Differences in Proinflammatory Cytokines and Monocyte Subtypes in Older as Compared With Younger Kidney Transplant Recipients.

Background:The number of elderly patients with end-stage kidney disease requiring kidney transplantation continues to grow. Evaluation of healthy older adults has revealed proinflammatory changes in the immune system, which are posited to contribute to age-associated illnesses via "inflamm-aging." Immunologic dysfunction is also associated with impaired control of infections. Whether these immunologic changes are found in older kidney transplant recipients is not currently known, but may have important implications for risk for adverse clinical outcomes. Methods:Three months after transplant, innate immune phenotype was evaluated by flow cytometry from 60 kidney transplant recipients (22 older [≥60 years] and 38 younger [<60 years old]). Multiplex cytokine testing was used to evaluate plasma cytokine levels. Younger patients were matched to older patients based on transplant type and induction immune suppression. Results:Older kidney transplant recipients demonstrated decreased frequency of intermediate monocytes (CD14++CD16+) compared with younger patients (1.2% vs 3.3%, P = 0.007), and a trend toward increased frequency of proinflammatory classical monocytes (CD14++CD16-) (94.5% vs 92.1%) (P = 0.065). Increased levels of interferon-gamma (IFN-γ) were seen in older patients. Conclusions:In this pilot study of kidney transplant recipients, we identified differences in the innate immune system in older as compared with younger patients, including increased levels of IFN-γ. This suggests that age-associated nonspecific inflammation persists despite immune suppression. The ability to apply noninvasive testing to transplant recipients will provide tools for patient risk stratification and individualization of immune suppression regimens to improve outcomes after transplantation

Criteria for and Appropriateness of Renal Transplantation in Elderly Patients With End-Stage Renal Disease : A Literature Review and Position Statement on Behalf of the European Renal Association-European Dialysis and Transplant Association Descartes Working Group and European Renal Best Practice

During the last 20 years, waiting lists for renal transplantation (RT) have grown significantly older. However, elderly patients (ie ≥65 years of age) are still more rarely referred or accepted to waiting lists and, if enlisted, have less chances of actually receiving a kidney allograft, than younger counterparts. In this review, we looked at evidence for the benefits and risks of RT in the elderly trying to answer the following questions: Should RT be advocated for elderly patients? What should be the criteria to accept elderly patients on the waiting list for RT? What strategies might be used to increase the rate of RT in waitlisted elderly candidates? For selected elderly patients, RT was shown to be superior to dialysis in terms of patient survival. Virtually all guidelines recommend that patients should not be deemed ineligible for RT based on age alone, although a short life expectancy generally might preclude RT. Concerning the assessment of comorbidities in the elderly, special attention should be paid to cardiac evaluation and screening for malignancy. Comorbidity scores and frailty assessment scales might help the decision making on eligibility. Psychosocial issues should also be evaluated. To overcome the scarcity of organ donors, elderly RT candidates should be encouraged to consider expanded criteria donors and living donors, as alternatives to deceased standard criteria donors. It has been demonstrated that expanded criteria donor RT in patients 60 years or older is associated with higher survival rates than remaining on dialysis, whereas living donor RT is superior to all other options.Peer reviewe

Influence of Recipient Race on the Outcome of Simultaneous Pancreas and Kidney Transplantation

Racial differences on the outcome of simultaneous pancreas and kidney (SPK) transplantation have not been well studied. We compared mortality and graft survival of African Americans (AA) recipients to other racial/ethnic groups (non-AA) using the national data. We studied a total of 6585 adult SPK transplants performed in the United States between January 1, 2000 and December 31, 2007. We performed multivariate logistic regression analyses to determine risk factors associated with early graft failure and immune-mediated late graft loss. We used conditional Kaplan–Meier survival and multivariate Cox regression analyses to estimate late death-censored kidney and pancreas graft failure and death between the groups. Although there was no racial disparity in the first 90 days, AA patients had 38% and 47% higher risk for late death-censored kidney and pancreas graft failure, respectively (p = 0.006 and 0.001). AA patients were twice more likely to lose the kidney and pancreas graft due to rejection (OR 2.31 and 1.86, p = 0.002 and 0.008, respectively). Bladder pancreas drainage was associated with inferior patient survival (HR 1.42, 95% CI 1.15, 1.75, p = 0.001). In the era of modern immunosuppresion, AA SPK transplant patients continue to have inferior graft outcome. Additional studies to explore the mechanisms of such racial disparity are warranted.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/79281/1/j.1600-6143.2010.03211.x.pd

Pancreas transplantation: differences in activity between Europe and the United States

Background. Although pancreas transplantation (PT) is the treatment of choice in selected diabetic patients, the International Pancreas Transplant Registry (IPTR) has reported important differences in activity between USA and Europe. Of all cases reported, 75% are from USA and only 23% from Europe. Therefore, an analysis of PT activity in selected European countries (SEC) and USA was performed

Improved Gastrointestinal Symptoms and Quality of Life after Conversion from Mycophenolate Mofetil to Enteric-Coated Mycophenolate Sodium in Renal Transplant Patients Receiving Tacrolimus

It is reported that a conversion from mycophenolate mofetil (MMF) to enteric-coated mycophenolate sodium (EC-MPS) relieves gastrointestinal (GI) symptom burden and improves health-related quality of life (HRQoL). However, it is unclear whether renal transplant recipients using tacrolimus receive the same benefit from the conversion. In this prospective, multi-center, open-label trial, patients were categorized into two groups by their GI symptom screening. Equimolar EC-MPS (n=175) was prescribed for patients with GI burdens; those with no complaints remained on MMF (n=83). Gastrointestinal Symptom Rating Scale (GSRS) and Gastrointestinal Quality of Life Index (GIQLI) were evaluated at baseline and after one month. Patients and physicians completed Overall Treatment Effect (OTE) at one month. EC-MPS-converted patients had worse GSRS and GIQLI scores at baseline than MMF-continued patients (all P<0.001). Significant improvements in GSRS and GIQLI scores were observed for EC-MPS-converted patients at one month, but MMF-continued patients showed worsened GSRS scores (all P<0.05). OTE scale indicated that EC-MPS patients improved in overall GI symptoms and HRQoL more than MMF patients did (P<0.001). In tacrolimus-treated renal transplant recipients with GI burdens, a conversion from MMF to EC-MPS improves GI-related symptoms and HRQoL

Cell-Free DNA and Active Rejection in Kidney Allografts

Histologic analysis of the allograft biopsy specimen is the standard method used to differentiate rejection from other injury in kidney transplants. Donor-derived cell-free DNA (dd-cfDNA) is a noninvasive test of allograft injury that may enable more frequent, quantitative, and safer assessment of allograft rejection and injury status. To investigate this possibility, we prospectively collected blood specimens at scheduled intervals and at the time of clinically indicated biopsies. In 102 kidney recipients, we measured plasma levels of dd-cfDNA and correlated the levels with allograft rejection status ascertained by histology in 107 biopsy specimens. The dd-cfDNA level discriminated between biopsy specimens showing any rejection (T cell-mediated rejection or antibody-mediated rejection [ABMR]) and controls (no rejection histologically), P1% indicate a probability of active rejection

Comparison of quality-of-care measures in U.S. patients with end-stage renal disease secondary to lupus nephritis vs. other causes

BACKGROUND: Patients with end-stage renal disease (ESRD) due to lupus nephritis (LN-ESRD) may be followed by multiple providers (nephrologists and rheumatologists) and have greater opportunities to receive recommended ESRD-related care. We aimed to examine whether LN-ESRD patients have better quality of ESRD care compared to other ESRD patients. METHODS: Among incident patients (7/05–9/11) with ESRD due to LN (n = 6,594) vs. other causes (n = 617,758), identified using a national surveillance cohort (United States Renal Data System), we determined the association between attributed cause of ESRD and quality-of-care measures (pre-ESRD nephrology care, placement on the deceased donor kidney transplant waitlist, and placement of permanent vascular access). Multivariable logistic and Cox proportional hazards models were used to estimate adjusted odds ratios (ORs) and hazard ratios (HRs). RESULTS: LN-ESRD patients were more likely than other ESRD patients to receive pre-ESRD care (71% vs. 66%; OR = 1.68, 95% CI 1.57-1.78) and be placed on the transplant waitlist in the first year (206 vs. 86 per 1000 patient-years; HR = 1.42, 95% CI 1.34–1.52). However, only 24% had a permanent vascular access (fistula or graft) in place at dialysis start (vs. 36%; OR = 0.63, 95% CI 0.59–0.67). CONCLUSIONS: LN-ESRD patients are more likely to receive pre-ESRD care and have better access to transplant, but are less likely to have a permanent vascular access for dialysis, than other ESRD patients. Further studies are warranted to examine barriers to permanent vascular access placement, as well as morbidity and mortality associated with temporary access, in patients with LN-ESRD

Steroids in kidney transplant patients

Any evaluation of steroids in kidney transplantation is hampered by individual variability in metabolism, the lack of clinically available steroid blood levels, and overall little attention to steroid exposure. Many feel that steroids were an essential part of chronic immunosuppression in past decades but may no longer be necessary in low-risk populations when our newer and more potent drugs are used. Potential differences in long-term outcome will be unapparent in short-term antibody induction studies in low-risk patients, particularly with low on steroid doses, as may have happened in the recent, well-done Astellas trial. In many studies, the evidence for the superiority of mycophenolate (MMF) and tacrolimus (TAC) was not as strong as the evidence for the benefit of steroids in the Canadian cyclosporine study. As the practice of steroid withdrawal has increased, we have not seen the improvement in long-term graft survival that many expected with our newer agents. Steroids have immunosuppressive effects even in doses that are low by historic standards, and side effects may not justify their abandonment