Feasibility Analysis of Ultrasound-Guided Placement of Tunneled Hemodialysis Catheters.

Introduction: Radiographic fluoroscopy is the current standard for placement of tunneled central venous catheters (CVCs) for hemodialysis. Radiographic fluoroscopy requires structural and personnel infrastructure and exposes the patient to ionizing radiation. Here, we investigate the feasibility of solely ultrasound-guided placement of tunneled central venous dialysis catheters (USCVCs). Methods: We evaluated prospectively collected single-center data regarding safety and catheter function of 134 consecutive patients who underwent USCVC implantation between 2020 and 2021. We used the inset guidewire to visualize the position of the catheter tip. In the case of inadequate visibility by ultrasound, we used intracardiac electrocardiography (ECG) recording or agitated saline. A total of 1844 catheter days were assessed. The optimal CVC position was defined as being within the upper right atrium (URA) and middle to deep right atrium. Results: Of the 134 USCVCs, 87% were placed on the right side. The primary success rate for optimal tip position and catheter function was 98%. Of the USCVCs, 97% were placed solely by ultrasound. Regarding positioning, 6% were in the vena cava superior zone, 70% in the URA and 24% in the middle to deep right atrium, resulting in a rate of 94% with optimal positioning. Effective blood flow averaged 292 ± 39 ml/min. There were no immediate procedure-associated complications. Conclusion: Placement of CVC for hemodialysis solely by ultrasound is an effective alternative to fluoroscopy-assisted placement.

[Treatment response and complications of older patients with ANCA(antineutrophil cytoplasmatic antibody)-associated vasculitis]. / Therapieansprechen und Komplikationen von älteren Patienten mit ANCA(antineutrophile cytoplasmatische Antikörper)-assoziierten Vaskulitiden.

BACKGROUND: ANCA (antineutrophil cytoplasmatic antibody)-associated vasculitis (AAV) mainly affects elderley people but adjusted therapy concepts for this patient group are lacking. AIM: The aim of this study was therefore to analyze differences in course and outcome of patients with AAV with respect to age. MATERIALS AND METHODS: 62 patients were analyzed for treatment response, of whom 53 (85%) experienced adverse events (AE and SAE) that could be evaluated. Older (> 65 yrs.) versus younger (< 65 yrs.) patients were compared. Treatment response was assessed at 6 months, complications were assessed over 18 months. RESULTS: Treatment response was not seen to differ by age groups. In multiple logistic regression, pulmonary involvement (OR = 6,9; CI = 1,7-27,8, p < 0,01) and ΔGFR [ml/min] (OR = 0,93; CI = 0,89-0,97, p < 0,01) were predictors of SAE. 14 patients had more than 1 SAE. Again, pulmonary involvement (28,2% vs. 78,6%, p < 0,01) was a risk factor and older patients (78,6% vs. 43,6%, p = 0,025) were more frequently affected. Patients with multiple SAEs received glucocorticoids of more than 5 mg/d for longer periods of time (171 ± 65 days vs. 120 ± 70 days, p = 0,03). DISCUSSION: No differences were found between older and younger patients with regard to treatment response. Multiple SAEs occurred more frequently in elderly patients. There was a correlation between pulmonary manifestation and duration of glucocorticoid therapy with a complicated course. The most frequent SAEs were infections requiring hospitalisation. CONCLUSION: Therapy for elderly patients should be individualized with the goal of a fast reduction of glucocorticoids. Special monitoring is indicated for elderly patients, especially those with pulmonary involvement.

Deceased-Donor Acute Kidney Injury and Acute Rejection in Kidney Transplant Recipients: A Multicenter Cohort.

RATIONALE & OBJECTIVE: Donor acute kidney injury (AKI) activates innate immunity, enhances HLA expression in the kidney allograft, and provokes recipient alloimmune responses. We hypothesized that injury and inflammation that manifested in deceased-donor urine biomarkers would be associated with higher rates of biopsy-proven acute rejection (BPAR) and allograft failure after transplantation. STUDY DESIGN: Prospective cohort. SETTING & PARTICIPANTS: 862 deceased donors for 1,137 kidney recipients at 13 centers. EXPOSURES: We measured concentrations of interleukin 18 (IL-18), kidney injury molecule 1 (KIM-1), and neutrophil gelatinase-associated lipocalin (NGAL) in deceased donor urine. We also used the Acute Kidney Injury Network (AKIN) criteria to assess donor clinical AKI. OUTCOMES: The primary outcome was a composite of BPAR and graft failure (not from death). A secondary outcome was the composite of BPAR, graft failure, and/or de novo donor-specific antibody (DSA). Outcomes were ascertained in the first posttransplant year. ANALYTICAL APPROACH: Multivariable Fine-Gray models with death as a competing risk. RESULTS: Mean recipient age was 54 ± 13 (SD) years, and 82% received antithymocyte globulin. We found no significant associations between donor urinary IL-18, KIM-1, and NGAL and the primary outcome (subdistribution hazard ratio [HR] for highest vs lowest tertile of 0.76 [95% CI, 0.45-1.28], 1.20 [95% CI, 0.69-2.07], and 1.14 [95% CI, 0.71-1.84], respectively). In secondary analyses, we detected no significant associations between clinically defined AKI and the primary outcome or between donor biomarkers and the composite outcome of BPAR, graft failure, and/or de novo DSA. LIMITATIONS: BPAR was ascertained through for-cause biopsies, not surveillance biopsies. CONCLUSIONS: In a large cohort of kidney recipients who almost all received induction with thymoglobulin, donor injury biomarkers were associated with neither graft failure and rejection nor a secondary outcome that included de novo DSA. These findings provide some reassurance that centers can successfully manage immunological complications using deceased-donor kidneys with AKI.

Diverse molecular causes of unsolved autosomal dominant tubulointerstitial kidney diseases.

Autosomal Dominant Tubulointerstitial Kidney Disease (ADTKD) is caused by mutations in one of at least five genes and leads to kidney failure usually in mid adulthood. Throughout the literature, variable numbers of families have been reported, where no mutation can be found and therefore termed ADTKD-not otherwise specified. Here, we aim to clarify the genetic cause of their diseases in our ADTKD registry. Sequencing for all known ADTKD genes was performed, followed by SNaPshot minisequencing for the dupC (an additional cytosine within a stretch of seven cytosines) mutation of MUC1. A virtual panel containing 560 genes reported in the context of kidney disease (nephrome) and exome sequencing were then analyzed sequentially. Variants were validated and tested for segregation. In 29 of the 45 registry families, mutations in known ADTKD genes were found, mostly in MUC1. Sixteen families could then be termed ADTKD-not otherwise specified, of which nine showed diagnostic variants in the nephrome (four in COL4A5, two in INF2 and one each in COL4A4, PAX2, SALL1 and PKD2). In the other seven families, exome sequencing analysis yielded potential disease associated variants in novel candidate genes for ADTKD; evaluated by database analyses and genome-wide association studies. For the great majority of our ADTKD registry we were able to reach a molecular genetic diagnosis. However, a small number of families are indeed affected by diseases classically described as a glomerular entity. Thus, incomplete clinical phenotyping and atypical clinical presentation may have led to the classification of ADTKD. The identified novel candidate genes by exome sequencing will require further functional validation.

[Frailty in renal diseases]. / "Frailty" bei nephrologischen Erkrankungen.

The term frailty describes a complex syndrome of reduced resistance to stress factors as a consequence of age-related degeneration in various organ systems.In the general population frailty is associated with poor clinical outcomes, including an increased risk of falls, hospitalization, functional impairment and mortality. Frailty occurs earlier and its prevalence is higher in patients with chronic kidney disease (CKD) compared to the general population. Frail patients with CKD, on dialysis or not, have reduced quality of life and increased hospitalization and mortality rates, regardless of age, sex or comorbidities.The identification of frailty in patients with CKD can lead to the detection of important and potentially modifiable risk factors. Early nephrological evaluation coupled with an interdisciplinary approach including primary care physicians, geriatricians, physiotherapists, occupational therapists and nutritionists, is fundamental in the prevention of frailty as well as in the management of frail patients with CKD.Several instruments have been developed to screen for and assess the degree of frailty; however, there is currently no recommendation as to which should be used in nephrology and how to manage frail patients with CKD. In this article we suggest an approach based on a multidimensional, interdisciplinary evaluation aimed at the early identification and management of frail CKD patients independent of the clinical setting of admission; however, more important than the method used is the need to identify and follow-up on frail CKD patients.

Deceased-Donor Acute Kidney Injury and BK Polyomavirus in Kidney Transplant Recipients.

BACKGROUND AND OBJECTIVES: BK polyomavirus (BKV) infection commonly complicates kidney transplantation, contributing to morbidity and allograft failure. The virus is often donor-derived and influenced by ischemia-reperfusion processes and disruption of structural allograft integrity. We hypothesized that deceased-donor AKI associates with BKV infection in recipients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We studied 1025 kidney recipients from 801 deceased donors transplanted between 2010 and 2013, at 13 academic centers. We fitted Cox proportional-hazards models for BKV DNAemia (detectable in recipient blood by clinical PCR testing) within 1 year post-transplantation, adjusting for donor AKI and other donor- and recipient-related factors. We validated findings from this prospective cohort with analyses for graft failure attributed to BKV within the Organ Procurement and Transplantation Network (OPTN) database. RESULTS: The multicenter cohort mean kidney donor profile index was 49±27%, and 26% of donors had AKI. Mean recipient age was 54±13 years, and 25% developed BKV DNAemia. Donor AKI was associated with lower risk for BKV DNAemia (adjusted hazard ratio, 0.53; 95% confidence interval, 0.36 to 0.79). In the OPTN database, 22,537 (25%) patients received donor AKI kidneys, and 272 (0.3%) developed graft failure from BKV. The adjusted hazard ratio for the outcome with donor AKI was 0.7 (95% confidence interval, 0.52 to 0.95). CONCLUSIONS: In a well-characterized, multicenter cohort, contrary to our hypothesis, deceased-donor AKI independently associated with lower risk for BKV DNAemia. Within the OPTN database, donor AKI was also associated with lower risk for graft failure attributed to BKV. PODCAST: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2021_03_10_CJN18101120_final.mp3.

Renal Function and Patient-Reported Outcomes in Stable Kidney Transplant Patients Following Conversion From Twice-Daily Immediate-Release Tacrolimus to Once-Daily Prolonged-Release Tacrolimus: A 12-Month Observational Study in Routine Clinical Practice in Germany (ADAGIO).

INTRODUCTION: This 12-month, noninterventional study on routine clinical practice in Germany evaluated renal function in stable kidney transplant recipients converted from immediate-release tacrolimus (IR-T) to prolonged-release tacrolimus (PR-T). METHODS: Renal function was assessed in 183 patients by estimated glomerular filtration rate using the modification of diet in renal disease-4 formula. Self-reported gastrointestinal health-related quality of life, adherence, satisfaction with PR-T, suspected rejection episodes, and safety were also assessed at conversion and at 3, 6, and 12 months. RESULTS: Conversion from IR-T to PR-T resulted in stable kidney function over 12 months, with a difference in estimated glomerular filtration rate between the first and final visits of 0.1 mL/min/1.73 m2 (95% confidence interval, -1.6, 1.8). Eight patients experienced an acute rejection episode (4.4%). At each assessment, gastrointestinal health-related quality of life was low and adherence was high. Most patients reported that they were very satisfied (69.8%) or satisfied (28.1%) with PR-T at the final visit. Among patients reporting a preference, 78.4% preferred PR-T, 2.2% preferred IR-T, and 19.4% reported no preference. The safety profile of PR-T was consistent with that previously described. CONCLUSION: Conversion of stable kidney transplant recipients from IR-T to PR-T provided stable kidney and graft function over 12 months (Verband Forschender Arzneimittelhersteller--registered study: NIS ADV-02).

Contemporary incidence and risk factors of post transplant Erythrocytosis in deceased donor kidney transplantation.

BACKGROUND: Post-Transplant erythrocytosis (PTE) has not been studied in large recent cohorts. In this study, we evaluated the incidence, risk factors, and outcome of PTE with current transplant practices using the present World Health Organization criteria to define erythrocytosis. We also tested the hypothesis that the risk of PTE is greater with higher-quality kidneys. METHODS: We utilized the Deceased Donor Study which is an ongoing, multicenter, observational study of deceased donors and their kidney recipients that were transplanted between 2010 and 2013 across 13 centers. Eryrthocytosis is defined by hemoglobin> 16.5 g/dL in men and> 16 g/dL in women. Kidney quality is measured by Kidney Donor Profile Index (KDPI). RESULTS: Of the 1123 recipients qualified to be in this study, PTE was observed at a median of 18 months in 75 (6.6%) recipients. Compared to recipients without PTE, those with PTE were younger [mean 48±11 vs 54±13 years, p < 0.001], more likely to have polycystic kidney disease [17% vs 6%, p < 0.001], have received kidneys from younger donors [36 ±13 vs 41±15 years], and be on RAAS inhibitors [35% vs 22%, p < 0.001]. Recipients with PTE were less likely to have received kidneys from donors with hypertension [16% vs 32%, p = 0.004], diabetes [1% vs 11%, p = 0.008], and cerebrovascular event (24% vs 36%, p = 0.036). Higher KDPI was associated with decreased PTE risk [HR 0.98 (95% CI: 0.97-0.99)]. Over 60 months of follow-up, only 17 (36%) recipients had sustained PTE. There was no association between PTE and graft failure or mortality, CONCLUSIONS: The incidence of PTE was low in our study and PTE resolved in majority of patients. Lower KDPI increases risk of PTE. The underutilization of RAAS inhibitors in PTE patients raises the possibility of under-recognition of this phenomenon and should be explored in future studies.

Post-transplant Diabetes Mellitus in Kidney Transplant Recipients: A Multicenter Study.

Background: De novo post-transplant diabetes mellitus (PTDM) is a common complication after kidney transplant (KT). Most recent studies are single center with various approaches to outcome ascertainment. Methods: In a multicenter longitudinal cohort of 632 nondiabetic adult kidney recipients transplanted in 2010-2013, we ascertained outcomes through detailed chart review at 13 centers. We hypothesized that donor characteristics, such as sex, HCV infection, and kidney donor profile index (KDPI), and recipient characteristics, such as age, race, BMI, and increased HLA mismatches, would affect the development of PTDM among KT recipients. We defined PTDM as hemoglobin A1c ≥6.5%, pharmacological treatment for diabetes, or documentation of diabetes in electronic medical records. We assessed PTDM risk factors and evaluated for an independent time-updated association between PTDM and graft failure using regression. Results: Mean recipient age was 52±14 years, 59% were male, 49% were Black. Cumulative PTDM incidence 5 years post-KT was 29% (186). Independent baseline PTDM risk factors included older recipient age (P<0.001) and higher BMI (P=0.006). PTDM was not associated with all-cause graft failure (adjusted hazard ratio (aHR), 1.10; 95% CI, 0.78 to 1.55), death-censored graft failure (aHR, 0.85; 95% CI, 0.53 to 1.37), or death (aHR, 1.31; 95% CI, 0.84 to 2.05) at median follow-up of 6 (interquartile range, 4.0-6.9) years post-KT. Induction and maintenance immunosuppression were not different between patients who did and did not develop PTDM. Conclusions: PTDM occurred commonly, and higher baseline BMI was associated with PTDM. PTDM was not associated with graft failure or mortality during the 6-year follow-up, perhaps due to the short follow-up time.

Uromodulin to Osteopontin Ratio in Deceased Donor Urine Is Associated With Kidney Graft Outcomes.

BACKGROUND: Deceased-donor kidneys experience extensive injury, activating adaptive and maladaptive pathways therefore impacting graft function. We evaluated urinary donor uromodulin (UMOD) and osteopontin (OPN) in recipient graft outcomes. METHODS: Primary outcomes: all-cause graft failure (GF) and death-censored GF (dcGF). Secondary outcomes: delayed graft function (DGF) and 6-month estimated glomerular filtration rate (eGFR). We randomly divided our cohort of deceased donors and recipients into training and test datasets. We internally validated associations between donor urine UMOD and OPN at time of procurement, with our primary outcomes. The direction of association between biomarkers and GF contrasted. Subsequently, we evaluated UMOD:OPN ratio with all outcomes. To understand these mechanisms, we examined the effect of UMOD on expression of major histocompatibility complex II in mouse macrophages. RESULTS: Doubling of UMOD increased dcGF risk (adjusted hazard ratio [aHR], 1.1; 95% confidence interval [CI], 1.02-1.2), whereas OPN decreased dcGF risk (aHR, 0.94; 95% CI, 0.88-1). UMOD:OPN ratio ≤3 strengthened the association, with reduced dcGF risk (aHR, 0.57; 0.41-0.80) with similar associations for GF, and in the test dataset. A ratio ≤3 was also associated with lower DGF (aOR, 0.73; 95% CI, 0.60-0.89) and higher 6-month eGFR (adjusted ß coefficient, 3.19; 95% CI, 1.28-5.11). UMOD increased major histocompatibility complex II expression elucidating a possible mechanism behind UMOD's association with GF. CONCLUSIONS: UMOD:OPN ratio ≤3 was protective, with lower risk of DGF, higher 6-month eGFR, and improved graft survival. This ratio may supplement existing strategies for evaluating kidney quality and allocation decisions regarding deceased-donor kidney transplantation.

Eculizumab in chemotherapy-induced thrombotic microangiopathy.

Thrombotic microangiopathy (TMA) is a rare but severe complication of tumors and their chemotherapeutic treatment. We report on two patients with chemotherapy-induced TMA who were successfully treated with a short course of the terminal complement inhibitor eculizumab. Both patients quickly achieved remission of microangiopathic hemolytic anemia and recovery of renal function. After withdrawal of eculizumab, remission was stable over an observation period of 47 months and 15 months, respectively. Our data show that eculizumab is effective in treating chemotherapy-induced TMA. Discontinuation of eculizumab is feasible once the complement-activating condition is controlled and the trigger is eliminated. Additional studies need to determine the optimal duration of complement-directed therapies and validate effective monitoring strategies after discontinuation of such therapy.

Relative incidence of thrombotic thrombocytopenic purpura and haemolytic uraemic syndrome in clinically suspected cases of thrombotic microangiopathy.

BACKGROUND: Data are lacking on the relative incidence of thrombotic thrombocytopenic purpura (TTP), haemolytic uraemic syndrome (HUS) caused by Shiga toxin-producing Escherichia coli (STEC) and atypical HUS (aHUS) in patients presenting with thrombotic microangiopathies (TMAs). METHODS: This was a prospective, cross-sectional, multicentre and non-interventional epidemiological study. Patients fulfilling criteria for TMAs (platelet consumption, microangiopathic haemolytic anaemia and organ dysfunction) were included in the study. The primary objective was to assess the relative incidence of TTP, STEC-HUS, aHUS and 'other' physician-defined diagnoses. The secondary objective was to develop an algorithm to predict a severe deficiency in ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) activity (≤10%) using routine laboratory parameters. A post hoc classification using the recent Kidney Disease: Improving Global Outcomes diagnostic criteria was then undertaken to further classify patient groups. RESULTS: aHUS was diagnosed with a relative incidence of 61%, whereas TTP, STEC-HUS and 'other' were diagnosed in 13, 6 and 20% of patients, respectively. In the post hoc analysis, 27% of patients with a TMA were classified as 'primary aHUS' and 53% as 'secondary aHUS'. Multivariate analysis revealed that severe deficiency in ADAMTS13 activity (≤10%) was unlikely to underlie TMA if platelet and serum creatinine were above threshold values of 30 × 109/L and 1.8 mg/dL, respectively (negative predictive value of 92.3 and 98.1, respectively, if one or both values were above the threshold). CONCLUSIONS: In this study, aHUS was the most common single diagnosis among patients presenting with a TMA. In the absence of an ADAMTS13 activity result, platelet count and serum creatinine may aid in the differential diagnosis.

Peritransplant eculizumab does not prevent delayed graft function in deceased donor kidney transplant recipients: Results of two randomized controlled pilot trials.

Animal models and observational human data indicate that complement, including C5a, pathogenically participates in ischemia reperfusion (IR) injury that manifests as delayed graft function (DGF) following deceased donor kidney transplantation. We report on the safety/efficacy of anti-C5 monoclonal antibody eculizumab (Ecu) administered in the operating room prior to reperfusion, to prevent DGF in recipients of deceased donor kidney transplants in two related, investigator-sponsored, randomized controlled trials. Eight recipients from a single center were enrolled in a pilot study that led to a 19-subject multicenter trial. Together, 27 deceased donor kidney transplant recipients, 16 Ecu-treated and 11 controls, were treated with rabbit antithymocyte globulin, tacrolimus, mycophenolate mofetil with or without glucocorticoids, and followed for 6 months. Data analysis showed no epidemiological or transplant-related differences between study arms. Ecu was well tolerated with a similar severe adverse event incidence between groups. The DGF rate did not differ between Ecu-treated (44%) and control (45%, P = 1.0) subjects. Serum creatinine reduction in the first week after transplantation, and graft function up to 180-days post-transplant, were also similar. Ecu administration was safe but did not reduce the rate of DGF in a high-risk population of deceased donor recipients.

Urine Injury Biomarkers Are Not Associated With Kidney Transplant Failure.

BACKGROUND: Kidneys transplanted from deceased donors with serum creatinine-defined acute kidney injury (AKI) have similar allograft survival as non-AKI kidneys but are discarded at a higher rate. Urine injury biomarkers are sensitive markers of structural kidney damage and may more accurately predict graft outcomes. METHODS: In the 2010-2013 multicenter Deceased Donor Study of 2430 kidney transplant recipients from 1298 donors, we assessed the association of donor urine injury biomarkers microalbumin, neutrophil gelatinase-associated lipocalin, kidney injury molecule-1, IL-18, and liver-type fatty acid binding protein with graft failure (GF) and death-censored GF (dcGF) using Cox proportional hazard models (median follow-up 4 y). We examined if serum creatinine-defined donor AKI modified this association to assess the relationship between subclinical donor AKI (elevated biomarkers without creatinine-defined AKI) and GF. Through chart review of a subcohort (1137 recipients), we determined associations between donor injury biomarkers and a 3-year composite outcome of GF, mortality, or estimated glomerular filtration rate ≤ 20mL/min/1.73m. RESULTS: Risk of GF, dcGF, and 3-year composite outcome did not vary with donor injury biomarker concentrations after adjusting for donor, transplant, and recipient characteristics (adjusted hazard ratio ranged from 0.96 to 1.01 per log-2 increase in biomarker). Subclinical injury in transplanted kidneys without AKI was not associated with GF. CONCLUSIONS: AKI measured using injury biomarkers was not associated with posttransplant graft outcomes (at median 4 y posttransplant). When assessing posttransplant graft viability, clinicians can prioritize other donor and recipient factors over donor kidney injury, measured by either serum creatinine or urine injury biomarkers.

Donor Urinary C5a Levels Independently Correlate With Posttransplant Delayed Graft Function.

BACKGROUND: Accumulating evidence implicates the complement cascade as pathogenically contributing to ischemia-reperfusion injury and delayed graft function (DGF) in human kidney transplant recipients. Building on observations that kidney injury can initiate in the donor before nephrectomy, we tested the hypothesis that anaphylatoxins C3a and C5a in donor urine before transplantation associate with risk of posttransplant injury. METHODS: We evaluated the effects of C3a and C5a in donor urine on outcomes of 469 deceased donors and their corresponding 902 kidney recipients in a subset of a prospective cohort study. RESULTS: We found a threefold increase of urinary C5a concentrations in donors with stage 2 and 3 acute kidney injury (AKI) compared donors without AKI (P < 0.001). Donor C5a was higher for the recipients with DGF (defined as dialysis in the first week posttransplant) compared with non-DGF (P = 0.002). In adjusted analyses, C5a remained independently associated with recipient DGF for donors without AKI (relative risk, 1.31; 95% confidence interval, 1.13-1.54). For donors with AKI, however, urinary C5a was not associated with DGF. We observed a trend toward better 12-month allograft function for kidneys from donors with C5a concentrations in the lowest tertile (P = 0.09). Urinary C3a was not associated with donor AKI, recipient DGF, or 12-month allograft function. CONCLUSIONS: Urinary C5a correlates with the degree of donor AKI. In the absence of clinical donor AKI, donor urinary C5a concentrations associate with recipient DGF, providing a foundation for testing interventions aimed at preventing DGF within this high-risk patient subgroup.

Deceased-donor acute kidney injury is not associated with kidney allograft failure.

Deceased-donor acute kidney injury (AKI) is associated with organ discard and delayed graft function, but data on longer-term allograft survival are limited. We performed a multicenter study to determine associations between donor AKI (from none to severe based on AKI Network stages) and all-cause graft failure, adjusting for donor, transplant, and recipient factors. We examined whether any of the following factors modified the relationship between donor AKI and graft survival: kidney donor profile index, cold ischemia time, donation after cardiac death, expanded-criteria donation, kidney machine perfusion, donor-recipient gender combinations, or delayed graft function. We also evaluated the association between donor AKI and a 3-year composite outcome of all-cause graft failure or estimated glomerular filtration rate ≤ 20 mL/min/1.73 m2 in a subcohort of 30% of recipients. Among 2,430 kidneys transplanted from 1,298 deceased donors, 585 (24%) were from donors with AKI. Over a median follow-up of 4.0 years, there were no significant differences in graft survival by donor AKI stage. We found no evidence that pre-specified variables modified the effect of donor AKI on graft survival. In the subcohort, donor AKI was not associated with the 3-year composite outcome. Donor AKI was not associated with graft failure in this well-phenotyped cohort. Given the organ shortage, the transplant community should consider measures to increase utilization of kidneys from deceased donors with AKI.

Reliability of deceased-donor procurement kidney biopsy images uploaded in United Network for Organ Sharing.

Prior studies demonstrate poor agreement among pathologists' interpretation of kidney biopsy slides. Reliability of representative images of these slides uploaded to the United Network of Organ Sharing (UNOS) web portal for clinician review has not been studied. We hypothesized high agreement among pathologists' image interpretation, since static images eliminate variation induced by viewing different areas of movable slides. To test our hypothesis, we compared the assessments of UNOS-uploaded images recorded in standardized forms by three pathologists. We selected 100 image sets, each having at least two images from kidneys of deceased donors. Weighted Cohen's kappa was used for inter-rater agreement. Mean (SD) donor age was 50 (13). Acute tubular injury had kappas of 0.12, 0.14, and 0.19; arteriolar hyalinosis 0.16, 0.27, and 0.38; interstitial inflammation 0.30, 0.33, and 0.49; interstitial fibrosis 0.28, 0.32, and 0.67; arterial intimal fibrosis 0.34, 0.42, and 0.59; tubular atrophy 0.35, 0.41, and 0.52; glomeruli thrombi 0.32, 0.53, and 0.85; and global glomerulosclerosis 0.68, 0.70, and 0.77. Pathologists' agreement demonstrated kappas of 0.12 to 0.77. The lower values raise concern about the reliability of using images. Although further research is needed to understand how uploaded images are used clinically, the field may consider higher-quality standards for biopsy photomicrographs.

Procurement Biopsy Findings Versus Kidney Donor Risk Index for Predicting Renal Allograft Survival.

BACKGROUND: Efforts to maximize transplantation by matching organ quality to recipient longevity require reliable tools. The US kidney allocation system uses the Kidney Donor Risk Index (KDRI) for this purpose, and many centers additionally rely on donor biopsies. The Leuven score combines donor age with procurement histology (glomerulosclerosis and interstitial fibrosis/tubular atrophy) to predict allograft survival. METHODS: We compared KDRI with Leuven scores for associations with kidney discard, delayed graft function, and allograft function and survival. We used Cox, modified Poisson, and linear regression to calculate risks based on KDRI and (separately) Leuven scores, adjusting for important transplant and recipient variables. RESULTS: From 890 donors, 1729 kidneys were procured and biopsied. Five hundred eighty-five (34%) kidneys were discarded. Median donor age was 53 years (interquartile range [IQR], 44-61 years). Median KDRI and Leuven scores were 1.56 (IQR, 1.28-1.90) and 59 (IQR, 49-69). Relative risk for discard was 1.21 (95% confidence interval [CI], 1.17-1.24) per 0.2-unit increase in KDRI and 1.38 (1.31-1.46) per 10-unit increase in Leuven score. Adjusted relative risks for delayed graft function were 0.98 (95% CI, 0.94-1.02) and 0.94 (95% CI, 0.90-0.99), adjusted hazard ratios for graft failure were 1.10 (95% CI, 1.04-1.16) and 1.11 (95% CI, 1.02-1.21), and adjusted linear regression coefficients for 3-year estimated glomerular filtration rate were -3.88 (-4.63 to -3.13) and -5.18 (-6.19 to -4.18). CONCLUSIONS: In kidneys clinically selected for procurement biopsy, the Leuven score was more strongly associated with discard but performed similarly to KDRI for predicting transplant outcomes, suggesting the need to reevaluate current procurement biopsy practices. Given modest associations for both tools; however, neither KDRI nor the Leuven score should be used in isolation for individual organ acceptance decisions.