Barriers to access by Indigenous Australians to kidney transplantation: the IMPAKT study

Although Indigenous Australians represent less than 2% of the national population, they account for 8-10% of new patients commencing treatment for end-stage renal disease (ESRD). Almost half come from remote regions lacking renal disease treatment services. In those regions, their incidence of ESRD is up to 30 times the incidence for all Australians. Kidney transplantation is the optimal treatment for ESRD. Compared with long-term dialysis, it results in better quality of life, longer life expectancy and lower costs of health care. Indigenous Australians with ESRD receive transplants at approximately one-third the rate of non-Indigenous patients. There are similar disparities in access to kidney transplants for Native Americans, Aboriginal Canadians and New Zealander Maori. The reasons for such disparities have not been studied in any detail. IMPAKT (Improving Patient Access to Kidney Transplantation) is an NHMRC-funded study, involving eight major renal units. It aims to identify the reasons for Indigenous Australians' poor access to transplantation. It will systematically examine each of the steps a new dialysis patient must negotiate in order to receive a transplant. Each of these steps can become a barrier.     

Barriers to access by Indigenous Australians to kidney transplantation: The IMPAKT study

SUMMARY:   Although Indigenous Australians represent less than 2% of the national population, they account for 8–10% of new patients commencing treatment for end-stage renal disease (ESRD). Almost half come from remote regions lacking renal disease treatment services. In those regions, their incidence of ESRD is up to 30 times the incidence for all Australians.
Kidney transplantation is the optimal treatment for ESRD. Compared with long-term dialysis, it results in better quality of life, longer life expectancy and lower costs of health care. Indigenous Australians with ESRD receive transplants at approximately one-third the rate of non-Indigenous patients. There are similar disparities in access to kidney transplants for Native Americans, Aboriginal Canadians and New Zealander Maori. The reasons for such disparities have not been studied in any detail.
IMPAKT (Improving Patient Access to Kidney Transplantation) is an NHMRC-funded study, involving eight major renal units. It aims to identify the reasons for Indigenous Australians' poor access to transplantation. It will systematically examine each of the steps a new dialysis patient must negotiate in order to receive a transplant. Each of these steps can become a barrier.     

Obesity impacts access to kidney transplantation

Current billing practices and mandates to report surgical outcomes are disincentives to surgical treatment of obese patients, who are at increased risk for longer hospital stays and higher complication rates. The objective of this study was to quantify the independent association between body mass index (BMI) and waiting time for kidney transplantation to identify potential provider bias against surgical treatment of the obese. A secondary data analysis was performed of a prospective cohort of 132,353 patients who were registered for kidney transplantation in the United States between 1995 and 2006. Among all patients awaiting kidney transplantation, the likelihood of receiving a transplant decreased with increasing degree of obesity, categorized by ranges of BMI (adjusted hazard ratios 0.96 for overweight, 0.93 for obese, 0.72 for severely obese, and 0.56 for morbidly obese, compared with a reference group of patients with normal BMI). Similarly, the likelihood of being bypassed when an organ became available increased in a graded manner with category of obesity (adjusted incidence rate ratio 1.02 for overweight, 1.05 for obese, 1.11 for severely obese, and 1.22 for morbidly obese). Although matching an available organ with an appropriate recipient requires clinical judgment, which could not be fully captured in this study, the observed differences are dramatic and warrant further studies to understand this effect better and to design a system that is less susceptible to unintended bias.     

Combined pancreas kidney transplantation after isolated kidney transplantation

Simultaneous pancreas kidney transplantation (SPK) is an established therapy for type 1 diabetics with end stage or preterminal renal disease. SPK is superior to isolated kidney transplantation (KTX) in diabetic patients. Even pancreas-re-transplantations are more common in these patients now, mostly after SPK. But Experience with SPK after KTX is rare. Between 1994 and 2003 six Re-SPK 4.5 to 8.5 years after KTX were performed in our department. Average age of the recipients was 40.5 years. They had been suffering from diabetes for an average of 29.3 years. Four recipients were on dialysis again, whereas two had preterminal renal insufficiency. Pancreas transplants were drained through the bladder (n = 1) or into the small intestine (n = 5) with systemic venous anastomosis. After a median observation period of 28 months (8 to 99 months) all six recipients are insulin free. One patient lost his kidney graft due to severe acute rejection. Therefore kidney graft survival is 83 %. Four acute rejections (66 %) were observed in 4 patients. Only one rejection was treated successfully by steroids. Two rejections could be stopped with antibodies. 3 patients had infections in the early postoperative period (sinusitis, urinary tract infection, wound infection). Even after KTX with graft failure, diabetic patients suffering from renal disease can be re-transplanted successfully with SPK.     

Exchange kidney transplantation: a good solution in living kidney transplantation

OBJECTIVES: Kidney transplantation seems to be the best treatment modality for end-stage renal disease patients. But not every patient on the waiting list is able to find a kidney. To increase transplantations, centers have tried to find new options. MATERIAL AND METHODS: In the period of November 1994 through June 2004, among 265 renal transplantations, 182 (68.6%) were from living related donors, namely first- and second-degree relatives, spouses, or parents-in-law of the patients. Four patients, who did not have living related donors, had the opportunity of renal transplantation from living donors by exchanging their donors. RESULTS: All the kidneys functioned immediately. No complications and no acute rejection episodes were observed in the postoperative period up to 12 months. Serum creatinine levels were 1.9, 1.2, 1.6, and 2.4 mg/dL on postoperative day 7; 1.4, 1.0, 1.1, and 1.1 mg/dL at 1 month after transplantation; 1.5 and 1.2 mg/dL at month 6 after transplantation; 1.6 and 1.4 mg/dL at 1 year after transplantation. CONCLUSION: We believe that exchange kidney transplantations represent a good alternative for end-stage renal patients who do not have suitable close living related donors.     

Outcomes in kidney transplantation

It is estimated that there are greater than 100000 kidney transplant recipients with a functioning graft in the United States. Recent advances in immunosuppression have improved short-term graft survival rates and decreased early mortality by decreasing the incidence and therapy for acute rejection episodes. For those accepted on the waiting list, transplant prolongs patient survival compared with remaining on dialysis. During the 1990s, 3 new immunosuppressive drugs were introduced in clinical kidney transplantation. All were approved for use by the Food and Drug Administration after large, controlled, randomized trials. Mycophenolate mofetil (MMF), when combined with cyclosporine (CSA) and prednisone, lowered acute rejection rates by nearly 50% compared with control. Tacrolimus compared with CSA also significantly reduced acute rejection rates in kidney transplant recipients, but was associated with a significant increase in posttransplant diabetes mellitus (PTDM) in the early trials. When evaluated in combination with MMF, the incidence of PTDM was much lower. At the end of the decade, sirolimus was shown in several randomized trials to lower acute rejection rates and is believed to be less nephrotoxic compared with calcineurin inhibitors. All of the randomized trials were not statistically powered to assess long-term superiority. Registry analyses have been performed that appear to show some long-term benefit of immunosuppressive therapy with MMF. Other outcome assessments in kidney transplant recipients include risk factors for chronic allograft nephropathy, hypertension, hyperlipidemia, and bone disease. Although there are few randomized trials, understanding of the significance of these common complications has progressed and strategies for therapy and intervention have been developed. This article focuses on the randomized trials of immunosuppressive therapy and complications associated with use of these drugs. In addition, we review the current management and intervention for the comorbidities associated with the long-term clinical management of the kidney transplant recipient.     

Immunosuppression in kidney transplantation

Kidney transplantation has become the treatment of choice in end-stage chronic renal failure since it significantly improves both the quality of life and the life duration of affected patients, when compared with dialysis. Some of these better results that were observed over the last thirty years are obviously due to significant improvements in the quality of immunosuppression. In the first part of this chapter, the allo-immune response is schematically described regarding the various signals. Then, the mechanisms of action of the available or future immunosuppressive therapies are described in the same order as the allo-immune response. In the third part, the various combinations of immunosuppressive regimens are presented from a historical perspective, outlining not only the positive aspects of each class of drugs but also their side effects and consequences on the practical use of immunosuppression over time. Finally, a brief review of current and future perspectives regarding the improvement of both efficacy and tolerability of immunosuppression in kidney transplantation is presented.     

Cancer in kidney transplantation

Cancer in the transplanted kidney is rare, and its clinical and surgical management can be controversial. We report 3 cases of cancer in renal transplantation (1 case of renal cell carcinoma and 2 cases of transitional cell carcinoma) and their treatment. Our data and those reported in the literature suggest that these cancers can be treated like a neoplasm in the general population. However, a higher number of cases and longer follow-up periods are necessary to confirm our findings.     

Hypertension in kidney transplantation

Arterial hypertension in renal transplant patients plays a major role in the progression to chronic allograft failure, and in morbidity and mortality associated with cardiovascular disease. Its cause is diverse, with contributions not only from donor and/or recipient factors, but it also is influenced strongly by the type of immunosuppressive regimen. Despite increased awareness of the adverse effects of hypertension in both graft and patient survival, long-term studies have shown that arterial hypertension in the transplant population has not been controlled adequately. Ambulatory blood pressure measurements provide the advantage of a better assessment of the diurnal blood pressure variation, a predictor of target organ damage and cardiovascular morbidity and mortality events. Although the available data do not support the recommendation of any class of antihypertensive medication as preferred agents for blood pressure management in the transplant population, angiotensin-converting enzyme inhibitors and angiotensin-receptor blockers have shown beneficial effects beyond their antihypertensive effects. Clinical data in transplant recipients are emerging that suggest that applying interventions proven to be effective in reducing cardiovascular morbidity and mortality in the general population may be effective for the transplant population.     

From ABO-incompatible human kidney transplantation to xenotransplantation

The development (in 1981) of a protocol for successful renal allotransplantation across ABO barriers is outlined. From this experience, the concept of "adaptation", subsequently termed "accommodation", was defined. It was then hypothesized that a similar approach might allow pig-to-human organ xenotransplantation. This hypothesis was explored in the pig-to-baboon renal transplantation model, with graft survival for a maximum of 23 days. Rejection episodes were temporarily reversed, providing encouragement that discordant xenotransplantation would one day prove successful. Finally, the preparation of the thymokidney, developed as a means of inducing xenotolerance, is briefly reviewed.     

Fat-soluble vitamins in advanced CKD/ESKD: a review

Patients requiring dialysis often experience a significant decline in their nutritional status through a combination of chronic disease, reduced appetite, and dietary restrictions, which places them at risk for vitamin deficiencies. The concept of vitamin deficiency has evolved from obvious deficiency states to the subtle effects that suboptimal intake may have on chronic disease prevalence or progression. The purpose of this study was to summarize the current state of knowledge regarding the status of the fat-soluble vitamins (A, D, E, and K) in patients with chronic kidney disease receiving hemodialysis.     

Antibodies to hepatitis C virus in kidney transplantation.

Ninety patients on dialysis, 241 cadaveric kidney donors and 27 cadaveric kidney recipients with a follow-up of 2 years, have been investigated as for anti-HCV positivity by means of 3 tests. As for patients on dialysis and cadaveric donors, the prevalence was 32 and 4%, respectively. As for transplanted patients, it must be noted that 4 negative recipients from positive donors seroconverted, but without any change in hepatic enzymes, while in 2 or 9 anti-HCV-positive recipients, hepatic enzymes increased after transplantation. Seroconversion in patients transplanted from a negative donor was not significantly different. We conclude that, according to their experience, anti-HCV positivity in the donors is not associated with a significant risk of infection in recipients of cadaveric grafts.     

Aden kidney transplantation

During the first Yemeni Congress of Uro-Nephrology in Aden, an international team performed the first kidney tranplantations in the region. We report the difficulties encountered and discuss the pros and cons for transplantations in developing countries.