The Israeli organ donor law was established in 2008. In the ensuing 10 years there have been some improvements in deceased donation and living donor rates and a reduction in the unethical practice of ...transplant tourism. There is, however, controversy regarding increased access to transplant for those who have been living donors, who are family members of deceased donors, or who have registered their intent to donate. The issue of routine retrieval versus obtaining consent for organ donation has also been raised. This commentary will address these issue, and propose some steps for improvement of the current Israeli organ donation system.
The disparity between supply and demand for transplantable solid organs has resulted in strategies to drive increased organ donation, including public solicitations for living donors. Public organ ...solicitation occurs when a recipient or their representative solicits an organ for transplantation by public broadcast (e.g., social media or a public notice). The intended donor and recipient may not have a prior relationship. Lack of regulation of public solicitations for organ donation in Canada is a cause for concern. We call for careful screening of altruistic donors within a well-organized system that links willing donors with a maximum number of beneficiaries. There are no guidelines for public solicitation of organs in Canada. Canadian transplant programs have had to address this issue on a case-by-case basis, often without consensus. Within Canada, different responses to organ solicitation by potential donors may be producing inequity of access to organs. Transplant programs and their patients could benefit from guidance on how to address the challenges raised by public solicitations. Many transplant doctors would be comfortable with public solicitation only if the donor became a nondirected altruistic donor, by which the organ is allocated to the next suitable recipient on the waiting list rather than to the actual solicitor (unpublished survey data, July 2015). Transplant doctors consider the next best thing to be to ensure that a relationship existed between the recipient and the solicited donor before donation occurs. Donors who respond to public solicitations should be considered for transplantation. However, transplant programs must ensure that the motivation for donation is based on altruism rather than secondary intention, and that donors meet medical and psychosocial criteria for living donors, provide informed consent and agree to meet the requirements of the program regarding contact with the recipient. Although they should not be dissuaded from donating to the intended recipient, solicited donors should be made aware of alternatives such as donating to the recipient with the greatest need. A model is Canada's National Kidney Paired Donation program. This program is the best option for candidates who have living kidney donors who are willing to donate and medically able, but who are incompatible with their intended recipient. The program coordinates a chain of multiple transplants so that a willing donor's organ can find its way to a compatible recipient while the intended recipient also receives an organ.10 This system allows the most people in need of an organ to get one. Even if the solicited donor and recipient are compatible, they can still choose to enter the National Kidney Paired Donation program as a pair, to benefit the greater transplant community, because a critical number of pairs are required for the overall success of the program.10 Whether donors from a public solicitation should remain anonymous to their recipients is a decision best left to the transplant program.
Medical assistance in dying followed by organ donation is new to North America. If chosen, this path offers potential donors the opportunity to fulfill their last requests and may also affect ...transplant waiting lists. This letter discusses organ donation after euthanasia and its implications.
Trimethoprim-sulfamethoxazole (TMP-SMX) is the drug of choice for anti-Pneumocystis jirovecii pneumonia (PcP) prophylaxis in kidney transplant recipients (KTR). Post-transplant management balances ...preventing PcP with managing TMP-SMX-related adverse effects. TMP-SMX dose reduction addresses adverse effects but its implications to incident PcP are unclear.
We performed a retrospective review of all patients transplanted between 2011 and 2015 prescribed daily single strength TMP-SMX for twelve months post-transplantation as PcP prophylaxis. Actual TMP-SMX dose and duration, adverse effects, number of dose reductions and reasons, and PcP events were captured. Multivariate logistic regression analyses for risk factors associated with dose reduction were performed.
Of 438 KTR, 233 (53%) maintained daily TMP-SMX and 205 (47%) sustained ≥1 dose reduction, with the point prevalence of a reduced dose regimen being between 18 and 25%. Median duration for daily TMP-SMX was 8.45/12 months, contributing 4137 patient-months daily TMP-SMX and 1110 patient-months with a reduced dose. PcP did not occur in any patients. There were 84 documented dose reductions for hyperkalemia and 102 for leukopenia, with 12 and 7 patients requiring TMP-SMX cessation. In multivariate analysis, a living donor transplant protected against hyperkalemia (Odds Ratio 0.46, 95% CI 0.26-0.83, p < 0.01) while acute rejection risked leukopenia (Odds Ratio 3.31, 95% CI 1.39-7.90, p = 0.006).
TMP-SMX dose reduction is frequent in the first post-transplant year but PcP does not occur. To limit the need for TMP-SMX dose reduction due to adverse effects, a clinical trial comparing daily to thrice weekly single strength TMP-SMX in de-novo KTR is justified.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Lithium carbonate is a psychiatric medication commonly used in the treatment of bipolar disorder. It has been implicated in inducing nephrogenic diabetes inspidus, chronic tubulointerstitial ...nephropathy, and acute tubular necrosis. We describe a case of lithium-induced minimal change disease (MCD) and acute kidney injury (AKI).
A 32-year-old female with a medical history of bipolar disorder treated with chronic lithium therapy presented with anasarca, fatigue, and tremors. Work-up revealed supra-therapeutic lithium levels, hypoalbuminemia, and significant proteinuria. The patient was treated conservatively with fluids and discontinuation of lithium therapy. Subsequently, she developed significant AKI and persistent proteinuria. She underwent a renal biopsy that demonstrated effacement of podocyte foot processes consistent with lithium-induced MCD. This was treated with corticosteroids, which decreased the proteinuria and resolved all the patient's symptoms.
Lithium-induced MCD is a rare disease that affects patients of all ages. It is often associated with therapeutic lithium and is typically resolved with discontinuation of lithium. In some cases, concurrent AKI may result due to vascular obstruction from hyperalbuminuria and associated renal interstitial edema. Corticosteroids may be needed to reduce the proteinuria and prevent progression to chronic kidney disease. As such, patients on lithium therapy may benefit from monitoring of glomerular function via urinalysis to prevent the onset of nephrotic syndrome.
Long-term kidney transplant survival at the population level is consistently favorable, but this survival varies widely at an individual level due to both recipient and donor factors. The distinct ...contribution of recipient and donor factors to individual post kidney transplant outcome remains unclear. Comparing outcomes in deceased donor (DD) recipients with potential but non-actualized living donors (DD1) to those recipients with actualized living donors (LD), and to DD recipients without potential living donors (DD0) may provide transplant candidates with more information about their own post-transplant prognosis.
We conducted an observational retrospective cohort study of kidney transplant candidates presenting to our centre for evaluation between 01/01/06 and 31/12/18, and who also received a transplant during that time. Patients were followed to 31/08/2019. Candidates were classified as DD0, DD1, or LD based on whether they had an identified living donor at the time of initial pre-transplant assessment, and if the donor actualized or not. Primary outcome was 5-year death-censored graft survival, adjusted for common pre- and post-transplant donor and recipient risk factors. Secondary outcomes analyzed included patient survival and graft function.
There were 453 kidney transplant recipients (LD = 136, DD1 = 83, DD0 = 234) who received a transplant during the study period. DD0 and DD1 did not differ in key donor organ characteristics. The 5-year death censored graft survival of DD1 was similar to LD (p = 0.19). DD0 graft survival was inferior to LD (p = 0.005), but also trended inferior to DD1 (p = 0.052). By multivariate Cox regression analysis, LD demonstrated similar 5-year graft survival to DD1 (HR for graft loss 0.8 95% CI 0.25-2.6, p = 0.72) but LD graft survival was superior to DD0 (HR 0.34 0.16-0.72, p = 0.005). The 5-year patient survival in DD1 was similar to LD (p = 0.26) but was superior to DD0 (p = 0.01).
DD recipients with potential but non-actualized living donors exhibit similar mid-term graft and patient survival compared to LD recipients. Having an identified living donor at the time of pre-transplant assessment portends a favorable prognosis for the recipient.
Transplant tourism, a form of transplant commercialization, has resulted in serious short-term adverse outcomes that explain reduced short-term kidney allograft survival. However, the nature of ...longer-term outcomes in commercial kidney transplant recipients is less clear. To study this further, we identified 69 Canadian commercial transplant recipients of 72 kidney allografts transplanted during 1998 to 2013 who reported to our transplant center for follow-up care. Their outcomes to 8 years post-transplant were compared with 702 domestic living donor and 827 deceased donor transplant recipients during this period using Kaplan-Meier survival plots and multivariate Cox regression analysis. Among many complications, notable specific events included hepatitis B or C seroconversion (7 patients), active hepatitis and/or fulminant hepatic failure (4 patients), pulmonary tuberculosis (2 patients), and a type A dissecting aortic aneurysm. Commercial transplantation was independently associated with significantly reduced death-censored kidney allograft survival (hazard ratio 3.69, 95% confidence interval 1.88–7.25) along with significantly delayed graft function and eGFR 30 ml/min/1.73 m2 or less at 3 months post-transplant. Thus, commercial transplantation represents an important risk factor for long-term kidney allograft loss. Concerted arguments and efforts using adverse recipient outcomes among the main premises are still required in order to eradicate transplant commercialization.
Calcineurin inhibitor nephrotoxicity remains an issue for recipients of solid organ transplants. After cyclosporine A (CsA) microemulsion administration, effective renal plasma flow (ERPF) and ...glomerular filtration rate(GFR) are decreased coincident with the maximal concentration (Cmax) of CsA. The pharmacokinetic (PK) profile of the once-daily formulation of tacrolimus extended release (Tac ER) includes an equivalent AUCPK 0-24 hr and a lower Cmax versus twice-daily Tac immediate release.
Eighteen healthy subjects were allocated once-daily Tac ER and twice-daily CsA in a prospective, randomized,open-label, two-period, two-sequence single crossover study. CsA was targeted to C2 of 700 to 1400 ng/mL, and Tac ER was targeted to C0 of 5 to 10 ng/mL. Pharmacodynamic (PD) assessments were conducted preexposure, and PD and PK were assessed during a 6-hr postdose period after 10-day exposure.
The achieved mean C(o) Tac and CsA were 6.4 +/- 1.16 and 201 +/- 57 ng/mL, respectively. At Cmax, the change in ERPF was +30 +/- 127 vs. -70 +/- 96 mL/min/1.73 m2 relative to baseline for Tac ER and CsA (P=0.0085). The ERPF and GFR AUC (PD 0-6) hr were 3645 +/- 887 vs. 3210 +/- 582 mL/1.73 m2 (P=0.027) and 604 +/- 98 vs. 543+/- 79 mL/1.73 m2(P=0.023) for Tac ER versus CsA, respectively. Both systolic and diastolic blood pressures were significantly greater with exposure to CsA compared with Tac ER.
Acute reductions in ERPF and GFR are attenuated with Tac ER compared with CsA and may correlate with the differing PK profiles of these calcineurin inhibitors.
BACKGROUNDEnsuring reliable gastrointestinal drug absorption of orally administered immunosuppressive medications posttransplant is critical to ensuring graft survival.
METHODSA 66-year-old man of ...East Asian origin with a previous total gastrectomy was evaluated for living donor kidney transplantation. Pretransplant pharmacokinetic testing was performed to determine the most appropriate posttransplant medication strategy. The Gastrointestinal Quality of Life Index and Gastrointestinal Rating Scale questionnaires were administered to gauge immunosuppressive medication-related side effects in the absence of a stomach.
RESULTSThe patientʼs ability to absorb cyclosporin, tacrolimus (Tac), enteric-coated mycophenolate sodium (EC-MPS) and sirolimus (SRL) in oral dosage forms was well-preserved. Compared to nongastrectomy reference populations, the rate and extent of absorption of SRL and mycophenolic acid from EC-MPS were similar. The absorption of Tac and cyclosporin was greater than expected. Mycophenolate mofetil did not provide mycophenolic acid absorption as well as EC-MPS. The patient had worsened gastrointestinal symptoms with mycophenolate mofetil or EC-MPS in combination with Tac and cyclosporin, but this was not seen with isolated SRL.
CONCLUSIONSThis case demonstrates that commonly used postkidney transplantation immunosuppressive regimes may be prescribed after total gastrectomy as long as their limitations are noted.
All drugs administered prior to the anaphylactic reaction were tested by prick and/or intradermal methods, and where appropriate, serologic testing was done for specific IgE by ImmunoCAP.
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