Abnormal Excretion Research Articles

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.

Serendipitous Gallbladder Uptake in a Bone Scan

Ectopic or serendipitous uptake of radiotracer can be a source of diagnostic confusion. A case is presented in which a bone scan showed accumulation of Tc-99m MDP in the gallbladder that initially was interpreted as the right kidney. The exact cause of gallbladder excretion of derivatives of Tc-99m MDP is not known. Our experience suggests that this is a rare finding and is not the result of the quality of radiopharmaceutical injected because none of the other patients injected with the same batch of Tc-99m or MDP kit showed gallbladder or abnormal intestinal excretion.

Microalbuminuria: Definition, Detection, and Clinical Significance

Proteinuria is a sign of abnormal excretion of protein by the kidney but is a nonspecific term including any or all proteins excreted. In contrast, albuminuria specifically refers to an abnormal excretion rate of albumin. Microalbuminuria refers to an abnormally increased excretion rate of albumin in the urine in the range of 30-299 mg/g creatinine. It is a marker of endothelial dysfunction and increased risk for cardiovascular morbidity and mortality especially, but not exclusively, in high-risk populations such as diabetics and hypertensives. Testing for microalbuminuria is now made easy by in-office dipstick tests (semiquantitative) and widely available laboratory testing (quantitative). Physicians should screen all diabetics for albuminuria and strongly consider screening hypertensives to identify those at higher risk for cardiovascular disease. Appropriate intervention, including use of drugs that block the renin-angiotensin-aldosterone system, may be appropriate in such cases as suggested by the American Diabetes Association and the Seventh Report of Joint National Committee on the Prevention, Detection, Evaluation, and Treatment of High Blood Pressure.

A new dimension of 1H-NMR spectroscopy in assessment of liver graft dysfunction.

High-resolution 1H-NMR spectroscopy of serum and urine samples of an 11-year-old male living related orthotopic liver transplant recipient is reported. Serum glutamine increased to abnormal levels along with simultaneous abnormal excretion of urinary glutamine post-transplantation. High levels of glutamine in both blood and urine and concomitant reduced urea levels in urine were found to be evidence of impairment in urea cycle and compatible with persistently abnormal graft function. Thus glutamine levels in serum and urine, and urea in the urine as observed by 1H-NMR spectroscopy highlight their important roles in monitoring liver graft function; increased glutamine levels lead to brain damage, if untreated.

Urinary protein excretion profile: A contribution for subclinical renal damage identification among environmental heavy metals exposure in Southeast Brazil

In Southeast Brazil. Ribeira Valley region has been a major public health concern due to the environmental heavy metals contamination indexes of vegetation, rocks and aquifers. caused by local mining in the past. Human contamination by low levels of heavy metals doesn't cause acute intoxication but in chronic exposure. renal damage may occur with progressive tubulointerstitial changes evolving to glomerular lesion. In this study we investigated the relationship between the profile of urinary excreted proteins (glomerular or tubular origin) of arsenic and mercury and blood lead concentration in children and adults from highly exposed regions of the Ribeira Valley. The subjects were classified as GROUP 1 (G1; higher environmental risk, n=333) and GROUP 2 (G2; lower risk of contamination. n=104) In order to determine the urinary excretion of total protein, albumin (MA. glomerular marker) and alpha 1 microglobulin (A1M, tubular marker) and the blood lead concentrations, random urine and blood samples were obtained. Plasmatic lead levels were assessed by atomic absorption spectrometry with graphite furnace. Total protein concentration (PROT) was assessed on a biochemical analyzer (pyrogallol red method). MA and AIM were determined by nephelometric method. Group 1 showed a higher frequency of altered urinary excretion of PROT (G1=34%; G2=1.0%), MA (G1=9.0%; G2=51%) and AIM (G1=7.5%; G2=3.8%), without significant differences between both groups. Elevated arsenic levels were more prevalent among subjects from Group 1 (28.8%) and demonstrated a significant correlation with abnormal urinary excretion of albumin and alpha-1-micrglobulin (p -0.019). Lead and mercury levels showed no difference among the groups and no correlation with MA and/or Al M. Our data suggests that abnormal urinary protein excretion is relatively frequent in this population independently of the plasmatic or urinary heavy metal levels. The early detection of possible renal damage become necessary for effective measures can be taken to prevent clinical nephropothies.

Asbjørn Følling and the Discovery of Phenylketonuria

In 1934, the Norwegian biochemist and physician Asbjørn Følling described an inherited metabolic disorder characterized by severe intellectual impairment, motor problems, and skin abnormalities. He found that affected individuals could be identified by the abnormal excretion of phenylpyruvic acid in their urine. The disorder, which Følling initially termed imbecillitas phenylpyrouvica, would later come to be known as phenylketonuria or PKU. The present paper focuses on the story of Følling's discovery and his subsequent contributions to the area of study. In the years that have followed, research on PKU has continued to play a major role in the neurosciences, shaping our understanding of genetic disorders, human metabolism, and brain development.

Dose of compound A, not sevoflurane, determines changes in the biochemical markers of renal injury in healthy volunteers.

Administration of sevoflurane in a circle absorption system generates Compound A, a nephrotoxin in rats. Reports examining the potential of Compound A to produce renal injury in humans have provided conflicting results. We tested the possibility that there is a threshold to Compound A-induced renal injury in humans and that, above this threshold, renal injury increases with increasing doses of Compound A. Eleven volunteers received 3% sevoflurane for 8 h at 2 L/min, and three volunteers received 3% sevoflurane for 8 h at 4-6 L/min. We measured inspired and expired concentrations of Compound A and urinary excretion of albumin, alpha-glutathione-S-transferase (GST), and glucose. The median urinary excretion of albumin, glucose, and alpha-GST for the first 3 days after anesthesia increased significantly from preanesthetic values in the 2-L/min group. Compound A doses < 240 ppm-h resulted in normal urinary excretion of albumin, glucose, and alpha-GST. Five of seven subjects who received doses > 240 ppm-h had abnormal excretion of albumin, and six of seven had abnormal alpha-GST urinary excretion (P < 0.05). Urinary excretion of albumin, alpha-GST, and glucose was normal by 14 days after exposure. We conclude that sevoflurane administration for 8 h at 2 L/min results in albuminuria and enzymuria when the dose of Compound A exceeds 240 ppm-h. That is, a Compound A concentration of 30 ppm breathed for > or = 8 h may produce transient renal injury. We examined the dose-response relationship of sevoflurane/Compound A and urinary excretion of albumin, glucose, and alpha-GST. Sevoflurane exposure for 8 h at a 2-L/min inflow rate produces transient albuminuria and enzymuria in healthy volunteers when the dose of Compound A exceeds 240 ppm-h (30 ppm for 8 h).

A pilot study of the use of a low oxalate diet in the treatment of vulval vestibulitis

Thirty-one women with vulval vestibulitis were evaluated for evidence of abnormal dietary oxalate intake and a wide range of dietary intakes was recorded. No woman was found to have abnormal urinary excretion. Sixteen women agreed to undertake a low oxalate diet and there was an apparent response in six (37%).

Plasma lipoproteins and the incidence of abnormal excretion of albumin in diabetic American Indians: the Strong Heart Study.

Animal studies suggest that lipids are risk factors for kidney diseases. Some prospective studies and clinical trials have reported predictive effects of lipoproteins on different stages of diabetic nephropathy in humans. We examined lipoprotein abnormalities to determine if they predict abnormal urinary excretion of albumin (> or = 30 mg albumin/g creatinine), using logistic regression. We followed 671 American Indians (211 men, 460 women) with Type II diabetes for a mean of 3.9 years (range 1.7-6.2). Participants were aged 45-74 years. They had normal excretion of albumin and normal serum creatinine at baseline. 67 men and 144 women developed abnormal excretion of albumin. In models controlled for age, treatment with oral hypoglycaemic agents or insulin, HbA1c, study site, degree of Indian heritage, mean arterial blood pressure, albumin excretion at baseline and duration of diabetes, a high HDL cholesterol was a protector for abnormal excretion of albumin in women [odds ratio (OR) comparing the 90th with the 10th percentile = 0.56, 95% confidence interval (CI) = 0.32-0.98], but not in men (OR = 1.5, 95% CI = 0.66-3.4). Further adjustment for obesity, insulin concentration, alcohol consumption or physical activity did not change the results. There was a tendency for high values of VLDL and total triglyceride and small LDL size to predict abnormal excretion of albumin in women only. We conclude that low HDL cholesterol was a risk factor for abnormal excretion of albumin in women, but not in men. Sex hormones may be responsible for sex differences in the association between HDL cholesterol and abnormal excretion of albumin.

Treatment of Patients with Essential Hypertension and Microalbuminuria

There has been increasing interest in the question of whether microalbuminuria can be used in the risk stratification of patients with essential hypertension. A cluster of cardiovascular and/or renal risk factors may be associated with microalbuminuria in hypertension. Despite this, prospective data about the potential role of microalbuminuria as a prognostic marker of cardiovascular and/or renal risk have been sparse and inconclusive until now. Blood pressure values have been considered the most important determinant of microalbuminuria in essential hypertension; however, hyperinsulinaemia--a metabolic component-was noted to be present in conjunction with high blood pressure. Furthermore, 2 other factors may be also related to microalbuminuria: salt sensitivity and renal structural changes (nephrosclerosis). We are now aware that the clinical and physiological implications of abnormal urinary albumin excretion (UAE) are much broader than anticipated, possibly involving haemodynamic, metabolic and vascular components overlapping several clinical syndromes. Achievement of short term UAE reduction with antihypertensive treatment depends on structural abnormalities established in the glomerulus, the extent of blood pressure reduction and the antihypertensive drug class used. In terms of UAE reduction, better results are obtained with ACE inhibitors or angiotensin II antagonists such as losartan and valsartan, than with other antihypertensive classes, although their true impact in preserving renal function needs to be assessed. The capacity of new calcium antagonists, such as amlodipine, lacidipine or mibefradil, to reduce UAE also needs to be assessed further. Thus, microalbuminuria may be seen as an integrated marker of risk and should be assessed in recently diagnosed patients with essential hypertension. In microalbuminuric patients, the target should be to decrease blood pressure < 135/85 mm Hg, reduce salt intake to around 100 mmol/day and prescribe a low-calorie diet if obesity is present. ACE inhibitors or angiotensin II antagonists have more potential benefits than the other classes of antihypertensive drugs in reducing UAE. Finally, a yearly assessment of microalbuminuria is recommended during treatment, to monitor the impact of therapy.

D87 Predictive factors of abnormal urinary albumin excretion in diabetic hypertensive patients

D87 Predictive factors of abnormal urinary albumin excretion in diabetic hypertensive patients

Inhibitory effect of 3-hydroxyacyl-CoAs and other long-chain fatty acid beta-oxidation intermediates on mitochondrial oxidative phosphorylation.

Among the abnormal biochemical findings, a mild to severe lactic acidaemia (Treem et al 1994) is frequently described in patients with a long-chain fatty acid β-oxidation disorder, together with a markedly increased plasma long-chain acylcarnitine fraction, abnormal excretion of C 6 -C 10 dicarboxylic acids and an accumulation of medium- and long-chain 3-hydroxydicarboxylic acids (Duran et al 1991). Our aim was to explain the lactic acidosis found in these patients and to associate this with the accumulation of long-chain fatty acid derivatives. Previously (Ventura et al 1995) we have reported that long-chain (C 14 -C 20 ) acyl-CoA esters, both saturated and unsaturated, inhibit the synthesis of ATP in digitonin-permeabilized normal human fibroblasts (Wanders et al 1993). Using the same system we investigated in this work the effects of palmitoyl-CoA, α,β-unsaturated palmitoyl-CoA, 3-hydroxy- and 3-ketopalmitoyl-CoA on the oxidative phosphorylation system.

Reduction of Leucocyte Proteolytic Enzyme Activity in Diabetic Patients with Microalbuminuria and Proteinuria: Its Possible Role in Diabetic Nephropathy

Mesangium enlargement and glomerular basement membrane thickening are cardinal features of diabetic nephropathy. The reasons for these changes are uncertain but decreased degradation of extracellular matrix may play a role. Mesangium degradation can be modulated by factors intrinsic to the kidney or by factors in the circulation. In this study the capacity of leucocyte proteolytic enzymes to degrade mesangium matrix materials was investigated. Leucocytes were obtained from 57 patients with NIDDM (age 58.3 +/- 8.8 years, duration 9.4 +/- 7.3 years, body mass index (BMI) 30 +/- 6 kg m-2, HbA1c 7.7 +/- 2.0%) and 21 control subjects (age 55.1 +/- 14.6 years, BMI 25 +/- 4 kg m-2). Leucocyte lysates from control and NIDDM subjects with normal AER degraded matrix to the same extent (40.6 +/- 8.2% vs 42.9 +/- 13.5%) while lysates from patients with microalbuminuria and proteinuria were less able to degrade matrix (33.0 +/- 14.2% and 26.1 +/- 12.7%, respectively). There was a significant inverse correlation between matrix degradation and AER (r = -0.49) and multiple regression analysis showed that AER was the most important factor determining degradation rate (R2 = 0.24). Degree of metabolic control, age, and blood pressure were not significant factors. The major enzyme(s) responsible for the matrix degradation was identified as metalloproteinase(s). We conclude that leucocytes from diabetic patients with abnormal albumin excretion have a decreased proteolytic capacity to degrade extracellular matrix. This may play a role in the glomerular basement membrane thickening and mesangium expansion which occurs in diabetic nephropathy.

Urinary excretion of type IV collagen and laminin in the evaluation of nephropathy in NIDDM: comparison with urinary albumin and markers of tubular dysfunction and/or damage

To clarify the diagnostic relevance of urinary type IV collagen (IV-C) and laminin in diabetic nephropathy, the excretion of these basement membrane proteins were determined by enzyme immunoassay in 172 non-insulin-dependent diabetic patients with different grades of nephropathy and 64 non-diabetic control subjects, and were evaluated in comparison with those of urinary albumin, N-acetyl-β- d-glucosaminidase (NAG) and α 1-microglobulin (α 1MG). These excretions were also compared between a group of non-diabetic renal disease (NDRD) patients ( n = 24) and a subgroup of the diabetic patients studied ( n = 76), whose urinary albumin excretion (UAE) varied within the ranges of micro-and macroalbuminuria. Of the diabetic patients studied, 49.7%, 53.4% and 32.4% had raised urinary albumin, NAG and α 1MG excretion, respectively. In these patients, 54% and 53% exceeded the upper limit of normal for urinary IV-C and laminin. The level of IV-C and laminin excretion and the prevalence of their abnormal excretion showed a trend to increase with increasing grade of nephropathy, as assessed by UAE. In the normoalbuminuric [UAE < 20 mg/g creatinine (Cr)] stage, 28.3% and 26.3% patients had raised urinary IV-C and laminin excretion, respectively. In this stage, the excretion values for IV-C and laminin also rose significantly even when the UAE was ≤ 10 mg/g Cr ( P < 0.05 and P < 0.005, respectively). There was a close linear relationship between IV-C and laminin excretion ( r = 0.73, P < 0.0001), together with their significant relationships with albumin, NAG and α 1MG excretion. The relationship of urinary IV-C and laminin with urinary NAG and α 1MG excretion remained significant even in normoalbuminuric patients. The normoalbuminuric patients with raised NAG and/or α 1MG excretion also had a higher prevalence of raised IV-C and laminin excretion than those with normal NAG and α 1MG excretion. The excretion values for IV-C and laminin, and the excretion ratios for IV-C albumin and laminin albumin were significantly higher in diabetic patients with evidence of incipient and clinical nephropathy than in NDRD patients, though the two patient groups had a comparable level of serum Cr and UAE. We conclude that the measurement of urinary IV-C and laminin may have potential for the evaluation of diabetic nephropathy. Furthermore, their determination might be helpful for distinguishing diabetic versus non-diabetic etiologies of altered renal function in diabetic patients.

Increased permeability of macroscopically normal small bowel in Crohn's disease

To investigate permeability alterations of the macroscopically normal jejunum in Crohn's disease, the permeation of two probes was measured during perfusion of an isolated jejunal segment. The data were compared with the results obtained by the standard per oral test in the same patients. Test probes were PEG-400 and [51Cr]EDTA. Ten normal individuals, 12 patients with Crohn's ileitis or ileocolitis, and seven patients with isolated Crohn's colitis all with normal jejunum on x-ray series were studied. Upon perfusion of the proximal small bowel, the 3-hr [51Cr]EDTA excretion was significantly increased in ileitis patients (P = 0.023) as compared to normals. The excretion exceeded the highest value of normals in eight of 12 ileitis patients. The excretion in Crohn's colitis patients was not significantly increased (P = 0.24) and abnormal excretion was found only in one of the Crohn's colitis patients. PEG-400 permeation during perfusion did not differentiate between the groups, but five of the seven patients with isolated Crohn's colitis had PEG-400 excretion exceeding the highest value in normals. Overall, 13 of the 19 patients had increased permeation of one of the two probes through jejunal mucosa during perfusion. These data suggest that the permeability is increased in the majority of patients even in segments that seem normal on x-ray.

A new syndrome with ethylmalonic aciduria and normal fatty acid oxidation in fibroblasts

We describe four Italian male infants with a novel clinical phenotype characterized by orthostatic acrocyanosis, relapsing petechiae, chronic diarrhea, progressive pyramidal signs, mental retardation, and brain magnetic resonance imaging abnormalities. The first symptoms appeared after the termination of breast-feeding and introduction of formula feeding. Marked persistent 2-ethylmalonic aciduria was associated with abnormal excretion of C 4-C 5( n-butyryl-, isobutyryl-, isovaleryl-, and 2-methylbutyryl-) acylglycines and acylcarnitines and with intermittent lactic acidosis. Short- and branched-chain plasma acylcarnitine levels were also elevated. 2-Ethylmalonic aciduria is generally regarded as being indicative of a defect in fatty acid oxidation. Extensive studies of cultured fibroblasts failed to reveal such a defect. The observation of intermittent urinary excretion of 2-ethylhydracrylic acid pointed to involvement of the isoleucine R pathway in ethylmalonate biosynthesis. This hypothesis was tentatively corroborated by the biochemical responses to an oral isoleucine challenge in two patients. However, fibroblast studies showed normal oxidation rates of [ 14C]isoleucine (ul), indicating that this is not a defect of isoleucine oxidation expressed in skin fibroblasts. In one of two patients tested, cytochrome c oxidase activity was partially reduced (45%) in cultured fibroblasts. This unique clinical and biochemical phenotype identifies a new metabolic encephalopathy of yet undetermined cause. (J P EDIATR 1994;124:79-86)

Abnormal Excretion of Urinary Phospholipids and Sulfatide in Patients with Mitochondrial Encephalomyopathies

We found that patients with mitochondrial encephalomyopathies excreted urinary phosphatidylethanolamine, cardiolipin, and phosphatidylserine most likely derived from mitochondria and sulfatide which is specific to myelin or the kidney. It is of interest that four patients with myoclonus epilepsy with ragged-red fibers and one patient with chronic progressive external ophthalmoplegia all showed qualitatively similar abnormal excretion of such urinary lipids. It is conceivable that the urinary acidic phospholipids reflect abnormalities in the mitochondrial phospholipids, which are very important for mitochondrial enzymatic activities.

Mevalonic aciduria in 3 siblings: A new recognizable metabolic encephalopathy

Mevalonic aciduria, due to mevalonate kinase deficiency, is the first recognized defect in the biosynthesis of cholesterol and isoprenoids. Very few patients with this disorder have been reported. Three siblings born from consanguineous parents are reported. Several clinical signs were present in all 3 children, including failure-to-thrive, susceptibility to infections, hepatosplenomegaly, cataract, and psychomotor retardation. Dysmorphic features were more apparent in the two older siblings. Urinary organic acid analysis by gas chromatography/mass spectrometry invariably revealed a high urinary excretion rate of mevalonic acid. Mevalonate kinase activity assayed in fibroblasts was very low. Diagnosis of this very rare disease may be suspected simply on clinical evidence; it is confirmed by abnormal excretion of mevalonic acid.

Urinary Excretion of Three Specific Renal Tubular Enzymes in Patients Treated with Nonsteroidal Anti-Inflammatory Drugs (NSAID)

Ten patients, mean age 51.50 +/- 3.03 years, with degenerative rheumatism on NSAID treatment without any sign of renal disease, and 11 control subjects, mean age 43.50 +/- 1.51 years, were studied. NSAID treatment was of 11.30 +/- 5.60 weeks duration in average, with ibuprofen, naproxen, or indomethacin. Urinary excretion of three specific renal tubular enzymes--AAP: alanine-amino-peptidase, GGT: gamma-glutamyl-transpeptidase, and beta-NAG: beta-N-acetyl-glucosaminidase, were determined in 8-h overnight urine samples, as well as GFR creatinine clearance/1.73 m2, urinary volume/8 h, specific gravity of the urine, proteinuria and glucosuria. In the group treated with NSAIDs, urinary excretion of the enzymes was significantly higher than in the control group--AAP: 1414.20 +/- 317.60, 864.20 +/- 94.42, p < 0.00001; GGT: 8034.6 +/- 1378.55, 5095.64 +/- 614.40, p < 0.00001, and beta-NAG: 1644.60 +/- 299.97, 964.82 +/- 142.00, p < 0.00001. Patients on NSAID treatment showed abnormal urinary excretion of AAP in 7/10 cases, of GGT in 6/10, and of beta-NAG in 7/10 cases. Duration of the treatment did not correlate with the urinary excretion of the enzymes. Age was in correlation with the urinary excretion of the enzymes only in the control group, r = 0.52, p < 0.005 for AAP, r = -0.43, p < 0.02 for GGT, and r = -0.23, p < 0.05 for beta-NAG.(ABSTRACT TRUNCATED AT 250 WORDS)

尿中β‐アミノイソ酪酸の異常高値を伴う巨赤芽球性貧血の１例

A 78-year-old man was admitted to our hospital with anemia and jaundice. Hematological studies revealed hyperchromic macrocytic anemia, and biochemical studies revealed findings of hemolysis. The folic acid level was low and megaloblasts were observed in the bone marrow. From these findings, the patient was diagnosed as having megaloblastic anemia due to folic acid deficiency. This patient had been a heavy alcohol drinker in the habit of drinking alcohol without meals. He began to eat regular meals in the hospital, and the anemia and jaundice improved gradually. Since liver cirrhosis was suspected, amino acid analysis of the urine was performed, and abnormal excretion of beta-amino-isobutyric acid (BAIB) was found. According to the amount of BAIB excreted, the Japanese population can be divided into low and high BAIB excretors comprising 65% and 36%, respectively. BAIB is also considered to reflect dissimilation of thymine. The present patient was included in the high excretion group because of the abnormally high urine level of BAIB, which was considered to be caused by ineffective hematopoiesis in the bone marrow as a result of his megaloblastic anemia. For this reason, dissimilation of thymine was considered to have been active in this patient.