The urinary excretion of epidermal growth factor in the rat is reduced by aprotinin, a proteinase inhibitor.

The present study on the rat shows that i.v. administration of the proteinase inhibitor aprotinin reduces the urinary output of immunoreactive epidermal growth factor (EGF) while the amount of immunoreactive EGF in the kidneys is increased. This indicates that the EGF-precursor in the rat kidney in vivo is processed by an aprotinin inhibitable proteinase. EGF is produced in the kidneys as a precursor with a molecular weight of approximately 130 kDa. In rat urine, nanomolar amounts of 6 kDa EGF are excreted per 24 h together with small amounts of high molecular weight forms of EGF. During i.v. administration of aprotinin the median urinary output of immunoreactive EGF is reduced to 15% of the excretion of control rats (23 pmol/2 h versus 157 pmol/2 h, P less than 0.001). Especially the excretion of 6 kDa EGF is reduced (median excretion 12 pmol/2 h versus 134 pmol/2 h, P less than 0.001). The amount of immunoreactive EGF in the kidney tissue is increased after aprotinin administration (median amount 0.11 pmol EGF/mg protein versus less than 0.04 pmol EGF/mg protein, P less than 0.001). Neither the creatinine clearance, the total urinary protein output, nor the volume of urine produced was affected by aprotinin.     

Effect of ethanol and linoleic acid on changes in biliary excretion of iodothyronines possibly related to thyroxine deiodination in rat liver

Groups of male rats weighing about 350 g were inserted polyethylene tubings into bile duct and femoral vein under pentobarbital anesthesia. Several iodothyronines (i.e. T4, T3, rT3, 3,5-T2, 3,3'-T2 and 3',5'-T2) were estimated in 2-hr portions of bile with the aid of specific radioimmunoassay. After the infusion of ethanol (0.3 ml/hr/rat for 4 hr) an increase of biliary excretion of rT3 and a decrease of 3,5-T2 was found as compared to controls. When 5 mg linoleic acid was added to 1.2 ml ethanol, the increase of rT3 was significantly higher than that after ethanol only and, in addition, significant increase of 3',5'-T2 excretion was found. It was concluded that both ethanol and unsaturated fatty acids may inhibit 5'-monodeiodination in the liver and that unsaturated nonesterified fatty acids may exert such effect even when administered intravenously without underlying metabolic disorders.     

Urinary selenium excretion in patients with cervical uterine cancer

In this work, we report on a relationship between urinary selenium and the development of cervical uterine cancer. A simple chemical method was developed to concentrate trace amounts of selenium from relatively large urine samples by use of small activated carbon filters. When these filters are irradiated with thermal neutrons, selenium can be determined either by ^77mSe (t _1/2=17.5 s) or ⁷⁵Se (t _1/2=120 d). In this article, we report the results for 82 urine samples from women with cervical uterine cancer in several stages of development and from healthy controls. These results show a statistically significant increase of selenium excretion in cancer patients as compared to controls. Urinary selenium excretion is highest for patients in the intermediate stages of the disease.     

The measurement of leukotrienes in urine as diagnostic option in systemic mastocytosis

Clinical symptoms of patients with mastocytosis may include skin reactions, but also gastrointestinal symptoms with hyperacidity and dysmotility (e.g. ulcer, diarrhea, pain). They are mostly caused by mediators derived from activated mast cells. In order to investigate the impact of leukotrienes on the clinical symptoms excretion of leukotriene B4 (LTB4) and leukotrienes C4-D4-E4 (cysteinyl-leukotrienes) into urine was studied in 9 patients with indolent systemic mastocytosis divided into a group with high and low intensity of symptoms and in 11 healthy volunteers. Leukotriene excretion was determined by ELISA and correlated with methylhistamine excretion. Patients with systemic mastocytosis with high and low intense symptoms showed significantly higher urinary excretion of cysteinyl-leukotrienes than controls. There was a positive correlation of cysteinyl-leukotriene excretion and urinary methylhistamine excretion. LTB4 excretion was also significantly increased in patients with systemic mastocytosis compared to healthy volunteers. No correlation of urinary LTB4 excretion with urinary methylhistamine was observed. The present study demonstrates that urinary excretion of LTB4 and cysteinyl-leukotrienes LTC4-D4-E4 is clearly enhanced in indolent systemic mastocytosis Hence, determination of leukotriene excretion into urine can be used as a tool in the diagnostic and in the therapeutic monitoring of systemic mastocytosis.     

Urinary zinc excretion and zinc status of patients with Β-thalassemia major

In this study, zinc status and urinary zinc excretion with and without desferrioxamine (DFO) infusion and the relationship between urinary zinc excretion and renal tubular dysfunction in thalassemia major (TM) patients were investigated. Forty TM patients were given four DFO infusions on alternate days over a 1-wk period prior to the transfusion. On each day that DFO was given, a 24-h urine collection initiated. DFO was omitted for 1-wk before the following transfusion and during the period four 24-h urine collections were performed. Twenty healthy children provided 24-h urine collection as controls. Blood samples were taken on each of two consecutive transfusion days of the patients and from the controls. Urinary zinc excretion was measured and plasma and red blood cell (RBC) zinc analysis were performed by inductively coupled plasma-atomic emission spectrophotometry. UrinaryN-acetyl-Β-D-glucosaminidase (NAG) activity and creatinine were determined in morning urine specimens. The mean plasma zinc concentration was significantly lower in the patients not given DFO compared to the values of the patients given DFO and the control group. The mean RBC zinc concentration (Μmol/g Hb) in the patients (with and without DFO) and the control group were similar. Urinary zinc excretion was significantly higher in the patients receiving DFO compared to the control group, whereas urinary zinc excretion in the patients not given DFO was not different from the controls. Urinary NAG indices (U/g Cr) were significantly higher in the patients compared to controls. Urinary zinc excretion was correlated with the urinary NAG indices.     

γ-Tocopherol biokinetics and transformation in humans

Background: The uptake and biotransformation of γ-tocopherol (γ-T) in humans is largely unknown. Using a stable isotope method we investigated these aspects of γ-T biology in healthy volunteers and their response to γ-T supplementation.

Methods: A single bolus of 100 mg of deuterium labeled γ-T acetate (d²-γ-TAC, 94% isotopic purity) was administered with a standard meal to 21 healthy subjects. Blood and urine (first morning void) were collected at baseline and a range of time points between 6 and 240 h post-supplemetation. The concentrations of d² and d⁰-γ-T in plasma and its major metabolite 2,7,8-trimethyl-2-(b-carboxyethyl)-6-hydroxychroman (-γ-CEHC) in plasma and urine were measured by GC-MS. In two subjects, the total urine volume was collected for 72 h post-supplementation. The effects of γ-T supplementation on α-T concentrations in plasma and α-T and γ-T metabolite formation were also assessed by HPLC or GC-MS analysis.

Results: At baseline, mean plasma α-T concentration was approximately 15 times higher than γ-T (28.3 vs. 1.9 µmol/l). In contrast, plasma γ-CEHC concentration (0.191 µmol/l) was 12 fold greater than α-CEHC (0.016 µmol/l) while in urine it was 3.5 fold lower (0.82 and 2.87 µmol, respectively) suggesting that the clearance of α-CEHC from plasma was more than 40 times that of γ-CEHC. After d²-γ-TAC administration, the d² forms of γ-T and γ-CEHC in plasma and urine increased, but with marked inter-individual variability, while the d⁰ species were hardly affected. Mean total concentrations of γ-T and γ-CEHC in plasma and urine peaked, respectively, between 0–9, 6–12 and 9–24 h post-supplementation with increases over baseline levels of 6–14 fold. All these parameters returned to baseline by 72 h. Following challenge, the total urinary excretion of d²-γ-T equivalents was approximately 7 mg. Baseline levels of γ-T correlated positively with the post-supplementation rise of (d⁰ + d²) – γ – T and γ-CEHC levels in plasma, but correlated negatively with urinary levels of (d⁰ + d²)-γ-CEHC. Supplementation with 100 mg γ-TAC had minimal influence on plasma concentrations of α-T and α-T-related metabolite formation and excretion.

Conclusions: Ingestion of 100mg of γ-TAC transiently increases plasma concentrations of γ-T as it undergoes sustained catabolism to CEHC without markedly influencing the pre-existing plasma pool of γ-T nor the concentration and metabolism of α-T. These pathways appear tightly regulated, most probably to keep high steady-state blood ratios α-T to γ-T and γ-CEHC to α-CEHC.     

Urine sugars for in vivo gut permeability: validation and comparisons in irritable bowel syndrome-diarrhea and controls

Mucosal barrier dysfunction contributes to gastrointestinal diseases. Our aims were to validate urine sugar excretion as an in vivo test of small bowel (SB) and colonic permeability and to compare permeability in patients with irritable bowel syndrome-diarrhea (IBS-D) to positive and negative controls. Oral lactulose (L) and mannitol (M) were administered with (99m)Tc-oral solution, (111)In-oral delayed-release capsule, or directly into the ascending colon (only in healthy controls). We compared L and M excretion in urine collections at specific times in 12 patients with IBS-D, 12 healthy controls, and 10 patients with inactive or treated ulcerative or microscopic colitis (UC/MC). Sugars were measured by high-performance liquid chromatography-tandem mass spectrometry. Primary endpoints were cumulative 0-2-h, 2-8-h, and 8-24-h urinary sugars. Radioisotopes in the colon at 2 h and 8 h were measured by scintigraphy. Kruskal-Wallis and Wilcoxon tests were used to assess the overall and pairwise associations, respectively, between group and urinary sugars. The liquid in the colon at 2 h and 8 h was as follows: health, 62 ± 9% and 89 ± 3%; IBS-D, 56 ± 11% and 90 ± 3%; and UC/MC, 35 ± 8% and 78 ± 6%, respectively. Liquid formulation was associated with higher M excretion compared with capsule formulation at 0-2 h (health P = 0.049; IBS-D P < 0.001) but not during 8-24 h. UC/MC was associated with increased urine L and M excretion compared with health (but not to IBS-D) at 8-24 h, not at 0-2 h. There were significant differences between IBS-D and health in urine M excretion at 0-2 h and 2-8 h and L excretion at 8-24 h. Urine sugars at 0-2 h and 8-24 h reflect SB and colonic permeability, respectively. IBS-D is associated with increased SB and colonic mucosal permeability.     

The renal excretion of selenium.

The excretion of selenium in urine was determined in West German healthy volunteers. Women excrete 17.7 +/- 4.2 micrograms Se/d and men 19.0 +/- 9.0 micrograms Se/d. The daily selenium excretion per gram creatinine is 13.5 +/- 3.8 micrograms Se/g crea for women and 9.8 +/- 3.3 micrograms Se/g crea for men. The clearance of selenium from the plasma is calculated with 0.18 mL/min. The selenium excretion per day is positively correlated with the 24 h excretion of urea and creatinine. The correlation of the selenium excretion with the urea excretion is most probably owing to the fact that the selenium intake of West Germans is linked primarily to foods with high protein contents. That the selenium excretion is directly correlated with the creatinine excretion is an indicator that the muscle, which accounts for nearly 50% of the whole body selenium in West German adults, influences the selenium excretion in urine. The positive correlation of the selenium excretion with the potassium excretion also indicates that the muscle mass contributes significantly to the selenium excretion in urine. Another indicator that the selenium excretion is influenced by the muscle is that after intensive muscular activity (running), selenium excretion is enhanced. The 24 h selenium excretion is dependent on the glomerular filtration rate of the kidney characterized by the creatinine clearance. This result is important, because if the selenium excretion is used as parameter for the selenium status of humans, the kidney function should be known. This is a limitation for the use of the urinary selenium excretion as parameter for the selenium status. This is especially important for patients whose glomerular filtration rate is low. The 24 h selenium excretion is further influenced by the 24 h urine volume. Selenium losses via urine may be concomitant with protein losses in urine.     

Human polyomaviruses JC and BK in the urine of Brazilian children and adolescents vertically infected by HIV

The aim of this study was to characterize the urinary excretion of the BK (BKV) and JC (JCV) human polyomaviruses in a cohort of human immunodeficiency virus (HIV)-infected children and adolescents. One hundred and fifty-six patients were enrolled: Group I included 116 HIV-infected children and adolescents [median age = 11.4 years (y); range 1-22 y]; Group II included 40 non-HIV-infected healthy controls (median age = 11.37 y; range 7-16 y). Single urine samples from both groups were screened for the presence of JCV and BKV DNA by polymerase chain reaction at enrolment. The overall rate of JCV and BKV urinary excretion was found to be 24.4% and 40.4%, respectively (n = 156). Group I had urinary excretion of JCV and BKV in 27.6% and 54.3% of subjects, respectively. In contrast, Group II showed positive results for JCV in 17.5% of subjects and for BKV in 12.5% of subjects (p Pearson JCV = 0.20; p Pearson BKV < 0.0001). In Group I, there was no association between JCV/BKV shedding and age, gender or CD4 values. Patients with an HIV viral load < 50 copies/mL had a lower excretion of BKV (p < 0.001) and a trend of lower JCV excretion (p = 0.07). One patient in Group I (1/116, 0.9%) showed clinical and radiological features consistent with progressive multifocal leukoencephalopathy, suggesting that children with HIV/polyomavirus coinfection should be kept under surveillance.     

Urinary platelet-activating factor excretion is elevated in non-insulin dependent diabetes mellitus.

Proteinuria is currently considered a very sensitive predictor of diabetic nephropathy, but 20-25% of all diabetic patients with negative Albustix reaction excrete higher than normal (< 20 mg/24 h) amounts of albumin in their urine. It is our hypothesis that platelet-activating factor (PAF), a potent glycerophospholipid that acts as a chemical mediator for a wide spectrum of biological activities, including increased vascular permeability, may be produced in significant amounts during periods preceding microalbuminuria. In this study, we compared urinary PAF excretion in Mexican-American subjects who were diagnosed with non-insulin dependent diabetes mellitus (NIDDM) with their healthy control counterparts. The age of the NIDDM subjects (45.9 +/- 2.1 years) was not significantly different from the healthy control group, which was 39.4 +/- 2.7 years (P < 0.0672). The NIDDM subjects (body mass index, 29.9 +/- 1.1 compared to 26.1 +/- 0.9 kg/m2 in healthy controls) were characterized by significantly increased (P < 0.05) fasting plasma glucose (192 +/- 11 vs. 97 +/- 4 mg/dl in healthy controls), fasting insulin (20.9 +/- 2.4 vs. 12.3 +/- 1.6 microU/ml), fasting C-peptide (2.93 +/- 1.26 vs. 1.48 +/- 0.51 ng/ml), and hemoglobin A1c (10.3 +/- 0.7 vs. 5.6 +/- 0.3%), respectively. The urine output for the NIDDM and control subjects were 1942 +/- 191 ml/24 h and 1032 +/- 94 ml/24 h, respectively, and urinary albumin excretion (UAE) rates were estimated to be 38 +/- 7 micrograms/min and 11 +/- 1 micrograms/min, respectively. The NIDDM subjects produced significantly increased levels of urinary PAF (2606.3 +/- 513.1 ng/24 h compared with 77.9 +/- 14.1 ng/24 h in controls (or 1706.3 +/- 420.8 ng/ml compared with 85.4 +/- 17.8 pg/ml of urine, in NIDDM and control subjects, respectively). We found that urinary PAF excretion was significantly correlated with microalbumin excretion (r = 0.7) especially at UAE rates greater than 30 mg/day and more importantly, some NIDDM patients with negative Albustix reaction (i.e. normal UAE) produced significantly more PAF, suggesting that PAF excretion may precede microalbuminuria and that subtle injury to the kidneys are present in NIDDM long before overt albuminuria ensues, urinary PAF measurements could potentially therefore serve as a sensitive indicator of renal injury in diabetes mellitus. These results lend further credence to our hypothesis that PAF may be the biochemical compound linking the various members of the insulin resistance syndrome.     

Idiopathic calcium nephrolithiasis. 2. Differences between hypercalciuric and normocalciuric persons with recurrent kidney stone formation and persons without such a history.

Normocalciuric and hypercalciuric patients with idiopathic recurrent calcium nephrolithiasis were compared with healthy individuals without such a history to examine the factors that predispose normocalciuric patients to stone formation. The urine calcium excretion rate was higher in the normocalciuric patients than in the control subjects (227 v. 183 mg/24 h; P less than 0.01), but the urine calcium concentration was not significantly different. The urine magnesium and citrate excretion rates and concentrations were lower in the normocalciuric patients than in the control subjects (P less than 0.001), while the urine uric acid and oxalate excretion rates and concentrations and the urine saturation with brushite (CaHPO4-2H2O) were not significantly different. These results suggest the importance of slight increases in the urine calcium excretion rate together with decreased urine magnesium and citrate excretion rates in normocalciuric persons with recurrent calcium stone formation. The urine of the hypercalciuric patients was more highly saturated with brushite than the urine of the normocalciuric patients and the control subjects, and the excretion rates of uric acid and oxalate were increased in the hypercalciuric patients. The hypercalciuric patients had a higher urine creatinine excretion rate than the normocalciuric patients and a higher daily urine volume than the control subjects, which suggests that differences in lean body mass or fluid and food intake, or both, may be important determinants of these differences in crystalloid excretion. As in the normocalciuric patients, the urine citrate excretion rate and concentration were decreased in the hypercalciuric patients compared with the control subjects.     

Urinary excretion of pyridinium crosslinks: a new marker of bone resorption in metabolic bone disease

The pyridinium derivatives hydroxylysylpyridinoline (HP) and lysylpyridinoline (LP) are intermolecular crosslinking compounds of collagen which are only present in its mature form. Contrasting to the wide distribution of type I and II rollagens, HP and LP are absent from skin, ligament and fascia, and their major sources are bone and cartilage. Using a specific HPLC assay, we have determined the 24-h excretion of HP and LP crosslinks in normal adults of both sexes, in patients with primary hyperparathyroidism and in patients with Paget's disease of bone before and after intravenous treatment with aminopropylidene bisphosphonate (APB). Mean adult normal values were 33 ± 13 pmol/μmol creatinine for HP and 6.3 ± 3.4 pmol/μmol creatinine for LP. In women, menopause induced a 2–3-fold increase of HP and LP reflecting the well documented postmenopausal increase of bone turnover. In the urine of patients with primary hyperparathyroidism and of patients with active Paget's disease of bone, urinary crosslinks were significantly higher than in age-matched controls, with a mean 3- and 12-fold increase, respectively. Urinary excretion of hydroxyproline is a well recognized but poorly sensitive marker of bone turnover, reflecting resorption. In the same patients, the effect of menopause and disease state on hydroxyproline excretion was much less dramatic than on HP and LP. During intravenous APB treatment of pagetic patients, there was an early decrease of HP and LP, which was significant after 24 h and reached 62% at 4 days, contrasting with a late and milder decrease of urinary hydroxyproline. Because APB is a potent inhibitor of resorption which does not have a direct short-term effect on bone formation, these data also indicate that urinary excretion of HP and LP reflect only coilagen degradation occurring during osteoclastic resorption and not the degradation of newly synthesized collagen. We conclude that urinary HP and LP excretion represents the firs sensitive and specific marker of bone resorption. Its use should be valuable in the clinical investigation of metabolic bone diseases, especially osteoporosis.     

Determination of tetrahydropapaveroline in the urine of Parkinsonian patients receiving l-dopa—carbidopa (Sinemet) therapy by high-performance liquid chromatography

Tetrahydropapaveroline (THP) concentrations were measured in the urine of Parkinsonian patients receiving l-dopa—carbidopa (Sinemet) therapy, using a method that employs a separation scheme that selectively isolates THP from urine and utilizes the Pictet—Spengler condensation of THP with formaldehyde combined with high-performance liquid chromatography for identification and determination. The mean (± S.D.) recoveries of THP from normal urine with 0.2 pmol/ml added and from Parkinsonian patients' urines with 0.5 pmol/ml added were 48.6 ± 5.7 and 44.6 ± 3.1%, respectively. Three Parkinsonian patients who were receiving either 250, 750 or 1000 mg of l-dopa (as Sinemet) daily had 24-h urinary THP excretion levels of 989, 1017 and 1600 pmol, respectively.     

Trefoil Factor 1 Excretion Is Increased in Early Stages of Chronic Kidney Disease

Chronic kidney disease (CKD) is associated with high morbidity and mortality. In many patients CKD is diagnosed late during disease progression. Therefore, the implementation of potential biomarkers may facilitate the early identification of individuals at risk. Trefoil factor family (TFF) peptides promote restitution processes of mucous epithelia and are abundant in the urinary tract. We therefore sought to investigate the TFF peptide levels in patients suffering from CKD and their potential as biomarkers for CKD. We analysed TFF1 and TFF3 in serum and urine of 115 patients with CKD stages 1–5 without dialysis by ELISA. 20 healthy volunteers served as controls. Our results showed, that urinary TFF1 levels were significantly increased with the onset of CKD in stages 1–4 as compared to controls and declined during disease progression (p = 0.003, < 0.001, 0.005, and 0.007. median concentrations: 3.5 pg/mL in controls vs 165.2, 61.1, 17.2, and 15.8 pg/mL in CKD 1–4). TFF1 and TFF3 serum levels were significantly elevated in stages 3–5 as compared to controls (TFF1: p < 0.01; median concentrations: 12.1, 39.7, and 34.5 pg/mL in CKD 3–5. TFF3: p < 0.001; median concentrations: 7.1 ng/mL in controls vs 26.1, 52.8, and 78.8 ng/mL in CKD 3–5). TFF3 excretion was increased in stages 4 and 5 (p < 0.001; median urinary levels: 65.2 ng/mL in controls vs 231.5 and 382.6 ng/mL in CKD 4/5; fractional TFF3 excretion: 6.4 in controls vs 19.6 and 44.1 in CKD 4/5). ROC curve analyses showed, that monitoring TFF peptide levels can predict various CKD stages (AUC urinary/serum TFF > 0.8). In conclusion our results show increased levels of TFF1 and TFF3 in CKD patients with a pronounced elevation of urinary TFF1 in lower CKD stages. Furthermore, TFF1 and TFF3 seems to be differently regulated and show potential to predict various CKD stages, as shown by ROC curve analysis.     

Antiproteinuric treatment reduces urinary loss of vitamin D-binding protein but does not affect vitamin D status in patients with chronic kidney disease

Vitamin D deficiency is common in chronic kidney disease (CKD). Increased urinary loss of vitamin D binding protein (VDBP), the main transporter of 25-hydroxyvitamin D(3) in the circulation, has been postulated to contribute to vitamin D deficiency in proteinuria. To test this hypothesis we analyzed urinary and plasma levels of VDBP, 25-hydroxyvitamin D(3) and 1,25-dihydroxyvitamin D(3) from proteinuric patients, before and after antiproteinuric interventions. We performed a post-hoc analysis of a clinical trial in CKD patients (n=13, creatinine clearance median 60 (range 25-177) ml/min) subjected to the following study periods: washout (no antiproteinuric treatment, 4 weeks), lisinopril 40mg QD (ACEi, 6 weeks), or indomethacin 75mg BID (NSAID, 4 weeks) in randomized sequence. Healthy subjects screened for donation (n=10) served as controls. Plasma and urine VDBP levels were measured by ELISA, 25-hydroxyvitamin D(3) levels by LC-MS and 1,25-dihydroxyvitamin D(3) levels by radioimmunoassay. In CKD patients urinary VDBP excretion was strongly increased (median (range) 5413 (155-211,027) μg/24h) as compared to healthy controls (64 (23-111) μg/24h, p<0.001). Both NSAID and ACEi significantly decreased urinary VDBP excretion, in proportion to proteinuria reduction. Plasma VDBP, 25-hydroxyvitamin D(3) and 1,25-dihydroxyvitamin D(3) levels, however, were similar between patients and controls and not affected by antiproteinuric intervention. Urinary VDBP excretion is markedly increased in proteinuria and responds to antiproteinuric treatment. Urinary VDBP loss is not associated with plasma VDBP or vitamin D(3) levels, suggesting that urinary loss of VDBP does not affect vitamin D status.     

Defective regulation and action of atrial natriuretic peptide in type 2 diabetes.

Increased plasma atrial natriuretic peptide (ANP) levels and impaired ANP action have been reported in patients with diabetes or insulin resistance. The aim of this study was to assess the interaction between insulin and ANP in type 2 diabetes. In 12 normotensive, normoalbuminuric type 2 diabetics, we infused insulin at a high (6.6 pmol/min/kg) or, on a different day, at a low rate (0.6 pmol/min/kg) during 4 hours of isoglycemia under isovolumic, isoosmolar conditions. The normal response was established in 12 healthy volunteers using an identical protocol. Despite higher baseline ANP levels (17.7 +/- 2.8 vs. 10.8 +/- 1.8 pg/ml, p = 0.04), urinary sodium excretion was similar in diabetics and controls (113 +/- 8.5 vs. 102 +/- 8.8 mEq/24 hours, p = ns). In both groups, hyperinsulinemia caused a decrease in blood volume (0.33 +/- 0.10 l, p < 0.01), diastolic blood pressure (6 %, p < 0.02), and natriuresis. However, plasma ANP decreased in controls (from 12.7 +/- 1.9 to 8.6 +/- 1.4 pg/ml, p = 0.01) but not in type 2 diabetics (15.1 +/- 2.7 vs. 17.2 +/- 3.8 pg/ml, p = ns). We conclude that ANP release is resistant to volume stimulation in type 2 diabetic patients, and natriuresis is resistant to ANP action. This dual disruption of ANP control may play a role in blood pressure regulation in diabetes.     

The renal excretion of selenium

The excretion of selenium in urine was determined in West German healthy volunteers. Women excrete 17.7±4.2 μg Se/d and men 19.0±9.0 μg Se/d. The daily selenium excretion per gram creatinine is 13.5±3.8 μg Se/g crea for women and 9.8±3.3 μg Se/g crea for men. The clearance of selenium from the plasma is calculated with 0.18 mL/min. The selenium excretion per day is positively correlated with the 24h excretion of urea and creatinine. The correlation of the selenium excretion with the urea excretion is most probably owing to the fact that the selenium intake of West Germans is linked primarily to foods with high protein contents. That the selenium excretion is directly correlated with the creatinine excretion is an indicator that the muscle, which accounts for nearly 50% of the whole body selenium in West German adults, influences the selenium excretion in urine. The positive correlation of the selenium excretion with the potassium excretion also indicates that the muscle mass contributes significantly to the selenium excretion in urine. Another indicator that the selenium excretion is influenced by the muscle is that after intensive muscular activity (running), selenium excretion is enhanced. The 24h selenium excretion is dependent on the glomerular filtration rate of the kidney characterized by the creatinine clearance. This result is important, because if the selenium excretion is used as parameter for the selenium status of humans, the kidney function should be known. This is a limitation for the use of the urinary selenium excretion as parameter for the selenium status. This is especially important for patients whose glomerular filtration rate is low. The 24h selenium excretion is further influenced by the 24h urine volume. Selenium losses via urine may be concomitant with protein losses in urine.     

Comparison of calcium oxalate values as indicators of risk for calcium oxalate calcinosis and the degree of urine saturation in patients with calcium urolithiasis and in healthy patients

Daily excretion of calcium, magnesium, oxalates, and citrates together with daily urine output were determined in 37 patients with calcium urolithiasis and in 25 healthy individuals. Basing on the obtained values, a degree of urine saturation with calcium oxalate with Marshall and Robertson technique and a value of risk factor with Tiselius technique were calculated. It was found that daily diuresis and excretion of calcium with the urine are significantly higher in patients with urolithiasis where as daily excretion of citrates with the urine is significantly lower than in healthy individuals. Risk index proved two-fold higher in the examined patients than in the healthy individuals (p greater than 0.001) while the degree of urine saturation with calcium oxalate did not differ significantly in both groups. The authors, discussing causes of seemingly different changes in both tested parameters, stressed diagnostic value of risk index which includes excretion of crystallization inhibitors (magnesium, citrates) and contrary to the degree of urine saturation is independent of daily urine output.     

Metabolic evaluation of urolithiasis patients from eastern Croatia

Metabolic parameters were determined in fasting blood serum, fasting first morning urine, and 24-hour urine of male patients with recurrent calcium oxalate stones (N = 26, age 39.1 +/- 6.2 years) as well as in male healthy controls (N = 18, age 35.0 +/- 7.1 years), recruited from the eastern part of Croatia. The 24-hour urinary calcium excretion was significantly higher (p < 0.01) for patients (5.6 +/- 2.5 mmol) than for controls (3.7 +/- 1.9 mmol), but potassium excretion was higher (p < 0.01) for controls (74.5 +/- 33.8 mmol) than for patients (49.2 +/- 15.7 mmol). The mean ionic activity product of calcium and oxalate ions, IAP(CaOx), calculated from the fasting first morning urine parameters, was 25% higher for patients than for controls, but the difference was not statistically significant (p > 0.05). Very strong correlation (r = 0.97) was obtained between IAP(CaOx) values and calculated Ogawa indices that were recommended for estimating the potential risk for calcium oxalate stone formation.     

Idiopathic calcium nephrolithiasis. 1. Differences in urine crystalloids,urine saturation with brushite and urine inhibitors of calcification between persons with and persons without recurrent kidney stone formation.

The propensity of urine to promote calcium stone formation was compared in 64 patients with recurrent idiopathic calcium nephrolithiasis and 30 healthy individuals without such a history. The rates of excretion of urine crystalloids, the urine saturation with brushite (CaHPO4-2H2O), the ability of the urine to calcify collagen in vitro, and the concentration of urine inhibitors of collagen calcification were measured. The patients had a reduced urine citrate excretion rate in addition to an increased urine calcium excretion rate, while the rates for urine magnesium, phosphate, uric acid and oxalate were not significantly different in the two groups of subjects. The urine concentration of magnesium, phosphate and uric acid was decreased in the patients because of the higher urine volume. The urine creatinine excretion rate correlated with the rates of excretion of urine calcium, magnesium, phosphate, uric acid and oxalate in both groups, which suggested that increased lean body mass, possibly associated with greater food intake, may be an important determinant of crystalloid excretion. The urine of the patients was significantly more saturated with brushite than the urine of the control subjects and resulted in greater collagen calcification when incubated in vitro. The urine concentration of inhibitors of collagen calcification, however, was not significantly different in the two groups. Thus, the urine of patients with recurrent idiopathic calcium nephrolithiasis is more highly saturated with brushite, largely as a result of an increased urine calcium excretion rate, and contains a lower concentration of magnesium and citrate, substances that tend to prevent the precipitation and growth of crystals in urine.