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At least 19 recordsLinked to original sources
PubMed1989

Primary acute renal failure ("acute tubular necrosis") in the transplanted kidney: morphology and pathogenesis.

"Acute tubular necrosis" (ATN) in the transplanted kidney, when properly differentiated from other causes of acute renal failure, appears to be a relatively benign condition. It has been widely assumed to be pathologically identical to ATN in the native kidney, but its histopathologic features have not been studied in detail. Because immunosuppressive therapy with cyclosporine adds an additional layer of complexity to the morphologic changes observed, in the present study we have confined our observations to patients immunosuppressed with steroids and azathioprine. Thirteen renal allograft biopsies from patients with ATN and 5 biopsies from patients with normal allograft function were compared with the previously obtained series of 57 native kidney ATN biopsies and 20 control biopsies. Both qualitative and quantitative differences between transplant and native kidney ATN were found. Compared with native kidney ATN, transplant ATN showed significantly less thinning and absence of proximal tubular brush border and less variation in size and shape of cells in individual tubular cross-sections. There were also significantly fewer casts and less dilatation of Bowman's space and a significantly greater number of polarizable crystals presumed to be oxalate in transplant ATN. In native kidney ATN the tubular injury sites were mostly characterized by desquamation of individual epithelial cells leaving areas of bare basement membrane (the "non-replacement" phenomenon). In transplant ATN, sites of tubular injury, although rare and affecting only short tubular segments, were characterized by the actual presence of identifiable necrotic tubular cells, a finding seldom seen in native kidney ATN. There also was a greater interstitial infiltrate of mononuclear inflammatory cells in transplant ATN compared to native kidney ATN. Electron microscopic studies of 9 transplant ATN biopsies showed a mild reduction in proximal tubular brush border compared with controls but this alteration was significantly less than that observed in native kidney ATN. There was no significant alteration in proximal or distal basolateral infoldings and this contrasted sharply with the marked reduction in basolateral infoldings of the plasma membrane observed in native kidney ATN. Disintegrated necrotic cells were found by electron microscopy in transplant ATN whereas these were not observed in native kidney ATN. There were significantly more cells with apoptosis (shrinkage necrosis) in transplant ATN than in native kidney ATN. There were significantly more cells with apoptosis (shrinkage necrosis) in transplant ATN than in native kidney ATN. On the other hand, there were significantly greater numbers of "non-replacement" sites in the distal tubules in native kidney ATN compared to transplant ATN.(ABSTRACT TRUNCATED AT 400 WORDS)

Actins↗
PubMed1994

Acute tubular necrosis in kidney transplant patients treated with enalapril.

We report two cases of acute renal failure in renal transplant patients using cyclosporine-A (CsA) after the introduction of angiotensin-converting enzyme inhibitor (ACEI) to control arterial hypertension. They had no renal artery stenosis or acute rejection. Both patients presented severe acute tubular necrosis (ATN), which subsided after discontinuation of the ACEI. Synergistic toxic effect of ACEI and CsA on the renal tubules might explain ATN in these two cases.

Cyclosporine↗
PubMed2006

Association of high pretransplant sIL-6R plasma levels with acute tubular necrosis in kidney graft recipients.

BACKGROUND: Delayed graft function is primarily caused by acute tubular necrosis (ATN). We studied in renal transplant recipients with posttransplant graft biopsy whether an up-regulated immune system in the recipient immediately before transplantation affects the risk of developing ATN and might be relevant for the pathogenesis of ATN. METHODS: In a retrospective study, we analyzed pretransplant and early posttransplant soluble interleukin (sIL)-1RA, interleukin (IL)-2, sIL-2R, IL-3, IL-4, IL-6, sIL-6R, IL-10, tumor necrosis factor (TNF)-alpha, transforming growth factor (TGF)-beta2, interferon (IFN)-gamma, and neopterin plasma levels in patients with ATN (n=26). Matched patients with acute rejection (AR) (n=26) or normal posttransplant biopsy (n=26) served as controls. RESULTS: Pretransplant sIL-6R was higher (P=0.0004) and pretransplant TGF-beta2 lower (P=0.002) in patients with ATN than in patients with normal biopsy. ROC curves showed that high pretransplant sIL-6R has a high sensitivity (77%) and high specificity (64%) for ATN (P=0.002). Posttransplant plasma sIL-6R continued to be higher in ATN patients than in patients with normal biopsy (P=0.001). Patients with acute rejection showed pre- and posttransplant sIL-6R and TGF-beta2 plasma levels similar to those of patients with normal biopsy (P=NS). CONCLUSION: High pretransplant sIL-6R plasma levels are associated with an increased risk of ATN and might contribute to the development of ATN early posttransplant. Our data suggest that preactivation of the recipient's immune system increases the risk of ATN.

Acute Disease↗
PubMed1975

Scanning and transmission electron microscopy of mercuric chloride-induced acute tubular necrosis in rat kidney.

Scanning (SEM) and transmission (TEM) electron microscopy were used to elucidate morphological changes associated with acute tubular necrosis induced by high doses of mercuric chloride. Marked morphological changes were demonstrated in proximal tubules with TEM at one hour and with both SEM and TEM at six hours. These changes appeared earlier than reported in previous studies using any dose. The scanning microscopic provided a three-dimensional view of proximal cells showing changes in early injury with subsequent separation of the injured cells from the remaining cells. Certain of these residual cells change into low-lying cells with reline the proximal tubule. Variability was seen in the number of residual cells. However, once cell injury was initiated, necrosis proceeded in a reproducible manner.

Acute Kidney Injury↗
PubMed2004

Early segmental changes in ischemic acute tubular necrosis of the rat kidney.

The background and mechanisms of ischemic acute tubular necrosis are still essentially unclarified. Therefore a quantitative morphological technique was applied for evaluation of the early structural changes in different fractions of the proximal convoluted tubule in the rat renal cortex. In male pentothal-anesthetized Wistar rats (body weight 200-250 g) ischemia of the right kidney was obtained by clamping (clamp diameter 0.15 mm) the ipsilateral renal artery for varying periods of time (10 min to 6 h) followed by removal and instant freezing of the kidney in isopentane at -165 degrees C and subsequent freeze-substitution in alcohol. The microscopic slides from the kidneys were silver methenamine-PAS stained. In the segments of the proximal convoluted tubules of the nephrons, presence of nuclear pyknosis, places of denuded basement membranes and presence of exfoliated tubular cells were counted. The results were statistically treated for comparison between the extent of damage in the initial postglomerular fraction and the later tubular loops. All three parameters showed a systematic, statistically significant increased number of lesions in the initial fraction of the proximal convoluted tubule versus the subsequent loops. The distribution of the structural lesions is in accordance with the previously reported presence of a tubulo-capillary counter-current flow in the proximal convoluted tubule and, when related to the highly variable oxygen tension in the normal renal cortex of the rat, indicates that the peculiar location of the early lesions might well be determined by these functional conditions.

Animals↗
PubMed1996

Gallopamil reduces the post-transplantation acute tubular necrosis in kidneys from aged donors.

Due to a shortage of suitable kidneys for transplantation there has been an increase in the use of kidneys taken from old and marginal donors, which has led to a high incidence of acute tubular necrosis. Several reports suggest that the administration of calcium channel blockers improves the initial function after renal transplantation. We conducted a randomized, double-blind placebo-controlled trial to study the effect of the calcium channel blocker gallopamil on the incidence and course of acute tubular necrosis following cadaveric renal transplantation. A trend developed showing a decrease in episodes of acute tubular necrosis in gallopamil versus placebo, and became statistically significant when the outcome of kidneys from donors older than 50 years was analyzed separately [gallopamil 6/14 (42%) vs. placebo 10/11 (91%), P <0.01 corrected chi2]. We conclude that pre-transplantation renal graft perfusion and post-transplantation recipient treatment with gallopamil reduces the incidence of post-transplantation acute tubular necrosis, particularly in kidney taken from older donors.

Adult↗
PubMed1977

Segmental acute tubular necrosis in kidneys with multiple renal arteries transplanted from living related donors.

Ten patients received kidneys from living, related donors, the transplants having multiple renal arteries; a retrospective analysis of the postoperative Hippuran renograms is presented. All seven kidneys that had the large artery reopened before anastomosis of the smaller, developed scintigram findings suggestive of acute tubular necrosis (ATN) in the region with the more prolonged ischemia. Three similar kidneys with simultaneous recanalization of both renal arteries had normal Hippuran scintiphotos. Electron photomicrographs from upper- and lower-pole biopsies--in one case undergoing sequential revascularization--confirm the development of ischemic changes consistent with ATN in the half of the kidney developing scan findings of ATN.

Acute Kidney Injury↗
PubMed2004

[Value of urinary sediment cytology in evaluation of acute tubular necrosis after kidney transplantation].

AIM: The aim of the study was to assess the clinical value of urinary sediment cytology (USC) by use of phase-contrast microscopy in the evaluation of acute tubular necrosis (ATN) during the early period after kidney transplantation. The study was performed at the Cytology Laboratory, Department of Nephrology and Dialysis, Clinical Hospital Center Rijeka, Croatia. PATIENTS AND METHODS: Patients included 141 kidney recipients, 99 male and 42 female, mean age 40 +/- 13 (range 8-72) years, who had received kidney allograft during the period of ten years, and who were treated at the University Department of Internal Medicine, Rijeka Clinical Hospital Center. The majority of patients (76%) had received cadaveric kidneys. Urinary sediment was analyzed for the presence of renal tubular cells, isomorphic erythrocytes, lymphocytes, casts and debris. Renal tubular cells on USC were recognized as the most constant sign of ATN. The presence of lymphocytes should arise suspicion of rejection. MAIN OUTCOME MEASURES: A typical cytologic profile of acute tubular lesion consists of tubular cells, isomorphic erythrocytes, casts, cellular and/or amorphic debris. RESULTS: USC by use of phase contrast microscopy is confirmed as a method of a very high sensitivity (82%) and specificity (93%) in the evaluation of ATN in transplanted kidney patients during early post-transplantation period. In situations of coexistence of several causes of allograft dysfunction, "mixed" cytologic pictures were frequently created, from which it is difficult or almost impossible to identify the actual cause of kidney dysfunction. In these cases, the final judgment should be made solely by histologic evaluation, which still represents the gold standard in the evaluation of kidney allograft dysfunction. CONCLUSION: Serial USC, when thoroughly examined using phase-contrast microscopy, is a simple, noninvasive, fast, easily repeatable and inexpensive diagnostic method of high sensitivity and specificity in the evaluation of ATN during the early phase after kidney transplantation.

Adolescent↗
PubMed2002

The role of technetium-99m MAG3 renal imaging in the diagnosis of acute tubular necrosis of native kidneys.

The differential diagnosis for patients with acute renal failure of their native kidneys, as a result of primary intrarenal disease, includes acute tubular necrosis, glomerulonephritis, and interstitial nephritis. The role of MAG3 renography has not been studied in this setting. The authors describe four patients with acute renal failure in whom MAG3 renal imaging reliably identified acute tubular necrosis, as confirmed by follow-up kidney biopsies. In contrast to the poor parenchymal uptake observed in glomerulonephritis and interstitial nephritis, MAG3 shows a distinctive pattern in patients with acute tubular necrosis. For patients with acute renal failure, a renal scan can facilitate decision-making regarding the initiation of therapy.

Acute Kidney Injury↗
PubMed1994

[Clinical studies of factors influencing acute tubular necrosis after kidney transplantation].

It is known that the earlier the graft begins functioning after cadaver kidney transplantation, the better the graft survival rate and function will be. In order to examine the possibility of shortening the period of acute tubular necrosis (AIN), we retrospectively studied the effect of several factors on the duration of postoperative hemodialysis. The subjects were 27 patients on whom a cadaver kidney transplantation was performed during a 6-year period from July 1, 1986. The mean duration of postoperative hemodialysis was 14.0 days in 26 out of the 27 patients. The remaining patient showed a primary non-functioning kidney. A significant correlation was observed between the anastomosis time and the duration of postoperative hemodialysis. No significant correlations were noted between the duration of postoperative hemodialysis and the age of the donor, renal function during the 24 hours preceding nephrectomy, or cold ischemic time. Moreover, no significant difference was observed in the duration of postoperative hemodialysis between patients using a roller pump for perfusion and patients who did not. The duration of postoperative hemodialysis was significantly shorter in patients using UW solution than in patients using Euro-Collins solution. Graft survival rate 6 months and one year after transplantation was 88.9% and 83.3%, respectively in the EC group, and 100% and 100%, respectively, in the UW group. It was concluded from these results that a short anastomosis time is essential in order to shorten the period of ATN after cadaver kidney transplantation, and that UW solution is effective in shortening the duration of postoperative hemodialysis and improving the graft survival rate thereafter.

Adenosine↗
PubMed2004

Calcium channel blockers for preventing acute tubular necrosis in kidney transplant recipients.

BACKGROUND: The incidence of delayed graft function in cadaveric grafts has increased over the last few years due in part to the large demand for cadaveric kidneys necessitating the use of kidneys from marginal donors. Calcium channel blockers have the potential to reduce the incidence of post-transplant acute tubular necrosis (ATN) if given in the peri-operative period. However, there is controversy surrounding their use in this situation with no consensus as to their efficacy. OBJECTIVES: To evaluate the benefits and harms of using calcium channel blockers in the peri-transplant period in patients at risk of ATN following cadaveric kidney transplantation. SEARCH STRATEGY: We searched the Cochrane Renal Group's specialised register, the Cochrane Central Register of Controlled Trials (CENTRAL, in The Cochrane Library issue 2, 2003) MEDLINE (1966 to January 2003) and EMBASE (1980 - January 2003). The Trials Search Coordinator was contacted to develop the search strategy. SELECTION CRITERIA: Randomised controlled trials comparing calcium channel blockers given in the peri-transplant period with controls were included. Quasi-randomised trials were excluded. DATA COLLECTION AND ANALYSIS: Data was extracted and quality assessed independently by two reviewers, with differences resolved by discussion. Dichotomous outcomes are reported as relative risk (RR) and measurements on continuous scales are reported as weighted mean differences (WMD) with 95% confidence intervals (CI). MAIN RESULTS: Nine trials were suitable for inclusion. Treatment with calcium channel blockers in the peri-transplant period was associated with a significant decrease in the incidence of post transplant ATN (RR 0.57, 95%CI 0.40 to 0.82) and delayed graft function (RR 0.44, 95% CI 0.28 to 0.69). There was no difference between control and treatment groups in graft loss, mortality, requirement for haemodialysis. There was insufficient information to comment on adverse events. REVIEWER'S CONCLUSIONS: These results suggest that calcium channel blockers given in the peri-operative period may reduce the incidence of ATN post-transplantation. The result should be treated with caution due to the heterogeneity of the trials which made comparison of studies and pooling of data difficult.

Calcium Channel Blockers↗
PubMed2005

Calcium channel blockers for preventing acute tubular necrosis in kidney transplant recipients.

BACKGROUND: The incidence of delayed graft function in cadaveric grafts has increased over the last few years due in part to the large demand for cadaveric kidneys necessitating the use of kidneys from marginal donors. Calcium channel blockers have the potential to reduce the incidence of post-transplant acute tubular necrosis (ATN) if given in the peri-operative period. However, there is controversy surrounding their use in this situation with no consensus as to their efficacy. OBJECTIVES: To evaluate the benefits and harms of using calcium channel blockers in the peri-transplant period in patients at risk of ATN following cadaveric kidney transplantation. SEARCH STRATEGY: We searched the Cochrane Renal Group's specialised register, the Cochrane Central Register of Controlled Trials (CENTRAL, in The Cochrane Library) MEDLINE (from 1966) and EMBASE (from 1980). The Trials Search Coordinator was contacted to develop the search strategy. Date of last database and register search: January 2005 SELECTION CRITERIA: Randomised controlled trials comparing calcium channel blockers given in the peri-transplant period with controls were included. Quasi-randomised trials were excluded. DATA COLLECTION AND ANALYSIS: Data was extracted and quality assessed independently by two reviewers, with differences resolved by discussion. Dichotomous outcomes are reported as relative risk (RR) and measurements on continuous scales are reported as weighted mean differences (WMD) with 95% confidence intervals (CI). MAIN RESULTS: Ten trials were suitable for inclusion. Treatment with calcium channel blockers in the peri-transplant period was associated with a significant decrease in the incidence of post transplant ATN (RR 0.57, 95%CI 0.40 to 0.82) and delayed graft function (RR 0.51, 95% CI 0.36 to 0.72). There was no difference between control and treatment groups in graft loss, mortality, requirement for haemodialysis. There was insufficient information to comment on adverse events. AUTHORS' CONCLUSIONS: These results suggest that calcium channel blockers given in the peri-operative period may reduce the incidence of ATN post-transplantation. The result should be treated with caution due to the heterogeneity of the trials which made comparison of studies and pooling of data difficult.

Calcium Channel Blockers↗
PubMed1977

Hypovolemic models of acute tubular necrosis in the rat kidney.

Studies were undertaken to determine whether a hypotensive episode under variable conditions is capable of inducing experimental acute renal failure in rats. Animals were subjected to hypovolemic shock by withdrawing volumes of blood necessary to maintain a systolic pressure of 30-40 mm Hg for 105-110 min. The blood was then reinfused and the animal was allowed to recover for 48 h prior to sacrifice. In an attempt to increase the injury, a second group of animals was salt-depleted prior to injury, a third group was volume-depleted by being deprived of H2O for 72 h prior of injury, a fourth group received 7.5 mg/kg indomethacin 30 min prior to injury, and a fifth group had 30% of the blood which was removed to produce shock hemolyzed and returned following the injury. In all groups examined, light microscopy revealed a moderate to severe acute tubular necrosis localized mainly in the outer stripe of the outer zone as defined by Peter (1909). Tubular damage was confined to the medullary pars recta of the proximal tubule and only in the most severe cases did injury involve the cortical pars recta and pars convoluta. Casts were present in the distal tubules and collecting ducts. Despite these significant histologic alterations, BUN values from all experimental groups remained within control levels. These studies clearly show that extensive necrosis of the medullary pars recta can be dissociated from the development of acute renal failure.

Acute Kidney Injury↗