) in healthy adults is reproducible. Therefore, we postulated that U_osm/U_cr of a spot urine sample may give an overall estimate of urinary excretion of solutes, renal concentrating ability and body hydration status. Method: Early morning spot urine samples were collected from healthy humans, frozen and analyzed in batches to establish spot U_osm/U_cr and its variation in relation to sex, age, body weight and height. Results: Two hundred and twenty-nine healthy volunteers participated. They were stratified into seven age groups: (a) 1.5–5, (b) >5–10, (c) >10–20, (d) >20–30, (e) >30–45, (f) >45–60, and (g) >60 years. Fifteen males and 15 females were allocated to each age category. A spot urine sample was collected from all subjects in the morning after the first void and was analyzed for osmolality and creatinine. The influence of age, sex, body weight and height on spot U_osm/U_cr was investigated using multiple linear regression. Only height showed a significant correlation (R² = 0.02). Further analysis after excluding the 1.5–5 years age group revealed no significant correlation between age, sex, body weight and height and the U_osm/U_cr ratio. Conclusion: Spot U_osm/ U_cr of healthy humans is a consistent index in steady state and needs no correction for sex, age and body weight above the age of 5 years.

Twenty-four-hour profiles of urinary excretion of calcium, magnesium, phosphorus, urea, and creatinine in healthy prepubertal boys

Objectives Available data on 24-h urinary solute excretion in healthy children are sparse. We thus documented the daily and overnight variations of urinary electrolytes (calcium, magnesium, and phosphorus), urea, and creatinine in prepubertal (Tanner stage I) boys. Design and methods Nine voluntary healthy prepubertal boys aged 10.8 ± 0.11 years participated in this study. Concentrations of variables were quantified in daytime samples (collected between 07:00 h ± 30 min and 21:00 h ± 30 min) and nighttime samples (collected between 21:00 h ± 30 min and 07:00 h ± 30 min) in spring, during a period of 24-h every 3 h. Results Significant differences were found between daytime and nighttime excretion of calcium ( p < 0.05), magnesium ( p < 0.001), phosphorus ( p < 0.01), and urea ( p < 0.05), with high concentrations during the night. The 24-h solute/creatinine ratio was 0.072 ± 0.008 mg/mg for calcium, 0.069 ± 0.008 mg/mg for magnesium, 0.698 ± 0.070 mg/mg for phosphorus, and 0.017 ± 0.001 g/mg for urea. Statistically significant correlation analyses showed that urea and creatinine were positively associated with body mass index (BMI) ( R = 0.790, p = 0.0113 for urea; R = 0.889, p = <0.0013 for creatinine) and weight ( R = 0.717, p = 0.0297 for urea; R = 0.978, p = < 0.001 for creatinine). The other urinary variables were independent of BMI and body mass. Conclusion These data are of interest for the diagnosis of certain renal disease in prepubertal children.

Increased acid excretion in kidney stone formers with essential hypertension

Although several studies have reported that kidney stone disease and hypertension are associated, the link between the two conditions has not been identified. This study investigated urinary excretion of different solutes, particularly citrate and acids, in kidney stone formers and examined their association with high blood pressure. The retrospective study included 234 consecutive subjects, aged 47.0 +/- 15.6, attending our metabolic clinic after episodes of kidney stones. Essential hypertension was present in 82 patients (35.0%). A difference in the urinary excretion of some of the investigated components was found between subjects with normal blood pressure and those with hypertension. The results showed that hypertensive subjects were older and had a higher body mass index (BMI) and serum uric acid. They had a significantly lower urinary pH (5.6 +/- 0.4 versus 6.0 +/- 0.5) and citrate (2.55 +/- 1.36 versus 2.83 +/- 1.65 mmol/24 h), higher titratable acid (38.8 +/- 19.0 versus 26.8 +/- 15.0 mEq/24 h) and ammonium (41.6 +/- 17.6 versus 34.2 +/-12.4 mmol/24 h). Logistic regression analysis with the presence of hypertension as the dependent variable produced a model with the following predictors: age (P < 0.0001), BMI (P = 0.026), titratable acid (P = 0.025) and low urinary citrate level (P = 0.033). Urinary acid excretion increased with the stage of hypertension. No difference was found in the urinary excretion of other solutes. These findings suggest that essential hypertension and acid excretion are linked in stone formers.

Urinary aquaporin-2 in children with acute pyelonephritis

Children with acute pyelonephritis develop polyuria and have reduced maximum urinary concentration capacity. We studied whether these abnormalities are associated with altered urinary excretion of the water channel aquaporin-2 (AQP2) in the renal collecting duct. AQP2 is the main target for antidiuretic action of arginine vasopressin (AVP), and the urinary excretion of this protein is believed to be an index of AVP signaling activity in the kidney. Children with acute pyelonephritis, aged 5-14 years, were examined for urinary flow rate, creatinine clearance, unchallenged urine osmolality, and urinary ion excretion. Urinary excretion of AQP2 was measured by dot immunoblotting technique. Studies were performed in the acute phase of pyelonephritis, in the same children after treatment, and in control patients. At the onset of pyelonephritis, urinary flow rate and solute excretion were increased, but the urinary osmolality was unchanged. The urinary level and urinary excretion of AQP2 was increased in acute pyelonephritis and decreased after treatment. Excretion of aquaporin-3 was unchanged, suggesting that the increase in AQP2 urinary excretion was not due to a shedding of collecting duct cells. The results suggest that a mechanism proximal to the collecting duct may be responsible for the polyuria observed in children with acute pyelonephritis. Increased urinary AQP2 levels suggest that a compensatory activation of apical plasma membrane targeting of AQP2 may occur in pyelonephritis.