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)

We evaluated a chronic renal injury in 37 cardiac transplant recipients treated for 12 to 24 months with cyclosporine (CsA). Twenty-four cardiac transplant recipients treated with azathioprine for more than 24 months served as controls. Despite equivalent cardiac performance, GFR in those treated with CsA was depressed, 47 +/- 3 versus 94 +/- 4 ml/min/1.73 m2 (P less than 0.001). CsA therapy was also associated with significant elevation of renal vascular resistance (RVR), proteinuria, arterial hypertension, and impaired intrarenal conversion of inactive prorenin to active renin. Histopathological changes associated with CsA included an obliterative arteriolopathy with deposition of proteinaceous material in necrotic arteriolar walls, and associated tubulointerstitial damage. A minority of glomeruli exhibited either ischemic collapse or sclerosis. Area perimeter analysis revealed enlargement of the remaining glomeruli with significant expansion of the mesangium. Longitudinal examination over a 48 month period (N = 15) during which CsA was reduced in dosage or withdrawn revealed persistent hypofiltration, increasingly elevated RVR and heavier proteinuria. Further histopathological deterioration was observed when renal tissue was sampled a second time in six patients, and three members of the experimental group developed end-stage renal disease. We conclude that continuous CsA therapy for more than 12 months causes a chronic injury to renal microvessels that is rarely reversible and potentially progressive.
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PMID:The long-term course of cyclosporine-associated chronic nephropathy. 328 2

The renal allograft is host to a number of injuries and all its structural components are prone to damage. The glomeruli respond to these varied stimuli in many ways. The fibrinoid necrosis, thrombosis, and polymorphonuclear cell exudation that accompany hyperacute or accelerated rejection are well-recognized. The transplant may also be afflicted by forms of de novo or recurrent glomerulonephritis. Apart from these, there are other patterns of reaction. The mesangium is often the site of a rapidly reversible change; it expands readily. Arterial changes initiate ischemia and collapse of glomerular capillary spaces. Glomerulitis accompanies cases of acute rejection, but when seen as a predominant feature, usually antedates chronic rejection. Heavy proteinuria may be associated with profound alterations in the peripheral capillary basal lamina including irregular thickening, interposition of mesangial cell cytoplasm, and lamellation. Allografts with these glomerular changes eventually fail.
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PMID:Glomerular changes in renal allografts. 351 May 33

Despite the widespread use of non-steroidal anti-inflammatory drugs (NSAIDs), the current number of reported cases of poisoning is small. However, with the introduction of 'over-the-counter' preparations of NSAIDs in some countries (e.g. ibuprofen in the UK and USA) an increased incidence of acute poisoning from this group of drugs can be expected. Conventionally, NSAIDs are divided into the following groups based on their chemical structure: arylpropionic acids, indole and indene acetic acids, heteroarylacetic acids, fenamates, phenylacetic acids, pyrazolones and oxicams. Unless NSAIDs are ingested in substantial overdose, acute poisoning with these agents does not usually result in significant morbidity or mortality. In most cases the clinical features are mild and confined to the gastrointestinal and central nervous systems, though acute renal failure, hepatic dysfunction, respiratory depression, coma, convulsions, cardiovascular collapse and cardiac arrest may complicate severe poisoning. Arylpropionic acid derivatives were thought initially to have a low order of toxicity in overdose but, in addition to anticipated gastrointestinal symptoms, headache, tinnitus, hyperventilation, sinus tachycardia, hypoprothrombinaemia, haematuria, proteinuria and acute renal failure have been described. In addition, drowsiness, coma, nystagmus, diplopia, hypothermia, hypotension, respiratory depression and cardiac arrest have been reported in severe cases of poisoning. Oxyphenbutazone and phenylbutazone are considerably more toxic in overdose. Complications of severe poisoning include coma, convulsions, hepatic dysfunction, acute renal failure, sodium and water retention, haematuria, cardiovascular collapse, respiratory alkalosis, metabolic acidosis, hypoprothrombinaemia and thrombocytopenia. In contrast, indomethacin appears to be much less toxic. In addition to gastrointestinal symptoms, indomethacin taken in overdose induces headache, tinnitus, dizziness, lethargy, drowsiness, confusion, disorientation and restlessness. Only 1 case of acute sulindac poisoning has been reported in the literature. A 16-year-old boy was admitted with hypokalaemia (2.2 mmol/L), transient granulocytosis and 'scanty' haematemesis after ingesting 12 g sulindac. No case of acute tolmetin poisoning have been reported. The fenamates (flufenamic acid, meclofenamic acid, mefenamic acid, tolfenamic acid) are, with the exception of mefenamic acid, not as widely prescribed as other groups of NSAIDs. In overdose, mefenamic acid may result in nausea, vomiting, diarrhoea, muscle twitching, convulsions and coma.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Acute poisoning due to non-steroidal anti-inflammatory drugs. Clinical features and management. 353 13

On the assumption that increased urinary lysozyme concentration (;lysozymuria') indicates tubular proteinuria and therefore impaired tubular function, urinary lysozyme has been estimated in acute disorders where transient disturbances of renal function might be expected, in cases diagnosed clinically as extrarenal uraemia, and in a few examples of acute renal disease. Reversible lysozymuria occurred with hypokalaemia, postoperative ;collapse', electrolyte depletion, severe extrarenal infection, acute pyelonephritis, the nephrotic syndrome, after a few apparently uncomplicated surgical operations, and very transiently after ventricular fibrillation abolished by DC shock. There was no lysozymuria with severe uraemic heart failure, aspirin and paracetamol poisoning, or severe jaundice, nor in two cases of acute glomerulonephritis. Although lysozymuria may occasionally be useful in the clinical diagnosis of acutely disordered renal function, the results suggest that its value is limited; on the other hand, they have provided information on renal pathophysiology in acute disease.
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PMID:Lysozymuria and acute disorders of renal function. 470 97

Fibrillary renal deposits and nephritis. The authors have studied 8 patients whose glomeruli contain abundant fibrils in their mesangial matrix and basement membranes. Although the location of these fibrils is very similar to that of amyloid, they are about twice the size of amyloid fibrils, averaging 20 nm in width, and fail to react as amyloid does with special stains. Immunofluorescence-microscopic studies are usually positive with antiserums to IgG, often IgM, and in some cases IgA, and also kappa and lambda light chains, C3, and C4. The fibrils are associated with diffuse mesangial widening and increased mesangial matrix strands. Although peripheral glomerular capillary walls appear to be spared initially, their eventual involvement leads to glomerular capillary collapse and glomerular obsolescence. Crescent formation occurred in 5 cases, focally in 3 and diffusely in 2. Tubular basement membrane involvement was seen in 1 case. These patients exhibit hematuria, and proteinuria, and often hypertension and renal insufficiency. Proteinuria was in the nephrotic range in 3 patients in whom involvement of glomerular capillary basement membranes was extensive. Unless electron microscopy is applied to renal biopsies, these cases may be considered to represent mesangiocapillary or rapidly progressive glomerulonephritis, or amyloidosis. The nature of these fibrils is as yet not determined. It is likely that they have been called "atypical amyloidosis" in the past.
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PMID:Fibrillary renal deposits and nephritis. 635 91

Because reduction of renal mass (nephrectomy) can promote the development of focal glomerulosclerosis in animals, we asked whether patients with unilateral renal agenesis might have similar lesions in the solitary kidney. We describe here the clinical course and pathologic findings of eight patients who developed focal and segmental glomerulosclerosis (FGS) in their solitary kidneys. A review of 586 surgical pathology renal specimens (452 biopsies and 134 nephrectomies) revealed 29 (4.9 per cent) cases of FGS; five also had unilateral renal agenesis (p = 2.1 x 10(-7)). In 9200 autopsies, seven cases of unilateral renal agenesis were found; two (29 per cent) died of chronic renal failure with FGS lesions, and five did not have FGS. The eighth patient was identified because he was the father of a patient in this series. At the time of diagnosis the median age of the patients with unilateral renal agenesis and FGS was 25 years; seven of eight were male. All had proteinuria; four had more than 3 gm. per 25 hours (range, 1.2 to 9.0 gm. per 24 hours). Six developed chronic renal failure, and four died of their renal disease. Two of the patients were related (father and son). One patient had clinical and morphologic evidence of reflux nephropathy. The glomerular lesions were characterized by focal and segmental scarring and adhesions in glomeruli, IgM and C3 deposition by immunofluorescence, and foot process loss and capillary loop collapse by electron microscopy. Our series, although small, indicates that patients with unilateral renal agenesis are significantly more likely to develop FGS than patients with two kidneys. In contrast, FGS did not develop after adult nephrectomy in 10 patients who died 8 to 46 years after adult unilateral nephrectomy. The reason for this association was not established; however, these findings are in accord with experimental studies in which subtotal nephrectomy in young animals promotes FGS. In that setting and in these patients, glomerular damage may result from glomerular overload.
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PMID:Focal and segmental glomerulosclerosis and porteinuria associated with unilateral renal agenesis. 706 25

In this analysis of 43 patients with IgA nephropathy, renal morphology was correlated with clinical data. Gross hematuria and mild proteinuria were typical among younger patients. Among older individuals the clinical spectrum was wider. A comparison with data previously obtained from the normal population indicated that disease-related glomerular sclerosis was present in 1/3 of initial biopsy specimens. The prevalent pattern of glomerular sclerosis was that of global tuft collapse, the type of sclerosis known to result from ischemia. Intrarenal vascular sclerosis was present in 1/3 of initial biopsies. Follow-up specimens from 6 patients showed progression of glomerular sclerosis, vascular sclerosis or both. Hypertension occurred in over 1/4 of patients. It is proposed that progressive renal damage in IgA nephropathy may not be solely immunologically mediated. Glomerular sclerosis may also be mediated by vascular sclerosis, or alterations in intrarenal hemodynamics in glomerulonephritis may have a direct damaging effect on both the glomerulus and the intrarenal vasculature.
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PMID:Intrarenal vascular sclerosis in IgA nephropathy. 714 32

A disseminated atrophy of the proximal tubule accompanies K2HPO4-induced nephropathy in dogs. These pathologic processes cause glomerular changes that pass through different inflammatory stages and terminate in glomerular sclerosis. Experimental animals, design of the experiment and methods have been described [15]. During the 14-week study we determined the amount of urine (24 hours), protein (mg/dl), protein excretion (mg protein/24 hr) and the macro- and microprotein fraction in the urine by SDS-polyacrylamide gel electrophoresis. Clinical examinations were at 15, 66, and 85 days. Beagle dogs treated with 0.8 g K2HPO4/kg body weight developed significant glomerular selective and unselective protienuria. During the experiment the macroproteins in the urine decreased markedly, and at the last examination (day 85) glomerular proteinuria was no longer detectable by electrophoresis. Morphologically, there were only slight glomerular changes in the biopsy material taken at four weeks. Widespread lesions at 14 and 38 weeks were dilatation of Bowman's space, thickening of the basement membrane, increase in mesangial matrix, interposition of non-argentophilic mesangial matrix into the glomerular basement membrane, protein deposits in the mesangium and parietal basement membrane, formation of crescents, shrinkage of the glomeruli with collapse of glomerular tufts, and finally glomerular sclerosis. The parietal epithelial cells contained cytoplasmic areas that were free of organelles and contained microfilamentous and fine-granular material. These areas were close to the capsular basement membrane. Bundles of filaments within parietal epithelial cells had contact with the basement membrane, thus resembling hemidesmosomes. The sequelae of tubular atrophy are retention of glomerular filtrate and dilatation of Bowman's space, followed by compression and shrinkage of the glomerular tufts, and inflammatory processes within the glomerulus. The latter may be characterized as mesangio-sclerosing, mesangio-proliferative, membrano-proliferative, and extra-capillary glomerulonephritis. The decrease of urinary protein excretion towards the end of the experiment may be related to intratubular lysosomal digestion of cellular and amorphous components.
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PMID:[Potassium hydrogen phosphate induced nephropathy in the dog. II. Glomerular alterations (author's transl)]. 742 31

Sixteen patients with renal biopsy findings of extensive focal glomerular capillary collapse, visceral epithelial cell hypertrophy and hyperplasia, and variable degrees of tubulointerstitial injury in the absence of evidence for human immunodeficiency virus (HIV) infection or intravenous drug abuse were prospectively identified by renal biopsy. The pathologic process was designated collapsing glomerulopathy to distinguish it from other patterns of focal glomerular sclerosis. The clinical and pathologic characteristics of these 16 patients were analyzed and compared to a group of 25 patients with noncollapsing focal segmental glomerulosclerosis (FSGS). Thirteen of 16 patients with collapsing glomerulopathy were black as compared with 11 of 25 with FSGS (P = 0.018). The most common findings at presentation were hypertension and manifestations of the nephrotic syndrome. Although the duration of symptoms prior to presentation was no longer in the collapsing glomerulopathy group, the presenting mean serum creatinine was higher in patients with collapsing glomerulopathy than in those with noncollapsing FSGS (3.5 +/- 3.4 mg/dl vs. 1.3 0.6 mg/dl, P = 0.001). Twenty-four-hour urine protein excretion was also higher in the collapsing glomerulopathy group (13.2 +/- 7.7 g/day vs. 4.6 +/- 4.5 g/day FSGS, P = 0.005). The collapsing glomerulopathy patients had a mean age of 41.4 +/- 19.1 (range 19 to 81), a male-to-female ratio of 11:5 and a black-to-white ratio of 13:3. Renal survival, evaluated by life-table analysis, was markedly worse in collapsing glomerulopathy patients than in FSGS patients (P = 0.0004). It is proposed that collapsing glomerulopathy is a distinct entity characterized by black racial predominance, massive proteinuria, relatively rapidly progressive renal insufficiency, and distinctive pathologic findings.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Collapsing glomerulopathy: a clinically and pathologically distinct variant of focal segmental glomerulosclerosis. 807 54

Glomerular visceral epithelial cells, unlike epithelial cells in other organs or in the more distal segments of the nephron, are highly differentiated, terminal cells that do not undergo cell division under physiological conditions in the postnatal period or during conditions that result in renal hypertrophy. Adjacent cells are connected to each other at the level of complex interdigitations or foot processes by filtration slit diaphragms. This particular arrangement contributes to the extremely high hydraulic conductivity of the normal glomerular capillary. Toxic and metabolic damage to the visceral epithelial cells or conditions of extreme glomerular hypertrophy result, in the short term, in diffuse or focal simplification and flattening of the foot processes. The areas of the capillary wall covered by such a simplified epithelium are likely to have a greatly reduced hydraulic conductivity which results from the greatly diminished surface area available for filtration. The rearrangement of foot processes also leads to focal areas of denudation of the basement membrane. Such denuded areas, however, are likely to result in an increase in local hydraulic flux, especially under conditions of capillary hypertension. Such defects have been shown to be the pathway of increased permeability to macromolecular markers and proteinuria. Large plasma proteins are retained in the subendothelium by the size-restrictive water-filled channels of the lamina densa and accumulate upstream in the form of hyaline which eventually occludes individual loops. More severe epithelial cell injury and denudation may also result in collapse of entire tuft segments.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:How does glomerular epithelial cell injury contribute to progressive glomerular damage? 815


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