Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033687 (proteinuria)
 24,015 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Determinations of total calcium, total magnesium, calcium ion, parathyroid hormone and 6-keto-prostaglandin-F1 alpha levels were carried out on 84 blood samples from 4 groups of women categorised as non-pregnant normotensive (NNP), pregnant normotensive (NP), pregnancy-induced hypertension (PIH) and pre-eclampsia (PE). PIH was clinically diagnosed when the diastolic pressure was more than 90 mmHg and was only hypertensive during pregnancy while PE was with additional proteinuria after 20 weeks of gestation. Compared to NNP women, total calcium and parathyroid hormone levels were of lower levels (p < 0.05) in NP women while in PIH women, total calcium and 6-keto-prostaglandin-F1 alpha levels were also lowered (p < 0.05). Compared to NNP women, PE women's levels of total calcium, calcium ion and 6-keto-prostaglandin-F1 alpha decreased (p < 0.05) while parathyroid hormone level increased (p < 0.05). When compared to the NP women, PE women had decreased levels (p < 0.05) of total calcium as well as calcium ion and increased level (p < 0.05) of parathyroid hormone. Calcium ion was found to be negatively correlated (NNP : r = -0.883, p = 0.008/NP : r = -0.931, p = 0.000) while parathyroid hormone was positively correlated (NNP : r = 0.904, p = 0.013/NP : r = 0.913, p = 0.000) with mean arterial pressure.
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PMID:Determination of mineral, parathyroid hormone, and 6-keto-prostaglandin-F1 alpha levels in pregnant women with hypertension and pre-eclampsia. 878 37

The human nephrotic syndrome (NS) is accompanied by important alterations of mineral and bone metabolism. The purpose of the present study was to examine bone metabolism in rats with experimental NS and normal creatinine clearance, and to evaluate the reversibility of this alteration. NS was induced by three injections of puromycin aminonucleoside (PAN) on days 0, 21, and 35 (10, 5, and 5 mg/100 g body weight, respectively). The biochemical markers of bone formation (osteocalcin and alkaline phosphatase) and bone resorption (hydroxyproline and pyridinoline), bone mineral content (BMC), and bone mineral density (BMD), determined by dual-energy x-ray absorptiometry (DEXA), were studied on days 0, 7, 14, 28, 42, 56, 84, and 112. Proteinuria was present throughout the study. Hypoproteinemia was seen on days 7, 28, 42, and 56, returning to control values on days 84 and 112. In serum, osteocalcin (OC) concentration increased (p < 0.001), and alkaline phosphatase (ALP) decreased (p = 0.002). In urine, hydroxyproline increased (p < 0.001), but urinary pyridinoline was not different from the control group throughout the study. Increased serum parathyroid hormone concentration and decreased levels of 25-hydroxy and 1,25-dihydroxyvitamin D were found from day 7. During the intense proteinuria, bone resorption predominates and decreased BMC and BMD ensues in PAN-nephrotic rats. PAN-nephrotic rats showed low BMC and BMD compared to control group (p < 0.001). At the end of the study, when proteinuria persisted but total serum protein returned to control values, the biochemical bone markers, BMC, and BMD returned to normal. In conclusion, PAN-nephrotic rats had reversible bone alterations that were related to the magnitude of proteinuria and the concentration of total serum protein.
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PMID:Biochemical bone markers, bone mineral content, and bone mineral density in rats with experimental nephrotic syndrome. 915 58

Bisphosphonates (BPs) are used for the treatment of both benign and malignant diseases characterized by increased bone resorption. Because of their potential nephrotoxicity, currently available BPs have to be administered by slow intravenous infusion, with conventional doses requiring an infusion time of at least 2 h. In the present investigation, we evaluated the safety and efficacy of the new BP ibandronate as administered by intravenous bolus injection. On day 0, 15 normocalcemic breast cancer patients with bone metastases were treated with 3 mg of ibandronate injected intravenously over 60-120 s. Ibandronate treatment led to significant decreases in serum levels of calcium (p < 0.0001) and phosphate (p < 0.0001) and to subsequent increases in serum concentrations of parathyroid hormone (p <0.0001) and calcitriol (p <0.0001). Moreover, there was a significant reduction in the urinary excretion of calcium (p <0.0001), pyridinoline (p <0.001), and deoxypyridinoline (p < 0.0001). Three serious adverse events were observed: vomiting (WHO grade 3), pulmonary infection (WHO grade 2), and deterioration of a pre-existing impaired glucose tolerance (WHO grade 3). Only vomiting appeared to be related to administration of the drug. The most frequent nonserious adverse events were 10 cases of transient clinically asymptomatic hypocalcemia and 8 cases of asymptomatic hypophosphatemia. Serum levels of creatinine and urea nitrogen did not increase, nor did creatinine clearance deteriorate. When tested with the dipstick method, proteinuria was present in five (33%) patients prior to ibandronate treatment (median protein concentration, 30 mg/dl). Following the BP injection, seven (47%) patients showed slight (highest protein concentration, 30 mg/dl) transient proteinuria at at least one time point, of which six cases appeared in conjunction with leucocyturia and three with microhematuria. Side effects specific to aminosubstituted BPs (fever, reduction in white blood cell counts, and lymphocyte counts) were not seen in these 15 patients. In conclusion, a single intravenous injection of 3 mg of ibandronate significantly inhibited osteoclast activity as reflected by the decrease in serum calcium and in urinary parameters of bone resorption. Serum creatinine levels and estimates of creatinine clearance were not affected by therapy. However, before repeated bolus injections of ibandronate at this dosage can be recommended for further clinical trials, whether a relationship exists between the transient pathological urinary findings and injected ibandronate needs to be determined.
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PMID:Administration of the bisphosphonate ibandronate (BM 21.0955) by intravenous bolus injection. 915 73

Hypocalciuria has been associated with preeclampsia (gestational hypertension with proteinuria or other maternal organ dysfunction) but not usually with pure gestational hypertension or normal pregnancy. We hypothesized that hypocalciuria would be a marker of emerging preeclampsia in women presenting with gestational hypertension who later developed preeclampsia. Eighty-one women with de novo hypertension in the second half of pregnancy (n = 81) were enrolled prospectively. At first assessment, calcium/creatinine ratio was determined in a spot urine. Patients were followed until delivery and were classified subsequently according to the occurrence of preeclampsia. Gestational hypertensive patients who became preeclamptic (n = 31) had lower urinary calcium/creatinine ratios at presentation (ratio = 0.07, interquartile range [IQR] = 0.04-0.11) than women who remained as gestational hypertensives (n = 50; ratio = 0.17, IQR = 0.08-0.21; P = .002). Intact plasma parathyroid hormone (PTH) concentrations were similar between groups. Using a receiver operator curve, the best threshold value for the development of preeclampsia was a calcium/creatinine ratio of 0.10, which yielded a sensitivity of only 68% and a specificity of 70%. A low calcium/creatinine ratio preceded the emergence of preeclampsia by 12 (7-24) (median [IQR]) days among a group of women with gestational hypertension. Though this implies primary or secondary disturbances of renal calcium handling even before preeclampsia is clinically apparent, this measurement does not have sufficient sensitivity to recommend its use as a screening test for the emergence of preeclampsia.
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PMID:Urinary calcium/creatinine ratio as a predictor of preeclampsia. 968 45

Dent's disease is an X-linked disorder associated with the urinary loss of low-molecular-weight proteins, phosphate and calcium, which often leads to kidney stones. It is caused by mutations in ClC-5, a renal chloride channel that is expressed in endosomes of the proximal tubule. Here we show that disruption of the mouse clcn5 gene causes proteinuria by strongly reducing apical proximal tubular endocytosis. Both receptor-mediated and fluid-phase endocytosis are affected, and the internalization of the apical transporters NaPi-2 and NHE3 is slowed. At steady state, however, both proteins are redistributed from the plasma membrane to intracellular vesicles. This may be caused by an increased stimulation of luminal parathyroid hormone (PTH) receptors owing to the observed decreased tubular endocytosis of PTH. The rise in luminal PTH concentration should also stimulate the hydroxylation of 25(OH) vitamin D3 to the active hormone. However, this is counteracted by a urinary loss of the precursor 25(OH) vitamin D3. The balance between these opposing effects, both of which are secondary to the defect in proximal tubular endocytosis, probably determines whether there will be hypercalciuria and kidney stones.
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PMID:ClC-5 Cl- -channel disruption impairs endocytosis in a mouse model for Dent's disease. 1109 45

Three strategies can help delay chronic kidney disease (CKD) progression: early identification of patients, modification of risk factors, and implementation of the best interventions. Early identification of patients requires accurate screening tools. As serum creatinine is an unreliable marker of kidney dysfunction, clinicians should focus on the glomerular filtration rate or other markers of true kidney function. Clinicians should also be aware of other indicators of abnormal kidney function, such as anaemia, acidosis, and increases in parathyroid hormone level. Additionally, both clinicians and patients should be aware of the "non-modifiable" and "modifiable" risk factors for CKD. Non-modifiable risk factors include age, gender, race, diabetes, and genetic make-up, while modifiable risk factors include elevated blood pressure and blood glucose, proteinuria, anaemia, metabolic disturbances, and dyslipidaemia. Patients should be particularly aware of the risk factors common to both cardiac and kidney disease, such as hypertension, proteinuria, anaemia, and (possibly) dyslipidaemia and diabetes. A single centre study demonstrated that inclusion in a multidisciplinary CKD clinic programme produced the greatest increases in time to renal replacement therapy, haemoglobin levels, and epoetin treatment usage at initiation of dialysis in comparison with standard nephrology care or no care. Two years after starting dialysis, the number of deaths was lowest, and the number of patients who had received a transplant or were still on dialysis was highest, in the CKD clinic-treated group. These results confirm those of previous studies, which showed that timely referral to a multidisciplinary team for management prior to dialysis decreases the risk of adverse patient outcomes. This suggests that a multidisciplinary, collaborative, proactive approach increases the likelihood of early identification of CKD patients and risk factor modification. However, further evidence-based demonstrations of success are required, showing benefit to both patients and health care systems.
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PMID:Identification of patients and risk factors in chronic kidney disease--evaluating risk factors and therapeutic strategies. 1159 Feb 59

Dent's disease is a nephrolithiasis disorder associated with hypercalciuria and low molecular weight proteinuria that is caused by mutations in the voltage-gated chloride channel ClC-5. Because the exact cause of hypercalciuria in this disease is unknown and could come from a renal, intestinal, or bone origin, we have investigated overall calcium handling in the ClC-5 knockout mouse (ClC-5 KO). On a high calcium diet, ClC-5 KO mice had elevated serum 1alpha,25-dihydroxyvitamin D3 (1alpha,25D3), alkaline phosphatase (AP), osteocalcin (OC), and urinary deoxypyridinoline (DPD), but serum parathyroid hormone (PTH), calcium, and intestinal calcium uptake was similar to that of wild-type (WT) mice. A 30-fold decrease in dietary calcium intake caused elevation of serum PTH and urinary cyclic adenosine monophosphate in ClC-5 KO mice and decreased the renal calcium excretion, which still remained 2-fold above that of WT mice. On this low calcium diet, both groups of mice had the same serum 1alpha,25D3, with similar increments in intestinal calcium absorption, serum AP, OC, and urinary DPD. These data indicate that the hypercalciuria in the ClC-5 KO mice on low and high calcium diets is of bone and renal origin and is not caused by increased intestinal calcium absorption, despite an elevated serum 1alpha,25D3. These mice data suggest that young patients with this disease may have a propensity for altered bone homeostasis that should be monitored clinically.
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PMID:The ClC-5 knockout mouse model of Dent's disease has renal hypercalciuria and increased bone turnover. 1267 22

A 5-year-old girl presented with short stature. She was found to have rickets due to renal phosphate wasting and nephrocalcinosis. Serum parathyroid hormone was suppressed, 25-OH vitamin D was within the normal range, and 1,25-(OH)(2 )vitamin D was elevated. In addition, she had hypercalciuria, proteinuria, which was partially tubular in origin, and a reduced glomerular filtration rate of 58 ml/min per 1.73 m(2). Treatment with phosphate supplements resulted in healing of the rickets and normalization of the serum 1,25-(OH)(2 )vitamin D level. This patient is an example of hypercalciuric rickets, most likely due to an inherited disorder of phosphate metabolism. Hypercalciuric rickets can be inherited as an autosomal recessive as well as autosomal dominant trait.
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PMID:A girl with rickets and nephrocalcinosis. 1464 29

There is a lack of evidence to support the belief that dietary measures are beneficial in slowing the progression of chronic renal insufficiency (CRI). We prospectively monitored nutrient intakes and progression of CRI over a 2-year period in children aged 2-16 years with differing levels of severity of CRI, as part of their ongoing joint medical/dietetic care. Children were grouped following [5'Cr]-labelled EDTA glomerular filtration rate(GFR, ml/min per 1.73 m 2) estimations, into 'normal'kidney function [GFR >75, mean 106 (SD 19.5), n=58],providing baseline data only, mild (GFR 51-75, n=25),moderate (GFR 25-50, n =21), and severe (GFR <25, n=19) CRI. Children with CRI were followed for 2 years,with 51 completing the study (19 mild, 19 moderate, 13 severe CRI) and were excluded if they subsequently required dialysis. Regular medical and dietary advice was provided and yearly 3-day semi-quantitative dietary di-aries and baseline and 6-monthly measurements of blood pressure and urinary protein/creatinine ratio were obtained. Mean reductions in estimated GFR over 2 years were -9.4, -5.8, and -6.0 ml/min per 1.73 m2 for mild,moderate, and severe CRI, respectively. Mean systolic blood pressure standard deviation score (SDS) fell significantly in all groups by 0.7 SDS, whereas there was little change in proteinuria. From reported dietary intakes,median sodium intakes increased (+10 mmol/day) and protein intakes decreased (-0.4 g/kg per day). Median phosphate intakes did not change significantly, where as calcium intakes fell in all groups, with an overall median of -20% reference nutrient intake (RNI) (F=33.3,P<0.001). Of children with moderate CRI, 65% finished with calcium intakes below 80% RNI, and parathyroid hormone (PTH) concentrations significantly increased in this group (F=6.0, P=0.021). Higher phosphate and sodium intakes were associated with greater deterioration in estimated GFR in children with mild CRI (r2=0.30,P=0.02; r-=0.31, P=0.02, respectively). There was no such correlation for protein intake or PTH. This study emphasises the need for a joint medical and dietetic approach and indicates a number of interventions other than protein restriction, which could be commenced early in children with CRI in an attempt to delay progression.
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PMID:Optimising nutrition in chronic renal insufficiency--progression of disease. 1534 63

We encountered a 16-year-old boy with Japanese Dent's disease who exhibited renal insufficiency and an osseous disorder of the spine. Proteinuria first was noted at the age of 2 years. At 13 years, the patient underwent analysis of the CLCN5 gene, which identified missense mutation (I524K) in exon 10. During follow-up, a marked increase in urinary beta2-microglobulin was associated with mild deterioration of renal function. At the age of 15 years, hypocalcemia (7.5 mg/dl) accompanied by an increased plasma concentration of alkaline phosphatase was first detected. At that time, plasma concentration of 25(OH)D3 and 1'alpha25(OH)2D3 were low accompanied by a high plasma parathyroid hormone concentration. A renal biopsy specimen revealed tubulointerstitial alterations including mononuclear cell infiltration, partial fibrosis and focal glomerular sclerosis. Immunofluorescence revealed weak, discontinuous staining of megalin along the brushborder of renal proximal tubules. Western blotting demonstrated decreased urinary excretion of megalin. Thus, clinical manifestations and prognosis may vary in Japanese Dent's disease. Reduced megalin expression may have disturbed calcium homeostasis, leading to osseous disorder in our patient.
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PMID:A boy with Japanese Dent's disease exhibiting abnormal calcium metabolism and osseous disorder of the spine: defective megalin expression at the brushborder of renal proximal tubules. 1552 62


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