Interactions Between Donor Age and 12-Month Estimated Glomerular Filtration Rate on Allograft and Patient Outcomes After Kidney Transplantation.

Reduced estimated glomerular filtration rate (eGFR) at 12-months after kidney transplantation is associated with increased risk of allograft loss, but it is uncertain whether donor age and types modify this relationship. Using Australia and New Zealand registry data, multivariable Cox proportional modelling was used to examine the interactive effects between donor age, types and 12-month eGFR on overall allograft loss. We included 11,095 recipients (4,423 received live-donors). Recipients with lowest 12-month eGFR (<30 ml/min/1.73 m2) experienced the greatest risk of allograft loss, with adjusted HR [95% CI) of 2.65 [2.38-2.95] compared to eGFR of 30-60 ml/min/1.73 m2; whereas the adjusted HR for highest eGFR (>60 ml/min/1.73 m2) was 0.67 [0.62-0.74]. The association of 12-month eGFR and allograft loss was modified by donor age (but not donor types) where a higher risk of allograft loss in recipients with lower compared with higher 12-month eGFR being most pronounced in the younger donor age groups (p < 0.01). Recipients with eGFR <30 ml/min/1.73 m2 12-months after transplantation experienced ≥2.5-fold increased risk of overall allograft loss compared to those with eGFR of >60 ml/min/1.73 m2, and the magnitude of the increased risk is most marked among recipients with younger donors. Careful deliberation of other factors including donor age when considering eGFR as a surrogate for clinical endpoints is warranted.

Conversion of Urine Protein-Creatinine Ratio or Urine Dipstick Protein to Urine Albumin-Creatinine Ratio for Use in Chronic Kidney Disease Screening and Prognosis : An Individual Participant-Based Meta-analysis.

BACKGROUND: Although measuring albuminuria is the preferred method for defining and staging chronic kidney disease (CKD), total urine protein or dipstick protein is often measured instead. OBJECTIVE: To develop equations for converting urine protein-creatinine ratio (PCR) and dipstick protein to urine albumin-creatinine ratio (ACR) and to test their diagnostic accuracy in CKD screening and staging. DESIGN: Individual participant-based meta-analysis. SETTING: 12 research and 21 clinical cohorts. PARTICIPANTS: 919 383 adults with same-day measures of ACR and PCR or dipstick protein. MEASUREMENTS: Equations to convert urine PCR and dipstick protein to ACR were developed and tested for purposes of CKD screening (ACR ≥30 mg/g) and staging (stage A2: ACR of 30 to 299 mg/g; stage A3: ACR ≥300 mg/g). RESULTS: Median ACR was 14 mg/g (25th to 75th percentile of cohorts, 5 to 25 mg/g). The association between PCR and ACR was inconsistent for PCR values less than 50 mg/g. For higher PCR values, the PCR conversion equations demonstrated moderate sensitivity (91%, 75%, and 87%) and specificity (87%, 89%, and 98%) for screening (ACR >30 mg/g) and classification into stages A2 and A3, respectively. Urine dipstick categories of trace or greater, trace to +, and ++ for screening for ACR values greater than 30 mg/g and classification into stages A2 and A3, respectively, had moderate sensitivity (62%, 36%, and 78%) and high specificity (88%, 88%, and 98%). For individual risk prediction, the estimated 2-year 4-variable kidney failure risk equation using predicted ACR from PCR had discrimination similar to that of using observed ACR. LIMITATION: Diverse methods of ACR and PCR quantification were used; measurements were not always performed in the same urine sample. CONCLUSION: Urine ACR is the preferred measure of albuminuria; however, if ACR is not available, predicted ACR from PCR or urine dipstick protein may help in CKD screening, staging, and prognosis. PRIMARY FUNDING SOURCE: National Institute of Diabetes and Digestive and Kidney Diseases and National Kidney Foundation.

The experiences and impact of being deemed ineligible for living kidney donation: Semi-structured interview study.

AIM: We aimed to describe the impact and experience of being deemed ineligible as a living kidney donor. METHODS: Semi-structured interviews were conducted with 27 ineligible donor candidates. Transcripts were analysed thematically. RESULTS: Seven themes were identified: deriving health and relationship benefits in the process (strengthening emotional connection, identifying problematic health conditions); devastating loss and disappointment (harbouring guilt over personal failings, shattering confidence and hope, undermining relationships with extended family and friends, disrupting home dynamics); constrained within a rigid system (denied autonomy, resorting to other avenues); acknowledging as matter of fact (accepting the clinical decision, reassured by preventing a poor outcome); reluctant to relinquish the donor identity (unable to fulfil family duty, having the donor role stolen, holding onto other opportunities to donate); uncertainty in unpredictability, inconsistency and ambiguities (frustrated by inefficiencies, questioning clinician motivation, suspended donor status, unfairness in changeable eligibility criteria, unresolved concerns and questions of own health); and abandoned in despair (lacking practical support to meet eligibility criteria, ill prepared for rejection, dismissed and discarded by the system). CONCLUSION: Being deemed unsuitable for donation took an emotional toll on ineligible donor candidates who felt immense guilt for 'failing' the potential recipient. Ineligible donor candidates were frustrated and angry with the perceived lack of support from clinicians and rigidity of the evaluation process. Informing potential donors of available services, including psychological support, communicating the decision sensitively and with sufficient time, and full disclosure of their health status, may contribute to improved adjustment following the ineligibility decision.

Living kidney donor and recipient perspectives on their relationship: longitudinal semi-structured interviews.

BACKGROUND AND OBJECTIVES: Many donors and recipients report an improved bond posttransplantation; however, unexpected conflicts and tension may also occur. Insights into the lived experiences of the donor-recipient relationship can inform strategies for interventions and support. We aimed to describe donor and recipient expectations and experiences of their relationship before and after living kidney donor transplantation. DESIGN, SETTING AND PARTICIPANTS: Semistructured interviews were conducted with 16 donor-recipient pairs before the transplant and 11-14 months post-transplant. Transcripts were analysed thematically. RESULTS: We identified seven themes (with respective subthemes): donation as enacting familial responsibility for care; analytical decision making to mitigate regret (avoiding anticipated regret and maintaining control, removing emotional impulsivity); strengthened interpersonal ties (gaining a deeper appreciation among family members, stronger empathy for each other, improving social participation); instability of relational impacts (anger and aggression threatening dynamics, unanticipated stress and emotional lability, triggering familial tension); renegotiating social roles (unexpected continuation of caregiving responsibilities, inability to relinquish the caregiving role, disappointment with unfulfilled renewal of intimacy, dissatisfaction over discrepant energy levels); guilt over unmet expectations and inevitability of the gift relationship (vague and transient indebtedness, expectation of reciprocity, transferring kidney ownership). CONCLUSIONS: Donor-recipient relationships may be improved through increased empathy, appreciation, and ability to participate in life together; however, unfulfilled expectations and behavioural and emotional changes in recipients (a side effect related to immunosuppression) remain unresolved consequences of living kidney donor transplantation. Education and counselling to help donors and recipients adjust to potential changes in relationship dynamics may help protect and foster relational stability postdonation.

Identifying Outcomes that Are Important to Living Kidney Donors: A Nominal Group Technique Study.

BACKGROUND AND OBJECTIVES: Living kidney donor candidates accept a range of risks and benefits when they decide to proceed with nephrectomy. Informed consent around this decision assumes they receive reliable data about outcomes they regard as critical to their decision making. We identified the outcomes most important to living kidney donors and described the reasons for their choices. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Previous donors were purposively sampled from three transplant units in Australia (Sydney and Melbourne) and Canada (Vancouver). In focus groups using the nominal group technique, participants identified outcomes of donation, ranked them in order of importance, and discussed the reasons for their preferences. An importance score was calculated for each outcome. Qualitative data were analyzed thematically. RESULTS: Across 14 groups, 123 donors aged 27-78 years identified 35 outcomes. Across all participants, the ten highest ranked outcomes were kidney function (importance=0.40, scale 0-1), time to recovery (0.27), surgical complications (0.24), effect on family (0.22), donor-recipient relationship (0.21), life satisfaction (0.18), lifestyle restrictions (0.18), kidney failure (0.14), mortality (0.13), and acute pain/discomfort (0.12). Kidney function and kidney failure were more important to Canadian participants, compared with Australian donors. The themes identified included worthwhile sacrifice, insignificance of risks and harms, confidence and empowerment, unfulfilled expectations, and heightened susceptibility. CONCLUSIONS: Living kidney donors prioritized a range of outcomes, with the most important being kidney health and the surgical, lifestyle, functional, and psychosocial effects of donation. Donors also valued improvements to their family life and donor-recipient relationship. There were clear regional differences in the rankings.

Recurrent glomerulonephritis after kidney transplantation: risk factors and allograft outcomes.

Recurrent glomerulonephritis after kidney transplantation is a feared complication because it is unpredictable and may have a negative impact on graft outcomes. To better understand this we collected data from the Australia and New Zealand Dialysis and Transplant (ANZDATA) Registry accumulated over 30 years. The incidence, risk factors, and outcomes of recurrent glomerulonephritis in transplant recipients were determined using adjusted Cox proportional hazard and competing risk modeling. A total of 6,597 recipients with biopsy-proven glomerulonephritis as the primary cause of end-stage kidney disease were followed for 51,871 person-years (median duration 7.7 years). The four most common types of glomerulonephritis were IgA nephropathy in 2501 patients, focal segmental glomerulosclerosis (FSGS) in 1403, membranous in 376, and membranoproliferative (MPGN) nephropathy in 357 patients. Among these four types, recurrence was reported in 479 of 4637 patients, and of these, 212 lost their allograft due to recurrence. Older age at transplantation (adjusted hazard ratio [per year increase] 0.96 [95% confidence interval 0.95 - 0.97]) was associated with a lower risk of recurrence. Significantly, the five-year graft survival was 30% for recipients with recurrent MPGN and 57-59% for recipients with FSGS, IgA, and membranous nephropathy. Transplant recipients with recurrent disease were twice as likely to lose their allografts compared to those without recurrence (adjusted hazard ratio 2.04 [1.81-2.31]). Thus, recurrent glomerulonephritis remains a significant cause of graft loss in transplant recipients.

Expectations and Experiences of Follow-up and Self-Care After Living Kidney Donation: A Focus Group Study.

BACKGROUND: Ensuring donor wellbeing warrants ongoing monitoring after living kidney donation. However, there is considerable variability in donor follow-up processes, including information provided to donors regarding self-care. Loss to follow-up is common, suggesting that the aims and benefits of monitoring and follow-up may not be apparent. We aimed to describe the experiences and expectations of living kidney donors regarding follow-up and self-care after donation. METHODS: Participants from 3 transplant centers in Australia and Canada participated in 14 focus groups (n = 123). Transcripts were analyzed thematically. RESULTS: We identified 4 themes: lacking identification as a patient (invincibility and confidence in health, immediate return to normality, avoid burdening specialty services, redundancy of specialist attention, unnecessary travel), empowerment for health (self-preservation for devastating consequences, self-advocacy and education, needing lifestyle advice, tracking own results), safety net and reassurance (availability of psychosocial support, confidence in kidney-focused care, continuity and rapport, and access to waitlist priority), and neglect and inattention (unrecognized ongoing debilitations, primary focus on recipient, hospital abandonment, overlooking individual priorities, disconnected from system, coping with dual roles, and lacking support for financial consequences). CONCLUSIONS: Living kidney donors who felt well and confident about their health regarded specialist follow-up as largely unnecessary. However, some felt they did not receive adequate medical attention, were prematurely detached from the health system, or held unresolved anxieties about the consequences of their decision to donate. Ongoing access to healthcare, psychosocial support, and education may reassure donors that any risks to their health are minimized.

Donor and Recipient Views on Their Relationship in Living Kidney Donation: Thematic Synthesis of Qualitative Studies.

BACKGROUND: Many donors and recipients report an improved relationship after transplantation; however, tension, neglect, guilt, and proprietorial concern over the recipient can impede donor and recipient well-being and outcomes. We aimed to describe donor and recipient expectations and experiences of their relationship in the context of living kidney donation. STUDY DESIGN: Thematic synthesis of qualitative studies. SETTING & POPULATION: Living kidney donors and recipients. SEARCH STRATEGY & SOURCES: Electronic databases were searched to October 2015. ANALYTICAL APPROACH: Thematic synthesis. RESULTS: From 40 studies involving 1,440 participants (889 donors and 551 recipients) from 13 countries, we identified 6 themes. "Burden of obligation" described the recipient's perpetual sense of duty to demonstrate gratitude to the donor. "Earning acceptance" was the expectation that donation would restore relationships. "Developing a unique connection" reflected the inexplicable bond that donor-recipient dyads developed postdonation. "Desiring attention" was expressed by donors who wanted recognition for the act of donation and were envious and resentful of the attention the recipient received. "Retaining kidney ownership" reflected the donor's inclination to ensure that the recipient protected "their" kidney. "Enhancing social participation" encompassed relieving both the caregiver from the constraints of dialysis and the recipient from increased involvement and contribution in family life. LIMITATIONS: Non-English articles were excluded. CONCLUSIONS: Living kidney donation can strengthen donor-recipient relationships but may trigger or exacerbate unresolved angst, tension, jealousy, and resentment. Facilitating access to pre- and posttransplantation psychological support that addresses potential relationship changes may help donors and recipients better adjust to changes in the relationship dynamics, which in turn may contribute to improved psychosocial and transplantation outcomes following living kidney donation.

Attitudes and beliefs about deceased organ donation in the Arabic-speaking community in Australia: a focus group study.

OBJECTIVES: To describe the beliefs and attitudes to organ donation in the Arabic-speaking community. DESIGN: Arabic-speaking participants were purposively recruited to participate in 6 focus groups. Transcripts were analysed thematically. PARTICIPANTS: 53 participants, aged 19-77 years, and originating from 8 countries, participated in 1 of 6 focus groups. Participants identified as Christian (73%), Islam (26%), Buddhist (2%) or did not identify with any religion (2%). RESULTS: 6 themes (with subthemes) were identified; religious conviction; invisibility of organ donation; medical suspicion; owning the decision; and reciprocal benefit. CONCLUSIONS: Although organ donation is considered a generous life-saving 'gift', representative members of the Arabic-speaking community in Australia were unfamiliar with, unnerved by and sceptical about the donation process. Making positive decisions about organ donation would likely require resolving tensions between respecting family, community and religious values versus their individual autonomy. Providing targeted education about the process and benefits of organ donation within the Arabic community may clarify ambiguities surrounding cultural and religious-based views on organ donation, reduce taboos and suspicion towards donation, and in turn, lead to increased organ donation rates.

Research Priorities in CKD: Report of a National Workshop Conducted in Australia.

Research aims to improve health outcomes for patients. However, the setting of research priorities is usually performed by clinicians, academics, and funders, with little involvement of patients or caregivers and using processes that lack transparency. A national workshop was convened in Australia to generate and prioritize research questions in chronic kidney disease (CKD) among diverse stakeholder groups. Patients with CKD (n=23), nephrologists/surgeons (n=16), nurses (n=8), caregivers (n=7), and allied health professionals and researchers (n=4) generated and voted on intervention questions across 4 treatment categories: CKD stages 1 to 5 (non-dialysis dependent), peritoneal dialysis, hemodialysis, and kidney transplantation. The 5 highest ranking questions (in descending order) were as follows: How effective are lifestyle programs for preventing deteriorating kidney function in early CKD? What strategies will improve family consent for deceased donor kidney donation, taking different cultural groups into account? What interventions can improve long-term post-transplant outcomes? What are effective interventions for post hemodialysis fatigue? How can we improve and individualize drug therapy to control post-transplant side effects? Priority questions were focused on prevention, lifestyle, quality of life, and long-term impact. These prioritized research questions can inform funding agencies, patient/consumer organizations, policy makers, and researchers in developing a CKD research agenda that is relevant to key stakeholders.

Dangers of broth after transplantation.

Serum creatinine is routinely used to monitor renal function in transplant recipients. External factors including diet, exercise and hydration status can also influence serum creatinine concentration on a day-to-day basis. We describe a case of a patient whose serum creatinine increased from 128 to 171 µmol/L after ingestion of creatinine-rich (3098 µmol/L) soup. A renal biopsy was performed but revealed no cause for the rise in creatinine and by the next day, serum creatinine had returned to baseline. We conducted two experiments to examine the effect of soup ingestion by healthy volunteers. We measured the creatinine concentration of various store-bought stock preparations and found creatinine concentrations less than one-quarter of that contained in our patient's homemade soup. A creatinine-rich soup (4334 µmol/L) was ingested by six healthy volunteers age 33 (± 6.5) years with baseline normal serum creatinine 68 (± 14) µmol/L. Mean (standard deviation) serum creatinine increased to 77 (± 11) µmol/L 4 hours after soup ingestion (P = 0.0015, paired t-test). Mean (standard deviation) creatinine clearance, extrapolated from the 4 hour urine collection following soup ingestion, was high (267 ± 198 mL/min) exhibiting a supra-normal creatinine clearance. The rate of serum creatinine rise was lower in volunteers compared with the transplant patient, consistent with the concept of renal functional reserve. Our case highlights the importance of taking dietary changes into account when interpreting serum creatinine as a measure of allograft function.

The expectations and attitudes of patients with chronic kidney disease toward living kidney donor transplantation: a thematic synthesis of qualitative studies.

BACKGROUND: Living kidney donation offers superior outcomes over deceased organ donation, but incurs psychosocial and ethical challenges for recipients because of the risks imposed on their donor. We aimed to describe the beliefs, attitudes, and expectations of patients with chronic kidney disease toward receiving a living kidney donor transplant. METHODS: We conducted a systematic review of qualitative studies of patients' attitudes toward living kidney donation using a comprehensive literature search of electronic databases to February 2013. The findings were analyzed using thematic synthesis. RESULTS: Thirty-nine studies (n ≥ 1791 participants) were included. We identified six themes: prioritizing own health (better graft survival, accepting risk, and desperate aversion to dialysis), guilt and responsibility (jeopardizing donor health, anticipating donor regret, and causing donor inconvenience), ambivalence and uncertainty (doubting transplant urgency, insufficient information, confronted by unfamiliarity, and prognostic uncertainty), seeking decisional validation (a familial obligation, alleviating family burden, reciprocal benefits for donors, respecting donor autonomy, external reassurance, and religious approval), needing social support (avoiding family conflict, unrelenting indebtedness, and emotional isolation), and cautious donor recruitment (self-advocacy, lacking self-confidence, avoiding donor coercion, emotional vulnerability, respecting cultural, and religious taboos). CONCLUSION: Enhanced education and psychosocial support may help clarify, validate, and address patients' concerns regarding donor outcomes, guilt, relationship tensions, and donor recruitment. This may encourage informed decision-making, increase access to living kidney donation, and improve psychosocial adjustment for transplant recipients.

Outcomes of kidney transplantation from older living donors.

BACKGROUND: The disparity between donor kidney availability and demand has increased utilization of kidneys from older living donors (OLD). We compared graft and patient outcomes of patients on maintenance dialysis after transplantation with OLD kidneys to those receiving younger live donor (YLD) kidneys and deceased donor (DD) kidneys. METHODS: Using Australia and New Zealand Dialysis and Transplant Registry, primary live and deceased donor renal transplant recipients aged 18 years or older between 1997 and 2009 were stratified into six groups: standard criteria deceased donor kidneys with total ischemic time of less than 12 hours (SCD, <12), SCD of 12 or greater, expanded criteria donor (ECD) less than 12, ECD of 12 or greater, YLD (LD, <60 years), and OLD kidneys (LD, ≥60 years). Preemptive and multiple-organ transplants were excluded. RESULTS: Of the 6,317 renal transplant recipients, 346 (5.5%) received OLD kidneys. Compared with kidneys from SCD of less than 12 hours, OLD kidneys were associated with a greater risk of death-censored graft failure (DCGF; adjusted HR 2.00; 95% confidence interval, 1.32-3.03) and inferior 5-year graft function (estimated glomerular filtration rate of 45 mL/min vs. 56 mL/min), although no increase in 5-year mortality (HR, 1.18; 95% confidence interval, 0.80-1.76). Outcomes for OLD kidneys were also inferior to YLD recipients, although modestly superior to ECD kidneys. Chronic allograft nephropathy was more commonly reported as the cause of DCGF among recipients of OLD kidneys than other donor types. CONCLUSION: Patient survival was equal, but graft outcomes for recipients of OLD kidneys were inferior to those obtained with YLD and SCD kidneys. This study suggests that OLD kidneys should be utilized cautiously, cognizant of the fact that younger recipients may have a life expectancy in excess of the life of the transplanted kidney.

Association between initial and pretransplant dialysis modality and graft and patient outcomes in live- and deceased-donor renal transplant recipients.

The association between pretransplant dialysis modality and transplant outcomes remains inconsistent. The aim of this study is to address the association between alteration in dialysis modality and post-transplant outcomes. Using Australia and New Zealand Dialysis and Transplant Registry, primary live- and deceased-donor renal transplant recipients (RTR) between 1997 and 2009 were examined. Pre-emptive and multiple-organ transplants were excluded. The association between initial and pretransplant dialysis modality and transplant outcomes were examined. Of the 6701 RTR, 18.6% were initiated-maintained on peritoneal dialysis pretransplant (PD-PD), 9.2% were initiated on PD, but maintained on haemodialysis (HD) pretransplant (PD-HD), 63.3% were HD-HD and 8.9% were HD-PD. PD-HD [odds ratio(OR)1.44, 95% CI 1.21,1.72] and HD-HD (OR1.25, 95% CI 1.12,1.41) were associated with a significantly greater risk of slow graft function compared with the overall mean of the groups, whereas a change in initial dialysis modality from HD to pretransplant PD was associated with higher risk of overall graft failure [hazard ratio(HR)1.19, 95% CI 1.04,1.36) and recipient death (HR1.34, 95% CI 1.13,1.59). Our registry analysis suggest that dialysis modality pretransplant may affect transplant outcomes and future studies evaluating patient selection, choice of modality and/or potential interventions in the pre and post-transplant period may have a beneficial effect on post-transplant outcomes.

Human leukocyte antigen mismatches associated with increased risk of rejection, graft failure, and death independent of initial immunosuppression in renal transplant recipients.

Human leukocyte antigen (HLA) mismatches have been shown to adversely affect renal allograft outcomes and remain an important component of the allocation of deceased donor (DD) kidneys. The ongoing importance of HLA mismatches on transplant outcomes in the era of more potent immunosuppression remains debatable. Using Australia and New Zealand Dialysis and Transplant Registry, live and DD renal transplant recipients between 1998 and 2009 were examined. The association between the number of HLA mismatches and HLA-loci mismatches and outcomes were examined. Of the 8036 renal transplant recipients, 59% had between 2 and 4 HLA mismatches. Compared with 0 HLA mismatch, increasing HLA mismatches were associated with a higher risk of graft failure and patient death in the adjusted models. HLA mismatches were associated with an incremental risk of rejection although the relative risk was higher for live donor kidney transplants. Increasing HLA-AB and HLA-DR mismatches were associated with a greater risk of acute rejection, graft failure, death-censored graft failure, and/or death. There was no consistent association between initial immunosuppressive regimen and outcomes. Our results corroborate and extend the previous registry analyses demonstrating that HLA mismatches are associated with poorer transplant outcomes independent of immunosuppression and transplant era.