The spleen--a potential source of new islets for transplantation?

Background/Purpose

Islet transplantation offers the potential to reverse diabetes soon after diagnosis and has achieved considerable success in adults. Its use in children has been limited by long-term immunosuppression requirements and donor pancreas shortages. An ideal alternative source of islets would be from autologous precursor cells. The aim of this study was to determine whether the spleen can produce insulin-producing cells (IPCs) in our established model of pancreatic development.

Methods

Embryonic quail spleens (day 4.5) and chick pancreatic epithelium (day 4) were microdissected and recombined in a ratio of 1:1 (n = 12), 2:1 (n = 9) and 2:2 (n = 5). They were cultured for 7 days, sectioned, and analysed by fluorescent immunochemistry. Controls were performed to ensure clean separation.

Results

Overall, 12 (46%) of 26 recombinants contained IPCs of splenic origin, occurring in 5 (42%) of 12 of the of 1 spleen-1 epithelium recombinants, 3 (33%) of 9 of the 2 spleen-1 epithelium recombinants, and 4 (80%) of 5 of the 2 spleen-2 epithelia recombinants. Controls were negative.

Conclusions

Preliminary results suggest developing avian spleens can differentiate into IPCs. Increased tissue mass enhanced the likelihood of this occurring. Mesenchyme-to-epithelia ratio did not influence this. The spleen could be an ideal autologous islet source for transplantation in children.     

Can a living kidney donor become a kidney recipient?

The living kidney donor represents a good resource for kidney transplantation. These grafts display better function and long-term graft survival at 5 and 10 years of follow-up. Furthermore, living donors prefer the possibility to increase kidney donation for a large waiting list of patients with end-stage renal disease (ESRD). However, kidney donation is a major surgical procedure associated with benefits and risks. The risks of donation have been studied in large series of living donors to focus on morbidity and mortality rates associated with the surgical procedure. New surgical laparoscopic techniques promote living kidney donation. While the benefits to the recipient are obvious, those for the donor are subjective and not quantifiable. However, donors describe donation as a great experience in life. The risk of kidney donation may be divided into the perioperative and the long-term risks. The evaluate the long-term risks for kidney donors requires a long follow-up. The main source of kidney donors in our transplant center has been living-related and -unrelated donors, with a minor percentage of cadaveric donors. In this report we present four kidney donors who developed ESRD thereafter, three becoming kidney recipients.     

Living donor kidney transplantation: chance for the recipient--financial risk for the donor?

BACKGROUND: With living donation, in addition to the medical risk, the financial risk for the donor is essential, especially in case of complications that potentially can led to disability and loss of work. We report the experiences of those who have donated a kidney in our transplant center. METHODS: We contacted 80 donors who donated a kidney at least 6 months prior to evaluation: 72% answered 33 questions. [mean age: 54 +/- 10 (33-75) years; 69% living related, 31% unrelated]. RESULTS: Of the 80 donors contacted, 91% (53) reported to have no financial expenses due to donation; 9% (5) had expenses, but only few of them clarified exact amount. One donor had to borrow money to cover the lack when he was unable to perform his job. Another claimed the disparity between normal salary and payment from insurance company as a financial expense. Evaluation procedure prior to donation was organized variously: some donors were on holiday while evaluated, some officially were ill, others had to take off some days without payment. None of the donors lost his or her job due to donation. CONCLUSION: The financial risk of living donation is theoretically well covered by different insurances. However, some of the donors had to cover some expenses by themselves. Fortunately, so far in our center no major complications occurred and all donors went home in good health after donation. If costs are covered when a healthy donor loses his or her ability to work due to donation remains unclear since no donor has experienced this problem.     

Use of stenting in living donor kidney transplantation: does it reduce vesicoureteral complications?

The risk of urologic complications after kidney transplantation is 0% to 30%. We studied the impact of prophylactic stent placement during transplantation by assessing the necessity for a percutaneous nephrostomy (PCN) after living kidney transplantation. From January 2003 to December 2007, 342 living donor kidney transplantations were performed. Intra- and postoperative data were collected retrospectively from 285 patients with stent and 57 without. Baseline characteristics were not significantly different between groups, except for the number of previous transplantations: 31 (11%) patients with versus 16 (28%) without stent had a history of >1 transplantation (P < .001). From patients with PCN, 55 (87%) patients in the stented group received a PCN <3 months versus 11 (100%) in the nonstented group (P = .71). The reoperation rate for urologic complications was similar in both groups (3% (stented) versus 5% (nonstented; P = .43). In multivariate analysis, risk for PCN was similar in both groups (odds ratio 1.21, 95% confidence interval 0.5-2.5). Recipient survival was not significantly different. One- and 3-year death-censored graft survival was not significantly different between stented (89% and 84%) and nonstented group (90% and 85%, P = .71 and P = .96). Ureteral stent insertion is not associated with a reduced rate of PCN placement in living donor kidney transplantation.     

Preoperative evaluation of living related kidney donor: which kidney to donate?

OBJECTIVES: As the number of cadaveric donor is far beyond the demand of the waiting list, living related kidney transplantation is important for the worldwide organ shortage. Besides, living related transplantation has advantages compared with cadaveric transplantation in terms of graft function and survival. However, the remaining kidney function of the living donor needs to be evaluated. METHODS: We collected 28 paired living kidney donations from March 2003 to March 2005. All patients underwent laparoscopic donor nephrectomy. The preoperative kidney evaluation included renal echography, renal nuclear scan, computed tomography angiography (CTA), and creatinine clearance (CCr). The renal function of the donor kidney was expressed as (donor kidney/both kidneys)%. The percentage renal function from renal echography, renal nuclear scan, and CTA were correlated with CCr. RESULTS: The mean percentage of donor kidney function according to renal echo, nuclear scan, and CTA were 49.77%, 51.83%, and 50.70%, respectively. The correlation coefficients for renal echography, nuclear scan, and CTA to CCr were -0.316, -0.201, and 0.123, respectively. The correlation coefficients for renal echography, nuclear scan, and CTA to postoperative serum creatinine of donor were 0.426, 0.036, and -0.119, respectively. CONCLUSION: From the viewpoint of donor postoperative residual renal function, preoperative renal sonography offered a better predictive value than nuclear scan or CTA.     

Preemptive living donor kidney transplantation: do the benefits extend to all recipients?

BACKGROUND: Preemptive kidney transplantation (prior to the institution of dialysis) avoids the morbidity and mortality of dialysis; however, detailed studies of high-risk patients are lacking. The aim of the current study was to compare recent outcomes of preemptive (P) versus nonpreemptive (NP) living donor kidney transplantation with an emphasis on high-risk recipients. METHODS: We retrospectively analyzed 438 sequential solitary living donor kidney transplants at our institution between January 2000 and December 2002. In all, 44% were preemptive. NP recipients were dialyzed for 21+/-36 months (range 1-312 months). RESULTS: Overall, three-year patient survival was similar in the NP and P groups. When stratified by diabetes and age >65 years, P and NP recipients again showed similar survival. Death-censored three-year graft survival was better in the P group (97% vs. 90%, P=0.01), but was not significant by multivariate analysis. Delayed graft function was more frequent in NP vs. P (10% vs. 4%; P=0.01), but other early complications were similar including: acute rejection, 16% vs. 11% (P=0.11); primary nonfunction, 3% vs. 2% (P=0.38); and wound complications, 19% vs. 17% (P=0.54). Glomerular filtration rate at three years was similar in the two groups (53+/-23 preemptive vs. 52+/-20 ml/min nonpreemptive; P=0.37). CONCLUSION: With prompt referral and workup, preemptive kidney transplantation can be performed successfully in a large percentage of renal allograft recipients. Preemptive transplantation avoids unnecessary dialysis and should be emphasized as initial therapy for many patients with end-stage renal disease.     

Kaposi’s sarcoma following living donor kidney transplantation: review of 7,939 recipients

Introduction  Kaposi’s sarcoma (KS) is one of the most common tumors to occur in kidney recipients, especially in the Middle East countries. Limited data with adequate sample size exist about the development of KS in living kidney recipients. Methods  Therefore, we made a plan for a multicenter study, accounting for up to 36% (n = 7,939) of all kidney transplantation in Iran, to determine the incidence of KS after kidney transplantation between 1984 and 2007. Results  Fifty-five (0.69%) recipients who developed KS after kidney transplantation were retrospectively evaluated with a median follow-up of 24 (1–180) months. KS occurred more often in older age when compared to patients without KS (49 ± 12 vs. 38 ± 15 years, P = 0.000). KS was frequently found during the first 2 years after transplantation (72.7%). Skin involvement was universal. Furthermore, overall mortality rate was 18%, and it was higher in patients with visceral involvement compared to those with mucocutaneous lesions (P = 0.01). However, KS had no adverse affect on patient and graft survival rates compared to those without KS. Forty-four patients with limited mucocutaneous disease and four with visceral disease responded to withdrawal or reduction of immunosuppression with or without other treatment modalities. Renal function was preserved when immunosuppression was reduced instead of withdrawn in patients with and without visceral involvement (P = 0.001 and 0.008, respectively). Conclusion  The high incidence of KS in this large population studied, as compared to that reported in other transplant patient groups, suggests that genetic predisposition may play a pathogenetic role.     

The spouse as a kidney donor: ethically sound?

A shortage of cadaver donor organs requires transplant units to examine all possible alternatives. Transplantation from living donors accounts for only approximately 10% of kidney transplants in the UK. Recent studies have shown that the results of kidney transplantation between spouses are at least as good as those of well-matched cadaver organs, but very few transplants of this type have been performed in this country so far. As part of the assessment process, the proposed donor and recipient are required to provide written statements about the issues. We reproduce here the personal statements made by one of our patients and his wife: we believe that the statements support our contention that spousal transplantation is ethically justifiable and should be more widely available. We report our early experience in Bristol with seven kidney transplants from spousal donors and we encourage other renal units in this country and elsewhere to consider this method of improving the prospects of kidney transplantation for their patients.     

Non-heart-beating organ donors: a potential source of islets for transplantation?

BACKGROUND: The shortage of organ donors relative to the number of patients on transplant waiting lists has led to a renewed interest in the use of non-heart-beating (NHB) organ donors in many centers. The lack of donors is also a problem for islet transplantation. The disparity between donor organs and potential recipients is further exacerbated by the requirement to transplant a large number of islets to increase the chance of success and the high level of variability in islet isolation yield. Non-heart-beating (NHB) donors have not previously been assessed as a source of islets for transplantation, and it is unknown what affects the additional factor of warm ischemic injury associated with NHB organs may have on the success of islet isolation. METHODS: This study assesses the yield and function of islets from NHB donors and compares the results with islets obtained from heart-beating brain-dead (HB) donors. RESULTS: There were no differences in the yield of islets per gram of pancreas, 1788 (0-4620) NHB vs. 1580 (26-2544) HB (median, range). The secretory function was also similar in both groups, with stimulation indices of 0.71-3.49 for NHB vs. 0.30-3.57 for HB (overall range). There was no correlation between islet yield and warm ischemia time in the NHB donor group. CONCLUSIONS: In conclusion, the study has demonstrated that it is possible to isolate large numbers of islets from NHB donor pancreata and that, where NHB donor programs exist, these could provide a significant addition to the number of potentially transplantable islets.     

The once-daily formulation of tacrolimus: a step forward in kidney transplantation?

Nonadherence is a critical issue in transplantation. Recently, Astellas designed a once-daily-extended release formulation of tacrolimus (Tac). Despite initial reports showing bioequivalence of Tac once-daily (Advagraf) with the original formulation requiring twice-daily intake (Tac twice-daily, Prograf), several groups have now shown a sustained decrease in Tac exposure upon conversion from Prograf to Advagraf. Here, we discuss the possible reasons for this observation and how it could affect the expected benefits of Advagraf, and we comment on the fact that a similar lack of bioequivalence might prevail with generic immunosuppressive drugs.