Role of native nephrectomy in renal transplant recipients.
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Biomedical subjects
Publications and source records attributed to E David-Neto.
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Chronic transplant nephropathy (CTN) is the most important cause of kidney graft dysfunction. Studies in adult populations have reported a beneficial effect of non-nephrotoxic mycophenolate mofetil (MMF) on graft function in this setting. However, few studies were reported in children in this setting. We therefore reviewed the charts/medical records of renal transplanted patients < 18 yr of age at a single center who had switched from azathioprine to MMF as a result of progressive loss in graft function, for which vascular, infectious, and urological causes were excluded. Serum creatinine (SCr) and calculated creatinine clearance were compared prior to and after MMF introduction. Thirteen patients (nine male/four female), followed-up for 59.3 +/- 35.4 months after transplantation, were analyzed. Age at MMF introduction was 14.2 +/- 3.6 yr. In 11 patients a previous biopsy had shown features of CTN and four patients also presented signs of chronic cyclosporin A (CsA) nephrotoxicity. MMF was started at a dose of 1211 +/- 351 mg/day, and the CsA dose was decreased from 6.69 +/- 3.15 mg/kg/day 6 months before MMF to 4.8 +/- 2.3 mg/kg/day at the time of MMF introduction. CsA was withdrawn in four patients. The median (25-75%) SCr value increased from 1.60 mg/dL (range 1.3 to 1.87 mg/dL) 6 months before MMF to 2.2 mg/dL (range 1.87-2.32 mg/dL) when MMF was introduced. Six months after introduction of MMF, the SCr level had decreased to 1.5 mg/dL (range 1.2-1.8 mg/dL) and remained stable until the last follow-up (17.5 +/- 9.2 months after MMF was started). A similar pattern occured with calculated SCr clearance. There were no acute rejections after changes in immunosuppression. The safety of MMF was also analyzed and in only one patient was the drug stopped as a result of intractable diarrhea. These findings suggest that MMF is sufficiently powerful to allow a decrease/withdrawal of CsA without the burden of acute rejection in a pediatric population with CTN.
BACKGROUND: In transplanted patients, viral hepatitis progresses to chronic liver disease and patient's death after many years of transplantation. Also, it is well known that azathioprine (AZA) is harmful to the liver of these patients. However, it is unclear whether a low dose of AZA still represents a threat to the viral liver disease. METHODS: A total of 79 patients with hepatitis C, B, or both, transplanted between 1973 and 1990, were grouped according to whether they had AZA either withdrawn from the immunosuppressive regimen [group (G) I, n=45] or a dosage reduction only (group II, n=34). The decision to remove or to keep AZA was restricted to the patient's doctor. Patients records were reviewed by April 1997. RESULTS: After an equal time of follow-up, after the AZA changing (64+/-26 vs. 58+/-29 months), patients in GI showed a significant decrease in the serum liver parameters when compared to baseline [alanine aminotransferase (ALT): P=0.001; gamma-glutamyl transferase (gamma-GT): P=0.001 and total bilirubin: P=0.002], whereas in GII only ALT decreased (P=0.04) although gamma-GT and total bilirubin did not. Compared to baseline, serum creatinine (SCr) increased only in GI (P=0.001) but, at last follow-up, did not differ from GII. The intention-to-perform liver biopsies was equal in GI and GII (16 vs. 14) but the hystological findings of severe chronic liver disease (either chronic active hepatitis or cirrhosis) were more frequent in GII (P=0.004). Death with a functioning graft was much more frequent in GII than in GI (P=0.001). Infection and cirrhosis were more common as a cause of death in GII than in GI. CONCLUSIONS: The use AZA is harmful to renal transplantation patients with both chronic hepatitis C and B and, therefore, should be avoided. AZA withdrawal, but not dose adjustments, diminishes the serum liver enzymes and the progression rate of the chronic viral liver disease as well as the rate of death secondary to infection and cirrhosis.
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Acute rejection is associated with a poor long-term prognosis for renal allografts. Sequential fine-needle aspiration cytology (FNAC) has been used to monitor rejection. However, FNAC diagnoses rejection only when the infiltrating cells are already damaging the graft and, in some borderline cases with a low increment of inflammatory cells in the graft, FNAC lacks the specificity to diagnose rejection. In these cases, the number of inflammatory cells within the graft can decline, stabilize or increase with time. In this study, we sought to determine whether the analysis of the expression of ICAM-I, HLA-DR and IL-2R along with borderline FNAC results increases the specificity to diagnose rejection. Of 117 FNAC samples taken from 24 patients after renal transplantation, 85 (72%) were considered suitable for cytological analysis. Of these patients, 9 (37%) did not suffer an acute cellular rejection (ACR) episode and 15 (63%) had at least one ACR episode. ICAM-1 and IL-2R were studied using an immune-peroxidase technique. The ICAM-1 results are expressed as the percentage of tubular cells in the aspirate stained with this marker and the IL-2R results are expressed as the absolute number of positively stained lymphocytes in the whole cytopreparation. With a total corrected increment (TCI) of > 3 there was a sharp increase in the specificity index for rejection that reached almost 100% at a TCI of > or = 4. Sensitivity for rejection at this level was only 20%. Between a TCI of 2.5 and 2.9 the sensitivity increased to 75%, with specificity for rejection around 75%. There was an upregulation of ICAM-1 and IL-2R when FNAC diagnosed rejection but with a large overlap of the results when compared either to normal graft or acute tubular neurosis. The mean TCI during the week preceding the rejection episode was 2.5 and the TCI reached a mean value of > or = 3 only during rejection. The peak ICAM-1 and IL-2R expression occurred during the week preceding the clinically evident rejection episode. The expression of ICAM-1 by > or = 70% of the tubular cells increased the specificity for rejection of a TCI of > or = 2.5 to 100%. In the same way, the specificity for rejection increased up to 90% when eight to ten IL-2R-positive lymphocytes were seen along with a TCI of > or = 2.5. There was no further increase in specificity after that. A specificity index of 100% for rejection could be obtained for moderate levels of both ICAM-1 (70% or more tubular cells) and IL-2R (eight or more lymphocytes). ICAM-1 expression in 70% or more tubular cells and/or IL-2R expression in eight or more lymphocytes was found in 58% of the FNAC aspirates with a TCI between 2.5 and 2.9. In conclusion, the expression of IL-2R in lymphoid cells and ICAM-1 in tubular cells was upregulated during rejection episodes and the upregulation preceded both the clinical and the routine FNAC diagnosis of rejection by 1 week. The ddition of these markers to the FNAC increased substantially the specificity of the FNAC to diagnose rejection.
Post-transplant neutrophilic interstitial nephritis (NIN) is characterized by an interstitial infiltrate consisting of polymorphonuclear cells that leads frequently to acute graft dysfunction. In 220 graft biopsies performed because of renal dysfunction over 2 years in our unit, 11 (5%) diagnoses of NIN were made. Only two patients had chronic pyelonephritis as original disease. Four patients had urological problems before transplantation. After transplantation, five patients had urinary tract infection, one had urethral stenosis, two had vesicourethral reflux and one patient had a perinephritic abscess. Seven patients had fever (63%). Only in six patients did urine culture lead to microorganism isolation. After 6 months, only two patients had a serum creatinine level < 1.4 mg/dl, five patients had abnormal function, three had lost their grafts, and one patient had died with sepsis. We conclude that 5% of the biopsies performed in our center disclosed NIN, an entity that causes graft dysfunction and progresses frequently to chronic renal failure. In some cases, no infectious etiology could be detected.
BACKGROUND: The unregulated renin release by native kidneys is one of the factors responsible for the high incidence of hypertension after renal transplantation but, even after three decades of transplantation, there is still a lack of a method to identify it as the major cause of hypertension. METHODS: We investigated whether or not peripheral renin activity, before and 90 min after 25 mg of captopril, can play this role. One hundred and five consecutive patients with SCr less than 2 mg/dl were studied 18 +/- 8 months after renal transplantation. Forty-seven of them were considered hypertensive and 58 normotensive. All hypertensive patients were submitted to the captopril test to analyse the peripheral renin activity profile. RESULTS: In the hypertensive group, 17 patients (36%) were considered Renin-pos and 30 (64%) Renin-neg. All Renin-pos (stimulated renin = 19.1 +/- 6.4 ng/ml/h) patients were submitted to bilateral nephrectomy (bNx) and re-evaluated 6 months later. All of them normalized renin activity (4.4 +/- 3.0 ng/ml/h, P = 0.0001) and 10 of 17 (60%) became normotensive and off drugs. The remaining seven (40%) decreased the number of hypotensive drugs from 2.2 +/- 0.5 to 0.5 +/- 0.7/pt/day. There was a correlation between b-Renin and dBP (r = 0.47, P < 0.05) which was lost after bNx. An 'in situ' renal-cell carcinoma was found in two cases. Serum creatinine did not change. CONCLUSIONS: This study shows that the unregulated renin-angiotensin system from the native kidneys plays a major role in the maintenance of hypertension in some patients with normal graft function and that peripheral renin activity can identify those who will benefit from bilateral nephrectomy.
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We evaluated the course of severe aluminum-related bone disease (ARBD) after the first year of a successful renal transplantation (RTx) in 11 adult patients. Bone pain and muscle weakness, presented in all patients previously to RTx, subsided, and all were able to walk, even the ones who were confined to wheelchairs. Bone necrosis developed in 6 patients, but none required surgical repair. Serum alkaline phosphatase activity increased 2.5 times the upper normal level, up to the 5th month and then declined to normal levels up the 12th month (p < 0.05). The inverse profile was observed in both serum calcium and phosphorus levels. In bone biopsies, there was a significant decrease in all of the following histomorphometric static parameters: osteoid volume, thickness and surface and also in aluminum surface. Also, there was a significant increase in all the dynamic parameters of mineralization: mineral apposition rate, mineralization surface, bone formation rate and adjusted apposition rate. In conclusion, ARBD remarkably improves after 1 year of successful RTx.
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