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.

Surgical Wound Dehiscence in Kidney Transplantation: Risk Factors and Impact on Graft Survival.

BACKGROUND: Surgical wound dehiscence (SWD) is a frequent complication after kidney transplantation (KT) but there is not enough evidence of its impact on graft survival. METHODS: A retrospective cohort study including all KT patients with SWD in our center from January 2015 to July 2020 was performed. A case-control study was performed and for each case of SWD, 2 controls were selected (2:1). To identify risk factors for SWD, a logistic regression analysis was carried out and a multivariable Cox regression was used to describe risk factors for graft survival. RESULTS: In our center, 503 KT were performed, and 39 patients presented SWD. They were older (62.1 vs 57.1 years; P = .030), most had diabetes mellitus (59% vs 28.6%; P = .002) and their body mass index was higher (31 vs 26.9 kg/m2; P < .001). In multivariable logistic regression analysis, diabetes mellitus (P = .024) and a body mass index ≥30 kg/m2 at time of transplantation (P = .018) were predictors of SWD. A higher rate of delayed graft function was described in SWD (P = .013) and it was associated with a longer hospital stay (20.9 vs 15 days; P = .004). Graft survival was lower in patients with SWD (P = .036). In multivariable Cox regression analysis, time in renal replacement therapy (P = .020) and SWD (P = .028) were predictors of shorter graft survival. CONCLUSION: SWD is a risk factor for graft survival. The presence of diabetes mellitus and a higher body mass index are predictors for the appearance of this complication.

Changes in Antihypertensive Therapy After Renal Transplantation.

INTRODUCTION: Post-transplant hypertension is extremely frequent, occurring in 60% to 90% of cases. It is involved in the pathogenesis of chronic graft dysfunction and patient survival. OBJECTIVES: We sought to describe changes in antihypertensive therapy after renal transplantation (RT) depending on the type of pretransplant renal replacement therapy (RRT), hemodialysis (HD) or peritoneal dialysis (PD). METHODS: We performed a retrospective cohort study of RT patients who were divided into 2 groups according to the type of pretransplant RRT (HD group: 69 patients; PD group: 38 patients). Patients with a diagnosis of nonessential hypertension etiology, diagnosis of renal artery stenosis of the graft, active urologic complications, and history of acute graft rejection were excluded. Variables related to chronic kidney disease and RT as well as antihypertensive therapy were studied. RESULTS: PD patients had reduced number of antihypertensive drugs at 1 month after RT (1.39 ± 1.03) compared with pre-RT (2.16 ± 1.30; P = .001), a trend that was maintained at 6 months (1.70 ± 1.18; P = .06). In HD group, the number of antihypertensive drugs increased at 6 months after RT (1.59 ± 1.17) compared with pretransplant (1.15 ± 1.13; P = .027). The use of calcium channel blockers increased by 10.2% by 1 month (P = .071) and 9.2% (P = .036) by 6 months after RT. CONCLUSION: By 1 month after RT, antihypertensive therapy was reduced. Calcium channel blockers were the most common drug group, although it is usually necessary to use more than 1 drug.

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.

Clinical Presentation and Determinants of Mortality of Invasive Pulmonary Aspergillosis in Kidney Transplant Recipients: A Multinational Cohort Study.

The prognostic factors and optimal therapy for invasive pulmonary aspergillosis (IPA) after kidney transplantation (KT) remain poorly studied. We included in this multinational retrospective study 112 recipients diagnosed with probable (75.0% of cases) or proven (25.0%) IPA between 2000 and 2013. The median interval from transplantation to diagnosis was 230 days. Cough, fever, and expectoration were the most common symptoms at presentation. Bilateral pulmonary involvement was observed in 63.6% of cases. Positivity rates for the galactomannan assay in serum and bronchoalveolar lavage samples were 61.3% and 57.1%, respectively. Aspergillus fumigatus was the most commonly identified species. Six- and 12-week survival rates were 68.8% and 60.7%, respectively, and 22.1% of survivors experienced graft loss. Occurrence of IPA within the first 6 months (hazard ratio [HR]: 2.29; p-value = 0.027) and bilateral involvement at diagnosis (HR: 3.00; p-value = 0.017) were independent predictors for 6-week all-cause mortality, whereas the initial use of a voriconazole-based regimen showed a protective effect (HR: 0.34; p-value = 0.007). The administration of antifungal combination therapy had no apparent impact on outcome. In conclusion, IPA entails a dismal prognosis among KT recipients. Maintaining a low clinical suspicion threshold is key to achieve a prompt diagnosis and to initiate voriconazole therapy.

Risk Factors Associated With Early Invasive Pulmonary Aspergillosis in Kidney Transplant Recipients: Results From a Multinational Matched Case-Control Study.

Risk factors for invasive pulmonary aspergillosis (IPA) after kidney transplantation have been poorly explored. We performed a multinational case-control study that included 51 kidney transplant (KT) recipients diagnosed with early (first 180 posttransplant days) IPA at 19 institutions between 2000 and 2013. Control recipients were matched (1:1 ratio) by center and date of transplantation. Overall mortality among cases was 60.8%, and 25.0% of living recipients experienced graft loss. Pretransplant diagnosis of chronic pulmonary obstructive disease (COPD; odds ratio [OR]: 9.96; 95% confidence interval [CI]: 1.09-90.58; p = 0.041) and delayed graft function (OR: 3.40; 95% CI: 1.08-10.73; p = 0.037) were identified as independent risk factors for IPA among those variables already available in the immediate peritransplant period. The development of bloodstream infection (OR: 18.76; 95% CI: 1.04-339.37; p = 0.047) and acute graft rejection (OR: 40.73, 95% CI: 3.63-456.98; p = 0.003) within the 3 mo prior to the diagnosis of IPA acted as risk factors during the subsequent period. In conclusion, pretransplant COPD, impaired graft function and the occurrence of serious posttransplant infections may be useful to identify KT recipients at the highest risk of early IPA. Future studies should explore the potential benefit of antimold prophylaxis in this group.

Proteinuria as a predictive factor in the evolution of kidney transplantation.

INTRODUCTION: Certain factors can change the course of renal transplantation, such as acute rejection, ischemia time, and compatibility. Other donor and recipient factors may modify this evolution. Proteinuria modifies glomerular disease progression and may influence renal graft survival. In this study we analyzed proteinuria in patients who received a transplant since 2000 in Andalusia. MATERIAL AND METHODS: We studied the Andalusian Renal Transplant Registry from January 2000 to March 2012, recording data on 1815 patients who had proteinuria, registered at the third month and first year after transplantation. Three groups were formed, including those with proteinuria < 300 mg/24 h, those between 300 and 1000 mg/24 h, and those >1000 mg/24 h. RESULTS: At the third month and the first year after transplantation, 65.7% and 71.6% of patients had proteinuria < 300 mg/24 h, 29.6% and 24.1% had proteinuria between 300 and 1000 mg/24 h, and 4.7% and 4.4% had proteinuria > 1,000 mg/24 h, respectively. We found differences between the three proteinuria groups in panel reactive antibodies (% PRA), serum creatinine at the third month and the first year, the etiology of the donor death, incidence of delayed renal function, and incidence of hypertension. The degree of proteinuria influenced graft and patient survival. In multivariate analysis, proteinuria was an independent risk factor for renal graft loss CONCLUSIONS: The degree of proteinuria at the third month and the first year after transplantation is predictive of graft and patient survival. The patients who had more proteinuria at the third and 12th month after transplantation had worse renal function and more hypertension. Proteinuria is an independent risk factor for renal graft loss.

A form of apolipoprotein a-I is found specifically in relapses of focal segmental glomerulosclerosis following transplantation.

Recurrence of idiopathic focal segmental glomerulosclerosis (FSGS) following kidney transplantation occurs in a large percentage of patients. Accurate prediction of recurrence and elucidation of its pathogenesis are major therapeutic goals. To detect differential proteins related to FSGS recurrence, proteomic analysis was performed on plasma and urine samples from 35 transplanted idiopathic FSGS patients, divided into relapsing and nonrelapsing. Several proteins were detected increased in urine of relapsing FSGS patients, including a high molecular weight form of apolipoprotein A-I, named ApoA-Ib, found exclusively in relapsing patients. This finding was verified by Western blot individually in the 35 patients and validated in an independent group of 40 patients with relapsing or nonrelapsing FSGS, plus two additional groups: FSGS-unrelated patients showing different proteinuria levels (n = 30), and familial FSGS transplanted patients (n = 14). In the total of 119 patients studied, the ApoA-Ib form was detected in 13 of the 14 relapsing FSGS patients, and in one of the 61 nonrelapsing patients. Only one of the 30 patients with FSGS-unrelated proteinuria tested positive for ApoA-Ib, and was not detected in familial patients. Urinary ApoA-Ib is associated with relapses in idiopathic FSGS and warrants additional investigation to determine its usefulness as biomarker of relapse following transplantation.

Renal replacement therapy in patients with HIV infection in a European region: outcomes following renal transplantation.

INTRODUCTION: The prognosis of HIV infection has improved dramatically in patients with end-stage renal disease (ESRD). Thus, HIV infection is no longer an absolute contraindication for renal transplantation. METHODS: A cross-sectional study was performed to analyze the characteristics of HIV patients receiving renal replacement therapy (RRT) in September 2011, using data from the Registry of Renal Patients in Andalusia. A retrospective cohort study was also carried out, analyzing patients receiving kidney transplants in the era of highly active antiretroviral therapy. RESULTS: In Andalusia in September 2011, 8744 patients were on RRT; of these, 48 had HIV infection (prevalence 0.54%). The RRT modality was very different between HIV-negative and HIV-positive patients: renal transplantation 49.2% and 16.7%, hemodialysis 46.8% and 81.3%, and peritoneal dialysis 4% and 2%, respectively. The most frequent ESRD etiology was glomerulonephritis (37.5%). Twenty-seven (56.3%) had hepatitis C coinfection. Only three patients (7.5%) were on the waiting list for renal transplantation. From 2001 to September 2011, 10 HIV-infected patients received a renal transplantation (median follow-up 40.5 months). The initial immunosuppressive treatment included tacrolimus and mycophenolate without induction therapy. Only two patients presented acute rejection, both borderline and corticosensitive. All remain alive and the graft survival was 100% in the first and third years posttransplant. We compared demographic and comorbidity variables between patients transplanted or included on the waiting list (n = 12) and patients excluded and never transplanted (n = 36). We found differences only in the ESRD etiology (higher incidence of glomerulonephritis in excluded patients). CONCLUSIONS: Renal transplantation is safe in correctly selected HIV-infected patients. The number of patients on the waiting list is very small. This may reflect the high comorbidity but it is also possible that these patients are still not being assessed systematically for transplant in all centers.

Impact of cold ischemia time on initial graft function and survival rates in renal transplants from deceased donors performed in Andalusia.

INTRODUCTION: Prolonged cold ischemic time (CIT) in cadaveric renal transplants has been associated with a high rate of delayed graft function, acute rejection, and even reduced graft survival. We analyzed the influence of CIT on both initial graft function (IGF) and survival rate. METHODS: We studied 2525 noncombined cadaveric cases in recipients over 17 years of age between 2000 and 2008, using data from the renal transplant records of Andalusia. We defined IGF as the need to resume dialysis within the first week or a nonfunctional kidney. The multivariate analyses were corrected by center and year of transplantation. RESULTS: The mean and median cold ischemic time was 17 hours. The duration of CIT was significantly associated (P < .001) with older donor and recipient age. The frequency of IGF increased progressively with longer CIT and older donors. However, the influence of CIT persisted among all donor age strata. Logistic regression analysis using both donor and recipient age as covariables showed a relative risk per hour of 1.05 (95% confidence interval = 1.04-1.07; P < .0001). In a univariable study, longer CIT led to a significant reduction in both recipient and graft survival rates. The multivariate study (Cox) using preprocedure covariables, showed CIT to produce significantly worse survival rates for both recipients (relative risk: 1.03, 1.005-1.05, P = .02) and for grafts (relative risk: 1.03, 1.01-1.04, P = .002). However, the survival rates showed no clear progression in terms of CIT within each individual donor age stratum. CONCLUSIONS: A longer CIT was associated with an increase in IGF independent of the age of both the donor and the recipient. Our data also suggested that CIT influenced patient and graft survival rates.

Efficacy and safety of conversion from twice-daily to once-daily tacrolimus in a large cohort of stable kidney transplant recipients.

Prolonged-release tacrolimus was developed to provide a more convenient once-daily dosing that could improve patient adherence. We conducted a multicenter, prospective, observational, 12-month study to describe the efficacy, safety and patient preference of conversion from tacrolimus twice-daily to once-daily formulation in stable kidney transplant recipients in routine clinical practice. Conversion was made on a 1 mg: 1 mg basis (1 mg: 1.1 mg in patients with trough levels <6 ng/mL). The study included 1832 patients (mean age (± SD): 50.0 ± 13.4 years; 62.7% male). After conversion, a modest reduction in tacrolimus trough levels, necessitating an increase in daily dose, was observed (mean changes at 12 months of -9.1% and +1.24%, respectively; p < 0.0001). Mean glomerular filtration rate did not change significantly (56.5 ± 19.7 mL/min at conversion vs. 55.7 ± 20.6 mL/min at 12 months). Proteinuria, blood pressure, lipid, hepatic and glucose parameters remained stable. Eight patients (0.4%) had acute rejection and 34 patients (1.85%) discontinued treatment. Almost all patients (99.4%) preferred the once-daily formulation, because of less frequent dosing (66%) and improved adherence (34%). In conclusion, at similar doses to twice-daily tacrolimus, once-daily formulation provided stable renal function, a low acute rejection rate, and good tolerability in stable kidney transplant recipients in the routine clinical practice setting.

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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.