Impact of BK Polyomavirus Plasma Viral Load in Kidney Transplant Outcomes.

BACKGROUND: BK polyomavirus infection (BKVi) is an important cause of kidney transplant (KT) loss, but there is scarce evidence on the impact of BK plasma viral load on graft function and long-term KT survival. METHODS: A retrospective cohort study including all KT recipients with BKVi (BK viremia identified in ≥3 consecutive samples by polymerase chain reaction) in our center from January 2010 to December 2020 was performed. A case-control study (1:2) was performed. We grouped the cases according to their highest peak viral load: low-level viremia (<10,000 copies/mL) and high-level viremia (≥10,000 copies/mL). To identify risk factors for BKVi, a logistic regression analysis was achieved, and a multivariable Cox regression was used to describe risk factors for graft loss. RESULTS: A total of 849 KTs were performed, and 67 presented BKVi (low-level viremia, n = 35 and high-level viremia, n = 26). In logistic regression analysis male sex (odds ratio [OR], 4.226; 95% CI, 1.660-10.758, P = .002), age (OR, 1.047; 95% CI, 1.008-1.088; P = .018), and retransplant (OR, 4.162; 95% CI, 1.018-17.015; P = .047) were predictors of BKVi. Acute rejection was more frequent in the BKVi group (18% vs 4.9%, P = .004), and graft survival was lower in patients with BKVi and high-level viremia (P = .027). In Cox regression analysis, BKVi (hazard ratio, 3.657; 95% CI, 1.146-11.670; P = .029) and specific BKV (BK polyomavirus) high-level viremia (hazard ratio, 1.988; 95% CI, 1.012-3.907; P = .046) were predictors of shorter graft survival. CONCLUSIONS: BKV high-level viremia was associated with BKV nephropathy and poorer graft survival. Additionally, acute rejection is more frequent after BKVi. It is necessary to develop strategies safe and effective for these patients.

Acute Kidney Injury and Urinary and Histopathological Disorders in Kidney Transplant Patients with SARS-CoV-2 Infection.

BACKGROUND: Acute kidney injury (AKI) is a manifestation of SARS-CoV-2 infection. The evidence in kidney transplant (KT) is limited, as there are scarce data about the histologic features in graft biopsies of these patients. MATERIAL AND METHODS: A retrospective cohort study of KTs with SARS-CoV-2 infection from August 28, 2020, to April 23, 2021. We collected the incidence of AKI and the presence of urinary and histopathological disorders. Both groups were compared (AKI vs no AKI). Immunohistochemical and reverse transcription-polymerase chain reaction studies were performed on the anatomopathological samples. RESULTS: In our study, 72 KTs had SARS-CoV-2 infection and, among them, 27 patients (35.1%) developed AKI related to increased severity and a worse evolution of the infection, defined by a greater presence of pneumonia (P < .001), hospitalization (P < .001), admission to the intensive care unit (P < .001), the need for ventilation support (P < .001), and continuous renal replacement therapy (P < .001). In the multivariable analysis, pneumonia behaved as an independent predictor for AKI development (P = .046). No differences were observed between proteinuria a month before and after infection (P = .224). In addition, 5 patients showed microhematuria and 2 patients presented transient glycosuria without hyperglycemia. Of the 5 kidney biopsies performed, 1 biopsy (20%) showed positive reverse transcription polymerase chain reaction for SARS-CoV-2. CONCLUSIONS: AKI is a frequent and potentially serious complication in KT patients. Occasionally it could be accompanied by abnormalities in the urinary sediment. Of 5 biopsied patients, 1 patient had positive reverse transcription polymerase chain reaction in renal tissue, which suggests the systemic spread of the virus and the tropism for the renal graft.

Evaluation of Expanded Criteria Donors Using the Kidney Donor Profile Index and the Preimplantation Renal Biopsy.

The increasing comorbidity of kidney transplant (KT) donors make it necessary to develop scores to correctly assess the quality of kidney grafts. This study analyzes the usefulness of the preimplantation biopsy and the Kidney Donor Profile Index (KDPI) as indicators of KT survival from expanded criteria donors (ECD). Retrospective study of KT in our center between January 2010 to June 2019 who received a kidney from an ECD and underwent a preimplantation biopsy. 266 KT were included. Graft survival was categorized by KDPI quartiles: Q1 = 86%, Q2 = 95%, Q3 = 99% and Q4 = 100%. KT from KDPI Q1 presented better survival (p = 0.003) and Q4 donors had worse renal function (p = 0.018) and poorer glomerular filtration rate (3rd month; p = 0.017, 1st year; p = 0.010). KT survival was analyzed according to KDPI quartile and preimplantation biopsy score simultaneously: Q1 donors with biopsy score ≤3 had the best survival, especially comparing against Q3 with a biopsy score >3 and Q4 donors (p = 0.014). In multivariable analysis, hyaline arteriopathy, glomerulosclerosis, and KDPI Q4 were predictors for graft survival. High KDPI and a greater histological injury in the preimplantation biopsy, especially glomerular and vascular lesions, were related to a higher rate of KT loss from ECD.

Multinational case-control study of risk factors for the development of late invasive pulmonary aspergillosis following kidney transplantation.

OBJECTIVES: To assess the risk factors for development of late-onset invasive pulmonary aspergillosis (IPA) after kidney transplantation (KT). METHODS: We performed a multinational case-control study that retrospectively recruited 112 KT recipients diagnosed with IPA between 2000 and 2013. Controls were matched (1:1 ratio) by centre and date of transplantation. Immunosuppression-related events (IREs) included the occurrence of non-ventilator-associated pneumonia, tuberculosis, cytomegalovirus disease, and/or de novo malignancy. RESULTS: We identified 61 cases of late (>180 days after transplantation) IPA from 24 participating centres (accounting for 54.5% (61/112) of all cases included in the overall study). Most diagnoses (54.1% (33/61)) were established within the first 36 post-transplant months, although five cases occurred more than 10 years after transplantation. Overall mortality among cases was 47.5% (29/61). Compared with controls, cases were significantly older (p 0.010) and more likely to have pre-transplant chronic obstructive pulmonary disease (p 0.001) and a diagnosis of bloodstream infection (p 0.016) and IRE (p <0.001) within the 6 months prior to the onset of late IPA. After multivariate adjustment, previous occurrence of IRE (OR 19.26; 95% CI 2.07-179.46; p 0.009) was identified as an independent risk factor for late IPA. CONCLUSION: More than half of IPA cases after KT occur beyond the sixth month, with some of them presenting very late. Late IPA entails a poor prognosis. We identified some risk factors that could help the clinician to delimit the subgroup of KT recipients at the highest risk for late IPA.

Kidney Transplantation Results in Very Highly Sensitized Patients Included in a Virtual Crossmatch Program: Analysis of Kidney Pairs.

BACKGROUND: Kidney transplantation in highly-sensitized (HS) patients can improve with organ-exchange strategies based on virtual crossmatch (V-XM). Experience in very-HS patients is limited. METHODS: In June 2012, Andalusia started a V-XM protocol for very-HS patients (calculated panel reactive antibodies ≥95%). After organ allocation a cytotoxic-XM performed immediately before transplantation had to be negative for surgery to proceed. We analyzed results up until December 2015. Whenever possible we also compared the course of the recipient (non-HS) of the other kidney from the same donor. RESULTS: Of the 57 grafts, 52 kidney transplantations were performed (the pretransplantation cytotoxic-XM was positive in 5; predictive value 91.3%). Five patients (9.6%) experienced acute rejection (4 antibody-mediated rejections [AMRs]; 7.6%). Donor-specific antibodies developed in 10 patients. No patient died. One-year graft survival was 98%. We compared the course of the non-HS recipient of the other kidney, excluding cases with no pair (n = 5), pairs who were children recipients (n = 3), pancreas-kidney recipients (n = 5), or pairs already included in the V-XM protocol (n = 4). Finally, 35 pairs were studied. More HS-patients developed donor-specific antibodies (P = .016). No significant differences were seen in acute rejection, but AMR was more common (P = .057). No deaths occurred in either group, and there were no differences in graft survival or renal function. CONCLUSIONS: Although a few patients still developed AMR, our V-XM based protocol with a final pretransplantation cytotoxic-XM achieved very satisfactory results. Although the number of patients was limited, the initial survival of these high-risk recipients was comparable to the controls.

Are we still making progress in patient survival after kidney transplantation? Results of a regional registry.

Many studies have shown a trend to improved long-term survival of renal transplant recipients. We analyzed the survival of recipients in Andalusia, Spain, from 1984-2007. The study included all the deceased donor, non-multiorgan grafts (n = 5599), grouped over successive 6-year periods, compared for corrected recipient survival. Changes were noted in the recipient characteristics: increased age, diabetes, vascular nephropathy, retransplantation, duration of prior replacement therapy, and reduction in positive hepatitis C virus (HCV+) serology. The univariate analysis showed a significantly worse survival associated with increased age (P < .001), diabetes (P < .001), HCV+ serology (P < .01; 1996-2007), and longer times on replacement therapy, but not with sex or retransplantation. The respective survivals at 1, 5, and 10 years in 1984-1989 were 93%, 86%, and 75%; in 1990-1995, 97%, 92%, and 84%; in 1996-2001, 96%, 91%, and 84%; and in 2002-2007, 96% and 92%, respectively. There was a significant improvement between the first and second periods (P < .001), but no change thereafter. The multivariate analysis (Cox) showed, a significant influence of age >40 years, female gender (relative risk [RR] 0.8; 95% confidence interval [CI] 0.7-0.9), diabetes (RR 2.5; 95% CI 1.8-3.4), and duration of prior replacement therapy (RR 1.08; 95% CI 1.05-1.1). The risk varied significantly depending on the period: using 2002-2007 as the reference period, the RR in 1984-1989 was 3.4 (95% CI 2.6-4.5); in 1990-1995, 1.8 (95% CI 1.3-2.3); and in 1996-2001, 1.4 (95% CI 1.1-1.8; all P < .02). The model remained for 1996-2007, though HCV+ serology was not significant. In conclusion, we showed a significant improvement in recipient survival in Andalusia over time. Correction for worse recipient characteristics suggests continued advances.

Increase in malignancies as cause of death in renal transplant patients.

The Andalusian Kidney Transplant Registry is a Public Health Service Regional Registry of Andalusia, Spain. We have analyzed the causes of death among 5599 kidney transplantations performed between January 1, 1984 and December 31, 2007. The total number of patients who died after renal transplantation was 1106. Of these, 656 patients died with functioning renal grafts, which constituted the group analyzed in this study. No significant differences in the causes of death were observed as a function of age, sex, retransplant status, cause of end-stage renal disease, diabetes, and duration of the previous renal replacement therapy. Infections were the most frequent cause of death in the first year posttransplantation (early deaths). A significant difference was observed when these early deaths were compared with those that occurred after the first year posttransplantation (late deaths); there were fewer deaths due to infections (40.4% vs 15.9%, early vs late) and more deaths from cancer (4.9% vs 23.7%). The causes of death in the period 1984-1995 were compared with those in 1996-2007, excluding the deaths that occurred more than 12 years posttransplantation (not possible in the 1996-2007 periods n = 583). The causes of early death did not change. A significant difference was observed among late deaths with an increase in infections (14% vs 17%) and cancers (20% vs 29.7%). Thus, malignancies became the most frequent cause of late death in the 1996-2007 period. In conclusion, in our region, a long-term change in renal transplant patient mortality is taking place, with a significant increase in deaths due to cancer.

Trends in kidney transplantation outcome: the Andalusian Kidney Transplant Registry, 1984-2007.

Herein we have presented the first report from the Andalusian Kidney Transplant Registry, a Public Health Service Regional Registry in Andalusia, Spain (general population, 8 million). The current analysis was limited to 5599 kidney-alone transplants from deceased donors, grouped into 4 time periods: 1984-1989 (n = 846); 1990-1995 (n = 1172); 1996-2001 (n = 1801); and 2002-2007 (n = 2060). The age of the transplant patients rose over time to 21.7% of recipients of ages >or=60 years in 2002-2007. In the later years we observed an increased incidence of vascular and diabetic causes of end-stage renal disease (ESRD). Patients who underwent retransplantation increased from 2.7% in 1984-1989 to 8.1% in 2002-2007. Time on previous renal replacement therapy (RRT) increased from 33.1 +/- 29 to 48 +/- 53 months. Patient survivals at 1, 5, 10, and 20 years were 96%, 91%, 83%, and 63%, respectively. Censoring for death, graft survivals were 90%, 80%, 67%, and 45%, respectively. Compared with the 1984-1989 period, patient survival improved by about 10% (P < .001) since 1990, remaining stable to 2007. Censored 5-year graft survivals progressively improved from 72% to 77%, 82%, and 85% (P < .001). Upon multivariate analysis, gender, age >39 years, diabetes, and RRT duration were independent predictors of patient survival. Age <18 years, retransplantation, and positive hepatitis C virus serology were independent predictors of lower graft survival. Considering 1984-1989 as the reference time period, both patient and graft mortality risks continuously decreased over the following 3 periods (relative risk [RR] = 0.5-0.4-0.3 for patient mortality; RR = 0.8-0.6-0.5 for graft mortality). In summary, despite an increased number of adverse risk factors, both patient and graft survivals have improved from 1984 to date.

[Renal transplantation in HIV-infected patients in Spain]. / Trasplante renal en pacientes con infección VIH en España.

HIV infection has experienced dramatic improvement in morbidity and mortality with the highly active antiretroviral therapy (HAART). This prompted a reevaluation of organ-solid transplantation as a treatment option for HIV-infected patients. Some trials in the United States have shown that one- and 2-year graft and patient survival is comparable to HIV-negative transplant population. In Europe the experience is still scarce. The aim of this study is to analyse the outcome and the clinical characteristics of HIV-infected patients who received kidney transplantation in Spain in the HAART era. Ten patients were transplanted in our country since 2001. Only one patient was black. The main cause of end-stage renal disease reported was glomerulonephritis. Six of the recipients were coinfected by hepatitis C virus. Inclusion criteria included undetectable HIV viral load and CD4 counts greater than 200/pL. Immunosuppression consisted of steroids, tacrolimus and mycophenolate mofetil, with antibody induction in 4 cases. The median and mean follow-up was 11 and 16.3+/-15.6 (3-46) months, respectively. One recipient lost his graft because of early renal venous thrombosis. The remaining patients are functioning graft with mean serum creatinina level of 1.5 +/- 0.5 mg/dl. Biopsy-proven acute rejection was diagnosed in 4 recipients and was reversed in all cases with antirejection treatment. The plasma HIV RNA levels have remained controlled and CD4 counts have been stable in excess of 200 cell/microL. None of patients have developed AIDS complications. Recipients receiving protease inhibitor-based HAART regimens required significant dosing modification to maintain appropriate tacrolimus levels. Our results show that renal transplantation can be a safe and effective treatment in select HIV-infected patients. Like other series, the acute rejection rate was higher than in non-HIV recipients. The reasons of this rejection incidence remain unknown.

Two doses of daclizumab with delayed introduction of low-dose tacrolimus in elderly recipients of cadaveric renal transplants from donors >55 years of age.

BACKGROUND: Renal transplants from elderly donors have a high incidence of delayed graft function, which can be increased by the initial use of calcineurin inhibitors. Our purpose was to assess the safety and efficacy of an immunosuppressive regimen using anti-IL-2R antibodies and MMF that allows delayed introduction of low-dose tacrolimus using elderly donors to elderly recipients. METHODS: This observational study involved 13 transplant centers. In total there were 119 patients (age 60.5 +/- 6.6 years, range 50 to 77) who received a kidney from a donor of mean age 64 +/- 5 years (range 55 to 76), 94% of whom died from a CVA. Immunosuppression consisted of daclizumab (1 mg/kg in two doses; preoperatively and on day 14) combined with steroids, mycophenolate mofetil (initial dose of 2 g/d), and tacrolimus (0.1 mg/kg per day). Tacrolimus was introduced before day 7 (mean 5.5 days) and adjusted to a target level of 5 to 8 ng/mL. The mean follow-up was 8 months. RESULTS: Two grafts were lost due to primary nonfunction and acute rejection and 48 patients (40%) required dialysis due to delayed graft function, although it was generally of short duration (median 4 days; only 2 cases >2 weeks). Acute rejection occurred in 16 patients (13.4%), of whom 13 were biopsy-confirmed (10.9%; Banff 1997 grades I and II). Three patients withdrew from the study, and three died (sepsis, accident, and cardiovascular event). The remaining 111 patients continued follow-up, with a median creatinine value of 1.5 mg/dL at 12-months. Eighty-six percent of patients had at least one episode of infection, half of which were urinary tract infections. There were 16 cases of CMV infection. CONCLUSIONS: Based on the initial results, our immunosuppressive regimen seems to offer good short-term renal function while maintaining an acceptable rejection rate and a low incidence of serious infections.

Efficacy of conversion to sirolimus in posttransplantation Kaposi's sarcoma.

UNLABELLED: The increased incidence of Kaposi's sarcoma (KS) in organ transplantation has been related to the KS herpes virus and the permissive effect of immunosuppressive therapy. We postulated that conversion to SRL in renal recipients with KS favored regression of KS lesions without increasing the risk of graft rejection. METHODS: In this study we performed a retrospective chart review of 7 caucasian renal transplant recipients affected by KS to determine demographic data, etiology of ESRD, immunologic risk factors, immunosuppressive treatment, KS disease follow-up, and renal function before and after SRL conversion. RESULTS: All seven patients were under calcineurin inhibitor treatment at the onset of KS which was limited to the skin, without regression despite attempts to minimize immunosuppression. After conversion to SRL, six patients showed progressive regression of KS lesions, with only hyperpigmented atrophic cutaneous lesions remaining after a mean time of 8.1 months (2-18 months). The seventh patient has completed 9 months follow-up with a near complete regression of KS lesions. One patient returned to hemodialysis after 13 months following irreversible acute renal failure not directly related to SRL conversion; in the other six, renal function was stable. The mean serum creatinine was 1.87 +/- 0.64 versus 1.74 +/- 0.68 mg/dL, pre-conversion versus the end of follow up, respectively. Mean SRL blood level was 9.2 +/- 2.0 ng/mL. CONCLUSION: After SRL conversion, patients with KS showed progressive regression without an increased risk of acute rejection. SRL offers a promising approach to the management of posttransplantation KS and probably other malignancies in organ transplant recipients.

Compressive myelopathy due to dialysis-associated amyloidosis.

A 66-year-old woman presented a spastic quadriparesis due to compression of the cervical cord 6 years after the beginning of chronic hemodialysis. Five years later, she developed a second episode of compressive myelopathy affecting the lumbar spine. On both occasions, surgical laminectomy with removal of fibroligamentous rings that compressed the cord led to a total recovery of the patient. Histological study demonstrated the presence of massive amyloid deposits in the surgically excised material.