Oral infections and their influence on medical rehabilitation in kidney transplant patients.

Infections seem to be the most common life-threatening complication of long-term immunosuppressive therapy following organ transplantation. Although sparse scientific evidence, potential oral infections are considered to contribute to these complications. The aim of this study was to examine whether there is an association between oral infections and rejections after kidney transplantation. A group of 46 kidney transplant candidates was enrolled. The patients were examined clinically and radiographically for dental caries, periodontal disease, mucosal lesions/infections, and general oral health problems. Examinations were conducted the day before transplantation, and one year post transplantation. Fifteen (32.6%) patients developed acute rejections during the first year. Six of these patients (40%) presented with oral opportunistic infections (candida or herpes infections of the oral mucosa). The number of dental infections and semi-impacted teeth were low. When rejections were related to probing pocket depths (PPDs) > or = 4 mm and apical lesions together, statistical significance was not reached (p=0.075, OR=3.17 [0.87; 11.55]). Similar results were obtained when PPDs > or = 4 mm, apical lesions, semi-impacted teeth, and opportunistic mucosal infections were compared to rejections. The results of the present study do not support that opportunistic oral mucosal infections or dental-related infections seem to increase the risk of rejection in kidney transplanted patients.

Variations in graft and patient survival after kidney transplantation in Sweden: caveats in interpretation of center effects when benchmarking.

Benchmarking and comparisons between transplantation centers are becoming more common. A crude comparison indicated a 50% difference in patient survival between centers in Sweden. A 'task group' was formed to refute or confirm and learn from this observation. Patient survival and graft survival of 5 933 patients transplanted at three different transplantation centers in Sweden (Stockholm, Göteborg, and Malmö) were followed up until February 2007. Patient survival and graft survival were compared between the centers with and without consideration being given to important covariates such as time period, type of donation (living or deceased donor), gender, and age. A refined cohort of 2,956 adult patients that had been transplanted for the first time between 1991 and 2007 was assessed in more detail using Cox regression analysis. The difference in patient and transplant outcome observed in the crude comparison diminished considerably after adjustment for differences in case mix and time period of transplantation, and was neither evident nor significant after 1999. Patient survival and graft survival have improved considerably during the time period since 1991. The adjusted hazards ratio for mortality was 0.39 (95% CI 0.29-0.53) for patients who were transplanted after 1999 when compared with those transplanted between 1991 and 1994. Crude comparisons between results from transplantation centers may be severely confounded not only by case mix but also by differences in the proportion of patients transplanted during different time periods. Patient outcome and graft outcome have improved considerably since 1991, and after 1999 center effects were no longer apparent in Sweden.

Nondirected living kidney donation: experiences in a Swedish Transplant Centre.

The lack of kidneys for transplantation is a worldwide problem. Different efforts to expand the donor pool have been made. One of them has been the acceptance of altruistic nondirected living kidney donors. This concept was first published by Matas et al. in 2000. Since then, several centres in the United States have started programmes with altruistic nondirected donors (NDD) for kidney transplantation. The use of NDD is still very controversial and rare in Europe. In Sweden, an NDD programme was initiated by the Swedish Transplantation Society in 2004. This article addresses central issues involved with NDD and describes our experiences with the programme so far at Sahlgrenska University Hospital in Göteborg, Sweden.

Blood group A and B antigen expression in human kidneys correlated to A1/A2/B, Lewis, and secretor status.

BACKGROUND: In the revived interest in crossing ABO barriers in organ transplantation renal A/B antigen expression has been correlated with donor ABO, Lewis, and secretor subtype to predict antigen expression. METHODS: A/B antigen expression was explored by immunohistochemistry in LD renal biopsies. Donor A1/A2/B, Lewis, and secretor status were determined by serology and polymerase chain reaction. RESULTS: In the renal vascular bed, three distinct A antigen expression patterns with a major, minor, and minimal staining distribution, and intensity (designated as types 3+, 1+ and (+) respectively) were identified. Type 3+ had a strong A antigen expression in the endothelium of arteries, glomerular/peritubular capillaries and veins. The type 1+ showed an overall weaker antigen expression, whereas type (+) had faint staining of peritubular capillaries only. In all cases, distal tubular epithelium was focally stained, whereas proximal tubules were negative. Type 3+ were all from blood group A1 subtype individuals while A2 cases expressed either a 1+ or (+) pattern. The secretor gene did not appear to influence renal A antigen expression. All B kidneys examined showed a B antigen pattern slightly weaker but otherwise similar to A type 3+. CONCLUSION: Renal vascular A antigen expression correlates to donor A1/A2 subtypes, whereas B individuals show one singular antigen pattern. From antigen perspective, A1 and B donors are a "major" and A2 individuals a "minor" antigen challenge in ABO-incompatible renal transplantation.

ABO-incompatible live donor renal transplantation using blood group A/B carbohydrate antigen immunoadsorption and anti-CD20 antibody treatment.

BACKGROUND: Blood group ABO-incompatible live donor (LD) renal transplantation may provide a significant source of organs. We report the results of our first 14 cases of ABO-incompatible LD renal transplantation using specific anti-A/B antibody (Ab) immunoadsorption (IA) and anti-CD20 monoclonal Ab (mAb) treatment. PATIENTS AND TREATMENT PROTOCOL: Recipients were blood group O (n = 12), A (n = 1) and B (n = 1). Donors were A1 (n = 2), A2 (n = 3), A2B (n = 1) and B (n = 8), and all were secretor positive. Anti-human leukocyte antigen (HLA) Ab panel reactivity was negative in all recipients except one. All recipients were pre-treated with 3 to 6 IA sessions, using A or B carbohydrate antigen columns, until their anti-A1/B RBC panel indirect antiglobulin test (IAT) titers were < or =8. CDC crossmatch was negative in all cases. Recipients received preoperative mycophenolic acid, and steroids/tacrolimus were started at transplantation. No splenectomy was performed. Eight recipients received one dose of anti-CD20 mAb (rituximab, 375 mg/m2) pre-operatively and 11 recipients had postoperative protocol IA. RESULTS: In the initial protocol, anti-CD20 mAbs were used only for recipients receiving A1 grafts. One B graft (HLA-identical donor, 84% panel reactivity) was lost in a severe anti-B Ab-mediated acute rejection. Subsequently, the protocol included anti-CD20 for recipients of both A1 and B grafts and postoperative protocol IA to all recipients. The subsequent 10 grafts had excellent function, giving a total graft survival of 13/14 (observation range 2 to 41 months). At 1 yr, mean serum creatinine was 113 micromol/l (n = 8) and mean glomerular filtration rate was 55 ml/min/1.73 m2 (range 24 to 77). In the remaining five cases, with less than 1 yr follow up, mean serum creatinine was 145 micromol/l at 2 to 9 months follow up. Pre-IA anti-A/B titers were in the range of 2 to 32 (NaCl technique) and 16 to 512 (IAT). More than 90 IA sessions were performed in 14 recipients without any significant side effects. Recipient anti-A/B titers returned after transplantation to pre-IA levels or slightly lower. Postoperative renal biopsies were performed in 10 patients. In the 13 patients with long-term function, one patient experienced cellular rejection (Banff IIB) at 3 months without anti-B titer rise. This rejection was concomitant with low tacrolimus plasma levels and was easily reversed by steroids. In 8 of 10 cases, C4d staining was positive in peritubular capillaries. CONCLUSION: Blood group ABO-incompatible LD renal transplantation using A and B carbohydrate-specific IA and anti-CD20 mAbs has excellent graft survival and function.

Incidence of end-stage renal disease among live kidney donors.

BACKGROUND: The increasing use of living kidney donors requires knowledge about long-term effects, especially number and causes of donors with end-stage renal disease (ESRD). METHODS: A retrospective data analysis of 1,112 consecutive living kidney donors who underwent nephrectomy from 1965 until 2005 at Sahlgrenska University Hospital. Case reports were sought with help from nephrologists in the region and data from Swedish Registry of Active Uremic Treatment (SRAU). RESULTS: The number of cases with end stage kidney failure among living kidney donors was 6/1112, that is 0.5%. The donors had reached ESRD during the years 2001-2006, that means 36-41 years after start of the living donor program. The donors were 45-89 years old, median 77 years, and five of six were males. Time since donation was 14-27 years, median 20 years, for the donors developing ESRD. The diagnoses were nephrosclerosis (4 cases), postrenal failure (1 case), and renal carcinoma (1 case). The expected incidence for development of ESRD according to incidence in the general population would have been two donors but we found six. However, considering the high age of the donors in this follow up, the age-matched incidence is calculated to be closer to six donors due to higher incidence in the aged. CONCLUSION: In all 0.5% of the donors developed ESRD. Due to high age of the uremic donors, there seems to be no increased incidence.

Macrovascular disease after simultaneous pancreas and kidney transplantation.

The objective of this study was to evaluate the outcome of simultaneous pancreas and kidney transplantation (SPK) with focus on cardiovascular mortality and morbidity in relation to graft function. From January 1985 through 1999, 87 SPK were performed in the unit. Sixty recipients were males, median age at diabetes onset 13 yr (1-40) and age at transplantation 39 yr (29-54). No case was lost to follow-up. Morbidity and mortality during median 8 yr of follow-up (range 1-15 yr) were recorded. Major macrovascular disease (MVD) was defined as myocardial infarction or sudden death (AMI), stroke or peripheral gangrene requiring amputation of leg, foot or fingers. At the evaluation, 26 of 87 patients (30%) had died, 19 after loss of the pancreas graft and 20 after loss of the kidney. MVD was the dominant cause of death. Non-lethal MVD had previously been recorded in 62%. Of the 61 patients alive, 22 had lost their pancreas graft and 12 the concomitant kidney. MVD had occurred in 32%. Whereas 89% of the concomitant kidneys functioned when the pancreas graft did so, only 37% of the kidneys functioned if the pancreas had been lost, p < 0.0001. The mortality rate was significantly higher among patients who lost both grafts (16/26) than in those who lost only the pancreas graft (3/15), p = 0.01. Progressive MVD is a major clinical problem for SPK transplant patients, particularly if the kidney fails.

Impact of cadaveric renal donor morbidity on long-term graft function.

The significance of donor age, cause of death, and morbidity for the outcome of renal cadaveric transplantation was evaluated in 534 cases from 1994 through 2001. Half of the kidneys (49.4%) were from donors without identified risk, the others were age 50-64 or > or =65 years, had died of cerebrovascular lesion (CVL), or had known cardiovascular disease, or hypertension. Only death from CVL influenced cumulative graft survival (P=0.04), the actual survival at 6 months being 87% vs 95% with other donors (P=0.004). Clearance of 51Cr EDTA (glomerular filtration rate, GFR) after 1 year was a more sensitive marker of graft quality and was significantly reduced with each tested risk factor. For instance, the median GFR (range) in the three donor age groups was 52 (9-125), 37 (13-83), and 29 (15-60) ml/min, respectively (P<0.0001). Combinations of risk factors significantly increased their impact on GFR. However, the overall results with such suboptimal donors should rather encourage a widening of the donor acceptance criteria.