Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022672 (acute tubular necrosis)
 2,175 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Glutathione transferase-pi released from kidney tubular epithelial cells was analyzed in the urine of recipients of renal allografts. Urinary content of alpha-class glutathione transferase was also determined for comparison. Control urine from healthy individuals contained detectable levels of the pi-isoenzyme (6.6 +/- 0.46 ng/ml, mean +/- SEM) and this concentration was not increased in the urine of patients demonstrating cyclosporine A-induced nephrotoxicity (6.3 +/- 0.29 ng/ml), in contrast to the alpha-form. Acute rejection increased excretion of the pi-isoenzyme (19.0 +/- 2.0 ng/ml), but not of the alpha-glutathione transferase. Thus, while the serum creatinine level increases in connection with both cyclosporine A-induced nephrotoxicity and acute rejection, analyses of urinary glutathione transferases distinguish well between these conditions. Acute tubular necrosis and renal transplant infarction resulted in a rapid elevation in urinary levels of both alpha- and pi-transferase. The advantages of this approach are that release of the protein into the urine occurs rapidly after tubular damage, the assay is sensitive and specific and can also distinguish between certain pathological conditions. These studies thus indicate that the urinary level of glutathione transferase-pi can be used for monitoring certain pathological processes in the kidney. Quantitation of this enzyme complements the information obtained by measurement of glutathione transferase-alpha.
Nephron 1994
PMID:Urinary pi-class glutathione transferase as an indicator of tubular damage in the human kidney. 793 21

The relevance of eosinophilia in the physiopathology of transplant rejection has yet to be established. The appearance of eosinophilia has been occasionally associated with an adverse prognosis on graft rejection episodes. The aim of the present study was to evaluate the role and prognostic implications of blood and graft eosinophilia in kidney transplant rejection. We have examined the intrarenal infiltrate in 173 fine-needle aspiration biopsies from 36 consecutively transplant patients, and blood samples obtained simultaneously with fine-needle aspirations. Two different immunosuppressive regimens were administered: triple therapy (azathioprine + prednisone + antilymphocytic globulin) in patients with posttransplant acute tubular necrosis and cyclosporine A monotherapy in the rest of the patients. Comparing the two immunosuppressive groups, more elevated eosinophil values were observed in the monotherapy group during stable graft and also at the rejection episode. In the monotherapy group, a significant increase in the eosinophil values, in peripheral blood samples and in the intragraft infiltrates were noted at the rejection episode with respect to the stable situation. Following pulsed-steroid treatment an immediate disappearance of the eosinophils was evident. In contrast, no differences could be demonstrated between these two clinical situations in the TT group. Higher rates of eosinophils in the intrarenal infiltrate with respect to peripheral blood samples were observed during rejection episodes, suggesting some role of the eosinophils in the physiopathology of graft rejection.(ABSTRACT TRUNCATED AT 250 WORDS)
Nephron 1993
PMID:Blood and graft eosinophilia as a rejection index in kidney transplant. 824 97

The ability to predict the outcome in acute tubular necrosis (ATN) remains elusive despite considerable efforts. Accurate prediction is a crucial priority and has large economical and ethical implications, mainly to judge when treatment is futile and further efforts only prolong miserable agony. To analyze the influence of risk factors in the prognosis of ATN, we applied, in an initial phase, a prospective protocol of demographic data, cause of renal failure, diuresis, need of dialysis and clinical conditions in 228 patients using multiple linear and logistic regression models. In a control phase with 100 consecutive patients, we checked the accuracy of the results previously obtained, evaluating further the overall population of 328 patients in a synthetic phase. Finally, the validation of the equations obtained was verified in 25 patients from another hospital. As a complement of this 4-phase study, detailed statistical comparisons between both linear and logistic multiple regression models were undertaken. Correlation between probability of death obtained with equations from the initial phase applied to control patients and real evolution of these patients, survival or death, was excellent. The study of the synthetic phase revealed coma, assisted respiration, hypotension, oliguria and jaundice as having an independent positive influence on mortality and nephrotoxic etiology and normal consciousness on good prognosis. For the linear model, the same cut-off point of discriminant score (0.9) above which there were no chances for survival could be established in the 4 phases. With the logistic model, it only was found at later phases. The multiple linear was better than the logistic regression model in terms of better correlation with real mortality, better sensitivity and specificity intervals, easier use of discriminant cut-off point and better adjustment of distribution of standardized residuals to expected normal function. Early prognosis of ATN is possible and can be given using simple clinical features. A discriminant score allows to distinguish patients without chances for survival. The multiple linear is better than the logistic regression model in the prediction of the outcome in ATN.
Nephron 1993
PMID:Prognosis of acute tubular necrosis: an extended prospectively contrasted study. 844 48

150 episodes of allograft dysfunction in 128 renal transplant recipients, 77 due to acute rejection, 32 secondary to acute-on-chronic rejection, 33 due to either prerenal factors, acute tubular necrosis, or ciclosporin A nephrotoxicity, and 8 secondary to multiple causes, were evaluated by fine-needle aspiration biopsy (FNAB), Doppler ultrasound (DUS), and radionuclide scintigraphy (RS), each performed within a 24-hour period and prior to any specific therapeutic intervention. Tests were interpreted by appropriate specialists in a large transplant center without access to clinical information. The final diagnosis was based primarily upon response to therapeutic maneuvers with histological (core biopsy) confirmation in 123 episodes. RS was the most sensitive (70%) test for the diagnosis of acute rejection during the early posttransplant period, exceeding both FNAB (52%) and DUS (43%). The predictive accuracy of either FNAB, DUS, RS, or core biopsy in the detection of a steroid-responsive component to acute rejection when superimposed upon chronic rejection was low at approximately 50%. When the underlying cause of renal dysfunction was either prerenal, acute tubular necrosis, or ciclosporin A nephrotoxicity, FNAB, DUS, and RS each gave an erroneous diagnosis of acute rejection in about 50% of the episodes. Cost analysis revealed that core biopsy was the most expensive test, but only 9% more than RS, with FNAB the least costly. In conclusion, the lack of ideal sensitivity and specificity combined with the expense of present-day FNAB, DUS, RS, and core biopsy in the diagnosis of a therapeutically reversible component to acute-on-chronic rejection and of FNAB, DUS, and RS in the diagnosis of acute rejection during the early posttransplant period should prompt research into ways to improve their diagnostic yield or alternate modalities.
Nephron 1993
PMID:Comparison of fine-needle aspiration biopsy, Doppler ultrasound, and radionuclide scintigraphy in the diagnosis of acute allograft dysfunction in renal transplant recipients: sensitivity, specificity, and cost analysis. 844 62

Tenascin, a large oligomeric glycoprotein, is a recent addition to a list of increasing extracellular matrix proteins. Previous studies have documented the strong expression of tenascin in embryonic kidney and in both normal and abnormal mature glomeruli implicating an important role of this extracellular matrix protein in nephrogenesis and glomerular scarring. Whether tenascin plays any role in interstitial fibrosis, a common final pathway of tubulointerstitial nephritis, is no known; on the other hand, a detailed knowledge of the structural components of interstitial fibrosis is essential for further studies on other fundamental aspects of this biologically and clinically important process. In this study, the expression of tenascin in the renal interstitium was immunohistochemically evaluated in 208 renal specimens during normal kidney (23 cases), acute tubular necrosis (8), acute tubulointerstitial nephritis (8), chronic primary tubulointerstitial nephritis (30), tubulointerstitial nephritis secondary to glomerular diseases of mild (46) and severe (55) degree, ischemic damage (24), and rejection (14). It was found that in normal kidney tenascin expression was limited to the medullary interstitium. In kidney with tubulointerstitial nephritis, tenascin was ubiquitously and constantly expressed in any areas with tubulointerstitial damage regardless of diagnosis, etiology, the cortical vs. medullary location of the lesions, stage of the fibrogenetic process, density of fibroblasts, or severity of interstitial inflammation in the affected areas. Indeed, strong tenascin expression was seen in areas where there was only interstitial edema or inflammation as judged by routine light microscopic preparations. In summary, this study systematically documents tenascin as a novel extracellular matrix protein selectively expressed in the medullary interstitium in normal kidney, and ubiquitously present in areas with interstitial fibrosis.
Nephron 1996
PMID:Tenascin is an ubiquitous extracellular matrix protein of human renal interstitium in normal and pathologic conditions. 873 Apr 25

The present study was designed to determine whether the administration of free radical scavengers, superoxide dismutase (SOD), catalase or dimethylsulfoxide (DMSO) is able to ameliorate ischemia/reperfusion injury in the canine kidney and also ascertain whether or not a relationship exists between oxygen free radicals and membrane-bound Na(+)-K(+)-ATPase activity. In 23 dogs, the vascular pedicle of the left kidney was clamped for 75 min at room temperature. The experimental animals received free radical scavengers for 30 min starting at 2 min prior to reperfusion. Renal tissue specimens were enzyme-histochemically examined regarding the activity of membrane-bound Na(+)-K(+)-ATPase, and a marked reduction just before reperfusion was revealed. The SOD- and the DMSO-treated groups showed a marked recovery of the membrane-bound Na(+)-K(+)-ATPase activity; however, the untreated and the catalase-treated groups still demonstrated a marked reduction 1 day after reperfusion. At the same time, widespread acute tubular necrosis in the cortex was observed in the untreated and catalase groups in comparison with the SOD and the DMSO groups. In addition, the SOD and the DMSO groups significantly preserved better renal function. Based on these findings, it was thus concluded that free radical scavengers ameliorate the recovery of depressed membrane-bound Na(+)-K(+)-ATPase activity and ischemia/reperfusion injury in the canine kidney.
Nephron 1996
PMID:The influence of oxygen free radical scavengers on the reduction of membrane-bound Na(+)-K(+)-ATPase activity induced by ischemia/reperfusion injury in the canine kidney. 873 Apr 34

After transplantation the kidney is subjected to rejection and other deleterious factors including ischemic damage, acute tubular necrosis, rejection and the use of cyclosporine A (CsA) or FK506. As a result, kidney damage may be generalized with azotemia as its hallmark. These tubular syndromes may cause profound changes in the acid base balance and in the level of certain blood electrolytes and minerals. As a general rule, the renal tubular acidosis (RTA) that appears early following transplantation disappears spontaneously and is predominantly a sequela to acute renal failure. On the other hand, defects occurring in the late posttransplant period are often due to chronic rejection or CsA-induced nephrotoxicity. Secondary hyperparathyroidism, urinary tract infection and obstructive uropathy may also play a contributory urinary role in the pathogenesis of RTA. Chronic RTA following transplantation may interfere with bone metabolism and at times lead to nephrocalcinosis and nephrolithiasis. Therefore, if the condition is prolonged, a supplement of bicarbonate should be given if for no other reason that to protect the skeleton. As these patients may develop either hyperkalemia or hypokalemia, treatment with potassium supplements or potassium-sparing diuretics should be carried out with caution and under constant surveillance. Furthermore, magnesium replacement may be advisable if hypomagnesemia by decreased proximal reabsorption becomes clinically evident. Tubular dysfunction may occur following renal transplantation even in patients with maintained glomerular filtration rate and may induce a number of clinical problems including deterioration of renal graft function.
Nephron 1996
PMID:Tubular dysfunction following kidney transplantation. 893 72

The clearance ratios of endogenous plasma proteins with the same size but a different charge, such as the amylase isoenzymes and the immunoglobulin (Ig) G subclasses, have been used to assess glomerular charge selectivity in man. These proteins are, however, subject to tubular reabsorption. In this study we measured the IgG subclass/IgG clearance ratios for IgG1 (pI 8.0-9.5), IgG2 (pI 7.0-7.5) and IgG4 (pI < 6) in 6 healthy volunteers. Our results suggested a selective influence of tubular reabsorption: the IgG1/IgG clearance ratio was 0.68 +/- 0.14 (mean +/- SD) and lower than IgG2/IgG (2.02 +/- 1.06, p < or = 0.01). IgG4/IgG was 0.89 +/- 0.39. In addition, we studied the clearance ratios of pancreatic (PA, pI 7.0) and salivary amylase (SA, pI 5.9-6.4) and of IgG1 and IgG2 in 8 patients with minimal change nephrotic syndrome (MCNS), 11 patients recovering from acute tubular necrosis (ATN) and 9 healthy volunteers (controls). In MCNS glomerular charge selectivity is lost, while in recovering ATN tubular function is severely disturbed. The PA/SA clearance ratio was 3.25 +/- 0.89 in controls, reflecting intact glomerular charge selectivity. In MCNS patients the PA/SA clearance ratio had decreased to 1.21 +/- 0.23 (p < or = 0.001). In ATN patients the PA/SA clearance ratio was reduced as well: 1.55 +/- 0.41 (p < or = 0.001), although the aselective nature of the proteinuria and the modest albuminuria indicated intact glomerular charge selectivity. The IgG1/ IgG2 clearance ratio was 0.54 +/- 0.15 in controls, again suggesting preferential tubular reabsorption of IgG1. In MCNS patients the IgG1/IgG2 clearance ratio was 0.16 +/- 0.10 (p < or = 0.001); this probably reflects the relatively increased glomerular sieving of IgG2 when glomerular charge selectivity is lost. In ATN patients the IgG1/IgG2 clearance ratio was 1.07 +/- 0.47 (p < or = 0.001), which suggests a partial loss of preferential reabsorption of IgG1. It was concluded that the PA/SA clearance ratio is influenced by loss of tubular function and therefore does not reflect glomerular charge selectivity specifically. The IgG1/IgG2 ratio cannot be used to assess glomerular charge selectivity either because of the interference of selective tubular reabsorption of the subclasses. These findings put the assessment of glomerular charge using endogenous proteins in a new light and bring forward the necessity to interpret these ratios with the utmost cautiousness.
Nephron 1997
PMID:Clearance ratios of amylase isoenzymes and IgG subclasses: do they reflect glomerular charge selectivity? 912 32

Based on 2 case presentations - acute renal failure (ARF) due to myeloma kidney and due to angiotensin-converting enzyme inhibitor administration in the presence of transplant artery stenosis - new aspects in the pathogenesis of ARF are presented and discussed. The multifactorial pathogenesis of ARF includes (a) a disturbance of glomerular microcirculation (afferent and perhaps mesangial constriction, inadequate efferent dilatation); (b) a disturbance of medullary microcirculation (medullary capillary congestion) attributed to a combination of endothelial damage and tubular dilatation; (c) tubular cell damage which, though rarely in humans justifying the term 'acute tubular necrosis', promotes both backleak of glomerular filtrate and shedding of brush border vesicles; (d) the latter promotes tubular obstruction by casts which consist of Tamm-Horsfall protein and brush border components. Once ARF is established, repair processes set in which appear to depend on growth factors such as epidermal growth factor and insulin-like growth factor 1, of which there is a relative shortage in established ARF. Experimental therapeutic approaches focus on the restitution of microcirculation (endothelin receptor antagonists, atriopeptins), interference with cast formation (integrin receptor blockers), and the promotion of recovery by growth factors.
Nephron 1997
PMID:Pathogenesis of acute renal failure: new aspects. 920 Apr 3

HIV-associated nephropathy is manifested by heavy proteinuria and renal insufficiency and characterized pathologically by the collapsing variant of focal and segmental glomerulosclerosis with acute tubular necrosis and mild interstitial inflammation. Untreated, it may result in end-stage renal disease in as little as 4 months. It may present in patients with any manifestation of HIV infection, and affects predominantly black individuals. Insights into pathogenesis have come from a transgenic mouse model, renal cell cultures, and from study of human biopsy material. Although the pathogenesis is not completely understood, current considerations revolve around the role of HIV or protein in renal epithelium and the effects of cytokines, including transforming growth factor-beta and basic fibroblast growth factor, on renal structures. Therapy with zidovudine, corticosteroids, or angiotensin-converting enzyme inhibitors has met with modest success; to date, protease inhibitors have not been assessed.
Nephron 1999
PMID:Distinguished Scientists Lecture Series. HIV-associated nephropathy. 1051 88


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