Peri-operative renal dysfunction: prevention and management.

Postoperative increases in serum creatinine concentration, by amounts historically viewed as trivial, are associated with increased morbidity and mortality. Acute kidney injury is common, affecting one in five patients admitted with acute medical disease and up to four in five patients admitted to intensive care, of whom one in two have had operations. This review is focused principally on the identification of patients at risk of acute kidney injury and the prevention of injury. In the main, there are no interventions that directly treat the damaged kidney. The management of acute kidney injury is based on correction of dehydration, hypotension, and urinary tract obstruction, stopping nephrotoxic drugs, giving antibiotics for bacterial infection, and commencing renal replacement therapy if necessary.

Salmonella survival and differential expression of fatty acid biosynthesis-associated genes in a low-water-activity food.

UNLABELLED: The purpose of this study was to investigate the difference in expression of fatty acid biosynthesis genes and survival of different serotypes of Salmonella when incubated in a low-water-activity (aw ) food over a 14-day period. Stationary cells of five strains of Salmonella enterica belonging to 3 different serovars (Typhimurium ATCC 2486, Enteritidis H4267, Tennessee ARI-33, Tennessee S13952 and Tennessee K4643) were inoculated into granular sugar (aW   = 0·50) and held aerobically over a 14-day period at 25°C. Survival was determined by enumerating colonies on TSA and XLT-4 plates at 0, 1, 3, 5, 7 and 14 days. Correspondingly, gene expression was evaluated for three selected genes involved in fatty acid biosynthesis and modification (fabA, fabD and cfa). After 14 days of incubation, the population was reduced from 2·29 to 3·36 log for all five strains. Salmonella Tennessee ARI-33 and Salm. Tennessee K4643 displayed greater survival than Salm. Typhimurium and Salm. Enteritidis. The increased expression of the cfa gene (involved in cyclopropane fatty acid biosynthesis) over 14 days was found associated with strains with a lower survival rate. The fabA gene (involved in unsaturated fatty acid biosynthesis) was observed up-regulated for all strains for at least one sampling time and for Salm. Tennessee ARI-33 for all time points tested, suggesting its potential role in enhancing Salmonella survival in low aw foods. SIGNIFICANCE AND IMPACT OF THE STUDY: Numerous outbreaks of salmonellosis associated with low-water-activity foods have been reported. Therefore, the adaptive mechanisms utilized by Salmonella to survive in low-water-activity foods for prolonged periods of time need to be better understood. The results in this study showed that low-water-activity environments increase expression of gene fabA, which is involved in unsaturated fatty acid biosynthesis of Salmonella, while the increased expression of cfa, associated with cyclopropane fatty acid synthesis, was associated with decreased survival over 14 days.

Heterogeneous atmospheric reactions: sulfuric Acid aerosols as tropospheric sinks.

The collisional reaction probabilities of several atmospheric species on bulk sulfuric acid surfaces indicate that heterogeneous processes may be important in tropospheric chemistry.

Antarctic Ozone Depletion Chemistry: Reactions of N2O5 with H2O and HCl on Ice Surfaces.

The reactions of dinitrogen pentoxide (N(2)O(5)) with H(2)O and hydrochloric acid (HCl) were studied on ice surfaces in a Knudsen cell flow reactor. The N(2)O(5) reacted on ice at 185 K to form condensed-phase nitric acid (HNO(3)). This reaction may provide a sink for odd nitrogen (NO(x)) during the polar winter, a requirement in nearly all models of Antarctic ozone depletion. A lower limit to the sticking coefficient, gamma, for N(2)O(5) on ice is 1 x 10(-3). Moreover, N(2)O(5) reacted on HCl-ice surfaces at 185 K, with gamma greater than 3 x 10(-3). This reaction, which produced gaseous nitryl chloride (ClNO(2)) and condensed-phase HNO(3), proceeded until all of the HCl within the ice was depleted. The ClNO(2), which did not react or condense on ice at 185 K, can be readily photolyzed in the Antarctic spring to form atomic chlorine for catalytic ozone destruction cycles. The other photolysis product, gaseous nitrogen dioxide (NO(2)), may be important in the partitioning of NO(x) between gaseous and condensed phases in the Antarctic winter.

Synthesis of todorokite.

Todorokite of chemical composition (Mg(0.77)Na(0.03))(Mg(0.18)Mn(2+)(0.60)Mn(4+)(5.22)22) O(12).3.07 H(2)O was synthesized by a two-step procedure. First, sodium birnessite was synthesized and magnesium was exchanged for sodium to form magnesium birnessite, which was autoclaved under a saturated steam pressure at 155 degrees C for 8 hours to form well-crystallized todorokite. Synthesized todorokite particles consisted of fibers extending from a central plate. The plate itself was made of twinned fibers forming a trilling pattern. The infrared spectra and x-ray diffraction patterns were similar to those of natural todorokite samples. Calcium birnessite and nickel birnessite, when autoclaved under conditions similar to those for magnesium birnessite, yielded a todorokite structure. However, the formation of todorokite from calcium and nickel birnessite was less extensive.

Reaction of chlorine nitrate with hydrogen chloride and water at antarctic stratospheric temperatures.

Laboratory studies of heterogeneous reactions important for ozone depletion over Antarctica are reported. The reaction of chlorine nitrate (ClONO(2)) with H(2)0 and hydrogen chloride (HCl) on surfaces that simulate polar stratospheric clouds [ice and nitric acid (HNO(3))-ice and sulfuric acid] are studied at temperatures relevant to the Antarctic stratosphere. The reaction of ClONO(2) on ice and certain mixtures of HNO(3) and ice proceeded readily. The sticking coefficient of ClONO(2) on ice of 0.009 +/- 0.002 was observed. A reaction produced gas-phase hypochlorous acid (HOCl) and condensed-phase HNO(3); HOC1 underwent a secondary reaction on ice producing dichlorine monoxide (Cl(2)O). In addition to the reaction with H(2)0, ClONO(2) reacted with HCl on ice to form gas-phase chlorine (Cl(2)) and condensed-phase HNO(3.) Essentially all of the HCl in the bulk of the ice can react with ClONO(2) on the ice surface. The gaseous products of the above reactions, HOCl, Cl(2)0, and Cl(2), could readily photolyze in the Antarctic spring to produce active chlorine for ozone depletion. Furthermore, the formation of condensed-phase HNO(3) could serve as a sink for odd nitrogen species that would otherwise scavenge the active chlorine.

Methylation perturbations in retroelements within the genome of a Mus interspecific hybrid correlate with double minute chromosome formation.

A reduction in the DNA modification of cytosine methylation has been linked directly to chromosome rearrangements concomitant with retroelement amplification in several marsupial hybrid genomes. While phenotypes observed for interspecific eutherian hybrids are suggestive of methylation perturbations and retroelement instability, no link between retroelements, DNA methylation, and chromosome instability has yet been identified. Previous studies in eutherian hybrids, however, have been limited to a gross examination of methylation using methylation-sensitive restriction enzyme analysis or focused on single-copy genes and/or have avoided examination of repetitive DNA. Methylation changes and retroelements are proposed as mechanisms for double minute chromosome formation and oncogene amplification, both present in the genome of a Mus hybrid model, thus making it an ideal system to evaluate methylation status more closely. We have used the PCR-based methodologies methylation-sensitive amplicon subtraction (MS-AS) and methylation-sensitive representational difference analysis (MS-RDA) to detect differentially methylated sequences between three complex genomes and to isolate methylation perturbations in a Mus musculusxMus caroli hybrid. This novel application of MS-AS and MS-RDA resulted in the isolation of differentially methylated retroelements surrounding the locus on Chromosome 10 responsible for double minute chromosome formation within this interspecific eutherian hybrid.

Practical allergy (PRACTALL) report: risk assessment in anaphylaxis.

Effector mechanisms in anaphylaxis were reviewed. Current approaches to confirmation of the clinical diagnosis were discussed. Improved methods for distinguishing between allergen sensitization (which is common in the general population) and clinical risk of anaphylaxis (which is uncommon) were deliberated. Innovative techniques that will improve risk assessment in anaphylaxis in the future were described.

Probabilistic modelling of European consumer exposure to cosmetic products.

In this study, we describe the statistical analysis of the usage profile of the European population to seven cosmetic products. The aim of the study was to construct a reliable model of exposure of the European population from use of the selected products: body lotion, shampoo, deodorant spray, deodorant non-spray, facial moisturiser, lipstick and toothpaste. The first step in this process was to gather reliable data on consumer usage patterns of the products. These data were sourced from a combination of market information databases and a controlled product use study by the trade association Colipa. The market information study contained a large number of subjects, in total 44,100 households and 18,057 habitual users (males and females) of the studied products, in five European countries. The data sets were then combined to generate a realistic distribution of frequency of use of each product, combined with distribution of the amount of product used at each occasion using the CREMe software. A Monte Carlo method was used to combine the data sets. This resulted in a new model of European exposure to cosmetic products being constructed.

Occurrence of Escherichia coli O157:H7 in diverse farm environments.

In the United States, foodborne outbreaks of Escherichia coli O157:H7 illness have often been linked to the consumption of contaminated, undercooked ground beef. However, the occurrence of E. coli O157:H7 has also been reported in other farm animals. The objective of this study was to evaluate the occurrence of E. coli O157:H7 on diverse farm types and from a variety of farm samples. Rectal swabs (n=1686) and environmental samples (n=576) were collected from 16 farms in five states over 24 months and analyzed for the presence of E. coli O157:H7. Overall, E. coli O157:H7 was found in 3.6% of beef cattle, 3.4% of dairy cattle, 0.9% of chicken, 7.5% of turkey, and 8.9% of swine samples. The pathogen was isolated sporadically from each of the environmental sample types. Of particular concern was the isolation of E. coli O157:H7 from fresh feed samples, indicating a potential vector for transmission. The data from this study indicate a high occurrence of E. coli O157:H7 on swine and turkey farms. This unexpected result suggests that more research on the occurrence of E. coli O157:H7 on these types of farms is required in order to better understand potential reservoirs of pathogenic E. coli.

Elevated olivine weathering rates and sulfate formation at cryogenic temperatures on Mars.

Large Hesperian-aged (~3.7 Ga) layered deposits of sulfate-rich sediments in the equatorial regions of Mars have been suggested to be evidence for ephemeral playa environments. But early Mars may not have been warm enough to support conditions similar to what occurs in arid environments on Earth. Instead cold, icy environments may have been widespread. Under cryogenic conditions sulfate formation might be blocked, since kinetics of silicate weathering are typically strongly retarded at temperatures well below 0 °C. But cryo-concentration of acidic solutions may counteract the slow kinetics. Here we show that cryo-concentrated acidic brines rapidly chemically weather olivine minerals and form sulfate minerals at temperatures as low as -60 °C. These experimental results demonstrate the viability of sulfate formation under current Martian conditions, even in the polar regions. An ice-hosted sedimentation and weathering model may provide a compelling description of the origin of large Hesperian-aged layered sulfate deposits on Mars.

Casein kinase 2 prevents mesenchymal transformation by maintaining Foxc2 in the cytoplasm.

Nuclear Foxc2 is a transcriptional regulator of mesenchymal transformation during developmental epithelial-mesenchymal transition (EMT) and has been associated with EMT in malignant epithelia. Our laboratory has shown that in normal epithelial cells Foxc2 is maintained in the cytoplasm where it promotes an epithelial phenotype. The Foxc2 amino terminus has a consensus casein kinase 2 (CK2) phosphorylation site at serine 124, and we now show that CK2 associates with Foxc2 and phosphorylates this site in vitro. Knockdown or inhibition of the CK2α/α' kinase subunit in epithelial cells causes de novo accumulation of Foxc2 in the nucleus. Mutation of serine 124 to leucine promotes constitutive nuclear localization of Foxc2 and expression of mesenchymal genes, whereas an S124D phosphomimetic leads to constitutive cytoplasmic localization and epithelial maintenance. In malignant breast cancer cells, the CK2ß regulatory subunit is downregulated and FOXC2 is found in the nucleus, correlating with an increase in α-smooth muscle actin (SMA) expression. Restoration of CK2ß expression in these cells results in cytoplasmic localization of Foxc2, decreased α-SMA expression and reduced cell migration and invasion. In contrast, knockdown of CK2ß in normal breast epithelial cells leads to FOXC2 nuclear localization, decreased E-cadherin expression, increased α-SMA and vimentin expression, and enhanced cell migration and invasion. Based on these findings, we propose that Foxc2 is functionally maintained in the cytoplasm of normal epithelial cells by CK2α/α'-mediated phosphorylation at serine 124, which is dependent on proper targeting of the holoenzyme via the CK2ß regulatory subunit.

The development of a rat model to investigate the formation of blast-related post-traumatic heterotopic ossification.

Currently, there is no animal model in which to evaluate the underlying physiological processes leading to the heterotopic ossification (HO) which forms in most combat-related and blast wounds. We sought to reproduce the ossification that forms under these circumstances in a rat by emulating patterns of injury seen in patients with severe injuries resulting from blasts. We investigated whether exposure to blast overpressure increased the prevalence of HO after transfemoral amputation performed within the zone of injury. We exposed rats to a blast overpressure alone (BOP-CTL), crush injury and femoral fracture followed by amputation through the zone of injury (AMP-CTL) or a combination of these (BOP-AMP). The presence of HO was evaluated using radiographs, micro-CT and histology. HO developed in none of nine BOP-CTL, six of nine AMP-CTL, and in all 20 BOP-AMP rats. Exposure to blast overpressure increased the prevalence of HO. This model may thus be used to elucidate cellular and molecular pathways of HO, the effect of varying intensities of blast overpressure, and to evaluate new means of prophylaxis and treatment of heterotopic ossification.

Causes of graft loss beyond two years in the cyclosporine era.

While CsA has improved renal-allograft survival rates in the first 2 years compared with Aza, Terasaki's multicenter study (1) failed to show any difference in long-term graft survival in CsA-Pred versus Aza-Pred-treated recipients. The present study examines the long-term graft-survival rates at a single center using CsA immunosuppression and seeks to discern the causes of 58 graft losses among 343 patients with functioning grafts beyond 2 years posttransplantation. The 6-year primary and cadaveric actuarial graft survival at this institution is 59% with a graft half-life of 10 years, which is better than the 40% and 7.7 years, respectively, reported by Terasaki (1) for primary cadaveric recipients on Aza-Pred. It is also better than the 41%, 6-year survival and 5.5-year half-life for primary cadaveric recipients treated with CsA-Pred as reported in the multicenter study. (1) Less experience with the use of CsA may explain the latter comparison. Primary LRD grafts at this institution (2/3 haploidentical) have a 6-year actuarial survival of 77% and a half-life very closely approximating that of HLA-identical LRD grafts under Aza (23.4 years). These results demonstrate that CsA mitigates the effects of HLA incompatibility to reduce graft survival. The most common cause of graft loss beyond 2 years was chronic rejection (36.2%) followed by noncompliance (27.6%). Patient deaths resulted in 13 of the 58 graft losses; most of the deaths were related to cardiovascular diseases. Only 3 patients died from causes that could be attributed to CsA immunosuppression; 2 from sepsis and 1 from viral hepatitis. Acute rejection caused 8.6% of the graft losses on continuous CsA therapy. When immunologic risk factors were analyzed, the entire graft-loss group had a significantly higher proportion of retransplant patients than the graft-survival group (P less than 0.005), suggesting that prior transplantation imposes a higher risk for graft loss not only acutely but long term as well. However, retransplanted patients were significantly less likely to lose their grafts because of noncompliance (P less than 0.005). Male patients were found to be significantly more noncompliant.

Chronic rejection in primary renal allograft recipients under cyclosporine-prednisone immunosuppressive therapy.

Although the introduction of cyclosporine-prednisone immunosuppression has improved early renal graft survival, chronic rejection remains a major cause of longterm graft dysfunction. This study retrospectively examined 69 cases of chronic rejection among 643 primary renal allograft recipients treated with cyclosporine-prednisone immunosuppression from July 1981 to October 1989. Chronic rejection was defined as a rejection episode diagnosed greater than 90 days posttransplantation with characteristics of progressive nonacute renal function deterioration, confirmed, in most cases, by renal biopsy. This group was compared with an equal-sized matched cohort. Among cadaveric recipients, 61 of 456 patients (13.4%) displayed chronic rejection, whereas among living-related recipients, 8 of 187 patients (4.3%) developed chronic rejection. The average time from the date of transplantation to diagnosis of chronic rejection was 15 +/- 14 months. One- and three-year graft survivals following diagnosis of chronic rejection were 51% (30/59) and 25% (13/51), respectively, compared with the cohort one- and three-year graft survivals of 98% (58/59) and 86% (32/37) at similar periods posttransplantation. HLA mismatch, PRA status, blood transfusion history, lipid levels, cyclosporine trough levels, incidence of prior acute rejection, and initial graft dysfunction were not significantly different between the chronic rejection group and the matched cohort. Hypertension and proteinuria were significantly associated with chronic rejection (P less than 0.001). Of 58 biopsies performed, findings solely consistent with chronic rejection were observed in 9 cases (15%) and "acute upon chronic" rejection in 49 cases (83%). Treatment of acute concomitants improved the renal function in 43% (27/63) by the time of hospital discharge. Nonetheless, at 12 months the incidence of improved renal function eroded to 22% (13/59), suggesting that the benefit was relatively short-lived. Although the overall incidence of chronic rejection in this group of cyclosporine-prednisone-treated patients was lower than previous azathioprine-prednisone cohorts, the clinical presentation and progression of chronic rejection was similar. Additionally, the incidence of chronic rejection within this series was lower among living-related recipients versus cadaveric recipients of donor organs.

Complications of cyclosporine-prednisone immunosuppression in 402 renal allograft recipients exclusively followed at a single center for from one to five years.

The therapeutic efficacy of cyclosporine (CsA) as an immunosuppressive agent was complemented by a modest, long-term incidence of toxic complications in 402 renal allograft recipients engrafted one to five years prior to analysis. The overall patient and graft survivals at one year were 97% and 84% (actual), and at five years 92% and 67% (actuarial). The immunosuppressive therapeutic index was excellent: only 12% of allografts were lost from rejection, with 5% of patients succumbing to infection. While infections were common, tending to emanate in the urinary tract or to be viral in etiology, they were generally mild and readily controlled. Only four patients displayed malignancies; none succumbed to this cause. The most common toxic complication was hypertrichosis, which was accentuated in pediatric patients. While tremors occurred in 20% of patients, primarily during the first three months, other neuroectodermal complications of parethesias, depression, somnolence, and seizures were rare. Hepatotoxicity, which was noted in 50% of patients, particularly recipients of cadaveric grafts, generally was first seen as a transaminase elevation, at least partially reversible by dose-reduction and abating by the third year. Associated disturbances of cholelithiasis and pancreatitis were occasionally observed. Nephrotoxicity was the only persistent, long-term complication. Hypertension occurred in 72% of patients during the first month, 36% in the second year, and about 15% thereafter. Hyperuricemia, which occurred in about 30% of recipients during the first two years, was occasionally associated with symptomatic gout. The mean serum creatinine level remained elevated throughout the follow-up period at 1.8-1.9 mg/dl, suggesting persistent, but nonprogressive, drug-induced renal injury. The present analysis documents the relative safety of CsA for long-term therapy, and highlights the need for new approaches to ameliorate drug-induced nephrotoxicity.

The impact of cytomegalovirus infection on seronegative recipients of seropositive donor kidneys versus seropositive recipients treated with cyclosporine-prednisone immunosuppression.

To assess the impact of cytomegalovirus (CMV) infection in D+R- patients treated with cyclosporine (CsA)-prednisone immunosuppression, we compared the incidence of CMV infection, severity of disease, and the 1, 2, and 3-year actual graft and patient survival rates of CMV-infected D+R- patients with R+ patients from a group of 516 renal allograft recipients at our center. CMV infection occurred more frequently in 27/56 D+R- patients (48%) versus 111/376 R+ patients (29%) (P less than 0.01). The incidence of CMV was also significantly greater in D+R- versus R- patients receiving CAD grafts (59% vs. 32%, P less than 0.01) and first transplants (47% vs. 30%, P less than 0.05). There were no significant differences in CMV disease severity between the aggregate D+R- and R+ patient groups and when subgroups of these patients receiving cadaveric donor (CAD), living-related donor (LRD), first, or retransplant allografts were compared. The actual 1, 2, and 3-year graft survival rates for D+R- patients (68%, 58%, 68%) were not significantly different from rates in R+ patients (83%, 77%, 63%) with CMV infection. When the 1, 2, and 3-year actual graft survival rates in subgroups of D+R- and R+ patients were compared in CAD, LRD, and first and retransplants, there were no significant differences. The actual 1, 2, and 3-year patient survival rates were not significantly different between D+R- (89%, 92%, 100%) and R+ patients (94%, 91%, 86%) with CMV infection, nor were they different when CMV infected D+R- and R+ patients with CAD, LRD, first or retransplant grafts were compared. These data do not support the policy of denying a seropositive kidney to a seronegative recipient, since the severity of CMV disease and the impact of CMV infection is not significantly different comparing D+R- and R+ patients receiving CsA-prednisone immunosuppression.

The adverse impact of cytomegalovirus infection on clinical outcome in cyclosporine-prednisone treated renal allograft recipients.

Cytomegalovirus (CMV) infection was diagnosed in 28% (n = 144) of 516 renal allograft recipients treated with cyclosporine-prednisone (CsA-Pred) immunosuppressive therapy. The majority of infections produced either asymptomatic (n = 37) or mild-to-moderate (n = 75) clinical disease, while 10% were lethal (n = 14). Transplantation from a seropositive donor to a seronegative recipient was associated with an increased incidence of (CMV) infection but did not predispose to more severe clinical disease. Similarly, donor source (cadaver [CAD] vs. living-related donor [LRD]), age greater than or equal to 45 years, and antecedent pulse steroid therapy for the treatment of acute rejection were not correlated with clinically more severe disease. An increase in serum creatinine to greater than or equal to 25% of preinfection nadir values occurred in association with CMV infection in 106 patients, returning to nadir values or below in 74.5% of these individuals. CMV infection did not impact on actual patient survival among recipients of LRD or CAD allografts or on actual 1-year HLA-haploidentical or HLA-identical LRD graft survival. In contrast, actual 1-year cadaveric graft survival was significantly lower among CMV-infected (n = 95) vs. uninfected (n = 198) patients (75.8% vs. 87.8%, P = .01). In association with the finding of reduced actual 1-year CAD graft survival, CMV-infected patients were found to be more predisposed to develop acute rejection episodes. Of the CMV-infected CAD graft recipients, 48.4% developed greater than or equal to 1 acute rejection episode during the first year following transplantation vs. 25.3% of their uninfected counterparts (P less than .001). The impact of CMV infection in CsA-Pred treated renal transplant recipients does not differ substantially from that reported historically in association with prednisone-azathioprine immunosuppressive therapy.

Preemptive transplantation--an analysis of benefits and hazards in 85 cases.

The benefit of transplantation without prior dialysis might be contravened by the failure to develop possible immunologic disabilities associated with chronic uremia and dialysis. This study compares graft and patient outcome, cyclosporine toxicity, pharmacokinetics, rejection episodes, nutritional status, and social and vocational rehabilitation between a preemptive group of 85 patients transplanted without prior dialysis and a cohort of 84 demographically, temporally, and disease-matched recipients of renal transplants after a minimum of 6 months' chronic dialysis therapy. The groups were matched for donor type, gender, and age, as well as immunologic risk factors of HLA-mismatch and percent panel-reactive antibody. All patients received CsA and prednisone immunosuppression. There were only two differences between the cohorts. The preemptive group included more diabetic patients: 32 versus 15 (P less than 0.01). The control cohort included more recipients who had received any pretransplant transfusion: 55 versus 28 (P less than 0.001). Both of these factors (if having any impact) would be expected to reduce graft survival in the preemptive group. All patients in the study had a minimum follow-up of 1 year and over half of the recipients are beyond 40 months. The preemptive patients showed survival rates of 94, 93, and 91 percent at 1, 2, and 5 years. These rates were not significantly different from those of the control group, namely 96, 96, and 93 percent, respectively. The actuarial graft survival rates in the preemptive group of 83, 81, 76, 73, and 73 percent at 1, 2, 3, 4, and 5 years were not statistically different from the control group rates, namely 90, 81, 80, 77, and 76 percent. Preoperative blood transfusion or percent positive panel-reactive antibodies had no effect on postoperative outcome in either group. The incidence of CsA nephrotoxicity was 9.4 percent in the preemptive group, which was not statistically different from the 17.9 percent in the control group. The incidence of rejection episodes in the absence of patient noncompliance was comparable between the groups. Seven of the irreversible rejection episodes in the preemptive group were due to noncompliance, compared with none in the control group (P less than 0.001). Preemptive recipients were also more likely than control group patients to be employed fulltime both before transplantation (36 vs. 22, P less than 0.05) as well as after transplantation (38 vs. 20, P less than 0.01).(ABSTRACT TRUNCATED AT 400 WORDS)

Stability of renal allograft function associated with long-term cyclosporine immunosuppressive therapy--five year follow-up.

To examine the evolution of renal allograft function in kidney transplant recipients receiving long-term cyclosporine therapy, we evaluated 50 cadaveric and 30 living-related renal transplant recipients having graft survival greater than or equal to 12 months and an opportunity for 5 years of follow-up. Linear analysis of long-term allograft function in each patient was undertaken by plotting reciprocal serum creatinine (1/Crs) values vs. time. Mean follow-up was 49 +/- 18 months. Actual 3-year and 5-year allograft survivals were 83.8% (n = 80) [corrected] and 73.3% (n = 75) [corrected], respectively. Collective analyses of values of 1/Crs measured at yearly intervals and of the slopes of the curves obtained by plotting 1/Crs vs. time for each patient suggested that long-term use of CsA is associated with impaired but generally stable allograft function 1-5 years posttransplant. The aggregate rate of decline of renal allograft function in the study population did not differ from that of a historical control group consisting of 59 renal transplant recipients treated with a conventional prednisone-azathioprine immunosuppressive regimen. Donor source, diabetes, and diastolic hypertension (diastolic BP greater than 95 mmHg in more than half the follow-up readings) were not correlated with a more rapid rate of decline of allograft function as reflected in the slopes of the 1/Crs vs. time curves between 12 months posttransplant and the end of follow-up. In contrast, a significantly greater rate of decline of cadaveric allograft function was observed in patients with 12-month Crs values greater than 2.5 mg% and recipients of greater than 2 HLA-A,B-mismatched cadaveric kidneys. The data do not support an indication for routine conversion from CsA to azathioprine following successful renal transplantation.