Search

Introduction: Previous studies show heterogeneity when applying estimated glomerular filtration (eGFR) equations to kidney transplant recipients (KTRs). However, research on the impact of transplantation-related characteristics on eGFR equations using creatinine (eGFRcr) compared to cystatin C (eGFRcys) is scarce., Methods: We conducted a comprehensive analysis with three eGFRcr equations (Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) 2009, European Kidney Function Consortium (EKFC) 2021, kidney recipient specific-glomerular filtration rate KRS-GFR) 2023), comparing them to two eGFRcys (CKD-EPI 2012 and EKFC 2023) in 596 KTRs. Bland-Altman plots demonstrated relative differences according to different eGFR-stages. Multivariable logistic regression identified transplantation-related characteristics independently associated with smaller or greater differences between eGFRcr and eGFRcys equations., Results: 94.3% of the cohort were White individuals. Median eGFR differed as much as 9 ml/min/1.73 m 2 between equations. The median relative differences (Q2) were greater (more negative) when comparing the eGFRcr equations to eGFRcys CKD-EPI 2012, than when comparing them to eGFRcys EKFC 2023 ( P  < .001). Better average eGFR was associated with smaller mean relative differences in all comparisons but eGFRcr CKD-EPI 2009 with eGFR EKFC 2023 and eGFRcr EKFC 2021 with eGFRcys EKFC 2023. Living kidney donation and belatacept use were independent factors associated with a smaller difference (≥Q3) between eGFRcr and eGFRcys equations, while prednisone use or higher HbA1c were independently associated with a greater difference (≤Q1) between equations., Conclusion: Different eGFR-stages, donor, or recipient characteristics, along with immunosuppression such as belatacept or prednisone, contribute to differences between eGFRcr and eGFRcys. These effects need to be considered in the clinical management of KTRs., Competing Interests: All authors had no competing interests to declare., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

Background and Hypothesis: Isolated Tubulitis, Borderline Changes, and Isolated Arteritis suspicious for histologic T cell-mediated rejection (hTCMR) remain findings of uncertain significance. Although the Molecular Microscope Diagnostics System (MMDx) has not been trained on those lesions, it was suggested that MMDx might reclassify a subgroup to molecular TCMR (mTCMR)., Methods: In this single-center cohort of 326 consecutive, unselected kidney allograft biopsies assessed by histology and MMDx, we analyzed 249 cases with Isolated Tubulitis (i0, t1-3, v0; n=101), Borderline Changes (according to Banff 2022, v0; n=9), Isolated Arteritis (no borderline, v1; n=37), No Inflammation (i0, t0, v0; n=67) and a Positive Control Cohort (hTCMR, n=27; Mixed histologic Rejection, n=8; both according to Banff 2022; total n=35). The first three groups were summarized as TCMR-Suspicion (n=147). Subcategorization included the presence and absence of microvascular inflammation (MVI; g+ptc≥2). Molecular rejection rates and differentiation were investigated., Results: Molecular rejection rates were 37/147 cases (25.2%; 32 with MVI) in TCMR-Suspicion, 6/67 (9%; 4 with MVI) in No Inflammation and 30/35 (85.7%; 19 with MVI) in the Positive Control Cohort. Molecular antibody-mediated rejection (mAMR) was present in 39/73 (53.4%) of cases. The presence of donor-specific antibodies (DSA) at the time of the biopsy was high (127/249, 51%). Only 3 mAMR/TCMR and no pure mTCMR cases were detected in TCMR-Suspicion and No Inflammation, compared to 12 mAMR/TCMR and 10 mTCMR cases in the Positive Control Cohort (p<0.001). Even though the TCMR-specific molecular (Classifier) score differentiated between TCMR-Suspicion and No Inflammation (p=0.005), rejection phenotype scores (R2 and R3) did not (p=0.157 and 0.121)., Conclusions: MMDx did not identify pure mTCMR among Isolated Tubulitis, Borderline Changes, or Isolated Arteritis, likely due to low sensitivity for TCMR-lesions. However, it identified mAMR or mAMR/TCMR, especially in cases with MVI. Subthreshold findings remain to be further studied., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

Background: Despite substantial improvements in short-term kidney allograft survival, median long-term survival remains at a standstill. It is unclear whether and to what extent a transplant centre's post-transplant care influences long-term outcomes., Methods: We retrospectively analysed 501 single kidney transplant recipients (KTRs) who underwent transplantation between 2009 and 2018 and did not develop rejection or de novo donor-specific antibodies (dnDSA) within the first post-transplant year. After that, KTRs were either followed exclusively every 3 months by the transplant centre ( n  = 197) or every 3 months by local nephrologists ( n  = 304) with only yearly follow-up by the transplant centre. We analysed kidney allograft outcomes regarding estimated glomerular filtration rate (eGFR) decline, proteinuria, development of dnDSA and rejection., Results: No differences between the two groups were observed in the baseline characteristics and the characteristics at the end of the first post-transplant year ( P  > .05). KTRs followed by local nephrologists were comparable to KTRs followed by the transplant centre concerning patient survival ( P  = .541), kidney allograft survival ( P  = .385), eGFR decline ( P  = .488), progression of proteinuria ( P  > .05), the development of dnDSA ( P  = .335) and T-cell-mediated rejection ( P  = .480). KTRs followed by the transplant centre were more likely to undergo indication biopsies in case of allograft dysfunction and dnDSA ( P  < .001). Antibody-mediated rejection was diagnosed earlier and more frequently ( P  = .059), recurrent glomerulonephritis was diagnosed earlier and more frequently ( P  = .026) and immunosuppression was modified earlier and more frequently in response to histological findings ( P  = .038)., Conclusions: Our findings suggest that close collaboration between local nephrologists and the transplant centre ensures good allograft outcomes independent of the caregiver. Greater biopsy activity in the transplant centre allows for earlier diagnosis of allograft dysfunction as the basis for novel treatment options., (© The Author(s) 2022. Published by Oxford University Press on behalf of the ERA.)

Background: Donation after circulatory death (DCD) represents up to 40% of used kidney grafts. While studies have shown similar outcomes compared with donation after brain death (DBD) in the short term and mid-term, no data on long-term outcomes exist., Methods: We retrospectively analysed patients transplanted at our institution between January 1985 and March 2000. All DCD recipients were matched one-to-one with patients transplanted with DBD grafts during this period according to sex, age and year of transplantation and followed up until December 2020. During this period, 1133 kidney transplantations were performed, of which 122 were with a DCD graft., Results: The median graft survival after 35 years of follow-up was 23 years [277 months {95% confidence interval (CI) 182-372}] in DBD recipients and 24.5 years [289 months (95% CI 245-333)] in DCD recipients (P = 0.65; hazard ratio 0.91). Delayed graft function occurred in 47 patients in the DCD group compared with 23 in the DBD group (P < 0.001), albeit without a significant long-term outcome difference in graft or patient survival. We could not show any difference in graft function in terms of creatinine levels (133 versus 119 µmol/L), proteinuria (370 versus 240 mg/24 h) and glomerular filtration rate slope (-0.6 versus -0.3 mL/min/year) between the two groups for graft survival >20 years., Conclusions: This is the first study to show similar graft survival and function in DCD kidneys compared with DBD kidneys after 35 years of follow-up. DCD grafts are a valuable resource and can be utilized in the same way as DBD grafts., (© The Author(s) 2021. Published by Oxford University Press on behalf of the ERA.)

Background: Cancer risk is increased by 2- to 4-fold in kidney transplant recipients (KTRs) compared with the general population. Little attention, however, has been given to KTRs with ultra long-term survival >20 years., Methods: We studied 293 of 1241 KTRs (23.6%), transplanted between 1981 and 1999, who showed kidney allograft survival >20 years. These long-term survivors were analysed for cancer development, cancer type, cancer-associated risk factors and patient and allograft outcomes., Results: By 10, 20 and 30 years post-transplantation, these long-term KTRs showed a cancer rate of 4.4%, 14.6% and 33.2%, and a non-melanoma skin cancer (NMSC) rate of 10.3%, 33.5% and 76.8%, respectively. By recipients' ages of 40, 60 and 80 years, KTRs showed a cancer rate of 3.4%, 14.5% 55.2%, and a NMSC rate of 1.7%, 31.6% and 85.2%, respectively. By 30 years post-transplantation, post-transplant lymphoproliferative disorder (PTLD) showed the highest incidence of 8.5%, followed by renal cell carcinoma (RCC) with 5.1%. Risk factors associated with the development of cancer were only recipient age (P = 0.016). Smoking history was associated with the risk of lung cancer (P = 0.018). Risk factors related to the development of NMSC included recipient age (P = 0.001) and thiazide diuretics (P = 0.001). Cancer increased the risk of death by 2.4-fold (P = 0.002), and PTLD increased the risk of kidney allograft loss by 6.5-fold (P = 0.001). No differences were observed concerning the development of donor-specific antibodies (P > 0.05)., Conclusions: In long-term KTRs, cancer is a leading cause of death. PTLD remains the most common cancer type followed by RCC. These results emphasize the need for focused long-term cancer surveillance protocols., (© The Author(s) 2022. Published by Oxford University Press on behalf of the ERA.)

Background: Novel messenger RNA (mRNA)-based vaccines play an important role in current vaccination campaigns against SARS-CoV-2. They are highly efficacious and generally well tolerated. Vaccination in patients with immune-mediated kidney diseases is recommended. A number of cases with de novo or relapsing glomerulonephritis shortly after vaccine application have been reported, some of which presented with gross haematuria., Methods: We collected 10 cases of macrohaematuria following mRNA-based severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination at our tertiary care institution and referring centres. Additionally, we pooled all 25 published cases from the literature with ours to analyse their clinical characteristics., Results: Most macrohaematuria episodes (72.2%) began within 2 days after vaccination, the majority after the second dose. In some individuals, repeated episodes occurred after subsequent doses of the same vaccine. A total of 65.7% of patients never had macrohaematuria before. A total of 45.7% were known to suffer from immunoglobulin A nephropathy (IgAN); the rest had no prior renal diagnosis. IgAN was the most frequent new diagnosis, but anti-neutrophil cytoplasmic antibody-associated vasculitis and anti-glomerular basement membrane disease were also identified. Acute kidney injury (AKI) occurred in 28.6% of patients, with an increase in serum creatinine not meeting Kidney Disease: Improving Global Outcomes AKI criteria in 28.6%. Treatment ranged from conservative management, renin-angiotensin-aldosterone system inhibitors, steroids and cyclophosphamide to plasmapheresis. While renal outcomes were mainly favourable in isolated IgAN, they were poor in patients with additional or isolated small vessel vasculitis., Conclusion: Awareness of gross haematuria after SARS-CoV-2 vaccination is important. Close follow-up and additional work up, particularly in individuals without known underlying kidney disease or worsening renal function, is essential. For patients with vaccine-associated macrohaematuria, an alternative vaccine class might be considered for subsequent vaccinations., (© The Author(s) 2021. Published by Oxford University Press on behalf of the ERA.)

Background: Long-term outcomes of the Eurotransplant Senior Program (ESP) are urgently needed to improve selection criteria and allocation policies in the elderly., Methods: We analysed patient and allograft outcomes of 244 ESP-kidney transplant recipients (KTRs) between 1999 and 2019 and assessed quality of living compared with 82 ESP-waitlisted dialysis patients using standardized short form-8., Results: We observed 1-, 5- and 10-year patient survival of 91.7, 66.3 and 38.0%, respectively. Mortality risk factors included male gender (P = 0.006) and T-cell-mediated rejection (P < 0.001). Median patient survival of male ESP-KTRs was 80 versus 131 months for female ESP-KTRs (P = 0.006). 1-, 5- and 10-year death-censored allograft survival was 93.3, 82.6 and 70.4%. Risk factors included high body mass index (P < 0.001) and T-cell-mediated rejection (P < 0.001). After re-initiation of dialysis median patient survival was 58 months. Change of estimated glomerular filtration rate showed a mean decline of 2.3 and 6.8 mL/min at 5 and 10 years. Median physical and mental component scores of ESP-KTRs were 40.2 and 48.3, significantly higher compared with dialysis patients (P < 0.05). Of ESP-KTRs, 97.5% who underwent transplantation would again do so., Conclusions: Long-term outcomes of ESP-KTRs ultimately support the effectiveness of an age-matched allocation system. Our data suggest that the survival advantage of women is maintained after kidney transplantation and calls for gender-specific care., (© The Author(s) 2019. Published by Oxford University Press on behalf of ERA-EDTA.)

Background: Kidney transplant recipients (KTRs) are at increased risk of avascular necrosis (AVN) due to bone disorder, steroid use and common comorbidities. However, knowledge on risk factors and outcomes of AVN among KTRs in the modern era of immunosuppression remains scarce., Methods: We analysed 765 KTRs between 2001 and 2013 for AVN. Cases of symptomatic AVN were diagnosed by hip X-ray, radioisotope bone scan or magnetic resonance imaging. We evaluated risk factors and clinical characteristics of AVN., Results: KTRs showed a constant incidence rate of AVN of 4.1% at 10 years after transplantation. The use of cyclosporine compared with tacrolimus was identified as an independent risk factor, with a rate of 8.0% compared with 2.7% at 10 years (P < 0.01). In addition, male gender was independently associated with AVN (P = 0.047). Eighty-three per cent of AVN cases were of the femoral head and treated operatively. None of the operated KTRs experienced complications in the long term. Thirty-three per cent of KTRs had bilateral AVN. Ninety-two per cent of KTRs showed AVN at the allograft side., Conclusions: The decreasing incidence of AVN may be attributed to the replacement of cyclosporine by tacrolimus over the last decade. Our data raise the hypothesis of an ischaemic steal syndrome due to the allograft kidney impacting AVN at the allograft side.

Background: The number of kidney transplant recipients (KTRs) being waitlisted for a subsequent transplantation has disproportionately increased to almost 25%. Evidence for the optimal management of the failed allograft, however, remains inconsistent., Methods: We studied 111 KTRs who underwent their second kidney transplantation from 1998 to 2015. In 51/111 KTRs (46%) the failed allograft was removed and in 60/111 (54%) the failed allograft was retained. KTRs with primary non-function and allograft loss <12  months of the first failed allograft were excluded from analysis. Samples were collected before transplantation and at  1  month posttransplantation and donor-reactive T cells were measured using an interferon-γ enzyme-linked immunosorbent spot assay., Results: KTRs with the previous allograft removed showed significantly higher rates of acute cellular rejection compared with KTRs with the previous allograft retained [27/51 KTRs (53%) versus 18/60 KTRs (30%); P = 0.019]. KTRs with the previous allograft removed showed significantly inferior death-censored allograft survival compared with KTRs with the previous allograft retained (P = 0.022). Here, KTRs with the previous allograft removed showed significantly higher donor-reactive T cells pretransplantation compared with KTRs with the previous allograft retained (P = 0.012). Interestingly, no differences were observed for the presence of panel reactive antibodies and for the development of de novo donor-specific antibodies., Conclusions: Our data suggest higher cellular presensitization among KTRs with the previous allograft removed, which is associated with higher rates of acute cellular rejection and inferior allograft survival. Immunological mechanisms that may account for these differences may include prolonged maintenance immunosuppression to save urine output in KTRs with the first kidney allograft retained and cellular presensitization after withdrawal of maintenance immunosuppression, which lead to allograft rejection and ultimately to allograft nephrectomy.

Background: It has been demonstrated that low birth weight gives rise to a reduction in nephron number with increased risks for hypertension and renal disease. Its impact on renal function in kidney donors, however, has not been addressed., Methods: To investigate the impact of birth weight, kidney weight, kidney volume and estimated nephron number on kidney function, we collected data from 91 living kidney donors before nephrectomy, at +12, +36 and +60 months after nephrectomy., Results: Birth weight showed a positive correlation with estimated glomerular filtration rate (eGFR) at +12, +36 and +60 months after nephrectomy (P < 0.05). The strongest link was observed in donors >50 years old (R = 0.535, P < 0.001 at +12 months). Estimated nephron number and eGFR showed a strong positive correlation at +12, +36 and +60 months after nephrectomy (R = 0.540; R = 0.459; R = 0.506, P < 0.05). Daily proteinuria at +12 months showed a negative correlation with birth weight (P = 0.009). Donors with new-onset hypertension showed significantly lower birth weights and higher uric acid levels (P < 0.05). Kidney weight and volume did not show any impact on donor outcomes (P > 0.05)., Conclusions: Low nephron number predisposes donors to inferior remaining eGFR, hypertension and proteinuria. The strong correlation in elderly donors may be attributed to reduced renal functional reserve due to the decline of renal function with age., (© The Author 2016. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Background: Infections have increased in simultaneous pancreas/kidney transplant recipients (SPKTRs) with BK polyomavirus (BKV)-associated nephropathy (BKVN) being the most important infectious cause of allograft loss. Comparisons of BKVN with kidney transplant recipients (KTRs), however, are lacking., Methods: We studied all SPKTRs and KTRs at our transplant centre between 2003 and 2012. Eleven of 106 SPKTs (10.4%) and 21 of 1062 KTRs (2.0%) were diagnosed with BKVN with allograft loss in 1 SPKTR (9.1%) and 2 KTRs (9.5%). A control of 95 SPKTRs without BKVN was used for comparison., Results: SPKTRs showed an increased incidence of BKVN compared with KTRs (P < 0.001). Onset of BKVN in SPKTRs was significantly later compared with KTRs (P = 0.033). While 67% of KTRs showed early-onset BKVN, 64% of SPKTRs developed late-onset BKVN. Older recipient age and male gender increased the risk of BKVN in SPKTRs (P < 0.05). No differences were observed for patient and allograft survival (P > 0.05). However, SPKTRs with BKVN showed inferior estimated glomerular filtration rate and a higher incidence of de novo donor-specific antibodies compared with SPKTRs without BKVN in long-term follow-up (P < 0.05). SPKTRs showed higher peak BKV loads, a need for more intense therapeutic intervention and were more likely not to recover to baseline creatinine after BKVN (P < 0.05)., Conclusions: Our results suggest a higher incidence, more severe course and inferior outcome of BKVN in SPKTRs. An increased vulnerability of the allograft kidney due to inferior organ quality may predispose KTRs to early-onset BKVN. In contrast, SPKTRs present with late-onset BKVN in the presence of high-dose immunosuppression., (© The Author 2016. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)