Anti-glomerular basement membrane (anti-GBM) is a rare autoimmune but life-threatening disease cause by pathogenic autoantibodies targeting a well characterized autoantigen (a-3 chain of type IV collagen) expressed in the basement membranes of the kidney and lung.Standard treatment normally includes the combination of plasma ex- change, oral cyclophosphamide and corticosteroids. Despite all therapeutic efforts, renal prognosis remains very poor in many cases.Recent studies demonstrated the pathogenic role of complement activation in renal damage of this disease. Eculizumab is a terminal complement inhibitor that binds to the human C5 complement protein, thus blocking the generation of proinflammatory C5a and C5b-9. This provides an immediate inhibition of the proinflammatory and cytotoxic sequelae of the complement system.Here, we report the successfully use of eculizumab in 2 patients with progressive anti-GBM disease.
KEY POINTS:In 134 kidney transplant recipients with recurrent C3 glomerulopathy/immune complex-mediated membranoproliferative GN, 58% lost the graft, confirming the poor long-term prognosis. Time-averaged proteinuria >1 g/d and eGFR decline >5 ml/min per 1.73 m 2 per year predicted higher graft failure risk. Complement profiling showed heterogeneity; autoantibody-positive patients lost grafts earlier, supporting personalized care. BACKGROUND:C3 glomerulopathy (C3G) and primary immune complex-mediated membranoproliferative GN (IC-MPGN) frequently recur after kidney transplantation and represent leading causes of graft loss. However, the natural history of recurrent disease and the prognostic value of longitudinal kidney biomarkers remain poorly defined. METHODS:We conducted a multinational, retrospective cohort study of adults and children with biopsy-proven recurrent C3G or primary IC-MPGN in the kidney allograft (2001-2023). Patients were enrolled from 48 centers across 11 countries and required ≥4 serial measurements of eGFR and proteinuria after recurrence. Longitudinal trajectories of eGFR and proteinuria and their association with graft failure were evaluated using linear mixed-effects and Bayesian joint longitudinal-survival models. Complement genetic and autoantibody testing was performed in a subset of patients. RESULTS:Of 332 eligible transplant recipients, 134 developed biopsy-proven recurrence (C3GN 60%, dense deposit disease 12%, IC-MPGN 28%). The median time to recurrence was 16 months, and 58% progressed to graft failure after a median follow-up of 62 months. Earlier recurrence, lower serum albumin, and higher histologic chronicity independently predicted failure. Joint models demonstrated that lower eGFR and higher proteinuria were dynamically associated with higher graft failure risk. Time-averaged proteinuria >1 g/d and eGFR lowering steeper than -5 ml/min per 1.73 m 2 per year identified high-risk trajectories. Among 71 tested patients, 34% carried pathogenic complement variants and 23% had complement-directed autoantibodies; autoantibody-positive patients experienced earlier graft failure despite similar overall failure rates. CONCLUSIONS:Recurrent C3G and primary IC-MPGN after transplantation are associated with poor long-term outcomes, substantial histologic injury, and marked biologic heterogeneity. Longitudinal eGFR and proteinuria provide powerful prognostic information and clinically meaningful thresholds (>1 g/d time-averaged proteinuria; eGFR slope steeper than -5 ml/min per 1.73 m 2 per year) refine risk stratification. Dynamic biomarkers may serve as surrogate end points, underscoring the need for prospective validation with emerging proximal complement therapies.
BACKGROUND:Although all-cause and cause-specific mortality trends are well studied in the general population, these trends were less explored in kidney transplant recipients with and without diabetes. Our aim was to examine time trends in (cause-specific) mortality in adult first kidney transplant recipients with and without diabetes as the cause of kidney failure in European countries. METHODS:We included adult patients who received a first kidney transplant between 2005 and 2022 from twelve European countries contributing data to the European Renal Association (ERA) Registry. We followed patients for a maximum of 5 years. We calculated age- and sex-standardised mortality rates, and the absolute and relative mortality differences between those with and without diabetes. Time trends were analyzed using Joinpoint regression. RESULTS:In total, 134,231 adults received a kidney transplant between 2005 and 2022, and 20,753 (15.5%) of them had diabetes as the cause of kidney failure. Mortality rates for kidney transplant recipients with diabetes were almost twice as high as for recipients without diabetes (45.5 deaths per 1000 person-years (py) and 24.9 per 1000 py, respectively). The higher mortality of recipients with diabetes was mainly due to excess cardiovascular mortality and infection-related mortality. Trends in all-cause and cause-specific mortality remained stable over time up to the COVID-19 pandemic for recipients with and without diabetes. During the COVID-19 pandemic, both groups experienced an increase in mortality rates, mainly driven by an increase in infection-related mortality. CONCLUSIONS:Contrary to trends observed in the general population, age- and sex-standardised all-cause and cardiovascular mortality rates among kidney transplant recipients, irrespective of diabetes status, did not improve over time. In addition, in contrast to the general population, the cardiovascular mortality gap in kidney transplant recipients with and without diabetes did not narrow over time.
INTRODUCTION:Although advanced age is no longer a contraindication for renal transplantation, real-world data on elderly transplant recipients remain limited. METHODS:This multicenter, prospective study enrolled de novo kidney transplant recipients aged 60 years or older receiving once-daily tacrolimus immunosuppression, following recovery of renal function and referral to the transplant clinic. The primary objective was to describe clinical characteristics and post-transplant outcomes over a 12-month follow-up. Secondary objectives included assessing changes in quality of life and the relationship between biopsy-proven acute rejection (BPAR) and tacrolimus levels. RESULTS:Of 280 evaluable patients, 239 completed the 12-month follow-up (mean recipient age: 69.8 years; mean donor age: 69.1 years) and 41 (14.6%) terminated due to graft loss (13, 31.7%), tacrolimus termination (12, 29.3%), death (10, 24.4%), loss to follow-up (3, 7.3%), other (2, 4.9%), and temporary tacrolimus interruption (1, 2.4%). BPAR occurred in 8.2% of patients who showed significantly higher tacrolimus levels vs those without BPAR over the follow-up (9.8 ng/mL vs. 8.9 ng/mL; p = 0.01). Opportunistic infections were reported in 78.3% patients with BPAR vs 58.8% without BPAR (p = 0.07). Quality of life improved across different domains of the Kidney Transplant Questionnaire and the ESRD-SCL. CONCLUSION:This study monitored clinical outcomes during the first year post-transplant in older de novo kidney transplant recipients receiving grafts from older donors and under a once-daily tacrolimus-based immunosuppressive regimen. The incidence of BPAR, graft loss, and mortality was low, and patients generally experienced an improvement in quality of life, indicating an effective and safe procedure in this population.
La enfermedad anti-membrana basal glomerular (anti-MBG) es una enfermedad autoinmune poco frecuente pero potencialmente mortal que se caracteriza por la presencia de una glomerulonefritis rápidamente progresiva y/o hemorragia alveolar. Esta originada por autoanticuerpos dirigidos contra la cadena α-3 del colágeno tipo IV expresado en las membranas basales del riñón y el pulmón.El tratamiento estándar incluye normalmente el intercambio plasmático, ciclofosfamida y corticosteroides. A pesar de todos los esfuerzos terapéuticos, el pronóstico renal sigue siendo muy pobre en muchos casos.Estudios recientes han sugerido el papel patogénico de la activación del complemento en el daño renal de esta enfermedad. Eculizumab es un inhibidor terminal del complemento que se une a la proteína C5, bloqueando así la generación de los componentes proinflamatorios C5a y C5b-9. Esto proporciona una inhibición inmediata de las secuelas proinflamatorias y citotóxicas del sistema del complemento.Aquí reportamos el uso exitoso de eculizumab en 2 pacientes con enfermedad anti-MBG.
Highly sensitized patients represent a significant challenge in kidney transplantation (KT) due to the limited availability of compatible donors and the high risk of antibody-mediated rejection. In this context, the delisting of forbidden HLA antigens emerges as a key strategy to expand transplantation opportunities for this population. This observational, multicenter, descriptive, and retrospective study included highly sensitized patients (cPRA ≥ 98%) who underwent delisting strategies prior to KT between December 2018 and June 2024. The delisting process was carried out gradually, initially allowing KT in the presence of low-intensity anti-HLA antibodies (MFI < 4000). In cases where cPRA levels did not decrease, a more aggressive delisting approach was adopted, permitting antibodies with an MFI of up to 10,000. Complement-binding antibodies detected by C1q assays and antibodies targeting antigens from previous transplants were excluded. The primary objective of the study was to analyze the outcomes of KT following the delisting of forbidden HLA antigens, aiming to reduce cPRA to <98%. The study included 17 KT patients from three hospitals in Andalusia, all with preformed donor-specific antibodies (DSA) after applying delisting strategies. All patients had a negative complement-dependent cytotoxicity cross-match. The average age was 50 ± 10 years, with 65% female patients and a median dialysis duration of 59 [39–127] months . The time from delisting to transplantation was 16 [4–23] months. Sixty-five percent had undergone a prior transplant. The mean cPRA before delisting was 99.5 ± 0.6, which decreased to 88 ± 14 after delisting. The mean number of mismatches was 5.2 ± 1.3. The number of DSAs at the time of KT was 2 [1.5–3]. Post-transplant desensitization was performed in 82% of patients following the routine clinical practice of each center, and all received induction therapy with Thymoglobulin. Six patients developed acute rejection (five humoral, one mixed) within 12 [9–35] days post-transplant. Among post-transplant complications, 47% experienced infections, including 23% with CMV. Ninety-three percent of grafts were functional at 7 [4–50] months post-transplant, with renal function at 6 and 12 months post-transplant of 48 [27–61] ml/min and 54 [40–66] ml/min, respectively. Patient survival was 100%. The implementation of delisting strategies optimizes the chances of KT in highly sensitized patients with preformed donor-specific antibodies. Despite a high incidence of acute rejection and infections, the majority of grafts remain functional with acceptable renal function. These findings highlight the effectiveness of delisting in improving access to transplantation in this complex population.
Frailty is a frequent condition among kidney transplant candidates (KTc) that confers poor outcomes after transplantation. We aimed to establish frailty prevalence in a representative sample of KTc in Spain. We conducted a multicenter cross-sectional study including 1194 KTc ≥50 years. Frailty was assessed by the FRAIL scale. Mean age was 64.2 years; 38.4% were female. Median Charlson comorbidity index (CCI) was 6 [4-7] and the total number of medications was 9 [7-12]. We found that 8.2% of patients were frail and 41.5% were pre-frail. Frailty was more frequent among females (60.2% of frail vs. 32.8% of robust; p < 0.001), hemodialysis patients (74.5% of frail vs. 67.1% of robust; p = 0.02), and those with a high burden of disease (54.6% of frail patients with CCI >6 vs. 29.3% of robust; p < 0.001). The multivariable analysis confirmed that frailty was associated with the female sex (OR 3.9 [2.5-6.2]); higher CCI (>6 OR 2.9 [1.6-54]); and the number of medications (OR -per medication- 1.13 [1.07-1.2]). Almost 50% of KTc in Spain are pre-frail or frail. Frailty is more prevalent between women and patients with high comorbidity burden. Identifying those candidates at risk is essential to establish risks and implement strategies to minimize them.
Organ donation after controlled cardiac death has been crucial to increase the number of kidney transplants (KT); however, it is associated with a higher risk of delayed graft function (DGF). To palliate this risk, various strategies have been developed, such as reducing cold ischemia time, preservation with ECMO, and delaying the introduction of calcineurin inhibitors through the use of antithymocyte agents as induction treatment. The two most commonly used drugs are Thymoglobulin® and Grafalon®, both rabbit antithymocyte globulins, although they have different antigenic profiles and antibody concentrations. The equivalence between both is unknown, though it is postulated that Thymoglobulin® is three times more potent than Grafalon®. The aim of this project is to analyse the evolution of renal graft function, severe infectious complications, and graft survival, in relation to the induction treatment received with Thymoglobulin® (Genzyme) or Grafalon® (Neovii Biotech) in KT patients with controlled cardiac death donors. We have carried out a retrospective, longitudinal, single-centre cohort study. The analysis includes 205 low immunological risk KT patients with Maastricht type III DCD donor performed at our hospital from January 2015 to December 2022. These patients received induction with Thymoglobulin® and Grafalon® according to the clinical practice of our centre, due to the risk of DGF. A comparative analysis was conducted regarding DGF, acute rejection, survival, infections, and bone marrow toxicity. Of the 205 KT patients, 165 received induction with Thymoglobulin® and 40 with Grafalon®. No significant differences were found in the characteristics of donor and recipient. There were also no differences in renal function nor in acute rejection (AR). There was a trend towards higher CMV infection in the Thymoglobulin® group, with no differences in other infections. A significantly higher lymphopenia was observed during the first year in the Thymoglobulin® group. These results suggest that Grafalon® and Thymoglobulin® are comparable in terms of efficacy and safety, with a more favourable haematological profile for Grafalon® in low-immunological-risk KT recipients. However, further studies are needed to confirm these findings.
Fibrillary glomerulopathy is a rare glomerulonephritis defined by the presence of medium-sized fibrils (15–20 nm), randomly arranged and usually Congo red negative. Its diagnosis requires the use of electron microscopy. It has been associated with multiple secondary causes, although in most cases, no association with another disease is found. To date, several series have shown the characteristics and progression of this disease. Our purpose is, following the work of other research groups, to describe the clinical and histological characteristics, as well as the progression of fibrillary glomerulopathy in a cohort of patients in Spain. A retrospective, single-center study describing the clinical, histological characteristics, progression, and response to treatment of fibrillary glomerulopathy in the province of Málaga between 2007 and 2023. 21 patients were diagnosed with fibrillary glomerulopathy through electron microscopy. Table 1 summarizes the baseline characteristics. The most common presentation was nephrotic syndrome (14, 66%). 10 (47%) patients had microhematuria at the time of diagnosis. Table 2 shows the values for serum creatinine, glomerular filtration rate, and protein/creatinine ratio at diagnosis and at the end of follow-up. No differences were found when comparing these parameters. In 4 patients, coexisting causes were identified (1 monoclonal gammopathy, 1 hepatitis C virus, 1 HIV, and 1 Sjögren's syndrome). 3 patients tested positive for DNAJB9 in the renal biopsy. Regarding histological characteristics, the most observed histological pattern was mesangial expansion (11, 55%), followed by the membranoproliferative pattern (6, 30%). 18 (94%) patients had low C3 levels in the biopsy, and the most identified light chain was lambda. 14 (66%) patients received only antiproteinuric (supportive) treatment, and 6 (28%) patients additionally received immunosuppressive (IS) treatment. All but one in the group that received IS treatment progressed to end-stage renal disease (ESRD), compared to 9 in the supportive group, without showing statistically significant differences (P = 0.3). The median time to the need for renal replacement therapy was 2 ± 3.75 years. After 5 years of follow-up, almost 70% had lost renal function. 8 (38%) patients underwent kidney transplantation. Any of them have showed recurrence of the disease. In our court the use of immunosuppression is comparable to supportive treatment in terms of renal response. Transplanted patients have not shown recurrence of the disease.
Sodium-glucose co-transporter-2 inhibitors (SGLT2i) are key therapeutic agents in cardiovascular and renal care. While widely used in kidney transplant recipients (KTRs) with diabetes, evidence on their safety and efficacy in non-diabetic KTRs remains limited. This study aims to evaluate the clinical outcomes of SGLT2i therapy in a cohort exclusively composed of non-diabetic KTRs. We conducted a multicenter retrospective study of 176 non-diabetic KTRs who initiated SGLT2i therapy. Clinical and analytical data were collected at baseline and after 6 months of treatment. The mean recipient age was 47.6 ± 13.5 years, with 32.4% being women. SGLT2i therapy was initiated at a median of 6.1 years [IQR 1.9–14.9] post-KT, predominantly with dapagliflozin (85.8%). The primary indication was non-nephrotic proteinuria (75%). Interestingly, 17% of patients were not receiving any concomitant antiproteinuric therapy. After 6 months of treatment, there was a significant reduction in protein/creatinine ratio (607.3 mg/g [IQR 217.8–1390] vs. 400 mg/g [IQR 129–1000], P < 0.001) and albumin/creatinine ratio (545 mg/g [IQR 221–1154] vs. 295.6 mg/g [IQR 106–753.2], P < 0.001) [Fig. 1A]. Adverse effects occurred in 22.7% of patients [Fig. 1B], with 8 (4.5%) requiring hospitalization due to probable SGLT2i-related complications (7 urinary tract infections [UTIs] and 1 case of acute kidney injury [AKI]). Temporary discontinuation occurred in 13.2% of patients, with a median time of therapy reinitiation of 6 months [IQR 4–10]. Additionally, 23.8% of patients permanently stopped therapy due to UTIs (30%), AKI (25%) or unspecified causes (35%). SGLT2i therapy in non-diabetic KTRs shows an acceptable safety profile with a low rate of severe adverse events. The significant reduction in proteinuria and albuminuria observed at 6 months supports its potential renoprotective effects in this population. However, risks such as UTIs and AKI warrant careful monitoring. Further studies are needed to confirm long-term safety and efficacy.
The demand for kidney transplantation (KT) remains high, with limited availability of suitable organs. In Spain, an increasing trend in utilizing kidneys from diabetic (DM) donors has been observed. Despite this, the rate of kidney discard from DM donors is rising due to concerns over poorer graft function and recipient outcomes. Recent advancements in DM management, such as sodium-glucose cotransporter-2 (SGLT2) inhibitors, have demonstrated efficacy in improving glycemic control and altering the progression of DM, yet their impact on KT outcomes from DM donors remains unexplored. This multicenter retrospective study aims to evaluate the role of SGLT2 inhibitors (SGLT2i) in DM kidney donors, focusing on graft survival, recipient survival, and proteinuria. We performed a multicenter retrospective cohort study from the KT recipients who received a kidney from a DM donor with at least 5 years of diagnosed DM and who had undergone SGLT2i therapy for 6 months or more. Study period was from 01/01/2016 to 31/12/2023. Data were collected from the Andalusian centers that perform KT and Badajoz. Three groups were defined and a case-control study was conducted in a 1:1:1 ratio. Group 1 (cases): DM donor with SGLT2i therapy, group 2 (control): DM donor without SGLT2i therapy and group 3 (control): non-DM donors. Donors were selected according to transplant date, donor type, age and duration of DM evolution. We collected clinical and demographical data from donors and recipients. Biopsy scores as well as glomerular filtration rate (eGFR) and proteinuria, were compared between the three defined groups. Finally, recipient survival was also analyzed. Thirty-six recipients were included in each group. Non-DM kidney donors exhibited significantly better histological quality, with a median biopsy score of 2, compared to DM donors treated with SGLT2i 4 and those untreated 4 (P < 0.001). Arteriolar hyalinosis was significantly higher in DM donors receiving SGLT2i than in those without (1 vs. 0; P = 0.013). Other histological parameters showed no significant differences among the groups. eGFR at all follow-up points was slightly better in non-DM donors but did not reach statistical significance. However, proteinuria was significantly lower in DM donors treated with SGLT2i at 1 year (P = 0.008) after KT, suggesting a potential protective effect. One year post-KT, eGFR was similar between DM donors treated with SGLT2i (44.6 ± 12.96 mL/min) and those untreated (42.3 ± 17.8 mL/min) compared to non-DM donors (50.9 ± 21.4 mL/min) (P = 0.253). Long-term outcomes revealed that 5-year graft survival remained high across all groups (100% in non-DM donors, 85.7% in DM donors with SGLT2i, and 89% in those without). However, 5-year recipient survival was markedly lower in DM donors without SGLT2i compared to those treated and non-DM donors (58.5% vs 84.2% vs 83.4%, P = 0.499). SGLT2i in DM kidney donors were significantly associated with lower proteinuria and may improve recipient survival compared to untreated DM donors. Although initial findings are promising, further studies with larger cohorts and longer follow-up are necessary to better elucidate the impact of SGLT2i on long-term graft and recipient survival outcomes.
Abstract Background and Aims Approximately 15% of recipients of non-kidney solid organ transplantation (NKSOT) develop end-stage chronic kidney disease (CKD), requiring kidney transplantation (KT). There are controversy whether KT after NKSOT outcomes are poor or whether these patients should be prioritized. Method Retrospective analysis of KT after NKSOT in Andalusia between 1978-2023. We performed a case-control study, choosing 2 controls for each case (1 recipient of a second KT [reKT] and 1 recipient of a first KT without previous NKSOT), the closest ones with KT date and similar age and gender between donor and recipient. Patients with renopancreatic transplantation were excluded. We compared clinical characteristics and outcomes. Results During this period, we followed 12217 KT in Andalusia. Of these, 35 (0.003%) are KT after NKSOT: 26 (74.3%) liver transplant recipients, 7 (20%) heart transplant recipients and 2 (5.7%) lung transplant recipients. All of them are recipients of a first KT. When comparing KT after NKSOT vs. reKT and first KT recipients, demographic characteristics and donor type are similar in all 3 groups. The reKT recipients were on dialysis longer before receiving the second KT, with no difference between the other 2 groups. Graft survival of reKT patients was lower than the rest (vs. KT after NKSOT, p = 0.014; vs. first KT p < 0.001). Survival between KT after NKSOT and first KT was slightly worse in those who had received a previous NKSOT, but without significant differences. In multivariate analysis, adjusted for time on waiting list, reKT remained a risk factor at the limit of statistical significance (p = 0.072). There was no difference in patient survival. Conclusion KT after NKSOT has similar graft and patient survival outcomes to recipients of a first KT, and better than in recipients of a second KT.
Abstract Background and Aims Kidney re-transplantation (Re-KT) is associated with worse outcomes. Better results have been described when the KT is performed preemptive, before the patient returns to dialysis. However, the experience is limited so far. Method We performed a retrospective analysis of KT patients who received a preemptive KT (pRe-KT) in Andalusia between 1978-2023. A case-control study was carried out, choosing 2 controls for each case, adjusted for donor and recipient demographic characteristics (1 patient receiving a second non-preemptive KT [npRe-KT] and 1 patient receiving a first KT). We compared clinical characteristics and evolution between the 3 groups. Results During this period, 12217 KT recipients were registered in Andalusia. Of these, 1380 (11.3%) received at least a second KT. Eighty-two (0.059%) patients were pRe-KT recipients, all of them with a second KT. In the npRe-KT patients, there was a lower proportion of living donors than in the other groups (pRe-KT 30.4%, npRe-KT 6.3%, first KT 28.4%; p < 0.001). There were no differences nor in age neither in gender of donors and recipients. Graft survival in pRe-KT and first KT patients was similar and significantly better than in npRe-KT. Adjusting for donor type (living/deceased), npRe-KT remained as a risk factor. However, we observed no differences in patient survival between groups. Conclusion In pRe-KT patients, outcomes are significantly better than npRe-KT outcomes and similar to that of the first KT. These patients, when their clinical situation allows it, should be evaluated for inclusion on the waiting list before the definitive graft loss. Living donor KT should be actively encouraged in patients who are losing the functionality of their renal graft.
Background: The persistent shortage of optimal kidney donors and the progressive increase in patients on the waiting list has led to an expansion of organ acceptance criteria, such as controlled donation after circulatory death (cDCD) donors, as well as an expansion of criteria for accepting these organs (age, comorbidities, etc). However, there are some concerns and doubts about the survival outcomes achieved with these allografts. Methods: A retrospective observational single-center study including all kidney transplants (KTs) from donors >= 70 years old using cDCD and donation after brain death (DBD) performed from January 2017 to December 2022. A comparative analysis was conducted between the 2 groups regarding clinical characteristics, medium and short-term clinical outcomes, and patient and graft survival rates. Results: We studied 123 KTs performed with donors >= 70 years old, 81 from DBD, and 42 from cDCD. The median follow-up was 41 months (18-60). The age of the recipients from cDCD was higher (68 vs 65 years; P = .03), without significant differences in associated comorbidities. The age of DBD was significantly higher (73 vs 71; P = .001), and cDCD donors had a higher prevalence of diabetes (16% vs 5%; P = .04); however, there were no significant differences in Kidney Donor Profile Index between the groups. There was a trend toward a higher percentage of Delayed Graft Function in the cDCD group, although renal function was similar between the groups during follow-up. There were also no differences between the percentages of acute rejection. The mean graft survival rate censored for death with a functioning graft at one year (81% for DBD vs 79% for cDCD) and at 3 years (83% for DBD vs 75% for cDCD) was satisfactory (P = .141). Conclusions: The medium-term results of KT with cDCD donors are promising and comparable to those of DBD, allowing for an expansion of the donor pool for selected transplant recipients.
Introduction: Death with a functioning graft (DWFG) is the most frequent cause of loss of kidney transplantation (KT).Objective: To analyze the evolution of the causes of DWFG and the frequency of the types of cancer causing DWFG.Methods: Retrospective study of KT in Andalusia from 1984 to 2018. We analyzed the evo-lution according to eras (1984-1995; 1996-2007; 2008-2018) and according to post-transplant period (early death: first year post-KT; late death: after first year post-KT).Results: A total of 9,905 KT were performed, registering 1,861 DWFG. The most frequent causes were cardiovascular disease (25.1%), infections (21.5%) and cancer (19.9%).In early death we did not observe changes, and infections were always the main cause. In late death, cardiovascular death decreased (1984-1995: 35.2%, 1996-2007: 22.6%, 2008-2018: 23.9%), but infections (1984-1995: 12.5%, 1996-2007: 18.3%, 2008-2018: 19.9%) and, above all, cancer-related deaths increased (1984-1995: 21.8%, 11996-2007: 29%, 2008-2018: 26.8%) (P < 0.001). In the multivariable analysis for late death due to cardiovascular disease, recipient age, retransplantation, diabetes, and the first period were risk factors, while the risk of late death due to cancer and infections was associated with recent eras.In the first year after transplantation, the most frequent neoplasia causing DWFG was post -transplant lymphoproliferative disease, and after the first year, it was lung cancer, without differences when it was analyzed by eras.Conclusions: Despite the greater comorbidity of the recipients, cardiovascular deaths have decreased. Cancer has been the main cause of late death in recent years. Lung cancer is the most frequent malignancy that causes DWFG in our transplant patients.& COPY; 2021 Sociedad Espanola de Nefrologia. Published by Elsevier Espana, S.L.U. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/ by-nc-nd/4.0/).
We investigated the evolution of serum klotho (s-Kl) and FGF-23 during the first two years post-kidney transplantation (KT), considering the cold ischemia time (CIT), glomerular filtration rate (GFR) and graft subclinical inflammation (SCI). We undertook a prospective, cohort, multicenter study of consecutive patients between April 2018 and January 2021 (with follow-up at 24 months). Subgroups were analyzed according to the median CIT (<14 vs. ≥14 h), the median GFR (≤40 vs. >40 mL/min/1.73 m2) and the presence of SCI at month 3. A total of 147 patients were included. s-Kl and fibroblast growth factor-23 (FGF-23) levels were measured at baseline and at months 3, 12 and 24. Graft biopsies (n = 96) were performed at month 3. All patients had low s-Kl levels at month 3. Patients with CIT < 14 h exhibited a significant increase in s-Kl at month 24. In patients with CIT ≥ 14 h, s-Kl at month 3 fell and lower s-Kl levels were seen at month 24. Patients with a GFR > 40 had a lesser decrease in s-Kl at month 3. FGF-23 fell significantly at months 3 and 12 in both GFR groups, a reduction maintained during follow-up. There were significant inter-group differences in s-Kl from months 3 to 24. CIT, GFR at 3 months and SCI were significantly associated with s-KI at month 3. A reduction in s-Kl at month 3 post-KT could be explained by longer CIT and delayed graft function as well as by impaired graft function. Early SCI may regulate s-Kl increase post-KT.
Introduction: SARS CoV2 infection has had a major impact on renal transplant patients with a high mortality in the first months of the pandemic. Intentional reduction of immunosuppressive therapy has been postulated as one of the cornerstone in the management of the infection in the absence of targeted antiviral treatment. This has been modified according to the patient`s clinical situation and its effect on renal function or anti-HLA antibodies in the medium term has not been evaluated.Objectives: Evaluate the management of immunosuppressive therapy made during SARS-CoV2 infection, as well as renal function and anti-HLA antibodies in kidney transplant patients 6 months after COVID19 diagnosis.Material and methods: Retrospective, national multicentre, retrospective study (30 centres) of kidney transplant recipients with COVID19 from 01/02/20 to 31/12/20. Clinical variables were collected from medical records and included in an anonymised database. SPSS statistical software was used for data analysis.Results: renal transplant recipients with COVID19 were included (62.6% male), with a mean age of 57.5 years. The predominant immunosuppressive treatment prior to COVID19 was triple therapy with prednisone, tacrolimus and mycophenolic acid (54.6%) followed by m-TOR inhibitor regimens (18.6%). After diagnosis of infection, mycophenolic acid was discontinued in 73.8% of patients, m-TOR inhibitor in 41.4%, tacrolimus in 10.5% and cyclosporin A in 10%. In turn, 26.9% received dexamethasone and 50.9% were started on or had their baseline prednisone dose increased. Mean creatinine before diagnosis of COVID19, at diagnosis and at 6 months was: 1.7 +/- 0.8, 2.1 +/- 1.2 and 1.8 +/- 1 mg/dl respectively (p < 0.001). 56.9% of the patients (N = 350) were monitored for anti-HLA antibodies. 94% (N = 329) had no anti-HLA changes, while 6% (N = 21) had positive anti-HLA antibodies. Among the patients with donor-specific antibodies post-COVID19 (N = 9), 7 patients (3.1%) had one immunosuppressant discontinued (5 patients had mycophenolic acid and 2 had tacrolimus), 1 patient had both immunosuppressants discontinued (3.4%) and 1 patient had no change in immunosuppression (1.1%), these differences were not significant.Conclusions: The management of immunosuppressive therapy after diagnosis of COVID19 was primarily based on discontinuation of mycophenolic acid with very discrete reductions or discontinuations of calcineurin inhibitors. This immunosuppression management did not influence renal function or changes in anti-HLA antibodies 6 months after diagnosis.