Renal transplantation from elderly living donors

A worldwide shortage of cadaveric donors has led to the increased utilization of elderly living donors, with controversial results. In an attempt to assess the effect of donor age on graft survival and subsequent renal function, we analyzed our clinical results in 276 consecutive recipients of living related renal transplants spanning both the cyclosporine and the azathioprine eras, of whom a total of 44 recipients received kidneys from donors over 55 years old. All recipients were otherwise similar in age, race, haplotype mismatch, number of retransplants, and number of pretransplant transfusions, apart from an increased number of diabetics among the CsA-treated recipients of elderly kidneys (38% vs. 14%). The cumulative patient and graft survival rates at 1 and 5 years were independent of donor age whether CsA or AZA was utilized. Nor was the incidence of rejection or infection significantly different in the older donor group when compared with the younger cohort. Short-term and intermediate-term renal function, as assessed by serum creatinine, was however poorer but stable in the older donor group when compared with the younger one. The mean serum creatinine levels at 1 year in the CsA- and AZA-treated recipients of kidneys from older donors were 2.4 and 2.0 mg/dl, respectively, compared with 1.6 and 1.4 mg/dl, respectively, when the donor age was less than 55 years (P less than 0.001). Since renal function at the end of the first posttransplant year is considered a determinant of long-term graft survival, this is a cause for concern, but in view of the universal shortage of organs and the negligible morbidity to donors, renal transplantation from elderly living donors remains an acceptable practice.     

Reduction in acute rejections decreases chronic rejection graft failure in children: a report of the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS).

Chronic rejection accounted for 32% of all graft losses in 7123 pediatric transplants. In a previous study acute, multiple acute and late acute rejections were risk factors for the development of chronic rejection. We postulated that the recent decrease in acute rejections would translate into a lower risk for chronic rejection among patients with recent transplants. We reviewed our data on patients transplanted from 1995 to 2000, and using multivariate analysis and a proportional hazards model developed risk factors for patients whose grafts had failed due to chronic rejection. A late initial rejection increased the risk of chronic rejection graft failure 3.6-fold (p < 0.001), while a second rejection resulted in further increase of 4.2-fold (p < 0.001). Recipients who received less than 5 mg/kg of cyclosporine at 30 days post-transplant had a relative risk (RR) of 1.9 (p = 0.02). Patients transplanted from 1995 to 2000 had a significantly lower risk (RR = 0.54, p < 0.001) of graft failure from chronic rejection than those who received their transplants earlier (1987-94). Since we were able to demonstrate that there is a decreased risk of chronic rejection graft failure in our study cohort, we would conclude that the goal of future transplants should be to minimize acute rejections.     

The 1989 report of the North American Pediatric Renal Transplant Cooperative Study

This report of the North American Pediatric Transplant Cooperative Study summarizes data contributed by 57 participating centers on 754 children with 761 transplants from 1 January 1989 to 16 February 1989. Data collection was initiated in October 1987 and follow-up of all patients is ongoing. Transplant frequency increased with age; 24% of the patients were less than 5 years, with 7% being under 2 years. Common frequent diagnoses were: aplastic/dysplastic kidneys (18%), obstructive uropathy (16%), and focal segmental glomerulosclerosis (12%). Preemptive transplant, i.e., transplantation without prior maintenance dialysis, was performed in 21% of the patients. Dialytic modalities pretransplant were peritoneal dialysis in 42% and hemodialysis in 25%. Bilateral nephrectomy was reported in 29%. Live-donor sources accounted for 42% of the transplants. Among cadaveric donors, 41% of the donors were under 11 years old. During the first post-transplant month, maintenance therapy was used similarly for live-donor and cadaver source transplants, with prednisone, cyclosporine, and azathioprine used in 93%, 83%, and 81%, respectively. Triple therapy with prednisone, cyclosporine, and azathioprine was used in 78%, 75%, and 75% of functioning cadaver source transplants at 6 months, 12 months, and 18 months as opposed to 60%, 63%, and 54% for live-donor procedures, with single-drug therapy being uncommon. Rehospitalization during months 1–5 occurred in 62% of the patients, with treatment of rejection and infection being the main causes. Additionally, 9% were hospitalized for hypertension. During months 6–12 and 12–17, 30% and 28% of the patients with functioning grafts were rehospitalized. Times to first rejection differed significantly for cadaver and live-donor transplants. The median time to the first rejection was 36 days for cadaver transplants and 156 days for live-donor transplants. Overall, 57% of treated rejections were completely reversible although the complete reversal rate decreased to 37% for four or more rejections. One hundred and fifty-two graft failures had occurred at the time of writing, with a 1-year graft survival estimate of 0.88 for live-donor and 0.71 for cadaver source transplants. In addition to donor source, recipient age is a significant prognostic factor for graft survival. Among cadaver donors, decreasing donor age is associated with a decreasing probability of graft survival. Thirty-five deaths have occurred; 16 attributed to infection and 19 to other causes. The current 1-year survival estimate is 0.94. There have been 9 malignancies.A list of all participating centers and the names of the investigators is printed on pages 552–553     

Absence of relaxation to lactate in human placental vessels of pregnancies with severe preeclampsia

OBJECTIVE: Our objective was to determine whether the observed relaxation to lactate and other agents in placental vessels of normal pregnancies is altered in severe preeclampsia.STUDY DESIGN: Isolated placental arteries and veins from women with severe preeclampsia and uncomplicated term pregnancies were precontracted with prostaglandin F_2α under 5% oxygen and 5% carbon dioxide with the balance nitrogen (Po₂ 35 to 38 torr) and then exposed to lactate (1 to 10 mmol/L, pH 7.4, n = 8 to 15), arachidonic acid (0.01 to 10 μmol/L, n = 6 to 13), nitroglycerin (1 nmol to 1 μmol/L, n = 4 to 12), or forskolin (0.01 to 10 μmol/L, n = 6 to 9). The response to lactate was also examined in placental vessels from appropriate-for-gestational-age preterm deliveries (n = 8) for comparison with a similar group with severe preeclampsia (n = 8). The t test and analysis of variance statistics were used.RESULTS: Relaxation to lactate was markedly inhibited in both placental arteries and veins of women with severe preeclampsia compared with vessels from uncomplicated term or preterm pregnancies. Responses to the other relaxing agents were not altered in the severely preeclampsia vessels.CONCLUSIONS: In severe preeclampsia absence of lactate-induced dilatation of placental vessels may contribute to the fetal complications associated with impaired blood flow and vasospasm.     

Occurrence of HLA Types in H. Influenzae Type B Disease

We have studied 50 Caucasoid children under 7 years of age with Haemophilus influenzae b disease. Half of the patients (Group A) had invasive disease shown by positive blood and/or spinal fluid culture. The other half (Group B) had noninvasive disease characterized by fever, nasopharyngitis, negative blood culture, and positive throat culture. Age, number of other siblings under 12 years old in the family, immune response, antibody production and genetic markers were compared in the two groups. Significant difference between the two groups was only seen in their genetic markers. HLA-B12 was present in 52% of Group A patients as opposed to 16% in Group B patients (P less than .01). HLA-Bw40 was present in 24% of group B patients and absent in all Group A patients (P less than .01). These findings would suggest that susceptibility and resistance towards developing invasive type b disease may be genetically determined.     

Increased nuclear factor-kappaB and angiotensinogen gene expression in posttransplant recurrent focal segmental glomerulosclerosis

In an attempt to identify potential markers of steroid-resistance in focal segmental glomerulosclerosis (FSGS) we evaluated intra-graft gene expression of IkappaBalpha, nuclear factor-kappaB (NF-kappaB), and angiotensinogen in 60 biopsies from 27 pediatric renal transplant recipients. Intra-graft NF-kappaB expression was significantly elevated in recurrent FSGS (R-FSGS) (218.3 + 55.6 ag/fg versus NON-FSGS 121.1 + 19.9, P=0.04) but not in acute rejection. NF-kappaB:IkappaBalpha ratios were higher in cadaveric donor versus living related donor recipients (15.7 + 2.8 vs. 8.8 + 1.3, respectively, P=0.015), and in African-American versus Caucasian recipients (15.6 + 2.9 vs. 9.1 + 1.3, respectively, P=0.03). Intra-graft angiotensinogen gene expression was significantly elevated in R-FSGS (30.5 + 8.8 ag/fg R-FSGS vs. 16.0 + 4.7 NON-FSGS, P=0.009). We conclude that increased NF-kappaB and angiotensinogen gene expression are associated with R-FSGS. Increased NF-kappaB:IkappaBalpha ratios are associated with cadaveric donor recipients and African-American race.     

Left main coronary artery aneurysm

Left main coronary artery aneurysm is rare finding at coronary angiography. We report a case of a large left main coronary artery aneurysm in a 59-year-old male who had cardiac catheterization for effort angina and inducible myocardial ischemia.