https://aasldpubs.onlinelibrary.wiley.com/doi/pdf/10.1002/hep.22759

Diagnosis, management, and treatment of hepatitis C: An update

Background Cardiovascular disease is common in older adults with end-stage renal disease who are undergoing regular dialysis, but little is known about the prevalence and extent of cardiovascular disease in children and young adults with end-stage renal disease. Methods We used electron-beam computed tomography (CT) to screen for coronary-artery calcification in 39 young patients with end-stage renal disease who were undergoing dialysis (mean [±SD] age, 19±7 years; range, 7 to 30) and 60 normal subjects 20 to 30 years of age. In those with evidence of calcification on CT scanning, we determined its extent. The results were correlated with the patients' clinical characteristics, serum calcium and phosphorus concentrations, and other biochemical variables. Results None of the 23 patients who were younger than 20 years of age had evidence of coronary-artery calcification, but it was present in 14 of the 16 patients who were 20 to 30 years old. Among those with calcification, the mean calcification score was ...

Coronary-Artery Calcification in Young Adults with End-Stage Renal Disease Who Are Undergoing Dialysis

Mortality rates in ESRD are unacceptably high. Disorders of mineral metabolism (hyperphosphatemia, hypercalcemia, and secondary hyperparathyroidism) are potentially modifiable. For determining associations among disorders of mineral metabolism, mortality, and morbidity in hemodialysis patients, data on 40,538 hemodialysis patients with at least one determination of serum phosphorus and calcium during the last 3 mo of 1997 were analyzed. Unadjusted, case mix-adjusted, and multivariable-adjusted relative risks of death were calculated for categories of serum phosphorus, calcium, calcium x phosphorus product, and intact parathyroid hormone (PTH) using proportional hazards regression. Also determined was whether disorders of mineral metabolism were associated with all-cause, cardiovascular, infection-related, fracture-related, and vascular access-related hospitalization. After adjustment for case mix and laboratory variables, serum phosphorus concentrations >5.0 mg/dl were associated with an increased relative risk of death (1.07, 1.25, 1.43, 1.67, and 2.02 for serum phosphorus 5.0 to 6.0, 6.0 to 7.0, 7.0 to 8.0, 8.0 to 9.0, and >/=9.0 mg/dl). Higher adjusted serum calcium concentrations were also associated with an increased risk of death, even when examined within narrow ranges of serum phosphorus. Moderate to severe hyperparathyroidism (PTH concentrations >/=600 pg/ml) was associated with an increase in the relative risk of death, whereas more modest increases in PTH were not. When examined collectively, the population attributable risk percentage for disorders of mineral metabolism was 17.5%, owing largely to the high prevalence of hyperphosphatemia. Hyperphosphatemia and hyperparathyroidism were significantly associated with all-cause, cardiovascular, and fracture-related hospitalization. Disorders of mineral metabolism are independently associated with mortality and morbidity associated with cardiovascular disease and fracture in hemodialysis patients.

Mineral Metabolism, Mortality, and Morbidity in Maintenance Hemodialysis

Background Anemia, a common complication of chronic kidney disease, usually develops as a consequence of erythropoietin deficiency. Recombinant human erythropoietin (epoetin alfa) is indicated for the correction of anemia associated with this condition. However, the optimal level of hemoglobin correction is not defined. Methods In this open-label trial, we studied 1432 patients with chronic kidney disease, 715 of whom were randomly assigned to receive a dose of epoetin alfa targeted to achieve a hemoglobin level of 13.5 g per deciliter and 717 of whom were assigned to receive a dose targeted to achieve a level of 11.3 g per deciliter. The median study duration was 16 months. The primary end point was a composite of death, myocardial infarction, hospitalization for congestive heart failure (without renal replacement therapy), and stroke. Results A total of 222 composite events occurred: 125 events in the high-hemoglobin group, as compared with 97 events in the low-hemoglobin group (hazard ratio, 1.34; 95% confidence interval, 1.03 to 1.74; P = 0.03). There were 65 deaths (29.3%), 101 hospitalizations for congestive heart failure (45.5%), 25 myocardial infarctions (11.3%), and 23 strokes (10.4%). Seven patients (3.2%) were hospitalized for congestive heart failure and myocardial infarction combined, and one patient (0.5%) died after having a stroke. Improvements in the quality of life were similar in the two groups. More patients in the high-hemoglobin group had at least one serious adverse event. Conclusions The use of a target hemoglobin level of 13.5 g per deciliter (as compared with 11.3 g per deciliter) was associated with increased risk and no incremental improvement in the quality of life. (ClinicalTrials.gov number, NCT00211120.)

https://www.nejm.org/doi/pdf/10.1056/NEJMoa065485

Correction of Anemia with Epoetin Alfa in Chronic Kidney Disease

Background Cardiovascular disease is common in older adults with end-stage renal disease who are undergoing regular dialysis, but little is known about the prevalence and extent of cardiovascular disease in children and young adults with end-stage renal disease. Methods We used electron-beam computed tomography (CT) to screen for coronary-artery calcification in 39 young patients with end-stage renal disease who were undergoing dialysis (mean [±SD] age, 19±7 years; range, 7 to 30) and 60 normal subjects 20 to 30 years of age. In those with evidence of calcification on CT scanning, we determined its extent. The results were correlated with the patients’ clinical characteristics, serum calcium and phosphorus concentrations, and other biochemical variables. Results None of the 23 patients who were younger than 20 years of age had evidence of coronary-artery calcification, but it was present in 14 of the 16 patients who were 20 to 30 years old. Among those with calcification, the mean calcification score was 1157± 1996, and the median score was 297. By contrast, only 3 of the 60 normal subjects had calcification. As compared with the patients without coronary-artery calcification, those with calcification were older (26±3 vs. 15±5 years, P<0.001) and had been undergoing dialysis for a longer period (14±5 vs. 4±4 years, P< 0.001). The mean serum phosphorus concentration, the mean calcium–phosphorus ion product in serum, and the daily intake of calcium were higher among the patients with coronary-artery calcification. Among 10 patients with calcification who underwent followup CT scanning, the calcification score nearly doubled (from 125±104 to 249±216, P=0.02) over a mean period of 20±3 months. Conclusions Coronary-artery calcification is common and progressive in young adults with end-stage renal disease who are undergoing dialysis. (N Engl J Med 2000;342:1478-83.)

/pdf/coronary-artery-calcification-in-young-adults-with-end-stage-4clow3rb3g.pdf

Coronary-artery calcification in young adults with end-stage renal disease who are undergoing dialysis

We examined data from the New England Organ Bank to characterize the influence of patient sensitization on allograft survival, and our current crossmatching strategy. To evaluate our recipient eligibility criteria, we compared computer-predicted crossmatch results to 3622 actual crossmatches. A computer-predicted positive crossmatch was highly predictive of an actual positive crossmatch, for patients with a percentage reactive antibody of 40% of more (positive predictive value 91-99%), thus obviating the need to perform the actual crossmatch. Given the high prevalence of sensitized patients on our waiting list, very few individuals are inappropriately excluded from consideration for an available organ. In contrast, a negative computer prediction was never sufficiently predictive of a negative crossmatch to dispense with the actual crossmatching procedure. We also compared graft survival in patients with positive antidonor crossmatches using historical (greater than 6 months old) sera with those with negative historical crossmatches (or with no history of humoral sensitization). One-year actuarial graft survival in the first group was 61.0 +/- 6.0%, compared with 85.2 +/- 1.4% in those without positive historical crossmatches (P less than 0.001). This adverse effect of a positive historical crossmatch was true in both first transplants (n = 41, 1-year graft survival 67.9 +/- 7.4% vs. 86.2 +/- 1.6%, P less than 0.05) and in regrafted individuals (n = 29, 1-year graft survival 50.7 +/- 9.8% vs. 78.9 +/- 3.7%, P less than 0.01). The inability to accurately predict negative crossmatches, and the possible adverse effect of positive historical crossmatches on graft survival, represent potential obstacles to a goal of national organ sharing.

Presensitization and the renal allograft recipient.

A further analysis of primary cytomegalovirus disease prevention in renal transplant recipients with a cytomegalovirus immune globulin: interim comparison of a randomized and an open-label trial.

Transmission of Hepatitis C Virus by Organ Transplantation

We studied the effects and mechanism of action of BWH-4, an IgG2a mouse antirat CD4 monoclonal antibody that recognizes a distinct epitope on the CD4 molecule, in LEW recipients of (LEW x BN)F1 vascularized heterotopic cardiac allografts. Ten animals received daily injections of 700 micrograms BWH-4 for ten days after engraftment. Median actuarial allograft survival was 37 days for the treated animals compared with 7.5 days for controls (n = 6). There was depletion of peripheral blood CD4+ lymphocytes to 4 +/- 1% one week posttransplant (normal = 48 +/- 4%, n = 6). Six additional animals were treated with a lower dose (100 micrograms) of BWH-4 daily for ten days. Median actuarial allograft survival was 10 days and the circulating CD4+ cells decreased to 30 +/- 6% at one week posttransplant. All six low-dose-treated animals mounted an anti-BN alloantibody response by 3 weeks, while only one of the ten high-dose-treated animals had positive alloantibodies two weeks posttransplant. Lymphocyte-mediated cytotoxicity against donor lymphoblasts was completely abolished in the high-dose-treated animals when compared with acutely rejecting controls. We also used low-dose (100 micrograms) BWH-4 to pretreat eleven experimental animals for 7 days prior to engraftment. The circulating CD4+ cells decreased to only 12 +/- 2% on the day of transplantation and 26 +/- 9% one week posttransplant. However, six (55%) pretreated animals survived more than 55 days. There was a 66% decrease in lymphocyte-mediated cytotoxicity against donor lymphoblasts when compared with acutely rejecting controls. We conclude that the anti-CD4 mAb, BWH-4, prevents acute rejection of vascularized heterotopic rat cardiac allografts; this effect is mediated by depletion of the CD4+ T cell subset, suppression of alloantibody production, and inhibition of lymphocyte-mediated cytotoxicity.

Edgar L. Milford

Papers

Presensitization and the renal allograft recipient.

A further analysis of primary cytomegalovirus disease prevention in renal transplant recipients with a cytomegalovirus immune globulin: interim comparison of a randomized and an open-label trial.

Transmission of Hepatitis C Virus by Organ Transplantation

Effects of BWH-4 anti-CD4 monoclonal antibody on rat vascularized cardiac allografts before and after engraftment.

Prophylactic use of monoclonal anti-IL-2 receptor antibody in cadaveric renal transplantation.