Long-term Outcome Of Kidney Transplantation Research Articles

Impact of donor kidney weight to recipient body weight ratio on long-term graft outcomes in live donor kidney transplantation

Background: Kidney weight has been suggested as a surrogate marker for nephron numbers and renal function. Small donor kid ney sizes relative to recipient body size is an important contributor to short-term graft renal function, but the impact of size mis matching on long-term graft outcomes remains unknown. This study is aimed to evaluate the impact of the donor kidney weight to recipient body weight ratio (KW/BW) on long-term graft survival in live donor kidney transplantation. Methods: We performed a longitudinal cohort study in 1,397 patients who underwent live donor kidney transplantation between 2000 and 2016 at Severance Hospital. Following cold perfusion and back table surgery, the kidney was weighted on the same electronic weighting scale by the surgeon. Patients were grouped into four groups according to KW/BW quartiles. Results: During a median follow-up period of 127 months, 245 graft losses occurred (172 graft failures and 73 patient deaths). The 10-year death-censored graft survival rates were 86.9% in the lowest quartile, 90.4% in the second quartile, 90.5% in the third quartile, and 92.4% in the highest quartile (P=0.002). Multivariable analysis revealed that the lowest KW/BW (hazard ratio [HR], 2.16; 95% confidence interval [CI], 1.33-3.48; P=0.002) and second lowest KW/BW (HR, 1.69; 95% CI, 1.06-2.70; P=0.029) groups were significantly associated with death-censored graft failure compared with the highest KW/BW group. Patients with lower KW/BW exhibited consistently lower estimated glomerular filtration rates than those with higher KW/BW. Conclusions: Low KW/BW ratio is significantly associated with long-term graft outcome in live donor kidney transplantation.

Long-term Outcomes of Sequential Hematopoietic Stem Cell Transplantation and Kidney Transplantation: Single-center Experience.

Experience with sequential hematopoietic stem cell transplant (HSCT) and kidney transplant (KT) is limited. We conducted a retrospective observational study of adult patients who underwent both HSCT and KT at our center, with a median follow-up of 11 y. In our 54 patients cohort (94% autologous HSCT), 36 (67%) patients received HSCT first followed by KT, while 18 (33%) received KT before HSCT. In both groups, AL amyloidosis represented 50% of hematologic diagnosis. Only 4 patients expired due to hematologic disease relapse (2 patients in each group) and only 3 allografts were lost due to hematologic disease recurrence (HSCT first n = 1 and KT first n = 2). Overall 1, 5, and 10 y death-censored graft survival rates were 94%, 94%, and 94%, respectively, for the HSCT first group and 89%, 89%, and 75%, respectively, for the KT first group. Overall 1, 5, and 10 y patients survival rates were 100%, 97% and 90%, respectively, for the HSCT first group and 100%, 76%, and 63%, respectively, for the KT first group. Our study supports safety of sequential KT and HSCT, with improved overall patient survival compared to recipients of HSCT remaining on dialysis and good long-term kidney allograft outcome.

A noninferiority design for a delayed calcineurin inhibitor substitution trial in kidney transplantation.

Improving long‐term kidney transplant outcomes requires novel treatment strategies, including delayed calcineurin inhibitor (CNI) substitution, tested using informative trial designs. An alternative approach to the usual superiority‐based trial is a noninferiority trial design that tests whether an investigational agent is not unacceptably worse than standard of care. An informative noninferiority design, with biopsy‐proven acute rejection (BPAR) as the endpoint, requires determination of a prespecified, evidence‐based noninferiority margin for BPAR. No such information is available for delayed CNI substitution in kidney transplantation. Herein we analyzed data from recent kidney transplant trials of CNI withdrawal and “real world” CNI‐ based standard of care, containing subjects with well‐documented evidence of immune quiescence at 6 months posttransplant—ideal candidates for delayed CNI substitution. Our analysis indicates an evidence‐based noninferiority margin of 13.8% for the United States Food and Drug Administration's composite definition of BPAR between 6 and 24 months posttransplant. Sample size estimation determined that ~225 randomized subjects would be required to evaluate noninferiority for this primary clinical efficacy endpoint, and superiority for a renal function safety endpoint. Our findings provide the basis for future delayed CNI substitution noninferiority trials, thereby increasing the likelihood they will provide clinically implementable results and achieve regulatory approval.

The relationship between donor-recipient genetic distance and long-term kidney transplant outcome

Background: We set out to quantify shared genetic ancestry between unrelated kidney donor-recipient pairs and test it as a predictor of time to graft failure. Methods: In a homogenous, unrelated, European cohort of deceased-donor kidney transplant pairs (n pairs = 1,808), we calculated, using common genetic variation, shared ancestry at the genic (n loci=40,053) and genomic level. We conducted a sub-analysis focused on transmembrane protein coding genes (n transcripts=8,637) and attempted replication of a previously published nonsynonymous transmembrane mismatch score. Measures of shared genetic ancestry were tested in a survival model against time to death-censored graft failure. Results: Shared ancestry calculated across the human leukocyte antigen (HLA) significantly associated with graft survival in individuals who had a high serological mismatch (n pairs = 186) with those who did not have any HLA mismatches indicating that shared ancestry calculated specific loci can capture known associations with genes impacting graft outcome. None of the other measures of shared ancestry at a genic level, genome-wide scale, transmembrane subset or nonsynonymous transmembrane mismatch score analysis were significant predictors of time to graft failure. Conclusions: In a large unrelated, deceased-donor European ancestry renal transplant cohort, shared donor-recipient genetic ancestry, calculated using common genetic variation, has limited value in predicting transplant outcome both on a genomic scale and at a genic level (other than at the HLA loci).

KIDNEY TRANSPLANTATION IN PEDIATRIC PATIENTS WITH LOWER URINARY TRACT DYSFUNCTION

Introduction: Approximately 30 % of children with end stage renal disease have lower urinary tract dysfunction which can have deleterious influence on kidney transplantation (KTx). The aim of the study is to present single center long-term outcome of kidney transplantation in pediatric recipients with bladder dysfunction. Material and Method: Between 2000 and 2018 there were 752 KTx performed in our center. Within them there were 545 KTx into normal bladder and 207 KTx in patients with bladder dysfunction (130 KTx into native dysfunctional bladder and 77 KTx into urinary diversion). Surgical complications rate, urinary tract infections rate and graft survival in groups of patients transplanted into normal bladder, dysfunctional bladder and urinary diversion were compared. Results: Surgical complications were higher in group of recipients with dysfunctional bladder and urinary diversion in comparison to recipients with normal bladder (33% vs 28% vs 20%). Urinary tract infecions rate was significantly higher in groups of recipients with dysfunctional bladder and urinary diversion in comparison to recipients with normal bladder (57% vs 59% vs 18%). Graft loss was 18.5 % versus 9 % versus 17.9% in groups of recipients with dysfunctional bladder, urinary diversion, and normal bladder, respectively. The major cause of graft failure in each group was chronic rejection. Conclusions: Kidney transplantation in children with lower urinary tract dysfunction and end-stage renal failure offers good long-term results. Urinary tract infections are the most common complications in these patients. The major cause of graft loss is chronic rejecion.

The relationship between donor-recipient genetic distance and long-term kidney transplant outcome.

Background: We set out to quantify shared genetic ancestry between unrelated kidney donor-recipient pairs and test it as a predictor of time to graft failure. Methods: In a homogenous, unrelated, European cohort of deceased-donor kidney transplant pairs (n pairs = 1,808), we calculated, using common genetic variation, shared ancestry at the genic (n loci=40,053) and genomic level. We conducted a sub-analysis focused on transmembrane protein coding genes (n transcripts=8,637) and attempted replication of a previously published nonsynonymous transmembrane mismatch score. Measures of shared genetic ancestry were tested in a survival model against time to death-censored graft failure. Results: Shared ancestry calculated across the human leukocyte antigen (HLA) significantly associated with graft survival in individuals who had a high serological mismatch (n pairs = 186) with those who did not have any HLA mismatches indicating that shared ancestry calculated specific loci can capture known associations with genes impacting graft outcome. None of the other measures of shared ancestry at a genic level, genome-wide scale, transmembrane subset or nonsynonymous transmembrane mismatch score analysis were significant predictors of time to graft failure. Conclusions: In a large unrelated, deceased-donor European ancestry renal transplant cohort, shared donor-recipient genetic ancestry, calculated using common genetic variation, has limited value in predicting transplant outcome both on a genomic scale and at a genic level (other than at the HLA loci).

A study from The Mayo Clinic evaluated long-term outcomes of kidney transplantation in patients with immunoglobulin light chain amyloidosis

Longer survival using modern therapies has increased the number of patients with immunoglobulin light-chain amyloidosis receiving kidney transplantation. We evaluated 60 patients with immunoglobulin light chain amyloidosis who underwent kidney transplantation based on their hematologic response for outcomes of death, graft failure, and complications. Patient hematologic responses (light-chain in blood or urine) prior to kidney transplantation were three patients had no response, five had a partial response, six had a very good partial response, 37 had a complete response, and nine were treatment-naive patients (never treated for this disorder). After transplantation, seven of nine treatment-naive patients achieved a complete response. The median follow-up for the entire transplant cohort was 61 months. The estimated median overall survival from the time of kidney transplantation was 123 months for the entire group. Median overall survival was not reached for the very good partial response plus complete response groups, it was 47 months for no response plus partial response groups, and 117 months for the treatment-naive group (all significantly different). Median overall survival of very good partial response was 81 months, while the median was not reached in the complete response group (no significant difference). The time to amyloid recurrence was significantly longer in complete response compared to very good partial response (median 181 vs 81 months). Death-censored graft survival at one- and five-years was 98.3%, and 95.8%, respectively for all groups. Of the 60 patients, three had allograft failure, 19 died with a functioning graft, and 13 had an amyloid recurrence. Thus, outcomes after kidney transplant in patients with immunoglobulin light-chain amyloidosis seem acceptable if a very good partial response or complete response is achieved either before or after transplantation.

Long-term outcome of kidney transplant by using restored kidney grafts after tumour ex vivo excision - a prospective study.

The aim of this study is to report long-term outcomes of kidney transplantation by using the kidney graft after a small tumour ex vivo excision. A structured programme was established to use the restored kidney graft from urological referral after radical nephrectomy. The criteria were defined as tumour size≤3cm, margin clear on frozen section and recipients aged≥60years or those on the urgent list for transplantation as a result of imminent lack of dialysis access. The recipients were followed up regularly for surveillance of tumour recurrence. Between February 2007 and February 2018, 28 recipients had kidney transplantation by using the restored kidney grafts. The tumour size was 2.6±0.7cm. The follow-up was median 7years without evidence of tumour recurrence. The patient and graft survival was satisfactory. Kidney transplantation by using restored kidneys after a small tumour excision is a novel source for selected recipients. The long-term patient and graft survival is satisfactory. Although there is a risk of tumour recurrence, it is rare event. Together with literature review, we would support use of kidney graft after a small tumour excision for selected recipients.

Long-term Results of Kidney Transplantation: Analysis of Selected Factors

BackgroundKidney transplantation is considered the most effective method of treating patients with end-stage renal disease. Despite continuous improvement of short-term outcomes, progression of long-term results is minimal. MethodsThe retrospective cohort study included 45 patients (24 women and 21 men). Terms of qualification for the study were time after kidney transplantation: minimum 25 years and satisfactory graft function. Medical documentation was analyzed from which specific laboratory parameters, information about transplantation procedure, and clinical data were selected. ResultsThe average time since transplantation in the study group was 30 years. Chronic glomerulonephritis was a major cause that led to end-stage renal disease among the study group. The average age of the respondents was 62 years ± 8.5 years. The average time patients had hemodialysis procedures lasted 30 months. Current estimated glomerular filtration rate (eGFR) concentration was correlated with level of creatinine measured 10 years after transplantation and current hemoglobin level (r = 0.447, P = .003, r = 0.586 P < .001). No statistically significant differences were noted in the eGFR level, depending on the current age of recipients (t = 0.511, P = .612), total ischemia time (Z = 0.334, P = .729), or hemodialysis duration (t = -1.944, P = .058). ConclusionsThe presented study emphasizes the impact of graft function on hemoglobin level and the predictive role of the creatinine measured 10 years after transplantation for long-term renal outcomes. Continuing research will enrich the knowledge about long-term care and treatment for patients after kidney transplantation.

Long-term outcomes of adult-size and size-matched kidney transplants in small pediatric recipients

Adult-size kidneys are usually used for kidney transplantation in small pediatric recipients, but the influence of graft size in transplant outcome remains controversial. Our aim is to compare long-term transplant outcomes of using adult-size and size-matched kidneys in small pediatric recipients. Since 1999, 61 of 226 kidney transplants were achieved in recipients weighing <20kg with 5 years of follow-up. Patients were analyzed according to the graft size received: (group-A) adult-size (n=32), (group-B) size-matched (n=29). Kidney size (KS), glomerular filtration rate (GFR) proteinuria and rejection were compared between groups at transplant time (T0), at one (T1), two (T2), five years (T5), and at the end of the follow-up (TF) (median follow-up 8.47(0-17) years). Graft and patient survival were determined and compared between groups. Mean KS was significantly different between groups at T0 (A:11.3±1.1cm, B:8.8±0.9cm), (pT0<0.01), group-B evidenced graft growth, reaching similar sizes to group-A at T5 (A:11.7±1cm, B:11.2±1cm; pT5=0.13) and TF (A:12.2±1.1cm, B:12.4±1.2cm; pTF=0.63), and group-A had a slight graft growth at TF (pT0-TF<0.01). Mean Schwartz-GFR at T0 was greater in group-A (138±33ml/min/1.73m2) than group-B (109±34mL/min/1.73m2) (pT0=0.01); during follow-up, it evidenced a reduction in group-A (T5:90±27, TF:71±24mL/min/1.73m2; pT0-T5<0.01; pT0-TF<0.01), meanwhile in group-B was stable until T5 (104±33mL/min/1.73m2; pT0-T5=0.54), declining at TF (76±31mL/min/1.73m2; pT0-TF<0.01); with no significant differences at T1, T2, T5, and TF between groups. Similar results were observed in mean Filler-GFR of both groups (Figure). Proteinuria and episodes of rejection were no significantly different between groups during the follow-up (p>0.01; p=0.23). Graft and patient survival at 5 and 10 years did not show significant differences (p=0.45; p=0.10). Despite the initial kidney size difference between groups, we have demonstrated that they tended to the same size during the follow-up. Adult-size kidneys presented a slight size increase in the long-term, suggesting that they have some growth potential in small recipients, in contrast to previous literature. Mean GFR between groups showed no significant differences in the long-term, suggesting that optimal graft perfusion and function can be achieved despite the size of the graft. We have demonstrated that there were no significant differences in long-term graft and patient survival; this results were similar to the most recent literature about this topic and different from the 90-2000s decades literature. Adult-size kidneys may be transplanted to small recipients (<20kg) with comparable outcomes to size-matched kidneys, with no significant differences in long-term KS, GFR, proteinuria, rejection, graft or patient survival.

A Retrospective Cohort Study of the Effect of Gout on Mortality Among Patients with a History of Kidney Transplantation.

BackgroundKidney transplantation is associated with increased prevalence of gout. However, evidence of the effect of gout on long-term kidney transplantation outcomes is mixed. This study examined mortality risk among patients with a history of kidney transplantation with vs. without gout.Material/MethodsA retrospective study was conducted using Medicare Fee-for-Service administrative claims of patients with a history of kidney transplantation. Cox proportional hazards models determined the effect of gout on all-cause mortality, controlling for confounders, including comorbid mortality risk, via the Charlson Comorbidity Index. Because the relationships between gout and components of the Charlson Comorbidity Index are also debated, 3 different model assumptions were used: 1) gout shares a common cause with these comorbidities, 2) gout is upstream of these comorbidities, 3) the effect of gout on mortality is modified by these comorbidities.ResultsGout increased the risk of all-cause mortality in the unadjusted model (hazard ratio: 1.44, 95% CI 1.27–1.63) and after adjustment for demographics and transplant vintage (hazard ratio: 1.16, 95% CI 1.02–1.32). Gout was not a significant risk after adjustment for baseline Charlson Comorbidity Index (hazard ratio: 1.03, 95% CI 0.90–1.17). Gout was associated with greater mortality among patients without baseline comorbidities (Charlson Comorbidity Index=0; hazard ratio: 3.48, 95% CI 1.27–9.57) in the stratified model.ConclusionsAmong patients with a history of kidney transplantation, gout did not have an independent effect on all-cause mortality. However, gout was a predictor of mortality among patients with no comorbidities, suggesting that gout is an early warning sign of poor health in kidney transplantation patients.

Long-Term Redistribution of Peripheral Lymphocyte Subpopulations after Switching from Calcineurin to mTOR Inhibitors in Kidney Transplant Recipients.

Classical immunosuppression based on steroids, calcineurin inhibitors, and mycophenolate results in several unwanted effects and unsatisfactory long-term outcomes in kidney transplantation (KT). New immunosuppressors search for fewer adverse events and increased graft survival but may have a distinct impact on graft function and immunological biomarkers according to their mechanism of action. This prospective study evaluates the immunological effect of tacrolimus to serine/threonine protein kinase mechanistic target of rapamycin inhibitors (mTORi) conversion in 29 KT recipients compared with 16 controls maintained on tacrolimus. We evaluated renal function, human leukocyte antigen (HLA) antibodies and peripheral blood lymphocyte subsets at inclusion and at 3, 12, and 24 months later. Twenty immunophenotyped healthy subjects served as reference. Renal function remained stable in both groups with no significant change in proteinuria. Two patients in the mTORi group developed HLA donor-specific antibodies and none in the control group (7% vs. 0%, p = 0.53). Both groups showed a progressive increase in regulatory T cells, more prominent in patients converted to mTORi within the first 18 months post-KT (p < 0.001). All patients showed a decrease in naïve B cells (p < 0.001), excepting those converted to mTORi without receiving steroids (p = 0.31). Transitional B cells significantly decreased in mTORi patients (p < 0.001), independently of concomitant steroid treatment. Finally, CD56bright and CD94/NK group 2 member A receptor positive (NKG2A+) Natural Killer (NK) cell subsets increased in mTORi- compared to tacrolimus-treated patients (both p < 0.001). Patients switched to mTORi displayed a significant redistribution of peripheral blood lymphocyte subpopulations proposed to be associated with graft outcomes. The administration of steroids modified some of these changes.

Short- and Long-term Outcomes of Kidney Transplants From Very Small (≤15 kg) Pediatric Donors With Acute Kidney Injury.

Kidneys from small deceased pediatric donors with acute kidney injury (AKI) are commonly discarded owing to transplant centers' concerns regarding potentially inferior short- and long-term posttransplant outcomes. We retrospectively analyzed our center's en bloc kidney transplants performed from November 2007 to January 2015 from donors ≤15 kg into adult recipients (≥18 y). We pair-matched grafts from 27 consecutive donors with AKI versus 27 without AKI for donor weight, donation after circulatory death status, and preservation time. For AKI versus non-AKI donors, median weight was 7.5 versus 7.1 kg; terminal creatinine was 1.7 (range, 1.1-3.3) versus 0.3 mg/dL (0.1-0.9). Early graft loss rate from thrombosis or primary nonfunction was 11% for both groups. Delayed graft function rate was higher for AKI (52%) versus non-AKI (15%) grafts (P = 0.004). Median estimated glomerular filtration rate was lower for AKI recipients only at 1 and 3 months (P < 0.03). Graft survival (death-censored) at 8 years was 78% for AKI versus 77% for non-AKI grafts. Late proteinuria rates for AKI versus non-AKI recipients with >4 years follow-up were not significantly different. Small pediatric donor AKI impacted early posttransplant kidney graft function, but did not increase risk for early graft loss and decreased long-term function. The presently high nonutilization rates for en bloc kidney grafts from very small pediatric donors with AKI appear therefore unjustified. Based on the outcomes of the present study, we infer that the reluctance to transplant single kidneys from larger pediatric donors with AKI lacks a rational basis as well. Our findings warrant further prospective study and confirmation in larger study cohorts.

SUN-345 Long-term outcome of kidney transplantation among Iranian children: A systematic review and meta-analysis

SUN-345 Long-term outcome of kidney transplantation among Iranian children: A systematic review and meta-analysis

Rethinking clinical endpoints in kidney transplant trials.

Clinical trials testing novel kidney transplant therapies are challenged by low rates of long-term clinical outcomes such as death and graft loss. Herein, we critically review traditional and more recent strategies to expedite new therapies by minimizing sample size and follow-up duration using surrogates (alone or in the context of composite endpoints), or using different clinical endpoints. Multiple surrogate endpoints are increasingly important for organ transplantation trial design: glomerular filtration rate slope, albuminuria, donor-specific alloantibodies, and histological score at graft protocol biopsies. However, surrogate endpoint use is limited by bias when data are missing. Hierarchical multiple primary endpoints - that are successfully used in other settings and frequently utilize surrogate endpoints - have not yet been integrated into kidney transplant studies. New clinical endpoints, focusing on treatment safety and patient quality of life have been recently standardized and should be reported regardless of the primary endpoint of any randomized controlled trial. Defining surrogates, standards for outcome reporting, and statistical strategies to appropriately analyze them are critical to effectively testing and implementing novel therapeutic strategies to improve long-term clinical outcomes in kidney transplantation.

Clinical and pathological features of thrombotic microangiopathy influencing long-term kidney transplant outcomes.

Thrombotic microangiopathy (TMA) in post-transplant setting has heterogeneous clinical manifestations. We retrospectively studied data of 89 patients with post-transplant TMA, which was characterized by thrombi in at least one glomerulus and/or arteriole. Systemic TMA was defined by thrombocytopenia and microangiopathic anemia and early onset TMA, when occurred less than 90 days post transplant. The cumulative incidence was 0.93%. The majority of the recipients were young (mean age 39 years), female (52%) and Caucasian (48%) with primary kidney disease of unknown etiology (37%). Early TMA occurred in 51% of the patients and systemic TMA, in 25%. Underlying precipitating factors were: infection (54%), acute rejection (34%), calcineurin inhibitor toxicity (13%) and pregnancy (3%). 18% of the patients had several triggers. Glomerular TMA was observed in 50% of the biopsies and endothelial cell activation, in 61%. The 1-year patient survival was 97% and corresponding graft survival, 66%. Allograft survival was inferior when acute antibody mediated rejection (ABMR) occurred (with 41%; without 70%, p = 0.01), however no differences were determined by hemolysis, time of onset, thrombi location or endothelial cell activation. Our results suggest that post-transplant TMA is a rare but severe condition, regardless of its clinical and histological presentation, mainly when associated to ABMR.

Physical activity and renal function in the Italian kidney transplant population

Background The well-documented benefits of physical activity (PA) are still poorly characterized in long-term kidney transplant outcome. This study analyzed the impact over a 10-year follow-up of PA on graft function in Italian kidney transplant recipients (KTRs). Methods Since 2002, the Italian Transplant-Information-System collected donor and recipient baseline and transplant-related parameters in KTRs. In 2015, ‘penchant for PA’ (PA ≥ 30-min, 5 times/week) was added. Stable patients aged ≥18 years at the time of first-transplantation were eligible. KTRs with at least 10-year follow-up were also analyzed. Mixed-effect regression models were used to compare eGFR changes over time in active versus non-active patients. Results PA information was available for 6,055 KTRs (active 51.6%, non-active 48.4%). Lower penchant for PA was found in overweight and obese patients (OR = 0.84; OR = 0.48, respectively), in those with longer dialysis vintage (OR = 0.98 every year of dialysis), and older age at transplant. Male subjects showed greater penchant for PA (OR = 1.25). A slower decline of eGFR over time was observed in active KTRs compared to non-active, and this finding was confirmed in the subgroup with at least 10-year follow-up (n = 2,060). After applying the propensity score matching to reduce confounding factors, mixed-effect regression models corroborated such better long-term trend of graft function preservation in active KTRs. Conclusions Penchant for PA is more frequent among male and younger KTRs. Moreover, in our group of Italian KTRs, active patients revealed higher eGFR values and preserved kidney function over time, up to 10-years of follow-up.

Impact of One-Year Serum Creatinine on Long-term Renal Graft Survival in a Living-Related Renal Transplant Program.

This study was carried out to determine the impact of one-year posttransplant serum creatinine (SCr) levels on the long-term outcomes of living-related donor kidney transplants. A retrospective cohort study included 773 adult living-related renal transplant recipients from 2010 to 2012, with a minimum follow-up period of five years. Demographics and posttransplantation follow-up data including immunosuppression regimens, rejection episodes, and survival rates were evaluated. Patients were divided into four cohorts (G1, G2, G3, and G4 based on SCr at the end of the 1st year: G1, SCr <88.4 μ mol/L; G2, 88.5≤ SCr ≤ 132.6 μmol/L; G3, 132.7≤ SCr ≤176.8 mol/L; and G4, SCr ≥176.9 μ mol/L). Comparisons between the groups used the Chi-square test for qualitative parameters and analysis of variance for continuous variables. Five-year graft survival for G1 was 98% as compared to 76% in G4 (P <0.001). Recipients of G4 encountered more acute rejection episodes in 21% of the cases as compared to 7.3% in G1 (P = 0.001). Donors were older in G4 (42.07 ± 10.4 years) as compared to G1 (30.1 ± 8.5 years) (P = 0.001). A third of the donors in G1 were HLA identical as compared to 7% in G4. Prediction of long-term graft survival is possible by the SCr level at one year post transplant. This can be of great importance, especially to identify those patients who require close monitoring in follow-up. Donor age, HLA, and acute rejection impact SCr at one year and hence graft outcome.

Practical Considerations for APOL1 Genotyping in the Living Kidney Donor Evaluation.

Association between the apolipoprotein L1 gene (APOL1) and nephropathy has altered the epidemiology of chronic kidney disease. In addition, donor APOL1 genotypes play important roles in the time to allograft failure in kidneys transplanted from deceased donors and the safety of living kidney donation. This article reviews genetic testing for inherited kidney disease in living kidney donors to improve donor safety. APOL1 genotyping in donors with recent African ancestry is considered. Based on current data, transplant physicians should discuss APOL1 genotyping with potential living kidney donors self-reporting recent African ancestry. Until results from APOL1 Long-term Kidney Transplant Outcomes Network ancillary studies are available, we present practical approaches from our experience for considering APOL1 genotyping in the living donor evaluation. Transplant physicians should inform potential living kidney donors at risk for APOL1-associated nephropathy about the gene and possibility of genetic testing early in the donor evaluation, well before scheduling the donor nephrectomy. Transplant programs must weigh risks of performing a donor nephrectomy in those with 2 APOL1 renal risk variants (high-risk genotypes), particularly younger individuals. Our program counsels kidney donors with APOL1 high-risk genotypes in the same fashion as with risk genotypes in other nephropathy genes. Because most African American kidney donor candidates lacking hypertension, proteinuria and reduced kidney function after workup will not possess APOL1 high-risk genotypes, genetic testing is unlikely to markedly increase donor declines and may reassure donors with regard to their long-term kidney outcomes, potentially increasing the number of African American donors.

Long-Term Kidney Transplant Outcomes: Role of Prolonged-Release Tacrolimus

Tacrolimus has significantly improved outcomes for kidney transplant patients and remains the cornerstone of immunosuppressive therapy. While improvements in short-term outcomes in transplantation have been achieved in recent years, maintaining long-term graft survival remains a challenge in kidney transplantation.Minimizing risk factors for poor long-term kidney graft function and survival, and modifying tacrolimus regimens in the early and maintenance phases post-transplantation are essential to maintain long-term kidney transplant outcomes. Tacrolimus has a narrow therapeutic window, resulting in a tightly defined range of optimal drug exposure. Underimmunosuppression is associated with long-term risks, such as the development of donor-specific antibodies and antibody-mediated rejection, with a high possibility of a decline in kidney function and progression to graft failure. Conversely, prolonged overimmunosuppression carries a risk of drug-related adverse events.This review provides an overview of the differences in the formulation, delivery, and pharmacokinetic profiles between immediate- and prolonged-release tacrolimus and evaluates the effect of prolonged-release tacrolimus on the risk factors for poor outcomes in kidney transplantation. Recent evidence is used to provide guidance on target tacrolimus trough levels in the early and maintenance phases post-transplantation, with a view to improving long-term kidney graft function.