BK polyomavirus infection: more than 50 years and still a threat to kidney transplant recipients.

BK polyomavirus (BKPyV) is a ubiquitous human polyomavirus and a major infection after kidney transplantation, primarily due to immunosuppression. BKPyV reactivation can manifest as viruria in 30%-40%, viremia in 10%-20%, and BK polyomavirus-associated nephropathy (BKPyVAN) in 1%-10% of recipients. BKPyVAN is an important cause of kidney graft failure. Although the first case of BKPyV was identified in 1971, progress in its management has been limited. Specifically, there is no safe and effective antiviral agent or vaccine to treat or prevent the infection. Even in the current era, the mainstay approach to BKPyV is a reduction in immunosuppression, which is also limited by safety (risk of de novo donor specific antibody and rejection) and efficacy (graft failure). However, recently BKPyV has been getting more attention in the field, and some new treatment strategies including the utilization of viral-specific T-cell therapy are emerging. Given all these challenges, the primary focus of this article is complications associated with BKPyV, as well as strategies to mitigate negative outcomes.

Oxalate Nephropathy After Kidney Transplantation: Risk Factors and Outcomes of Two Phenotypes.

Describing risk factors and outcomes in kidney transplant recipients with oxalate nephropathy (ON) may help elucidate the pathogenesis and guide treatment strategies. We used a large single-center database to identify patients with ON and categorized them into delayed graft function with ON (DGF-ON) and late ON. Incidence density sampling was used to select controls. A total of 37 ON cases were diagnosed between 1/2011 and 1/2021. DGF-ON (n = 13) was diagnosed in 1.05% of the DGF population. Pancreatic atrophy on imaging (36.4% vs. 2.9%, p = 0.002) and gastric bypass history (7.7% vs. 0%; p = 0.06) were more common in DGF-ON than with controls with DGF requiring biopsy but without evidence of ON. DGF-ON was not associated with worse graft survival (p = 0.98) or death-censored graft survival (p = 0.48). Late ON (n = 24) was diagnosed after a mean of 78.2 months. Late ON patients were older (mean age 55.1 vs. 48.4 years; p = 0.02), more likely to be women (61.7% vs. 37.5%; p = 0.03), have gastric bypass history (8.3% vs. 0.8%; p = 0.02) and pancreatic atrophy on imaging (38.9% vs. 13.3%; p = 0.02). Late ON was associated with an increased risk of graft failure (HR 2.0; p = 0.07) and death-censored graft loss (HR 2.5; p = 0.10). We describe two phenotypes of ON after kidney transplantation: DGF-ON and late ON. Our study is the first to our knowledge to evaluate DGF-ON with DGF controls without ON. Although limited by small sample size, DGF-ON was not associated with adverse outcomes when compared with controls. Late ON predicted worse allograft outcomes.

Outcomes of Deceased Donor Kidney Recipients From the Same Donor Based on Donor-Recipient Sex Discordance.

INTRODUCTION: Outcomes of deceased donor kidney transplant (DDKT) recipients from the same donor with donor-recipient sex discordance have been studied with inconsistent results. METHODS: Adult DDKT where both kidneys from the same donor occurred at our center in two different recipients of different sexes were included. Outcomes were analyzed separately for male and female donors, based on the concordance or discordance between donor-recipient sex: Male-male (M-m) versus Male to female (M-f) or vice versa, F-f versus F-m. Acute rejection (AR) and uncensored graft failure were primary outcomes of interest. The univariate and multivariate risks for AR and graft failure were conducted using the Cox proportional hazards model and log-rank tests. RESULTS: A total of 130 donors, 84 male and 46 female fulfilled our selection criteria and were transplanted in 260 recipients. With respect to the concordant groups (M-m or F-f), sex discordance was not significantly associated with the risk of rejection in multivariate analysis (M-f vs. M-m HR 1.15 [0.53-2.53, P = 0.72]; F-m vs. F-f HR 1.77 [0.71-4.39, P = 0.23]). Sex discordance was also not significantly associated with graft failure in multivariate analysis. Interestingly, risk factors for AR differed among male donors and female donors. The higher calculated panel reactive antibodies (cPRA) and nonwhite recipients were at increased risk for AR in F-m, but not in M-f. CONCLUSIONS: Donor-recipient sex discordance was not significantly associated with AR or graft failure. Risk factors for AR may differ across male and female donors.

Effect of End-Stage Renal Disease Prospective Payment System on Utilization of Peritoneal Dialysis in Patients with Kidney Allograft Failure.

INTRODUCTION: The Center for Medicare and Medicaid Services introduced an End-Stage Renal Disease Prospective Payment System (PPS) in 2011 to increase the utilization of home dialysis modalities, including peritoneal dialysis (PD). Several studies have shown a significant increase in PD utilization after PPS implementation. However, its impact on patients with kidney allograft failure remains unknown. METHODS: We conducted an interrupted time series analysis using data from the US Renal Data System (USRDS) that include all adult kidney transplant recipients with allograft failure who started dialysis between 2005 and 2019. We compared the PD utilization in the pre-PPS period (2005-2010) to the fully implemented post-PPS period (2014-2019) for early (within 90 days) and late (91-365 days) PD experience. RESULTS: A total of 27,507 adult recipients with allograft failure started dialysis during the study period. There was no difference in early PD utilization between the pre-PPS and the post-PPS period in either immediate change (0.3% increase; 95% CI: -1.95%, 2.54%; p = 0.79) or rate of change over time (0.28% increase per year; 95% CI: -0.16%, 0.72%; p = 0.18). Subgroup analyses revealed a trend toward higher PD utilization post-PPS in for-profit and large-volume dialysis units. There was a significant increase in PD utilization in the post-PPS period in units with low PD experience in the pre-PPS period. Similar findings were seen for the late PD experience. CONCLUSION: PPS did not significantly increase the overall utilization of PD in patients initiating dialysis after allograft failure.

Avascular Necrosis in Kidney Transplant Recipients is Associated With an Increased Risk of Patient Death.

Introduction: Avascular necrosis is a debilitating osseous complication in transplant recipients. Project Aim: This program evaluation sought to describe risk factors and adverse outcomes of avascular necrosis in kidney transplant recipients. Design: This was a retrospective evaluation of all recipients of kidneys and simultaneous pancreas and kidneys between 2001 and 2018 from a single center. Controls were selected based on the incidence density, sampling at a 1:3 ratio based on the post-transplant interval. Outcomes of interest were acute rejection, death-censored graft failure, and patient mortality. Results: A total of 88 kidney recipients had avascular necrosis and were compared with 257 controls. Most of the recipient's and donors' baseline characteristics were similar between the groups, except calcineurin inhibitor-based immunosuppression was more prevalent, and non-white donors were less prevalent in the control group. Looking for risk factors for avascular necrosis, calcineurin inhibitor-based immunosuppression was associated with a lower risk for avascular necrosis in the univariate analysis, but this was not found after adjustment of multiple variables. In multivariate analysis, avascular necrosis was associated with an increased risk for patient death (hazard ratio: 1.68; 95% confidence interval: 1.16-2.44; P = .008) but not for acute rejection or death censored graft failure. Conclusion: Although limited by small sample size, this evaluation found avascular necrosis to be associated with an increased risk of patient death. This finding may be useful for the provider taking care of the patients and discussing the various outcomes after the transplant.

Twelve Thousand Kidney Transplants Over More Than 55 Y: A Single-center Experience.

Background: Kidney transplant outcomes have dramatically improved since the first successful transplant in 1954. In its early years, kidney transplantation was viewed more skeptically. Today it is considered the treatment of choice among patients with end-stage kidney disease. Methods: Our program performed its first kidney transplant in 1966 and recently performed our 12 000th kidney transplant. Here, we review and describe our experience with these 12 000 transplants. Transplant recipients were analyzed by decade of date of transplant: 1966-1975, 1976-1985, 1986-1995, 1996-2005, 2006-2015, and 2016-2022. Death-censored graft failure and mortality were outcomes of interest. Results: Of 12 000 kidneys, 247 were transplanted from 1966 to 1975, 1147 from 1976 to 1985, 2194 from 1986 to 1995, 3147 from 1996 to 2005, 3046 from 2006 to 2015, and 2219 from 2016 to 2022 compared with 1966-1975, there were statistically significant and progressively lower risks of death-censored graft failure at 1 y, 5 y, and at last follow-up in all subsequent eras. Although mortality at 1 y was lower in all subsequent eras after 1986-1995, there was no difference in mortality at 5 y or the last follow-up between eras. Conclusions: In this large cohort of 12 000 kidneys from a single center, we observed significant improvement in outcomes over time. Kidney transplantation remains a robust and ever-growing and improving field.

Risk factors and outcomes of persistent post-transplant hypotension among simultaneous pancreas and kidney transplant recipients.

BACKGROUND: The risk factors and outcomes associated with post- transplant hypotension after simultaneous pancreas and kidney (SPK) Transplantation are poorly defined. METHODS: SPK recipients at our center between 2010 and 2021 with functioning pancreas and kidney grafts for >6 months were included. Recipients were then divided into three groups based on active medications for the treatment of hypo-or hypertension at 6-months post-transplant: those with normal blood pressure (NBP) not requiring medication (NBP group), those on antihypertensive medications (HTN group), and those on medications for hypotension (fludrocortisone and/or midodrine) (Hypotensive group). RESULTS: A total of 306 recipients were included in the study: 54 (18%) in the NBP group, 215 (70%) in the HTN group, and 37 (12%) in the Hypotensive group. On multivariate analysis, the use of T-depleting induction (aHR = 9.64, p = .0001, 95% Cl = 3.12-29.75), pre-transplant use of hypotensive medications (aHR = 4.53, p = .0003, 95% Cl = 1.98-10.38), and longer duration of dialysis (aHR = 1.02, p = .01, 95% Cl = 1.00-1.04) were associated with an increased risk of post-transplant hypotension. Post-transplant hypotension was not associated with an increased risk of death-censored kidney or pancreatic allograft failure, or patient death. CONCLUSION: Hypotension was common even 6 months post-SPK transplantation. With appropriate management, hypotension was not associated with detrimental graft or patient outcomes.

Delayed Graft Function Among Kidney Transplant Recipients Is Associated With an Increased Risk of Urinary Tract Infection and BK Viremia.

Background: Delayed graft function (DGF) among deceased donor kidney transplant recipients (DDKTRs) is a well-known risk factor for allograft rejection, decreased graft survival, and increased cost. Although DGF is associated with an increased risk of rejection, it is unclear whether it also increases the risk of infection. Methods: We reviewed all adult DDKTRs at our center between 2010 and 2018. The primary outcomes of interest were BK viremia, cytomegalovirus viremia, pneumonia, and urinary tract infection (UTI) within the first year of transplant. Additional analysis was made with censoring follow-up at the time of allograft rejection. Results: A total of 1512 DDKTRs were included, of whom 468 (31%) had DGF. As expected, several recipient, donor, and baseline immunological characteristics differed by DGF status. After adjustment, DGF was significantly associated with an increased risk of BK viremia (hazard ratio: 1.34; 95% confidence interval, 1.0-1.81; P = 0.049) and UTI (hazard ratio: 1.70; 95% confidence interval, 1.31-2.19; P < 0.001) but not cytomegalovirus viremia or pneumonia. Associations were similar in models censored at the time of rejection. Conclusions: DGF is associated with an increased risk of early infectious complications, mainly UTI and BK viremia. Close monitoring and appropriate management are warranted for better outcomes in this unique population.

Analysis of Individual Components of Frailty in Simultaneous Pancreas and Kidney, and Solitary Pancreas Transplant Recipients.

Backgrounds: It is not known which of the 5 components of the Fried frailty score have the most predictive value for outcomes in simultaneous pancreas-kidney transplant (SPK) and solitary pancreas transplant (SPT) recipients. Methods: In this study, we sought to investigate the association between pretransplant overall frailty and individual frailty components, with posttransplant outcomes among SPK and SPT recipients. Outcomes of interest were length of stay, kidney delayed graft function (K-DGF), readmission within 30 d after discharge, cardiovascular events, acute rejection, pancreas death-censored graft failure (DCGF), kidney DCGF, and death. Results: Of the individual frailty components among SPK (n = 113), only slow walk time was associated with an increased risk of mortality (adjusted odds ratio [aOR]: 4.99; P = 0.03). Among SPT (n = 49), higher sum frailty scores (coefficient correlation 0.29; P = 0.04) and weight loss (coefficient correlation = 0.30; P = 0.03) were associated with prolonged length of stay. Similarly, weight loss among SPT was associated with an increased risk of DCGF (aOR: 4.34; P = 0.049). Low grip strength was strongly associated with an increased risk of early readmission (aOR: 13.08; P = 0.008). Conclusions: We found that not all components of frailty contribute equally to predicting outcomes. Objective measurements of slow walk time, unintentional weight loss, and low grip strength were found to be associated with less optimal outcomes in pancreas transplant recipients. Targeted interventions may improve posttransplant outcomes.

Hypoalbuminemia is a risk factor for invasive fungal infections and poor outcomes in infected kidney transplant recipients.

INTRODUCTION: Invasive fungal infections (IFI), are estimated to occur in 2%-14% of kidney transplant recipients (KTRs) in the current era of immune suppression and are associated with high mortality rates. We hypothesized that hypoalbuminemia in KTRs is a risk factor for IFI and would be associated with poor outcomes. METHODS: In this study, using data from a prospective cohort registry, we describe the frequency of IFI due to Blastomycosis, Coccidioidomycosis, Histoplasmosis, Aspergillosis, and Cryptococcus in KTRs with serum albumin levels measured 3-6 months before diagnosis. Controls were selected based on incidence density sampling. KTRs were divided into three groups based on the pre-IFI serum albumin level: normal (≥4 g/dL), mild (3-4 g/dL), or severe (<3 g/dL) hypoalbuminemia. Outcomes of interest were uncensored graft failure after IFI and overall mortality. RESULTS: A total of 113 KTRs with IFI were compared with 348 controls. The incidence rate of IFI among individuals with normal, mild, and severe hypoalbuminemia was 3.6, 8.7, and 29.3 per 100 person-years, respectively. After adjustment for multiple variables, the trend for risk of uncensored graft failure following IFI was greater in KTRS with mild (HR = 2.1; 95% CI, .75-6.1) and severe (HR = 4.47; 95% CI, 1.56-12.8) hypoalbuminemia (P-trend < .001) compared to those with normal serum albumin. Similarly, mortality was higher in severe hypoalbuminemia (HR = 1.9; 95% CI, .67-5.6) compared to normal serum albumin (P-trend < .001). CONCLUSION: Hypoalbuminemia precedes the diagnosis of IFI in KTRs, and is associated with poor outcomes following IFI. Hypoalbuminemia may be a useful predictor of IFI in KTRs and could be incorporated into screening algorithms.

Pseudohyponatremia: Mechanism, Diagnosis, Clinical Associations and Management.

Pseudohyponatremia remains a problem for clinical laboratories. In this study, we analyzed the mechanisms, diagnosis, clinical consequences, and conditions associated with pseudohyponatremia, and future developments for its elimination. The two methods involved assess the serum sodium concentration ([Na]S) using sodium ion-specific electrodes: (a) a direct ion-specific electrode (ISE), and (b) an indirect ISE. A direct ISE does not require dilution of a sample prior to its measurement, whereas an indirect ISE needs pre-measurement sample dilution. [Na]S measurements using an indirect ISE are influenced by abnormal concentrations of serum proteins or lipids. Pseudohyponatremia occurs when the [Na]S is measured with an indirect ISE and the serum solid content concentrations are elevated, resulting in reciprocal depressions in serum water and [Na]S values. Pseudonormonatremia or pseudohypernatremia are encountered in hypoproteinemic patients who have a decreased plasma solids content. Three mechanisms are responsible for pseudohyponatremia: (a) a reduction in the [Na]S due to lower serum water and sodium concentrations, the electrolyte exclusion effect; (b) an increase in the measured sample's water concentration post-dilution to a greater extent when compared to normal serum, lowering the [Na] in this sample; (c) when serum hyperviscosity reduces serum delivery to the device that apportions serum and diluent. Patients with pseudohyponatremia and a normal [Na]S do not develop water movement across cell membranes and clinical manifestations of hypotonic hyponatremia. Pseudohyponatremia does not require treatment to address the [Na]S, making any inadvertent correction treatment potentially detrimental.

The Trend of Serum Creatinine Does Not Predict Follow-Up Biopsy Findings Among Kidney Transplant Recipients With Antibody-Mediated Rejection.

Traditionally, antibody-mediated rejection (AMR) has been suspected mainly by a rise in serum creatinine (Scr) and confirmed by allograft biopsy. There is limited literature describing the trend of Scr after treatment, and how that trend might differ between patients with histological response and with no response to treatment. Methods: We included all cases of AMR at our program between March 2016 and July 2020 who had a follow-up biopsy after the index biopsy, with initial diagnosis of AMR. We trended the Scr and change in Scr (delta Scr) and its association with being a responder (microvascular inflammation, MVI ≤1) or nonresponder (MVI >1), as well as graft failure. Results: A total of 183 kidney transplant recipients were included, 66 in the responder group and 177 in the nonresponder group. The MVI scores and sum chronicity scores, along with transplant glomerulopathy scores, were higher in the nonresponder group. However, Scr at index biopsy was similar in responders (1.74 ± 0.70) versus nonresponders (1.83 ± 0.65; P = 0.39), as were the delta Scr at various time points. After adjustment for multiple variables, delta Scr was not associated with being a nonresponder. Also, delta Scr value at follow-up biopsy compared with index biopsy among responders was 0 ± 0.67 (P = 0.99) and among nonresponders was -0.01 ± 0.61 (P = 0.89). Being a nonresponder was significantly associated with an increased risk of graft failure at the last follow-up in univariate analysis but was not in multivariate analysis (hazard ratio 1.35; 95% confidence interval, 0.58-3.17; P = 0.49). Conclusions: We found that Scr is not a good predictor of the resolution of MVI, supporting the utility of follow-up biopsies after treatment of AMR.