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)

Patients with the nephrotic syndrome and normal renal function have low levels of 25(OH)D in serum presumably due to the loss of this metabolite in the urine. Osteomalacia and hyperparathyroidism have been recently reported to occur as a consequence of those low levels of 25-hydroxyvitamin D (25OHD). We studied six patients (aged 26-52 yr) with the nephrotic syndrome (mean duration, 6.7 yr; range, 2-12 yr) and normal renal function, and evaluated their calcium, phosphorus, PTH, and vitamin D metabolite levels. Bone biopsies were obtained in all patients. The creatinine clearance ranged from 83-134 ml/min . 1.73 m2 of body surface, serum albumin was 2.65 +/- 0.42 (+/- SD) g/100 ml, and proteinuria ranged from 3.5-13.2 g/24 h. All patients had normal serum magnesium, phosphorus, ionized calcium, and alkaline phosphatase (total and bone fraction), and normal roentgenographic metabolic bone survey. Serum PTH, measured by the carboxy-terminal RIA, was 5.1 +/- 2.3 mu leq/ml (normal, 2-10), serum 250HD was 8.8 +/- 4.0 ng/ml (normal, 15-30), and 1,25-dihydroxyvitamin D3 was 38 +/- 25 pg/ml (normal, 17-58). Serum vitamin D-binding protein was 420 +/- 42 micrograms/ml (normal, 400-800). The histological appearance of bone biopsies obtained in these patients was not different from that in a group of sex- and age-matched controls. Specifically, there was no increase in the volume of osteoid (unmineralized bone), the percentage of trabecular surface covered by osteoid, or the number of osteoclasts. The cellular rate of mineralization was normal in all six patients. Thus, these data indicate that low serum levels of 250HD in patients with the nephrotic syndrome and normal renal function do not necessarily result in the development of osteomalacia and/or hyperparathyroidism.
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PMID:Absence of metabolic bone disease in adult patients with the nephrotic syndrome and normal renal function. 682 51

A review of the health effects of cadmium is presented. Overexposure to cadmium produces numerous acute and chronic effects. Cases of acute poisoning resemble metal-fume poisoning. The first and most distinctive indication of chronic effects is renal tubular dysfunction characterized by proteinuria. Other chronic effects include liver damage, emphysema, osteomalacia, neurological impairment, testicular, pancreatic, and adrenal damage, and anemia. Tumorigenic effects have been observed in animals, and excessive prostatic and lung cancer has been observed in worker studies. In vitro and in vivo mutagenic effects have been noted. Cadmium has been shown to cause hypertension in animals; however, it is unclear whether it is capable of causing similar effects in exposed human populations. Normal urinary excretion is less than 2 micrograms/day and correlates with exposure. Normal blood concentration is below 10 ng/gm of whole blood, and although levels are elevated in exposed groups, there is no apparent direct correlation. Hair values correlate well with exposure. Occupational and environmental standards are discussed.
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PMID:A review of the health effects of cadmium. 704 11

The detailed study of a battery plate maker, who had worked with cadmium for 36 years, showed that proteinuria, typical of renal tubular dysfunction, had been observed for 25 years and during the last 12 years of his life the patient had suffered increasing disability from gross bone disease. Several bone biopsies and detailed metabolic studies showed typical severe osteomalacia, which responded well initially to calcium and vitamin D treatment. Examination of the liver both in life and after death showed a gross excess of cadmium. This was also found in the kidneys after death. Previously unreported changes were present in the bones, especially the lumbar vertebrae which were probably more the result of gross bone deformity than cadmium deposition. The mechanism of development of the severe acquired Fanconi syndrome was thought to be a combination of dietary calcium and vitamin D deficiency and impaired calcium absorption from abnormal vitamin D synthesis, related to the cadmium deposition in the renal tubules, which also caused the defect in renal tubular reabsorption.
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PMID:Cadmium-induced osteomalacia. 742 80

This study demonstrates that a missense mutation in the voltage gated chloride channel, CLCN5, can cause X-linked renal failure without X-linked recessive hypophosphatemic rickets. A large kindred (Family A), initially evaluated in 1974 with an inherited syndrome characterized by hypercalciuria, nephrocalcinosis, low molecular weight proteinuria, renal tubular acidosis, and renal failure, was clinically re-evaluated and genetically characterized. Medical histories, physical examinations, blood chemistries, and 24-hour urine collections were obtained from 48 family members. Both female and male family members exhibited hypercalciuria, nephrolithiasis, and low molecular weight proteinuria. However, only men developed renal insufficiency, consistent with an X-linked recessive gene defect. Genetic linkage located the disease locus on the proximal short arm of the X chromosome (Xp11) where a voltage gated chloride channel gene, CLCN5, had previously been mapped. DNA sequence of the CLCN5 gene demonstrated a missense mutation (Ser244Leu) in affected family members. The same missense mutation has previously been shown to cause X-linked recessive hypophosphatemic rickets. No affected member of Family A had evidence of chronic hypophosphatemia, clinically significant rickets, or osteomalacia. We hypothesize that genetic background, environment, diet, or an unidentified modifying gene may account for the differing phenotypes resulting from this shared gene defect.
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PMID:CLCN5 mutation Ser244Leu is associated with X-linked renal failure without X-linked recessive hypophosphatemic rickets. 945 24

The Fanconi syndrome is a generalized disorder of proximal renal tubular transport characterized by wasting of phosphate, amino acids, glucose, bicarbonate, and uric acid. The association of the acquired Fanconi syndrome with lambda light-chain proteinuria is rare. We report the third case in the English language literature. A 65-year-old man presented with severe pelvic pain. Investigations showed an elevated serum creatinine level, and a 24-hour urine collection contained 2.56 g protein. The Fanconi syndrome was diagnosed, with findings of phosphaturia, glycosuria, and aminoaciduria. Bence Jones protein (lambda sub-type) was present in the urine at a concentration of 0.58 g/L. Monocytic cells in the bone marrow and proximal tubular cells in the kidney contained cytoplasmic crystalline inclusions. Undecalcified bone sections confirmed the clinical diagnosis of osteomalacia. The patient was treated with phosphate, calcium, and ergocalciferol and experienced significant symptomatic improvement. The Fanconi syndrome caused by light-chain deposition in proximal tubular cells is well described in the literature. However, it is rare for the light chains to be of the lambda subtype. This may reflect differences in the physicochemical properties of kappa and lambda light chains.
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PMID:Lambda light chain induced nephropathy: a rare cause of the Fanconi syndrome and severe osteomalacia. 1007 97

Osteoporosis is a major cause of morbidity worldwide. A number of risk factors, such as age and gender, are well established. High cadmium exposure causes renal damage and in severe cases also causes osteoporosis and osteomalacia. We have examined whether long-term low-level cadmium exposure increases the risk of osteoporosis. Bone mineral density (BMD) in the forearm was measured in 520 men and 544 women, aged 16-81 years, environmentally or occupationally exposed to cadmium, using dual-energy X-ray absorptiometry (DXA) technique. Cadmium in urine was used as the dose estimate and protein HC was used as a marker of renal tubular damage. There was a clear dose-response relation between cadmium dose and the prevalence of tubular proteinuria. Inverse relations were found between cadmium dose, tubular proteinuria, and BMD, particularly apparent in persons over 60 years of age. There was a dose-response relation between cadmium dose and osteoporosis. The odds ratios (ORs) for men were 2.2 (95% CI, 1.0-4.8) in the dose group 0.5-3 nmol Cd/mmol creatinine and 5.3 (2.0-14) in the highest dose category (> or = 3 nmol/mmol creatinine) compared with the lowest dose group (< 0.5 nmol Cd/mmol creatinine). For women, the OR was 1.8 (0.65-5.3) in the dose group 0.5-3 nmol Cd/mmol creatinine. We conclude that exposure to low levels of cadmium is associated with an increased risk of osteoporosis.
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PMID:Low-level cadmium exposure and osteoporosis. 1093 57

Osteomalacia of cadmium (Cd) poisoning (Itai-Itai disease) is induced by renal tubular dysfunction; however, the precise pathological changes and mechanisms have not been adequately elucidated. Of the 25 inhabitants in a Cd-polluted area who developed chronic tubular proteinuria, 22 individuals died over a 16-year period. Autopsies were performed in 11 cases and osteomalacia was detected in 9 cases (mean age at death 82.2 +/- 7.8 years; 1 man and 8 women). Histologically, osteomalacia occurred coincidentally with diffuse atrophy of the proximal tubules, moderate thickening of the tubular basement membrane and mild interstitial fibrosis in the renal cortex. Ultrastructurally, mitochondria in the proximal tubules were decreased in number and showed abnormal structure, while membrane enzymes, such as 5'-nucleotidase and ALPase, were still well preserved in their brush border. Glomeruli and distal tubules were minimally damaged. Severity of osteomalacia correlated with the damage of the proximal tubules as well as reduced serum calcium (Ca), serum Ca x phosphorus (P) and hematocrit, increased urine beta2-microglobulin, lysozymes, N-acetyl-b-D-glucosaminidase, retinol binding protein, creatinine, and reduced percent tubular reabsorption of phosphate. Multiple regression analysis showed that among these factors, serum Ca x P was an independent factor for predicting the severity of osteomalacia. Our findings suggest that osteomalacia by Cd poisoning causes degenerative changes in the proximal tubules, especially in mitochondria, which might affect the disturbance of the intracellular active transport energy system for calcium and phosphorus, resulting in osteomalacia.
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PMID:Cadmium induces osteomalacia mediated by proximal tubular atrophy and disturbances of phosphate reabsorption. A study of 11 autopsies. 1099 41

Nephrotoxicity is an inherent adverse effect of certain anticancer drugs. Renal dysfunction can be categorised as prerenal uraemia, intrinsic damage or postrenal uraemia according to the underlying pathophysiological process. Renal hypoperfusion promulgates prerenal uraemia. Intrinsic renal damage results from prolonged hypoperfusion, exposure to exogenous or endogenous nephrotoxins, renotubular precipitation of xenobiotics or endogenous compounds, renovascular obstruction, glomerular disease, renal microvascular damage or disease, and tubulointerstitial damage or disease. Postrenal uraemia is a consequence of clinically significant urinary tract obstruction. Clinical signs of nephrotoxicity and methods used to assess renal function are discussed. Mechanisms of chemotherapy-induced renal dysfunction generally include damage to vasculature or structures of the kidneys, haemolytic uraemic syndrome and prerenal perfusion deficits. Patients with cancer are frequently at risk of renal impairment secondary to disease-related and iatrogenic causes. This article reviews the incidence, presentation, prevention and management of anticancer drug-induced renal dysfunction. Dose-related nephrotoxicity subsequent to administration of certain chloroethylnitrosourea compounds (carmustine, semustine and streptozocin) is commonly heralded by increased serum creatinine levels, uraemia and proteinuria. Additional signs of streptozocin-induced nephrotoxicity include hypophosphataemia, hypokalaemia, hypouricaemia, renal tubular acidosis, glucosuria, aceturia and aminoaciduria. Cisplatin and carboplatin cause dose-related renal dysfunction. In addition to increased serum creatinine levels and uraemia, electrolyte abnormalities, such as hypomagnesaemia and hypokalaemia, are commonly reported adverse effects. Rarely, cisplatin has been implicated as the underlying cause of haemolytic uraemic syndrome. Pharmaceutical antidotes to cisplatin-induced nephrotoxicity include amifostine, sodium thiosulfate and diethyldithiocarbamate. Dose- and age-related proximal tubular damage is an adverse effect of ifosfamide. In addition to renal wasting of electrolytes, glucose and amino acids, Fanconi syndrome, rickets and osteomalacia have occurred with ifosfamide treatment. High dose azacitidine causes renal dysfunction manifested by tubular acidosis, polyuria and increased urinary excretion of electrolytes, glucose and amino acids. Haemolytic uraemia is a rare adverse effect of gemcitabine. Methotrexate can cause increased serum creatinine levels, uraemia and haematuria. Acute renal failure is reported following administration of high dose methotrexate. Urinary alkalisation and hydration confer protection against methotrexate-induced renal dysfunction. Dose-related nephrotoxicity, including acute renal failure, are reported subsequent to treatment with pentostatin and diaziquone. Acute renal failure is a rare adverse effect of treatment with interferon-alpha. Haemolytic uraemic syndrome occurs with mitomycin administration. A mortality rate of 50 to 100% is reported in patients developing mitomycin-induced haemolytic uraemic syndrome. Capillary leak syndrome occurring with aldesleukin therapy can cause renal dysfunction. Infusion-related hypotension during infusion of high dose carmustine can precipitate renal dysfunction.
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PMID:Anticancer drug-induced kidney disorders. 1121 85

Fibrous dysplasia (FD) of bone is characterized by focal replacement of normal bone and marrow with abnormal bone and fibrous tissue. It arises from postzygotic activating mutations of the GNAS1 gene. Hypophosphatemia due to renal phosphate wasting has been reported in association with FD as a part of the McCune-Albright Syndrome (MAS), which is characterized by FD, skin hyperpigmentation, and precocious puberty. To date, the prevalence and mechanism of phosphate wasting has not been well studied. We evaluated 42 patients with FD/MAS. Serum and urine samples were tested for indices of mineral metabolism, amino acid handling, and markers of bone metabolism. Twenty (48%) patients had some degree of renal phosphate wasting. Nephrogenous cyclic adenosine monophosphate (cAMP) was normal in FD patients, suggesting that the underlying cause of phosphate wasting is not the presence of activating GNAS1 mutations in the kidney. In addition, there was evidence of a more generalized renal tubulopathy as represented by the presence of abnormal vitamin D metabolism, proteinuria in 36 (86%) patients, and aminoaciduria in 39 (94%) patients. Renal phosphate wasting significantly correlated with the degree of bone involvement, as assessed by serum and urine markers of bone metabolism, suggesting that a circulating factor produced by FD bone and impacting on the kidney may be the mechanism. These data show that phosphaturia as part of a generalized renal tubulopathy represents the most common extraskeletal manifestation of FD and that the observed tubulopathy is similar to that seen in tumor-induced osteomalacia (TIO).
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PMID:Renal phosphate wasting in fibrous dysplasia of bone is part of a generalized renal tubular dysfunction similar to that seen in tumor-induced osteomalacia. 1134 25

Studies suggest that cadmium is associated with several clinical complications, primarily renal dysfunction and bone disease, but also some cancers. Cadmium toxicity has been associated with clinical manifestations at exposure levels that are well below the limits set by the World Health Organization. Here I review the OSCAR study, which demonstrates an association between environmental and occupational cadmium exposure and renal tubular damage, as well as the Cadmibel study, a cross-sectional population study demonstrating an association of cadmium exposure with renal dysfunction. The paper also reviews the association of end-stage renal disease prevalence with occupational and environmental exposure to cadmium in the Swedish population of Kalmar County. Renal tubular damage was shown to develop at levels of exposure much lower than previously thought. Cadmium-induced tubular proteinuria is irreversible, and continued exposure may lead to glomerular damage with decreased glomerular filtration rate. Itai-itai disease in the Jinzu river basin is discussed, as are the implications of low-level cadmium exposure in the PheeCad project. Cadmium accumulates in bone and is associated with osteomalacia and osteoporosis. Other bone-seeking trace elements, such as chromium, lanthanum, strontium and zinc, are of concern because of low level environmental, occupational or clinical exposure. As techniques are perfected for detecting smaller amounts of trace elements in various tissues in the body, investigators are finding that the threshold for toxicity from trace elements is much lower than expected. Further research on cadmium is necessary to reveal the mechanisms of toxicity and true environmental and occupational exposure limits.
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PMID:Cadmium overload and toxicity. 1190 57


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