EULID project: European living donation and public health.

The choice of transplantation from a living donor offers advantages over a deceased donor. However, it also carries disadvantages related to donor risks in terms of health and safety. Furthermore, there are several controversial ethical aspects to be taken into account. Several national and international institutions and the scientific community have stated standards that have great influence on professional codes and legislations. Living organ donation and transplantation are to some extent regulated by parliamentary acts in most European countries. It is necessary to take a step forward to develop a legal framework to regulate all of these processes to guarantee the quality and to prevent illegal and nonethical practices. It is also necessary to develop and implement living donor protection practices not only in terms of physical health, but also to minimize potential impacts on the psychological, social, and economic spheres. Finally, an additional effort should be made to create a database model with recommendations for registration practices as part of the standardized follow-up care for the living donor. The European Living Donation (EULID) project's (http://www.eulivingdonor.eu/) main objective was to contribute to a European consensus to set standards and recommendations about legal, ethical, and living donor protection practices to guarantee the health and safety of living donors.

HLA class I donor-specific triplet antibodies detected after renal transplantation.

The purpose of this study was to investigate whether IgG, non-donor-specific anti-HLA class I antibodies (HLAabI) detected after renal transplantation recognize immunogenic amino acid triplets expressed on the foreign graft. In addition, we sought to evaluate the effect of these antibodies as well as other posttransplant HLAabI on graft outcome. Posttransplant sera from 264 renal recipients were tested for the presence of IgG HLAabI and HLA class II-specific alloantibodies (HLAabII) by ELISA. The HLAMatchmaker computer algorithm was used to define the HLA class I non-donor-specific antibodies, which seem to recognize immunogenic amino acid triplets. Donor-specific triplet antibodies (DSTRab) were detected in 16 of 22 (72.7%) recipients based on at least one HLA-A or -B mismatched antigen with the donor. DSTRab were found either without (n = 7) or with (n = 9) HLA donor-specific antibodies (HLA-DSA). The presence of DSTRab alone in the periphery was associated with acute rejection, whereas the presence of both DSTRab and HLA-DSA was associated with chronic rejection and graft failure.

Use of cyclosporine in renal transplantation.

Since 1983, cyclosporine has been the backbone of immunosuppression in clinical organ transplantation. Cyclosporine is usually used in combination with steroids and with another second-line immunosuppressant like azathioprine or mycofenolate mofetil. With these regimens, graft survival at 1 year exceeds 90% and long-term results are excellent. The main complication is renal toxicity, which is usually secondary to excessive exposure. The new microemulsion formulation of cyclosporine, introduced in recent years, has improved intestinal absorption and bioavailability and resulted in much less intrapatient variation than the older formulation. The introduction of 2-hour peak blood level monitoring, which corresponds closely to the area under the curve of the drug, allows more appropriate dosing, thus minimizing rejection owing to underexposure or toxicity owing to overexposure. As new effective immunosuppressants are currently becoming available for use in combination with cyclosporine, the transplant community can look forward to more effective and safer immunosuppression.

Septicemia due to multiresistant Klebsiella pneumoniae in a neonatal unit: a case-control study.

An unusually high incidence of septicemia due to multiresistant Klebsiella pneumoniae occurred in the Aristotle University Neonatology Department. Forty neonates suffered from 42 episodes of septicemia. Mortality was 43% ranging from 32% in neonates with birth weight (BW) - 1,500 g to 55% with < 1,500 g. No differences were found between 17 neonates who died and 23 survivors. All isolates were resistant to aminoglycosides, third-generation cephalosporins, and aztreonam, but susceptible to imipenem and ciprofloxacin. The neonates with septicemia due to K. pneumoniae were matched 1:1 with neonates without septicemia (31 pairs) or with neonates with septicemia due to other organisms (8 pairs) according to BW and time of admission. Factors associated with septicemia were mechanical ventilation (p = 0.004) and ongoing parenteral nutrition (p = 0.027). In a multivariate model, nutrition exhibited no independent association after adjusting for ventilation. No differences were detected between the patients with Klebsiella septicemia and those with septicemia due to other organisms. Enhanced Infection Control measures and a temporary change of antibiotic policy reduced this serious complication. Three small outbreaks of multiresistant K. pneumoniae previously reported in neonates are reviewed.

Loss of heterozygosity in polycystic kidney disease with a missense mutation in the repeated region of PKD1.

Loss of heterozygosity (LOH) is a molecular phenomenon that denotes the loss of one of the two alleles at a specific locus. It is frequently associated with tumour suppressor genes in various cancers and also with hyperproliferative disorders, although not exclusively. Interestingly, in conditions where there is an inherited germline mutation, the lost allele is always the functional one, thereby rendering a phenotypically dominant disease of recessive character at the cellular level. A disease more recently shown to be associated with LOH is polycystic kidney disease type 1, a systemic disorder characterized by significant pleiotropy. The main pathology is from renal cyst formation that eventually leads to end-stage renal failure during adult life. We describe the identification of a missense mutation in the repeated part of the PKD1 gene, exon 31, that substitutes valine for methionine. The mutation, M3375V, cosegregates with the disease phenotype in a large Cypriot family. During transplantation of one patient, one of the polycystic kidneys was removed and DNA was isolated from cystic epithelial cells. In 3 of 17 cysts examined with intragenic and flanking polymorphic markers on chromosome 16 we detected LOH, since the wild-type allele was lost, thereby rendering the affected kidneys of mosaic character. The degree of LOH was extensive and varied among the three cysts, supporting the multiplicity of expression of the phenomenon on different occasions. No LOH was detected for other selected loci examined. Our work further supports the hypothesis that the rate-limiting step in cyst formation may be the occurrence of a second somatic hit, although other factors may be also involved. The high frequency of mutations at this locus may, to a great extent, explain the variability in phenotype observed among patients in the same families, and the relatively high frequency of the disease worldwide.

Long-term results of kidney transplantation at the University of Miami.

Of 631 renal allografts performed at our center between January 1, 1979 and June 30, 1989, 368 were from cadaver donors (CAD) and 263 were from living-related donors (LRD). The recipients were almost equally divided among 3 ethnic groups: Black, Hispanic, and non-Hispanic, non-Black (primarily of northern European background). Recipient ages ranged between 1 and 70 years. In the CAD group HLA matching was emphasized so that no patient received a kidney with less than a 1 DR match, and for the entire series there was a mean of 2.4 of 6 HLA antigens matched between donor and recipient. All patients (LRD and CAD) received at least 3 pretransplant blood transfusions. Overall actuarial 10-year patient and graft survival were 68% and 48% respectively, with 72% patient and 56% graft survival for LRD and 58% patient and 36% graft survival for CAD recipients. Factors adversely affecting long-term graft outcome were: a) Black race. Overall 10-year graft survival was 23% versus 55% for non-Blacks (p = 0.008); b) Type I Diabetes before transplant. Overall 10-year graft survival was 35% versus 51% for nondiabetics; and c) Compliance. This was the most significant factor influencing long-term survival, other than death due to cardiovascular disease. In a non-Black, nondiabetic category of less than 36 years of age at transplantation (n = 169), 10-year patient survival in LRD and CAD groups was 95% and 85%, respectively, and graft survival was 78% and 70%, respectively. This was markedly different from the entire series (p = 0.008). Even in this group, 4 of the 17 graft losses (including mortality) were due to documented prolonged noncompliance in teenagers. The 6 other deaths that occurred were due to hepatitis/cirrhosis (2), CMV (3), and AIDS (1). Among the factors not influencing graft survival in the CAD group was HLA matching after the minimum requirements were fulfilled, either by comparing 1 with 2 DR antigens, or total HLA (1-6) antigens matched.

Single-dose captopril scintigraphy in the diagnosis of renovascular hypertension.

Renal scintigraphy with [99mTc]diethylenetriaminepentaacetic acid (DTPA) and/or sodium-iodine-131-o-iodohippurate (HIP) was performed before and after an oral dose of captopril (50 mg) in 18 patients with renovascular hypertension (RVH) due to renal artery stenosis (RAS) and 18 controls. In every patient with RVH, captopril induced, enhanced or sustained abnormal findings on HIP scintigraphy depending on the degree of RAS. With DTPA scintigraphy, renal function decreased after captopril in ten kidneys with RVH-related RAS and adequate baseline renal function, but this phenomenon was not evident in 11 kidneys with RVH and poor renal function. Captopril did not influence HIP or DTPA studies of kidneys with patent renal arteries (patients after successful renal angioplasty, patients with essential hypertension, contralateral kidneys of patients with unilateral RVH) or ipsilateral kidneys with mild and subcritical (less than 60%) RAS in patients without hypertension and/or normal renal vein renin activity. When HIP and DTPA scintigraphy were compared in the same patients, HIP demonstrated greater sensitivity and specificity than DTPA, particularly in patients with poor renal function. HIP scintigraphy before and after a single dose of captopril may provide a rapid sensitive and minimally invasive test for screening patients with hypertension.