Effective prophylaxis of early post-transplant urinary tract infections (UTI) in the cyclosporine (CSA) era.
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Biomedical subjects
Publications and source records attributed to M F Mozes.
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The incorporation of 3H2O and/or 14C-glycerol into lipids and the specific activities of the enzymes acetyl CoA carboxylase and lipoprotein lipase were measured in the perirenal and subcutaneous adipose tissue of human subjects. The perirenal adipose tissue of younger subjects with higher brown adipocyte content had higher rates of lipogenesis and enzyme activities per gram tissue than the corresponding subcutaneous tissue. However, in individual specimens, the perirenal/subcutaneous ratios of all but one of the above parameters failed to show a correlation with the brown adipocyte content of the perirenal adipose tissue. One parameter, namely 3H2O incorporation into fatty acids per adipocyte, did relate to the brown adipocyte content of the perirenal adipose tissue in four normal-weight patients only.
Fluid collections following renal transplantation are not rare and may be associated with serious complications. We studied the incidence, clinical features, pathology and treatment outcome of perirenal fluid collections after kidney transplantation. Between January 1977 and June 1985, 386 consecutive renal transplants were performed at our university. All allografts were studied with B-mode ultrasonography together with a renal scan in the immediate post-transplant period, at 6-month intervals or when clinically indicated. Symptomatic fluid collections, those associated with rejection episodes and those containing more than 50 to 100 ml. fluid were aspirated under sonographic control via aseptic techniques. There were 190 fluid collections (49 per cent) observed during followup (2 to 11 years). Of these collections 98 (51 per cent) were estimated to be less than 50 ml. in volume, were clinically insignificant and resulted in no morbidity. A total of 92 collections was aspirated with 1 aspiration being diagnostic and therapeutic in 57 instances (serous or serosanguinous fluid). The 35 collections remaining were revealed to be lymphoceles on biochemical grounds. Of 13 lymphoceles associated with rejection episodes 8 resolved on initial aspiration. Of the recurrent lymph collections 27 were treated with repeated aspiration, tetracycline sclerotherapy or an operation (10 were treated with marsupialization into the peritoneal cavity). No large collections of urine or blood were detected and 1 infected lymphocele required external drainage. No renal allograft was lost as a result of a fluid collection and over-all graft survival was not affected by the development of perirenal fluid collections. We conclude that perirenal fluid collections are detected commonly in the post-transplant period using B-mode ultrasonography. The majority of these collections are small and will require careful observation only or they will resolve with a single aspiration. Aggressive diagnostic and therapeutic measures are used only for those collections that are symptomatic or result in allograft dysfunction. A rational approach to the diagnosis and treatment of peritransplant fluid collections is described in the form of an algorithm.
Flow cytometry (FC) T and B cell crossmatches were done retrospectively for 38 cadaver renal transplant recipients (29 first and 9 retransplants--minimum follow-up 12 months) using both current pretransplant serum and peak-reactive sera. An increase in median fluorescence intensity (channel shift) and/or an increase in the number of donor T and/or B cells binding antibody in test sera occurred in 23 cases. These 23 patients experienced a greater number of reversible rejection episodes as compared with patients with negative FC crossmatches (65% vs. 33%), P = 0.031. Graft outcome, however, was not different in the two groups. Thus, a positive FC crossmatch allows for the detection of subliminal levels of donor presensitization and is associated with a greater number of rejection episodes. A positive FC crossmatch is not predictive of ultimate graft loss.
Post-transplant erythrocythemia (PTE) is a common finding in renal allograft recipients, although the etiology of this disorder has not been clearly established. We identified 22 patients (9.8%) with PTE from among 225 renal transplant recipients followed for an average of 5.5 years. To characterize possible predisposing factors and to study the clinical significance of PTE, these patients were compared with a control group matched for age, race, sex and etiology of renal failure. Plasma volume (PV) and red blood cell mass (RBCM) were measured in the majority of patients with PTE. Peripheral serum erythropoietin (Ep) levels were determined in the majority of patients in the control and PTE groups. PTE occurred an average of 11.4 months after transplantation. Risk factors for the development of PTE were pretransplant hypertension, retention of native kidneys, higher pretransplant hematocrit, and diuretic use for treatment of post transplant hypertension. Ep levels in the PTE and control groups were not significantly different. Twenty of the 22 patients with PTE were receiving concurrent diuretic therapy, and hematocrits fell to normal levels in all of these patients following cessation or dose reduction of diuretic. No other treatment of PTE was utilized, excluding the phlebotomy of a single unit of blood from one patient. No thromboembolic complications were noted during the follow-up period. We conclude that PTE is frequently induced by overzealous diuretic therapy for treatment of post-transplant hypertension. Discontinuation or reduction of diuretic therapy results in resolution of PTE in nearly all patients. From this experience we have developed an algorithm for the investigation and management of PTE.
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Forty-four living-related donor kidney (LRD) recipients (19 HLA-identical and 25 haploidentical) were followed prospectively to determine the posttransplant incidence and sequelae of cytomegalovirus (CMV) infection as they relate to the CMV status of recipients and donors. CMV titers were measured in all patients before transplantation by an immunofluorescent assay (IFA). Recipients similarly had CMV titers measured at selected intervals after transplant and during febrile episodes. Appropriate viral cultures were simultaneously performed. Laboratory evidence of infection was correlated with symptoms and signs of active CMV disease. Mean follow-up period was 20 +/- 12 months with a range of 3-51 months. Three patients were excluded due to early acute rejection resulting in graft loss. Twenty-eight of 41 donors (68%) and 22 of 41 recipients (54%) had positive CMV titers before transplantation. Six of 41 recipients (15%) subsequently developed clinical and laboratory evidence of CMV infection: three of 19 seronegative recipients and three of 22 seropositive recipients. All six patients received kidneys from seropositive donors. Four patients had severe CMV disease (2 seronegative, 2 seropositive), whereas two patients had leukopenia and fever only. Two patients with severe CMV infections subsequently lost their grafts due to unrelated causes. Overall, actual patient and graft survival of the entire group is 95% and 82%, respectively. In conclusion, individuals who receive LRD kidneys from seronegative individuals are unlikely to develop CMV infection, and transplantation of seropositive LRD kidneys may be associated with transmission of CMV in susceptible recipients regardless of their serologic status. With appropriate management of CMV illness in the posttransplant period, LRD kidney donation is safe and efficacious and should not be discouraged on the basis of pretransplant CMV serology in any donor-recipient pairing.
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An alternative antirejection protocol using corticosteroids or ALG for reversal of initial acute rejections was studied during a 2-year period in 112 mismatched renal transplant recipients receiving CsA. The majority of patients were cadaver transplant recipients. Thirty-five initial episodes of acute rejection occurred; twelve patients with early or histologically severe rejection were treated with ALG and 23 patients with late, nonsevere rejection received corticosteroid therapy. The overall success rate was approximately 90%, with 21 of 23 corticosteroid-treated patients and ten of 12 ALG-treated patients responding to therapy. The two treatment modalities did not differ with respect to subsequent hospital admissions for fever, second rejections, graft survival, or patient survival. Corticosteroid-treated patients realized significant cost savings and required a shorter hospital stay when compared to ALG-treated patients. An alternative antirejection treatment protocol may be highly effective, safe, and cost beneficial.
Thirty of 110 HLA-mismatched renal allograft recipients were converted from CsA to Aza due to CsA nephrotoxicity or side effects, persistent posttransplant ATN, noncompliance, or patient desire to reduce the cost of maintenance immunosuppression. The majority of patients studied were cadaver transplant recipients. Renal function improved significantly in all patients following conversion. Converted patients did not demonstrate an increased incidence of rejection or hospitalization for fever or infection when compared with nonconverted, matched controls. The rate of allograft loss in converted patients did not differ from that of all nonconverted patients during the study period. The monthly cost of maintenance immunosuppression was significantly less in converted patients, resulting in an annual savings of $2,489 per patient. Posttransplant conversion from CsA to Aza appears to be safe and cost-beneficial.
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A method for measuring pretransplant CsA levels to predict posttransplant pharmacokinetic behavior was studied in a total of seven pediatric patients. Comparison of drug levels and single-dose pharmacokinetic characteristics in the pretransplant and posttransplant study periods suggest that this method (1) is useful in predicting early posttransplant blood levels and beta-phase half-life; (2) may prevent early episodes of acute allograft rejection associated with subtherapeutic cyclosporine immunosuppression; and (3) may identify those patients who should not be empirically treated with only cyclosporine and prednisone in the early posttransplant period.
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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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