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BACKGROUND: Limited research has focused on the predictive nature of organizational culture and trust on registered nurses' perceived health care quality in reformed health care systems. PURPOSES: The purpose of this article was to investigate nurses' perceptions of organizational culture factors, trust in employer, and perceived health care quality during and 5 years after major organizational reform in the acute care setting and to test a model linking culture to perceived health care quality. METHODOLOGY: Survey data collected from two samples of nurses (N = 222,343) during and 5 years after major organizational reform in the acute care setting of one Canadian province were analyzed, and an exploratory model linking aspects of culture, trust, and quality was tested. FINDINGS: For both periods, most variable scores were in the low range and depicted moderately positive intercorrelations with each other. Support for the proposed model was mixed. Select culture variables predicted health care quality at both periods, but trust emerged as a significant predictor in 2000 only. The findings support the negative impact of system transformation on nurses and the link between culture and health care quality. PRACTICE IMPLICATIONS: The study findings suggest that managers and policy makers must develop and implement supportive and nurturing strategies that will enhance the organizational culture (emotional climate, collaborative relations), which should result in more positive perceptions of health care quality. However, further research is required to gain a better understanding of the relationships among trust, organizational culture, and perceptions of health care quality and what implications this may or may not have for nursing practice. [ABSTRACT FROM AUTHOR]

Background: We previously showed a survival benefit of the implantable cardioverter defibrillator (ICD) in males with arrhythmogenic right ventricular cardiomyopathy caused by a p.S358L mutation in TMEM43. We present long-term data (median follow-up 8.5 years) after ICD for primary (PP) and secondary prophylaxis in males and females, determine whether ICD discharges for ventricular tachycardia/ventricular fibrillation were equivalent to an aborted death, and assess relevant clinical predictors., Methods and Results: We studied 24 multiplex families segregating an autosomal dominant p.S358L mutation in TMEM43. We compared survival in 148 mutation carriers with an ICD to 148 controls matched for age, sex, disease status, and family. Of 80 male mutation carriers with ICDs (median age at implantation 31 years), 61 (76%) were for PP; of 68 females (median age at implantation 43 years), 66 (97%) were for PP. In males, irrespective of indication, survival was better in the ICD groups compared with control groups (relative risk 9.3 [95% confidence interval 3.3-26] for PP and 9.7 [95% confidence interval 3.2-29.6] for secondary prophylaxis). For PP females, the relative risk was 3.6 (95% confidence interval 1.3-9.5). ICD discharge-free survival for ventricular tachycardia/ventricular fibrillation ≥ 240 beats per minute was equivalent to the control survival rate. Ectopy (≥ 1000 premature ventricular complexes/24 hours) was the only independent clinical predictor of ICD discharge in males, and no predictor was identified in females., Conclusions: ICD therapy is indicated for PP in postpubertal males and in females ≥ 30 years with the p.S358L TMEM43 mutation. ICD termination of rapid ventricular tachycardia/ventricular fibrillation can reasonably be considered an aborted death., (© 2016 American Heart Association, Inc.)

Background: Patients with kidney disease have disordered bone and mineral metabolism, including elevated serum concentrations of fibroblast growth factor-23 (FGF23). These elevated concentrations are associated with cardiovascular and all-cause mortality. The objective was to determine the effects of the calcimimetic cinacalcet (versus placebo) on reducing serum FGF23 and whether changes in FGF23 are associated with death and cardiovascular events., Methods and Results: This was a secondary analysis of a randomized clinical trial comparing cinacalcet to placebo in addition to conventional therapy (phosphate binders/vitamin D) in patients receiving hemodialysis with secondary hyperparathyroidism (intact parathyroid hormone ≥300 pg/mL). The primary study end point was time to death or a first nonfatal cardiovascular event (myocardial infarction, hospitalization for angina, heart failure, or a peripheral vascular event). This analysis included 2985 patients (77% of randomized) with serum samples at baseline and 2602 patients (67%) with samples at both baseline and week 20. The results demonstrated that a significantly larger proportion of patients randomized to cinacalcet had ≥30% (68% versus 28%) reductions in FGF23. Among patients randomized to cinacalcet, a ≥30% reduction in FGF23 between baseline and week 20 was associated with a nominally significant reduction in the primary composite end point (relative hazard, 0.82; 95% confidence interval, 0.69-0.98), cardiovascular mortality (relative hazard, 0.66; 95% confidence interval, 0.50-0.87), sudden cardiac death (relative hazard, 0.57; 95% confidence interval, 0.37-0.86), and heart failure (relative hazard, 0.69; 95% confidence interval, 0.48-0.99)., Conclusions: Treatment with cinacalcet significantly lowers serum FGF23. Treatment-induced reductions in serum FGF23 are associated with lower rates of cardiovascular death and major cardiovascular events., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00345839., (© 2015 American Heart Association, Inc.)

Purpose of Review: Recent randomized controlled trials (RCTs) have reported risks and benefits in the correction of anemia using erythropoietin-stimulating agents (ESAs) in patients with predialysis chronic kidney disease (CKD) or end-stage renal disease. The purpose of this review is to critically appraise the RCTs most relevant to clinical decision-making., Recent Findings: The Trial to Reduce cardiovascular Events with Aransep Therapy (TREAT) is the biggest and best designed RCT performed so far, enrolling 4038 diabetic patients with CKD in a double-blind, placebo-controlled trial. Comparing the high hemoglobin (Hb) darbopoietin group with placebo, it reported no difference in cardiac and renal outcomes, a significantly increased risk of stroke, and modest improvement in fatigue and transfusion rate. Meta-analysis demonstrated that correction of anemia with ESA was associated with a significantly increased risk of hypertension and vascular access clotting and an increased risk of death that approached statistical significance. Quality-of-life improvements appeared to maximize in the target Hb range of 10-12 g/dl., Summary: Treatment of renal anemia using ESAs to target Hb higher than 13 g/dl is harmful. Treatment of Hb below 9 g/dl provides substantial transfusion and quality-of-life benefits, but safety is unknown. Target Hb levels of 10-12 g/dl seem reasonable, but increasing ESA doses in hyporesponsive patients to achieve a specific target is not.

Background: Concentric and eccentric left ventricular hypertrophy are common progressive disorders in dialysis patients and are associated with cardiac failure and death. Although partial regression of these abnormalities is known to occur during the first post-transplant year, their long-term evolution is unknown., Methods: A total of 143 of 433 dialysis patients participating in a long-term prospective cohort study received renal transplants. Laboratory parameters were assessed monthly. Echocardiography was performed annually. Left ventricular mass index (LVMI) and cavity volume index were calculated according to standard formulae. Multiple linear regression was used to model change in LVMI as a function of baseline clinical and laboratory variables., Results: LVMI fell from 161 g/m2 at 1 year to 146 g/m2 (P=0.009) g/m2 after 2 years. No further regression was seen in years 3 and 4. Left ventricular volume index showed similar trends, with a decline from year 1 to year 2 (P=0.05) followed by stabilization in years 3 and 4. Older age, long duration of hypertension, need for more than one antihypertensive, high pulse pressure in normal-size hearts, and low pulse pressure in dilated hearts were significantly associated with failure of regression of LVMI between the first and second years (MLR, P<0.000001, r2=0.57)., Conclusions: Regression of left ventricular hypertrophy continues beyond the first year after renal transplantation, reaching a nadir at 2 years and persisting into the third and fourth posttransplant years. Failure to regress was associated with older age, hypertension, high pulse pressure in normal-size hearts and low pulse pressure in dilated hearts.

The target hematocrit to be achieved when treating anemia in hemodialysis patients with erythropoietin is controversial. Current evidence-based recommendations suggest a target hematocrit range of 33% to 36%. Small studies suggest that normalization of hematocrit with erythropoietin may benefit hemodialysis patients in terms of brain function, physical performance, quality of life, and prevention of progressive left ventricular dilatation. However a recent study of the effects of erythropoietin-induced normalization of hematocrit in hemodialysis patients with symptomatic heart disease has shown an increase in both mortality and the rate of vascular access thrombosis. Currently, normalization of hematocrit in patients with symptomatic heart disease is not recommended, nor is it possible to conclude that possible benefits of normalization of hematocrit will outweigh risks in hemodialysis patients without symptomatic heart disease.

Objectives: Recommendations to restrict low-osmolality contrast to high-risk patients having cardiac angiography have been challenged because of safety and uncertainty about selection criteria. The authors document frequency and severity of adverse events with diagnostic cardiac angiography under the influence of guidelines for selective use of low-osmolality contrast in high-risk patients and refine high-risk criteria., Methods: Subjects of this prospective cohort study were 7,448 unselected patients having diagnostic cardiac angiography in St. John's, Newfoundland or Ottawa, Ontario. Measures included prespecified risk factors, procedure, contrast, and adverse events such as death within 24 hours, myocardial infarction, stroke, arrhythmias, hypotension, and anaphylactoid reactions., Results: Patients were similar at both sites. Fourteen point two percent received low-osmolality nonionic agents in St. John's. Thirty-four point one percent received low-osmolality (mostly ionic) media in Ottawa. Overall adverse event rates were similar at both sites: death, 0.07%; myocardial infarction or stroke, 0.03%; moderate events, 2%; and mild events, 16.8%. Event rates were low in those given high-osmolality media: death, 0.02%; myocardial infarction or stroke, 0.24%; moderate events, 1.6%; and mild events, 18%. The risk with cardiogenic shock and prior severe reaction to contrast could not be examined, but otherwise only current heart failure and markers of recent ischemia were associated with events after high-osmolality media., Conclusions: Clinicians, using guidelines, can identify high-risk patients and should be able to safely limit use of low-osmolality media to them.

In chronic uremia, cardiomyopathy manifests itself as systolic dysfunction, concentric left ventricular (LV) hypertrophy, or LV dilatation. To determine the impact of renal transplantation on uremic cardiomyopathy, all dialysis patients participating in a long-term cohort study who received a successful renal transplant were followed with echocardiography. The transplanted group comprised 102 of 433 (24%) endstage renal disease (ESRD) patients. They were significantly younger and, on starting ESRD therapy, had significantly less ischemic heart disease and cardiac failure than the overall ESRD cohort. During followup, ischemic heart disease developed in only 1 patient and none experienced cardiac failure. In the 12% (n = 12) of patients with systolic dysfunction before renal transplant, fractional shortening normalized in all patients, increasing from 21.5 +/- 4.6% to 33.5 +/- 5.6% after transplantation. In the 41% (n = 41) with concentric LV hypertrophy before transplantation, the LV mass index improved from 158 +/- 39 g/m2 to 132 +/- 39 g/m2. LV dilatation was present in 32% (n = 32) of patients before transplantation. After transplantation, LV volume fell from 116 +/- 3.1 ml/m2 to 89 +/- 21 ml/m2, and LV mass index in this group fell from 166 +/- 55 g/m2 to 135 +/- 37 g/m2. It was not possible to associate risk factors characteristic of the uremic state with the improvement in cardiac structure and function, although the fall in LV mass was significantly associated with fall in blood pressure. We conclude that correction of the uremic state by renal transplantation leads to normalization of LV contractility in systolic dysfunction, regression of hypertrophy in concentric LV hypertrophy, and improvement of cavity volume in LV dilatation. The degree of improvement suggests that dialysis patients with uremic cardiomyopathy would benefit from renal transplantation.

Hypertension occurs frequently in autosomal dominant polycystic kidney disease. Increased activity of the renin-angiotensin system contributes to the development and maintenance of hypertension before the development of renal failure. Angiotensin-converting enzyme inhibitors are indicated for treatment of hypertension before the development of renal failure, but in severe renal failure these agents may cause further deterioration in renal function. Treatment of hypertension may not retard the progression of renal failure but is necessary for the prevention of cardiovascular disease.

Clinical and echocardiographic manifestations of cardiac disease are frequently present in patients starting end-stage renal disease therapy. Congestive heart failure, ischemic heart disease, systolic dysfunction, concentric left ventricular hypertrophy, and left ventricular dilatation are significant, adverse prognostic indicators, independent of age, diabetes mellitus, and smoking. Risk factors related to the uremic state, which are potentially reversible, include inadequate dialysis, anemia, hypoalbuminemia and hypocalcemia. Hypertension predisposes patients to congestive heart failure, following the development of which hypotension becomes an independent predictor of mortality.

The burden of cardiac disease is high in chronic uremia. Cardiomyopathy results from a combination of cardiac disorders, particularly dilated cardiomyopathy, left ventricular hypertrophy with normal systolic function, and ischemic heart disease. The prognosis for these cardiac disorders is poor. Known potentially reversible risk factors include uremia, anemia, hypertension, smoking, coronary artery disease, hyperparathyroidism, hyperlipoproteinemia, and left ventricular hypertrophy. Randomized controlled clinical trials of interventions that may prevent or ameliorate cardiac disease in dialysis patients are required. These interventions include normalization of hematocrit with erythropoietin compared with partial correction of anemia, increased amount of dialysis compared with that provided by a dialysis prescription of KT/V of 1., control of blood pressure using angiotensin-converting enzyme inhibitors compared with other antihypertensive agents, control of hyperlipidemia, and treatment of diabetes with agents that prevent collagen cross-linking.

Huge strides have been made in the molecular genetics and clinical investigation of several inherited renal diseases. In autosomal dominant polycystic kidney disease 1) the genetic localization of the defective gene that causes type 1 disease has been narrowed to 500 to 750 kb on chromosome 16; 2) cystogenesis has been associated with increased cell proliferation, continuing cyst secretion, and a defect in cell polarity; however, the mechanisms by which the genetic defects in autosomal dominant polycystic kidney disease translate into cyst formation are unknown; 3) activation of the renin system has been reported as an important potential cause of hypertension; and 4) factors that influence the progression to renal failure have been identified. In Alport's syndrome, mutations in the alpha 5 (IV) collagen gene on the X chromosome have been demonstrated that may induce defective assembly of alpha 3 (IV) chains by an unknown mechanism, which leads to the disruption of the glomerular basement membrane. In diabetic nephropathy, it has been suggested that familial factors, perhaps genetic in origin, may play an important role in its development.

Our primary objective was to test the hypothesis that a defect in acidification is more common in patients who have idiopathic calcium phosphate kidney stones than in those whose stones are formed mainly of calcium oxalate. Additionally, other risk factors might differ for these 2 stone types. Urine pH was measured serially over 24 hours, and along with ammonium and titratable acid, it was measured before and serially after ingestion of ammonium chloride in 3 groups of subjects: 24 patients with predominantly calcium phosphate stones, 30 patients with calcium oxalate stones, and 15 health non-stone-formers. Twenty-six parameters potentially related to stone formation and acidification were assayed on urines collected over 24 hours, and 15 parameters on blood. The data base was a computerized list of 5900 analyses of stones from patients living in Newfoundland. Patients not known by their physician to have had urinary tract infection, anatomical abnormality, hyperparathyroidism, or renal tubular acidosis were asked to participate in the study. Differences between means were considered significant if p values were less than 0.05 for F by analysis of variance and also less than 0.01 by t-test. In all patients with calcium oxalate stones and all non-stone-formers, urine acidified to pH less than 5.25, but in 8 of the 23 phosphate stone formers who completed the ammonium chloride study urine failed to acidify to pH less than 5.25. As all 8 had normal values for venous pH, total CO2, and chloride, they were considered to have incomplete renal tubular acidosis (IRTA). The 8 phosphate stone formers with IRTA had greater mean values for urine pH on all 9 specimens collected serially over 24 hours (all means greater than 6.2), and after administration of ammonium chloride (p less than 0.01), as well as lower mean values for urine titratable acid excretion (p less than 0.01), both after administration of ammonium chloride and in 24-hour urine samples, compared with the remaining phosphate stone formers whose urine acidified and the oxalate and non-stone-forming control groups. Nearly all the phosphate stone formers had 1 or more risk factors for stone formation, but with frequencies not significantly higher than those found in the oxalate group. Hypercalciuria and hypocitruria were the commonest, but increased oxalate or urate also occurred. Thus, idiopathic calcium phosphate stone formation can be associated with 1 or more of several risk factors, and, with the possible exception of those with IRTA, treatment should be similar to that given to patients with calcium oxalate stones.

We prospectively studied 89 patients to assess the diagnostic use of renal allograft biopsy in the first three months after transplantation. These biopsies were done in patients in whom diagnosis was not clear or clinical rejection was deemed to be severe. Clinical diagnosis at initial biopsy was compared with the morphological diagnosis. To determine if morphological data improved the prognostic usefulness of the clinical data, we performed multiple logistic regression relating clinical variables at initial biopsy and histological changes in the transplant to the outcome of 120 patients one year after biopsy. The clinical and morphological diagnosis differed in 41 of 89 patients (46%). Of 120 patients in the prognostic study, 35 returned to dialysis during the first year following transplantation. Using multiple logistic regression, a categorical variable that took into account both the serum creatinine and its rate of change before biopsy was the best clinical predictor of return to dialysis. Further increase in chi 2 occurred with type of donor, number of transfusions, and age. Using the clinical variables we produced an index, from 0 to 1 to predict outcome. Only 8 had index less than 0.2, of whom 7 returned to dialysis. The best morphological predictor of outcome was interstitial hemorrhage. Further increase in chi 2 was obtained with vascular endothelial proliferation, glomerular endothelial swelling, and glomerular necrosis. With an index derived from the morphological variables only 11 had index less than 0.2, of whom 9 returned to dialysis. Combining both clinical and morphological data, the best predictor of return to dialysis was interstitial hemorrhage, followed by creatinine, glomerular endothelial swelling, and type of donor. Using both clinical and morphological variables we produced another index to predict outcome. A group of 65 patients had index greater than 0.8, of whom 63 (94%) did not return to dialysis, and 18 patients had index less than 0.2, 17 of whom returned to dialysis. The remaining 12 patients in the dialysis group and 15 in the nondialysis group had indices greater than 0.2 less than 0.8. We conclude that a transplant biopsy yields important diagnostic and prognostic information. Unexpected diagnoses were made in 46% of cases. The addition of morphological data to the clinical data available at time of biopsy greatly improved the prediction of return to dialysis.

A prospective study of the clinical and pathological sequelae of hepatitis B disease in 22 immunosuppressed renal transplant patients is reported. All patients had allografts that functioned for more than 1 year, and all were hepatitis B surface antigen (HBsAg)-positive following transplantation. None of the 18 patients who had serial HBsAg tests converted to HBsAg negative. Serial liver biopsies were performed in 19 patients and one liver biopsy was available in the remaining three patients. Follow-up ranged from 12 to 93 months. Seven patients ultimately developed cirrhosis, 6 developed chronic active hepatitis, 5 developed chronic persistent hepatitis, and in 4 the presence of HB virus in hepatocytes was the sole morphologic alteration. The initial liver biopsy was not an accurate predictor of ultimate severity of liver disease because 5 of the 12 patients with virus only or chronic persistent hepatitis subsequently developed chronic active hepatitis or cirrhosis. Clinical liver dysfunction occurred in 8 patients, all of whom had chronic active hepatitis or cirrhosis. Three patients died with hepatic failure and 2 with hepatoma. The risk of death from liver disease in HBsAg-positive renal transplant patients was 5% per patient-year. For comparison, 10 HBsAg-positive patients whose renal failure had been treated by hemodialysis were also studied over a comparable period. Biochemical evidence of persistent liver dysfunction recurred in 1 patient only; 4 patients converted to the HBsAg-negative state; and no patient has died from complications of liver disease. We conclude that in the immunosuppressed renal transplant patient HB infection often results in the development of chronic active hepatitis, leading to cirrhosis and death from hepatoma and hepatic failure.

To establish the impact of transplantation on the course of chronic hepatitis B liver disease we performed a prospective study of the clinical and pathological sequelae of hepatitis B disease in all 22 patients who had renal allografts that functioned for more than 1 year and who were hepatitis B surface antigen (HBsAg)-positive following transplantation. No patient converted to HBsAg-negative. During a mean follow-up of 83 months serial liver biopsies were performed in 20 patients and 1 liver biopsy was available in the remaining 2 patients. Eleven patients died of liver disease, 5 of whom died of hepatic failure, 3 with hepatoma, 2 of gastrointestinal hemorrhage, and 1 of ascites with pleuroperitoneal fistula. Aggressive liver disease was observed in the vast majority of patients: 12 ultimately developed cirrhosis, (mean follow-up 81 months), 6 chronic active hepatitis (mean follow-up 93 months), 3 chronic persistent hepatitis (mean follow-up 89 months), and in 1 patient the presence of HB virus in hepatocytes was the sole morphologic alteration (follow-up 42 months). There was a marked tendency to progression in that 82% of patients with virus only, reactive hepatitis, or chronic persistent hepatitis on initial biopsy subsequently developed chronic active hepatitis or cirrhosis. For comparison, 10 HBsAg-positive patients whose renal failure had been treated by hemodialysis were also studied over a comparable period. Four patients converted to the negative state. Biochemical evidence of persistent liver dysfunction occurred in only 1 patient and no patient has died from complications of liver disease. We conclude that in the immunosuppressed renal transplant patient HB infection often results in the development of cirrhosis, leading to death from hepatoma and hepatic failure. This course is worse than that in dialysis patients. Renal transplantation of HBsAg-positive patients with end-stage renal failure may be inadvisable.

Before 1971 the incidence of aseptic necrosis in renal transplant recipients was 29%, and after 1971 it was 5%. To investigate the reasons for this decreased incidence and to elucidate the causes of aseptic necrosis we studied all 26 transplant patients with aseptic necrosis and 42 controls matched for year of transplantation, age, and sex. Development of aseptic necrosis was not related to duration of dialysis before transplant, severity of uremia at the time the patient started dialysis, adequacy of dialysis before transplantation, transplant dysfunction at the time aseptic necrosis was diagnosed, hyperparathyroidism before or after transplantation, lack of Vitamin D supplementation after transplantation, or fatty infiltration of liver. Total steroid dose 1 month after transplantation was actually lower in aseptic necrosis compared with the control group (2.47 +/- 0.3 g vs. 3.6 +/- 0.3 g SEM g) and was similar after 4 months (6.72 +/- 0.55 g vs. 7.14 +/- 0.6 g), as were total numbers of i.v. doses of methylprednisolone or hydrocortisone. However, blood urea nitrogen (BUN) during the dialysis period was significantly higher in the aseptic necrosis group. Of the aseptic necrosis group, 27% had a previous transplant compared with 5% of controls. Half the aseptic necrosis group (5/10) had parenchymal iron on liver biopsy one year after transplant compared with 15% (2/13) of those without aseptic necrosis. Patients transplanted before 1971 (with and without aseptic necrosis) received significantly more i.v. hydrocortisone and less i.v. methylprednisolone, had higher BUN levels at the time of starting dialysis, and had lower serum calcium and higher serum phosphate at transplantation compared with patients transplanted in or after 1971. The incidence of aseptic necrosis following transplantation has decreased during the past 13 years for reasons that are unclear. Risk factors for aseptic necrosis may include previous transplantation, severe iron overload that may lead to marrow fibrosis and osteopenia, and increased protein catabolism/turnover during dialysis.

To determine whether prolonged reduction of azathioprine in renal transplant recipients with chronic hepatitis affected the progression of liver disease without an adverse effect on graft survival we studied all transplant patients with a raised serum glutamic oxaloacetic transaminase level greater than normal for more than 1 year who had azathioprine reduced below 100 mg/day for longer than 1 year. Six HBsAg-positive patients had chronic hepatitis for 67 +/- 7 (SE) months before reduction of azathioprine and were followed for a further 49 +/- 14 months. None of the six patients remitted, 3 patients died from liver disease, and none returned to dialysis. In the group of 12 patients who did not have azathioprine reduced, none remitted, 4 died from liver disease, and none returned to dialysis during a follow-up of 115 +/- 9 months. Seven HBsAG-negative patients had chronic hepatitis for 32 +/- 11 months before reduction of azathioprine and were followed for a further 46 +/- 8 months. One of the seven remitted, none died from liver disease and one returned to dialysis. In the group of 15 patients who did not have azathioprine reduced 5 patients remitted, none died from liver disease, and none returned to dialysis. We conclude that prolonged reduction of azathioprine does not slow the progression of liver disease in renal transplant recipients with HBsAg-positive or HBsAg-negative chronic hepatitis, nor does it predispose to graft failure. However reduction of immunosuppression early in the course of hepatitis B disease may be necessary to prevent adverse long-term sequelae.

As hepatitis B virus (HBV) infection in renal transplant recipients is associated with a high incidence of progressive liver disease it may be inadvisable to transplant hemodialysis patients with hepatitis B antigenemia. To determine the natural history of HBV disease in hemodialysis patients, all 49 patients on hemodialysis treatment for at least 1 year, at 3 centers, who developed circulating hepatitis B surface antigen (HBsAG), were studied. A subgroup of these patients (n = 31) aged less than or equal to 50 years, followed for 55 +/- 6 months after detection of HBsAg was compared with 22 previously studied HBsAg-positive transplant patients followed for 81 +/- 9 months. Significantly more transplant patients developed chronic hepatitis defined biochemically (P less than .001) and none of the transplant patients became HBsAg-negative compared with 19% of the hemodialysis group. Taking difference in follow-up into account, mortality was significantly higher in the transplant recipients (P less than .005) following development of HBsAg antigenemia, and the mortality difference was attributable to deaths from liver disease. A total of 36 serum samples from 14 of the 22 HBsAg-positive renal transplant recipients was analyzed for hepatitis B e antigen (HBeAg), antibody to hepatitis D virus (anti-HD), and hepatitis B virus deoxyribonucleic acid (HBVDNA) concentration. No serum sample was anti-HD-positive. Twelve of the 14 patients were HBeAg-positive. Five patients became HBeAg-negative, 3 of whom developed aggressive liver disease. One HBeAg-negative anti-HBe-positive patient had progression of liver disease from asymptomatic carrier status to chronic active hepatitis (CAH). Of 14 patients, 9 developed progressive CAH. HBVDNA concentration was not diagnostic of disease activity on liver biopsy. However only 1 sample of 10 measured in 5 patients with nonprogressive disease had a level greater than 100 pg/L, compared with 9 of 17 in the group who progressed to CAH. During the interval when the liver histology progressed from asymptomatic carriage or chronic persistent hepatitis (CPH) to CAH, the HBVDNA concentration increased by greater than 10 times baseline in 4 of 5 patients who had serial samples, whereas this did not occur in 4 patients with nonprogressive disease. We conclude that the long-term outcome of hepatitis B infection in transplant recipients is significantly worse than in hemodialysis patients. Therefore it may be inadvisable to transplant HBsAg-positive hemodialysis patients.(ABSTRACT TRUNCATED AT 400 WORDS)

Loss of renal mass has been associated with the development of glomerular sclerosis in animals and human beings. The pathophysiology of this renal injury is unknown, but glomerular sclerosis in animals can be aggravated or accelerated following exposure to nephrotoxic antibodies, puromycin aminoglycoside or renal irradiation. We describe here the outcome of the first renal transplant performed in the British Commonwealth. Glomerular sclerosis occurred in identical twins who were kidney donor and recipient, renal failure occurring 14 and 16 years after transplantation, respectively. Examination of these twins and all living immediate family members showed that six of the seven family members (both twins, their mother, and three sisters) had increased concentrations of circulating immune complexes, decreased total hemolytic complement, and low or borderline concentrations of C4. Only twins with single kidneys had detectable renal disease. Other preexisting causes of renal disease in these twins that would account for the glomerular sclerosis could not be identified. We suggest that a familial immune defect contributed to the development of glomerular sclerosis in these twins who were predisposed to renal disease due to loss of renal mass.

A group of 123 patients who had functioning renal transplants for more than 5 years were studied to discover whether prolonged reduction of azathioprine could predispose to late allograft failure. From the point of entry into the study (5 years after transplantation), the 5-year cumulative graft survival among living-related-donor recipients was 91.7%, and among non-living-related-donor recipients it was 84.8%. The azathioprine dose was reduced in 21 patients, for medical reasons, below 100 mg/day for more than one year when serum creatinine was stable and less than 2 mg/dl. Eight patients subsequently required dialysis. In the control group of 35 patients (transplanted in the same years, with serum creatinine that was similar at the same time posttransplantation to that of those who had azathioprine reduced) only 1 patient required dialysis. The likelihood of dialysis was significantly greater in those who had azathioprine reduced compared with those who did not (chi 2 = 12.0, P less than 0.001). No patient who had azathioprine reduced because of low white cell counts or chronic hepatitis subsequently required dialysis. It was concluded that a prolonged reduction of the azathioprine dose may predispose to late allograft failure.