Determination of urinary retinol and creatinine as an early sensitive marker of renal dysfunction.

Determination of urinary retinol, which is a new promising early biomarker of renal damage typically expressed in the clinical environment as retinol/creatinine ratio, is currently difficult to accomplish. We have developed and validated the new ultra-high-performance liquid chromatography method with UV and mass spectrometry detection for the separation and quantification of retinol and creatinine in human urine in a single run. The separation of these two substances with completely different physicochemical properties was achieved using a column packed with fluorinated stationary phase and acetonitrile and aqueous ammonium formate buffer as the mobile phases. The separation was completed within 4 min. Our new method involves very fast and simple sample preparation requiring small amount of sample matrix and solvents. Deuterium labeled internal standard was used for the more precise quantification. The method was tested with real-life samples using urine collected from patients suffering from breast, colorectal, head, and neck cancer.

Vitamin A and D intake in pregnancy, infant supplementation, and asthma development: the Norwegian Mother and Child Cohort.

Background: Western diets may provide excess vitamin A, which is potentially toxic and could adversely affect respiratory health and counteract benefits from vitamin D. Objective: The aim of this study was to examine child asthma at age 7 y in relation to maternal intake of vitamins A and D during pregnancy, infant supplementation with these vitamins, and their potential interaction. Design: We studied 61,676 school-age children (born during 2002-2007) from the Norwegian Mother and Child Cohort with data on maternal total (food and supplement) nutrient intake in pregnancy (food-frequency questionnaire validated against biomarkers) and infant supplement use at age 6 mo (n = 54,142 children). Linkage with the Norwegian Prescription Database enabled near-complete follow-up (end of second quarter in 2015) for dispensed medications to classify asthma. We used log-binomial regression to calculate adjusted RRs (aRRs) for asthma with 95% CIs. Results: Asthma increased according to maternal intake of total vitamin A [retinol activity equivalents (RAEs)] in the highest (≥2031 RAEs/d) compared with the lowest (≤779 RAEs/d) quintile (aRR: 1.21; 95% CI: 1.05, 1.40) and decreased for total vitamin D in the highest (≥13.6 µg/d) compared with the lowest (≤3.5 µg/d) quintile (aRR: 0.81; 95% CI: 0.67, 0.97) during pregnancy. No association was observed for maternal intake in the highest quintiles of both nutrients (aRR: 0.99; 95% CI: 0.83, 1.18) and infant supplementation with vitamin D or cod liver oil. Conclusions: Excess vitamin A (≥2.5 times the recommended intake) during pregnancy was associated with increased risk, whereas vitamin D intake close to recommendations was associated with a reduced risk of asthma in school-age children. No association for high intakes of both nutrients suggests antagonistic effects of vitamins A and D. This trial was registered at http://www.clinicaltrials.gov as NCT03197233.

Effect of vitamin A supplementation on the urinary retinol excretion in very low birth weight infants.

UNLABELLED: Despite high-dose vitamin A supplementation of very low birth weight infants (VLBW, <1500 g), their vitamin A status does not improve substantially. Unknown is the impact of urinary retinol excretion on the serum retinol concentration in these infants. Therefore, the effect of high-dose vitamin A supplementation on the urinary vitamin A excretion in VLBW infants was investigated. Sixty-three VLBW infants were treated with vitamin A (5000 IU intramuscular, 3 times/week for 4 weeks); 38 untreated infants were classified as control group. On days 3 and 28 of life, retinol, retinol-binding protein 4 (RBP4), glomerular filtration rate, proteinuria, and Tamm-Horsfall protein were quantified in urine. On day 3 of life, substantial retinol and RBP4 losses were found in both groups, which significantly decreased until day 28. Notwithstanding, the retinol excretion was higher (P < 0.01) under vitamin A supplementation as compared to infants of the control group. On day 28 of life, the urinary retinol concentrations were predictive for serum retinol concentrations in the vitamin A treated (P < 0.01), but not in the control group (P = 0.570). CONCLUSION: High urinary retinol excretion may limit the vitamin A supplementation efficacy in VLBW infants. Advanced age and thus postnatal kidney maturation seems to be an important contributor in the prevention of urinary retinol losses.

Vitamin A deficiency associated with urinary retinol binding protein wasting in Dent's disease.

BACKGROUND: Three patients with Dent's disease presented with complaints of impaired night vision or xerophthalmia and were found to have severely decreased serum retinol concentrations. Retinol, bound to its carrier retinol-binding protein (RBP), is filtered at the glomerulus and reabsorbed at the proximal tubule. We hypothesized that urinary loss of retinol-RBP complex is responsible for decreased serum retinol. OBJECTIVE AND METHODS: The study aim was to investigate vitamin A status and RBP in serum and urine of patients with genetically confirmed Dent's disease. RESULTS: Eight patients were studied, three boys had clinical vitamin A deficiency, three had asymptomatic deficiency, and two young men with Dent's disease and impaired renal function had normal retinol values. Serum RBP concentrations were low in patients with vitamin A deficiency and were correlated with vitamin A levels. Urinary RBP concentrations were increased in all patients (2,000-fold), regardless of vitamin A status. This was in contrast to patients with glomerular proteinuria who had only mildly increased urinary RBP with normal serum RBP and vitamin A, and patients with cystinosis with impaired renal function who had massive urinary RBP losses but without a decrease in serum RBP or vitamin A levels. Treatment with vitamin A supplements in patients with retinol deficiency resulted in rapid resolution of ocular symptoms and an increase in serum retinol concentrations. CONCLUSIONS: Vitamin A deficiency is common in patients with Dent's disease and preserved renal function. We therefore recommend screening these patients for retinol deficiency and treating them before visual symptoms develop.

Kidney function and retinol status in type 2 diabetes mellitus patients.

Kidneys play an important role in retinol turnover. We postulated that retinol homeostasis is disturbed in diabetic nephropathy. The aim of this research was to study the effect of kidney impairment on urinary excretion and on serum concentrations of retinol in type 2 diabetes mellitus patients. For this purpose, 41 type 2 diabetes patients and 9 sex -and age-matched healthy subjects were enrolled. Serum and urinary retinol and retinol-binding protein (RBP) were assessed by high-pressure liquid chromatography and enzyme-linked immunosorbent assay, respectively. The study showed that 17 out of 41 diabetic patients (41.5%) and none of the controls excreted retinol in urine (P < 0.02). Retinol excretion in the urine in these patients was 1.5-fold more prevalent than hypercreatininemia. Urinary retinol significantly correlated with clinically diagnosed nephropathy (P = 0.02). All but one of the patients with hypercreatininemia excreted retinol in the urine. Serum retinol and RBP in patients with hypercreatininemia were higher than in controls (P < 0.002). Values of urinary retinol, unlike urinary RBP, albumin and total protein, did not overlap between patients and controls. Our results indicate that (i) urinary retinol is a specific sign of tubular damage in type 2 diabetic patients and (ii) urinary retinol enables a more clear-cut identification of proximal tubule dysfunction in type 2 diabetes patients than urinary RBP or albumin.

Redução transitória nos níveis séricos de retinol em crianças com pneumonia e resposta de fase aguda / Transient decreased retinol serum levels in children with pneumonia and acute phase response

OBJETIVO: Comparar os níveis séricos de retinol em crianças pré-escolares durante um episódio de pneumonia e 45 dias após a resolução da infecção. MÉTODOS: O estudo foi conduzido com crianças pré-escolares sem infecção (grupo controle, n = 9) ou com pneumonia (n = 12), após a hospitalização (fase 1) e 45 dias após a alta (fase 2). A avaliação nutricional incluiu antropometria, questionário alimentar e exames laboratoriais, incluindo os níveis urinários e séricos de retinol. Aplicou-se o teste pareado de Student ou de Mann-Whitney. RESULTADOS: Não houve diferença na ingestão alimentar. Documentaram-se menores valores de hemoglobina sanguínea e dos níveis séricos de sódio e albumina durante a fase 1, além de maiores valores da proteína C reativa. Não houve mudança no retinol urinário, enquanto os níveis séricos aumentaram após a recuperação da pneumonia. CONCLUSÕES: Durante a pneumonia, as crianças apresentam redução transitória nos níveis séricos de vitamina A, um epifenômeno da resposta de fase aguda.

OBJECTIVE: To compare serum retinol levels in preschool children during an episode of pneumonia and 45 days after the resolution of the infection. METHODS: The study was conducted with preschool children without any infection (control group, n = 9) or children hospitalized for pneumonia (n = 12), who were evaluated soon after hospitalization (phase 1) and 45 days later (phase 2). Nutritional assessment included anthropometric measurements, a food questionnaire, and laboratory blood routine examination, including urinary and serum retinol levels. Paired Student t or Mann-Whitney tests were used as required. RESULTS: Food intake was similar between groups. Blood hemoglobin and serum sodium and albumin decreased during phase 1, while there were higher C-reactive protein serum values. Urinary retinol levels remained unchanged whereas serum retinol increased significantly after pneumonia recovery. CONCLUSIONS: During the course of pneumonia, children had transient decrease in serum levels of vitamin A, an epiphenomenon of the acute phase response.

Transient decreased retinol serum levels in children with pneumonia and acute phase response.

OBJECTIVE: To compare serum retinol levels in preschool children during an episode of pneumonia and 45 days after the resolution of the infection. METHODS: The study was conducted with preschool children without any infection (control group, n = 9) or children hospitalized for pneumonia (n = 12), who were evaluated soon after hospitalization (phase 1) and 45 days later (phase 2). Nutritional assessment included anthropometric measurements, a food questionnaire, and laboratory blood routine examination, including urinary and serum retinol levels. Paired Student t or Mann-Whitney tests were used as required. RESULTS: Food intake was similar between groups. Blood hemoglobin and serum sodium and albumin decreased during phase 1, while there were higher C-reactive protein serum values. Urinary retinol levels remained unchanged whereas serum retinol increased significantly after pneumonia recovery. CONCLUSIONS: During the course of pneumonia, children had transient decrease in serum levels of vitamin A, an epiphenomenon of the acute phase response.

Rapid HPLC method for the determination of vitamin A and E and cotinine concentration in human serum in women with CIN and cervical cancer.

OBJECTIVE: The aim of this study was to elaborate on the analytical method for quantitative determination of retinol and alpha-tocopherol in serum of women diagnosed with CIN and cervical cancer. The basic problem in the analysis of the vitamins content in biological material is their low physiological concentration level and instability. Liquid chromatography with diode array detector (DAD) was applied. MATERIAL AND METHODS: The material consisted of serum and urine collected from 12 women diagnosed with cervical intraepithelial neoplasia (CIN) and 16 diagnosed with cervical cancer. The method was evaluated for the following parameters: linearity, recovery, sensitivity, precision, accuracy, selectivity, stability, limit of quantification (LOQ) and limit of detection (LOD). RESULTS: Results showed good linearity (r2> or =0.99) in the range 0.1 microg/ml-10 mg/ml for retinol and 0.25 microg/ml-15 microg/ml for alpha-tocopherol. The Lower Limit of Detection was 0.15 microg/ml for vitamin E and 0.05 microg/ml for vitamin A. The within-run R.S.Ds were below 5.2% at all concentration levels and the between-run R.S.Ds were below 10.0% at all concentration levels. CONCLUSIONS: The advantage of this method is that it measures both compounds in a more rapid, reproducible and accurate manner when compared to the previous HPLC studies. The compounds (vitamin A and E and internal standards) are measured in the same sample at the same time. Quantitative determination of cotinine may reveal active smokers and subjects exposed to environmental tobacco smoke, which is independent measurable carcinogenetic co-factor. The following study is a part of a project determining non-viral causative agents in cervical carcinogenesis.

Urinary vitamin A excretion in very low birth weight infants.

Vitamin A (VA) deficiency in very low birth weight (VLBW) infants is associated with an increased risk for disorders related to kidney and lung maturation and function. VA losses through increased urinary retinol (ROH) excretion might contribute to this deficiency risk. The mechanism accounting for ROH loss in the urine has not yet been clarified. The aim of this study was to assess the excretion of ROH, retinol-binding protein 4 (RBP4) and transthyretin (TTR) in urine from VLBW infants in comparison with that in term infants in relation to kidney function. Urine specimens were collected from 15 VLBW infants (birth weight < 1,500 g) as well as from 20 term infants during the first 2 days after birth. ROH in urine was detectable in 14 of the 15 VLBW infants at a median concentration of 234 nmol/g creatinine. In the group of term infants, 17 of the 20 excreted ROH, but at an approximately five-times lower concentration (P < 0.001). Excretion of RBP4 and TTR was also much higher in VLBW infants (both P< 0.001). The urinary ROH excretion in VLBW infants may be related to the impaired tubular handling of its carrier proteins RBP4 and TTR. Thus, ROH excretion might contribute to an increased risk of VA deficiency, especially in VLBW infants.

Microalbuminuria is a major determinant of elevated plasma retinol-binding protein 4 in type 2 diabetic patients.

Plasma retinol-binding protein 4 (RBP4) may be a new adipokine linked to obesity-induced insulin resistance and type 2 diabetes. The impact of diabetic nephropathy on plasma RBP4 levels, however, is not known. We tested the hypothesis that microalbuminuria is associated with elevated plasma concentrations of RBP4 in type 2 diabetic subjects. Retinol, its binding protein and transthyretin (TTR) were measured in the plasma and urine of 62 type 2 diabetic subjects, 26 of whom had microalbuminuria. The results were compared to 35 healthy control subjects. Despite no differences in plasma retinol, concentrations of the RBP4 were significantly elevated in plasma of diabetic patients and significantly higher in those with microalbuminuria. The higher plasma levels of the binding protein in subjects with microalbuminuria were accompanied by both significantly elevated plasma TTR and increased urinary levels of RBP4. There were no correlations of plasma-binding protein levels and parameters of insulin resistance. Our study suggests that plasma RBP4 levels in type 2 diabetic patients are affected by incipient nephropathy. Therefore, further studies evaluating RBP4 as a regulator of systemic insulin resistance and type 2 diabetes will need to take renal function into consideration.

Recommended dose for repair of serum vitamin A levels in patients with HIV infection/AIDS may be insufficient because of high urinary losses.

OBJECTIVE: Retinol deficiency is quite frequent in the population of human immunodeficiency virus (HIV)-infected individuals. Serum retinol levels of less than 1.05 micromol/L determine a 3.5 to five times higher death risk. However, studies evaluating the efficacy of retinol supplementation in HIV-seropositive individuals have reported conflicting results. The World Health Organization recommends the treatment of vitamin A deficiency in seropositive individuals in the same manner as for seronegative individuals, but clinical studies proving the efficacy of this scheme are lacking. The proposal of the present study was to assess the efficacy of supplementation with high retinol doses in HIV-infected patients with vitamin A deficiency. METHODS: Twenty-five adult HIV-seropositive individuals were monitored over a period of 9 months, with determination of serum and urinary retinol every 3 months. The subjects received retinol palmitate doses ranging from 300,000 IU to 600,000 IU. Patients whose retinol levels were higher than 1.60 micromol/L were only observed. RESULTS: Eighteen patients received supplementation during clinical monitoring. The dose of 600,000 IU induced a significant mean increase in serum levels of 0.47 micromol/L (P = 0.049) within a period of three months. Those who received 300,000 IU presented a mean increase of 0.29 micromol/L. In contrast, the patients who did not receive replacement therapy presented a significant decrease (P = 0.017) in serum retinol levels, with initial and final values of 1.77 micromol/L and 1.55 micromol/L. The individuals with the worst response to supplementation presented a higher urinary loss of retinol at the beginning of the study. Even with a mean retinol supplementation of 771,428 IU during the study period, six patients had marginal serum retinol levels at the end of the study. CONCLUSION: We conclude that, in view of the high urinary loss of this nutrient, there is the need to redefine the ideal dose for the treatment of HIV-infected individuals.

Renal pathology and retinol status in multiple myeloma patients.

Renal dysfunction is a common and serious complication in multiple myeloma (MM) patients. Renal proximal tubule injury is characteristic in MM, and may result in disturbed renal handling of various vitamins. The abnormal excretion of vitamins in urine may result in their low serum levels. The goal of this study was to investigate the urinary excretion of retinol in MM and its relationship with serum retinol concentration. For this purpose, 24 MM patients and 10 healthy individuals were studied. Serum and urinary retinol and retinol-binding protein (RBP) were measured by the high-performance liquid chromatography method and enzyme-linked immunosorbent assay, respectively. The study showed that 58% of MM patients excreted retinol in urine, while only 29% had elevated serum creatinine (P<0.05). There was a strong and highly significant correlation between urinary retinol and RBP (r=0.973, P<0.006). Patients with normal and mildly elevated serum creatinine who excreted retinol in urine had a marked decrease in serum retinol (P<0.007). On the other hand, serum retinol was not decreased in patients with moderate or severe renal failure, despite its urinary loss. Our data indicate that (i) urinary retinol is a more frequent marker of renal dysfunction than elevated serum creatinine in MM patients, (ii) serum retinol is decreased in MM with normal or mildly elevated serum creatinine, but not in patients with moderate/severe renal failure, and (iii) urinary retinol may serve as a diagnostic marker of renal proximal tubule dysfunction in MM patients.

Effect of the diuretic furosemide on urinary essential nutrient loss and on body stores in growing rats.

Studies using a model of non-infectious diarrhea, have shown that increasing fecal mass by using laxatives resulted in greater fecal losses of nutrients and lower intestinal absorption. In the present study we used a diuretic to determine if increasing urine volume could result in greater urinary losses of essential nutrients. This is a relevant question because diuretics are widely and successfully used in the treatment of diseases associated with water retention and hypertension. They are known to increase potassium losses. However, there is less information on the effect of diuretics on the urinary losses of essential nutrients. Accordingly, urinary nitrogen, phosphorous, sodium, potassium, magnesium, zinc and retinol were measured in young rats consuming increasing concentrations of furosemide (0, 0.5, 1.0, 1.5 mg/g diet) in the diet over 15 days. The results showed that dietary furosemide caused a dose-dependent polyuria. In addition it reduced food intake and feed efficiency and leaded to poor growth and greater urinary losses of all the measured nutrients and electrolytes. These losses were proportional to urine volume and represented an important fraction of the rats daily intake. The losses were negatively associated with the body and liver content of the same electrolytes and nutrients. In general, this study showed that the diuretic furosemide caused malnutrition in a short period of time by reducing food intake as well as the capacity of retaining macro and micronutrients including the liposoluble vitamin A in a relatively short period of time. This study, together with our previous studies on diarrhea, indicate that proper nutrient utilization requires both an adequate intestinal and renal function.

Megalin-mediated reuptake of retinol in the kidneys of mice is essential for vitamin A homeostasis.

The reuptake of retinol (ROH) and retinol-binding protein (RBP) in the kidneys is mediated by the endocytic receptor megalin, suggesting an important role for this receptor in vitamin A (VA) metabolism. We examined the extent to which megalin deficiency may affect urinary ROH excretion, levels of ROH and RBP in plasma, as well as storage of VA in liver and kidney. For this purpose, mice with a kidney-specific megalin gene defect (megalin(lox/lox); apoE(Cre)) and control mice (megalin(lox/lox)) were fed either a basal diet containing 4500 retinol equivalents (RE)/kg diet or a diet without VA during experimental periods of 42 and 84 d. Urinary ROH excretion was observed only in megalin(lox/lox); apoE(Cre) mice (P < 0.0001, 2-way ANOVA) and not in the controls. Plasma ROH and RBP differed only by diet (P < 0.05), but not genotype (P = 0.615). A major effect of megalin deficiency, however, was evident in retinyl ester levels in the liver (P < 0.05), which were approximately 37% lower than those in megalin(lox/lox) controls (P < 0.05, Student's t test) during the 84-d period of dietary VA deprivation. Kidney levels of VA were not affected by the receptor gene defect. The findings demonstrate that urinary ROH excretion caused by megalin deficiency requires accelerated mobilization of hepatic VA stores to maintain normal plasma ROH levels, which suggests that megalin plays an essential role in systemic VA homeostasis.

Excretion of vitamin A in urine of women during normal pregnancy and pregnancy complications.

BACKGROUND/AIMS: The renal function, including the excretion of low-molecular-weight proteins, changes during pregnancy and may cause a urinary excretion of retinol-binding protein (RBP). Whether it is accompanied by a substantial loss of vitamin A (retinol) has not been established yet. We therefore determined the excretion of retinol and RBP in urine of pregnant women. METHODS: The study involved analyses of urine samples from 40 healthy pregnant women and 29 women with pregnancy complications during the third trimester. Analyses of plasma and urine of 7 healthy women and 5 women with pregnancy complications were also carried out 6 weeks antepartum, at time of delivery and 1 week postpartum. RESULTS: Urinary retinol was higher in women who suffered from pregnancy disorders with an influence on maternal metabolism (p < 0.01). RBP was excreted at substantial concentrations in the urine of all 69 women, but there were no differences between the groups. Women with a concomitant excretion of retinol had higher levels of urinary RBP than those without a retinol excretion (p < 0.05). Differences in plasma retinol and RBP were not significant. CONCLUSION: The excretion of urinary retinol may increase significantly during pregnancy complications, which needs further clarification to which extent this condition may negatively affect the vitamin A status in such women.

Urinary excretion of vitamin A in critically ill patients complicated with acute renal failure.

OBJECTIVE: Study the possible excretion of vitamin A in urine of critically ill patients complicated with acute renal failure. PATIENTS AND METHODS: Nine Intensive Care Unit patients, age 71.2 +/- 15.7 (mean +/- SD) with acute renal failure were studied. Urinary retinol, creatinine, protein, albumin, and serum creatinine were measured. RESULTS: All patients excreted retinol in urine; individual values ranged from 0.007 to 0.379 micromol retinol/mmol creatinine. There was no correlation of urinary retinol/creatinine ratio with serum creatinine or with urinary protein/creatinine and albumin/creatinine ratios. CONCLUSION: Excretion of retinol in urine may be indicative of acute renal failure in critically ill patients.

The multiple vitamin status of Chinese pregnant women with anemia and nonanemia in the last trimester.

Iron-deficiency or anemia in pregnancy is a major public health problem in China. This cross-sectional study was carried out to observe the association between iron status and multiple vitamin levels of Chinese pregnant women in the third trimester. We measured iron, ascorbic acid, retinol, folate and vitamin B12 in serum, and riboflavin in urine specimens of 1,163 pregnant women in four sites throughout rural and city areas in China. Based on hemoglobin concentrations (Hb), the subjects were divided into an anemia group with Hb < 110 g/L or Hb < or = 100 g/L as severe anemia group, and nonanemia group with Hb > or = 110 g/L. Results showed that 41.58% of the population with serum iron < 700 microg/L and 51.04% of the population with ferritin < 12 microg/L in the anemia group, percentages that were much higher than those in the nonanemia group. Relationships between five vitamins and hemoglobin concentrations of all subjects were observed. There was a lower level of serum ascorbic acid (291.05 microg/dL) in the Hb < or = 100 g/L group than in the Hb > or = 120 g/L group (487.79 microg/dL) (p < 0.001). Serum levels of vitamin B12 and folate were 445.67 pg/mL and 5.94 ng/mL in the Hb < or = 100 g/L group, whose levels were much lower than the levels of 502.01 pg/mL (p < 0.012) and 8.07 ng/mL (p < 0.010) respectively in the Hb > or = 120 g/L group. Further, cross-sectional analysis showed positive correlations between abnormal hematological results and prevalences of vitamin deficiencies. The subjects with iron-deficiency anemia had much higher rates of vitamin C, folate and vitamin B12 deficiencies than those in the nonanemic subjects, and especially in the deficient rates of ascorbic acid and folate in the anemia (Hb < 110 g/L) group, which reached 64.04% and 22.70% respectively. Moreover, we observed that the decreasing trends of hemoglobin concentrations were accompanied by the decreases of serum levels of vitamin A, ascorbic acid, folate and vitamin B12. In conclusion, multiple vitamin deficiencies, especially ascorbic acid, retinol and folic acid, may be associated with anemia or iron deficiency in pregnant women in the last trimester. The study suggested that anemic pregnant women in China should be supplemented with iron and multiple vitamins simultaneously.

Some dietary fibers increase elimination of orally administered polychlorinated biphenyls but not that of retinol in mice.

Dietary fiber supplementation can increase the size and nutrient absorption capacities of the small intestine in some mammals, but does this increase the risk of accumulating environmental contaminants? This study addressed this question by feeding mice diets containing various types of fiber at 0 or 100 g/kg (cellulose, lactosucrose, polydextrose, indigestible dextrin, soy polysaccharide, rice bran and chitosan) for 10 wk. During the final 2 wk, the mice were fed retinol and a dose of Arochlor 1254 [polychlorinated biphenyls (PCB)] estimated to be 5% of the median lethal dose. Accumulation was determined using whole blood samples collected on days 1, 3 and 7 as well as eight tissues (whole blood, small and large intestine, liver, gall bladder, mesentery, kidney and brain). Elimination of Arochlor 1254 and retinol was determined using daily collections of feces and urine. The patterns of accumulation and elimination differed between Arochlor 1254 and retinol, among tissues, and among mice fed diets with various amounts and types of fiber. Dietary fiber supplementation did not decrease accumulation of PCB. However, the diet with chitosan increased fecal excretion of Arochlor 1254 compared to the fiber-free diet (P<0.05). The diets with fermentable fiber (polydextrose, indigestible dextrin and soy polysaccharides) increased urinary excretion of PCB compared to the diets with water-insoluble fiber (cellulose, rice bran and chitosan; P<0.05). The most efficacious diets for minimizing accumulation of environmental contaminants and accelerating elimination likely include a combination of soluble and insoluble fiber, but the specific types, proportions and amounts remain to be determined.

Levels of retinol and retinyl esters in plasma and urine of dogs with urolithiasis.

Vitamin A (VA) deficiency and Tamm-Horsfall glycoprotein (THP), a protein that binds retinol and retinyl esters in canine urine, might be involved in the pathogenesis of urolithiasis in dogs. In the present study, we assessed levels of retinol, retinyl esters, retinol-binding protein (RBP) and THP in plasma and urine of dogs with a history of urolithiasis (n = 25) compared with clinically healthy controls (n = 18). Plasma retinol concentrations were higher in dogs with uroliths of struvit (P < 0.01), calcium oxalate (P < 0.05), urate (P < 0.01) and cysteine, but there were no differences in the concentrations of plasma RBP and retinyl esters. Excretion of urinary retinol and retinyl esters were tentatively, but not significantly higher in the stone-forming groups, which was accompanied by increased levels of urinary RBP (P < 0.01) and lower excretions in THP (P < 0.01). The results show that VA deficiency may be excluded as a potential cause for canine urolithiasis. However, the occurrence of RBP and a concomitant reduction of THP in urine indicates a disturbed kidney function as cause or consequence of stone formation in dogs.

Urinary excretion of retinol in patients with multiple myeloma: a preliminary study.

Urinary excretion of vitamin A was studied in patients with multiple myeloma (MM). Eight of the 12 patients studied excreted retinol in urine; only one of them had elevated serum creatinine (115-150 micromol/L). There was a highly significant correlation between urinary retinol and serum creatinine (P < 0.0004). Urinary retinol correlated also with urine protein (P < 0.0001) and albumin (P = 0.001), but not with urinary immunoglobulin light chains. Urinary retinol excretion may be an early manifestation of renal dysfunction in MM patients. The effect of urinary retinol excretion on vitamin A homeostasis in MM deserves further study.