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)

Neonates, especially preterms, are known to have low glomerular filtration rates (GFR). This may result in elevated trough concentrations during multiple administration of aminoglycosides (AGs), potentially leading to nephro- and ototoxic reactions. The once-daily administration (q.d.) of AGs has been shown to be equally or better tolerated in adults and children than the conventional schedules (twice daily, b.i.d.; thrice daily, t.i.d.), while offering potential pharmacodynamic and nursing advantages. No data, however, are available for neonates. As a consequence, this pilot study was conducted in order to assess the tolerance of the once-a-day administration of amikacin in comparison with the twice daily dose regimen, in relation to the pharmacokinetics of the drug under these two schedules. 22 Male neonates (gestational age > or = 34 weeks; postnatal age < or = 2 days) were randomized to receive amikacin (AK) (15 mg/kg/day) q.d. (n = 10) or b.i.d. (n = 12) together with ampicillin (50 mg/kg/12 h). AK plasma levels were measured at days 1, 3, 5 and 7 of treatment just before the next dose (trough level) and 1 h after completion of infusion (peak level) and after 3 and 6 h only at day 1. Due to the small size of the samples, no difference in efficacy could be assessed and was not the aim per se. Glomerular dysfunction was assessed by creatinine clearance, and tubular injuries by the urinary excretion of proteins (retinol binding protein, beta 2-microglobulin, clara cell protein (P1) and microalbumin), enzymes (N-acetyl-beta-D-glucosaminidase, alkaline phosphatase, alanine aminopeptidase, and gamma-glutamyltransferase), and total phospholipids (TPL) in urine. Ototoxicity was assessed by brainstem auditory evoked potentials (BAEPs) at days 0, 3 and 9 of therapy. Eight healthy neonates served as controls. All patients showed a normal and similar increase of GFR during the first postnatal days. Proteinuria did not increase, but enzymuria and TPL increased significantly during the treatment in both AK groups without significant difference between groups. BAEPs at day 9 were not significantly different between treated and untreated patients. We conclude from this pilot study that, in the absence of more toxicity, the q.d. administration of AK in neonates of > or = 34 weeks of gestational age may be recommended over its bid schedule in view of its potential advantages.
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PMID:Once-a-day administration of amikacin in neonates: assessment of nephrotoxicity and ototoxicity. 782 57

Two dogs were seen at the University Veterinary Teaching Hospital, Nairobi, Kenya, both having histories of dyspnoea, progressively enlarging abdomens, anasarca, ascites, pleural and pericardial effusion, and pulmonary oedema. One of the dogs had a mild neutrophilic leucocytosis, elevated levels of alkaline phosphatase, alanine aminotransferase, lactate dehydrogenase and proteinuria. Histopathological examination of the myocardium revealed some damage to myocytes and a mononuclear cellular infiltration involving the myocardium, liver and kidneys. The two dogs had a fondness for avocado fruits and, as the presenting syndrome is identical to that seen in goats, sheep and horses poisoned by avocados, a comparison is made and the probable manifestation of this poisoning presented.
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PMID:Putative avocado toxicity in two dogs. 789 92

A 6-month protocol of oral pulse calcitriol was used in nine uraemic children (2-14 years old) on dialysis who presented with renal osteodystrophy. Calcitriol was administered twice a week, 4 micrograms per dose for patients over 30 kg and 3 micrograms for patients less than 30 kg. Plasma levels of parathyroid hormone, calcium, phosphorus and alkaline phosphatase were carefully controlled during the study. Parathyroid hormone levels decreased by 68% and 56% by the 2nd and 6th months of treatment in seven patients, while they remained unchanged in two patients with focal segmental glomerulosclerosis and massive proteinuria. Eight hypercalcaemic episodes from 77 determinations were observed, all of them recovered after 1 week of vitamin D withdrawal. We conclude that oral calcitriol pulse therapy is a good alternative for renal osteodystrophy in uraemic children. Careful monitoring of plasma parathyroid hormone and calcium is needed during follow-up when using this approach in paediatric patients.
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PMID:Calcitriol oral pulse therapy in children with renal osteodystrophy. 858 20

Merbarone, NSC 336628, is an investigational anticancer drug with activity against experimental animal tumors including melanoma. This paper presents results of a Phase II clinical study of merbarone in patients with biopsy proven stage IV malignant melanoma without prior chemotherapy and with no evidence of CNS involvement. Thirty-five patients with median age 58 (range 27-81), with performance status 0-2 were treated with merbarone 1000 mg/m2/day for five days by intravenous continuous infusion repeated every 3 weeks. All patients (21 males and 14 females) were evaluable for toxicity. Two patients were not evaluable for response having been removed from protocol treatment due to toxicity and received other treatment during the first course of chemotherapy. Among the evaluable patients there was one complete response in a supraclavicular lymph node lasting four months and one partial liver response lasting three months. The remaining thirty-one patients were non-responders. Of these one had a stable disease lasting 21 months. The overall objective response rate was 6% (2/35) with a 95% confidence interval of 1%-19%. Twenty-six of the 35 patients have died. The estimated median survival of the entire group was 9 months with a 95% confidence interval six to eleven months. Renal toxicity was dose-limiting and manifested as increasing serum creatinine (54% of patients), proteinuria (51%) and hematuria (9%). One patient experienced grade 4 creatinine increase, proteinuria and acute renal failure. Other toxicities included nausea (71%), vomiting (51%0, malaise (23%), weakness (20%), alopecia (17%), diarrhea (17), anorexia (14%) transaminase (SGOT, SGPT) increase (14%), constipation (14%), alkaline phosphatase or 5'nucleotidase increase (9%), and fever (9%). Hematologic toxicity (granulocytopenia, leukopenia, and anemia) was generally mild and infrequent (29%, only one patient had grade 4 granulocytopenia). Overall 9 patients (26%) had at least one grade 3 toxicity. We conclude that merbarone at this dose and schedule has detectable but minimal activity in the treatment of metastatic malignant melanoma and given the significant renal toxicity this schedule does not merit further evaluation in this disease.
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PMID:Evaluation of merbarone (NSC 336628) in disseminated malignant melanoma. A Southwest Oncology Group study. 861 77

Certain chromium compounds are known to be nephrotoxic, but renal damage from long-term environmental or occupational exposure to chromium has not been documented. To detect possible preclinical renal damage, we tested the urine of 55 lifelong residents of an area contaminated with chromium landfill. The levels of four proteins were determined in urine samples: (1) human intestinal alkaline phosphatase, (2) tissue nonspecific alkaline phosphatase, (3) N-acetyl-beta-D-glucosaminidase, and (4) microalbumin. No elevated levels of proteins were found, and there were no significant correlations between urine protein and urine chromium concentrations. We concluded that long-term environmental exposure to chromium dust did not lead to tubular proteinuria.
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PMID:Absence of tubular proteinuria following environmental exposure to chromium. 875 13

The activity of gamma-glutamyl transferase (GGT), alkaline phosphatase (AP), lactate dehydrogenase (LDG), N-acetyl-beta-D-glucosaminidase (NAG) was assessed in 53 patients with psoriasis (PS), 24 PS patients with affected kidneys, 50 patients with type 1 diabetes mellitus(DM). Enhanced activity of the enzymes occurred not only in nephropathy patients but also in those without proteinuria. AP and NAG were more active in PS, while LDG and NAG in DM. Both in PS and DM, NAG activity rose 3-4-fold compared to control. A direct correlation was found between enzymuria and uremia, glycemia (in hyperglycemia only) and cholesterolemia. An inverse relationship existed between enzymuria and uricosuria. The above changes in enzymic activity are attributed to impairment of tubules of the kidney induced by PS and DM. Diagnostic significance of enzymuria as a marker of early tubular involvement is confirmed by investigations of renal biopsies.
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PMID:[Urinary enzymes in the assessment of the early stage of kidney involvement in psoriasis and diabetes mellitus]. 877 18

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

Gemcitabine is a novel fluorine-substituted cytarabine (Ara-C) analogue with activity against a range of solid tumours. Besides dose-limiting haematological toxicity, renal side-effects were observed from phase I and II studies concerning elevations of serum creatinine, proteinuria and erythrocyturia. The aim of this study was to investigate the effect of gemcitabine on renal function in 11 untreated patients with non-small cell lung cancer (NSCLC). Gemcitabine was given as weekly infusions of 1250 mg/m2 for 3 weeks, followed by 1 week rest. This comprised one cycle (maximum of six cycles). The glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were measured simultaneously with a constant infusion of 125I-iothalamate and 131I-hippuran, respectively. Tubular damage was monitored by excretion of tubular enzymes (lactic dehydrogenase (LDH), alkaline phosphatase (ALP), gamma-glutamyltransferase (GT) and beta 2-microglobulin); glomerular damage was monitored by excretion of albumin in the urine. In 9 patients, the effect of the first infusion was evaluated. After the first infusion of gemcitabine, no change was observed in renal function. After two, three, and six cycles of treatment, no significant changes in GFR and ERPF were noticed in 9 evaluable patients. However, in 3 patients, a decrease in GFR of > 10% was observed after multiple cycles. In one of them this was accompanied with albuminuria (360 mg/24 h) and erythrocyturia. There were no significant changes in urinary excretion of tubular enzymes or albumin. In conclusion, we did not observe acute renal toxicity with gemcitabine. No significant cumulative effects of gemcitabine on renal function could be detected, although 3 patients, treated with multiple cycles of gemcitabine, showed a moderate decrease in renal function. Glomerular damage might play a role in the development of renal function loss.
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PMID:Effects of gemcitabine on renal function in patients with non-small cell lung cancer. 962 59

Arterial hypertension, which represents a common problem in patients with renal transplant, contributes to the cardiovascular morbidity and mortality of these patients. The most usual immunosuppressive drugs (cyclosporine and FK-506) collaborate on the development of hypertension. Calcium channel blockers are the most habitually used antihypertensive drugs in this population, although its long-term hemodimamycs effects could be deleterious especially in transplanted patients with chronic graft nephropathy. Losartan, a specific blocker of angiotensin II (AT1) receptors, has demonstrated a potent antihypertensive effect with a good safety and tolerance profile. The glomerular effects of losartan could be useful in transplanted patients. The present open, prospective and multicenter study evaluated the efficacy and safety of losartan in the treatment of hypertension in a group of patients with a renal transplant. Seventy-six patients with systolic blood pressure > or = 140 and/or diastolic blood pressure > or = 90 mm Hg, and/or patients on therapy with one antihypertensive drug and related side effects were included. After inclusion, therapy with losartan 50 mg/24 hr was started, discontinuing the previous antihypertensive therapy and/or therapy which caused the side effects. At four weeks, if blood pressure (BP) was not controlled, hydrochlorothiazide 25 mg or furosemide 40 mg/24 hr was added. At baseline and at weeks 2, 4, 8 and 12, the following parameters were monitored: BP, creatinine, hematocrit, hemoglobin, glucose, ions, uric acid, cholesterol, triglycerides, bilirubin, SGOT, SGPT, GGT, LDH, calcium, phosphate, alkaline phosphatase, proteinuria, and both cyclosporine and FK-506 levels in whole blood. Sixty-seven patients completed the 12-week study period. Mean blood pressure decreased from 113 +/- 10 to 102 +/- 9 mm Hg at the end of the study (P < 0.0001); 38 of the 67 patients (56.7%) who completed the study had a SBP lower than 140 mm Hg and a DBP lower than 90. These blood pressures were obtained in 30 patients on monotherapy with losartan (78.9%). Proteinuria decreased significantly at week 4 and was confirmed at week 12, especially in patients with proteinuria > or = 300 mg/24 hr. Nine patients were withdrawn during the study period for different reasons. Serum creatinine showed a slight, non-clinically significant increase at week 4, remaining stable until the end of the study. Two patients developed a mild normocytic anemia, and three others presented a mild impairment of pre-existent anemia. No interactions with cyclosporine or FK-506 were described. These results indicate that losartan is effective in reducing BP in hypertensive patients with a renal transplant. It has a good tolerance profile and does not interfere with immunosuppressive therapy.
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PMID:Efficacy and safety of losartan in the treatment of hypertension in renal transplant recipients. 983 98

Infestation with a short-tailed demodectic mite and Demodex canis was diagnosed in both a six-and-a-half-year-old and a four-year-old dog. The clinical picture was compatible with generalised demodicosis complicated by staphylococcal pyoderma (case 1), or localised demodicosis (case 2). In both cases, the short-tailed demodectic mite outnumbered D canis in superficial skin scrapings. The laboratory findings (lymphopenia, eosinopenia, increased serum alkaline phosphatase and alanine aminotransferase activities, diluted urine and proteinuria) and the results of a low dose dexamethasone suppression test were suggestive of underlying hyperadrenocorticism in the first case. Hypothyroidism was considered a possibility in the second case, owing to the sustained bradycardia and the extremely low basal total thyroxine value. Systemic treatment with ivermectin and cephalexin (case 1), or topical application of an amitraz solution in mineral oil, along with sodium levothyroxine replacement therapy (case 2), resulted in a complete resolution of the skin lesions and the disappearance of both types of demodectic mite after two and one and a half months, respectively.
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PMID:Adult-onset demodicosis in two dogs due to Demodex canis and a short-tailed demodectic mite. 1064 97


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