Do pre-transplant cultural factors predict health-related quality of life after kidney transplantation?

BACKGROUND: Post-transplant health-related quality of life (HRQOL) is associated with health outcomes for kidney transplant (KT) recipients. However, pretransplant predictors of improvements in post-transplant HRQOL remain incompletely understood. Namely, important pretransplant cultural factors, such as experience of discrimination, perceived racism in healthcare, or mistrust of the healthcare system, have not been examined as potential HRQOL predictors. Also, few have examined predictors of decline in HRQOL post-transplant. METHODS: Using data from a prospective cohort study, we examined HRQOL change pre- to post-transplant, and novel cultural predictors of the change. We measured physical, mental, and kidney-specific HRQOL as outcomes, and used cultural factors as predictors, controlling for demographic, clinical, psychosocial, and transplant knowledge covariates. RESULTS: Among 166 KT recipients (57% male; mean age 50.6 years; 61.4% > high school graduates; 80% non-Hispanic White), we found mental and physical, but not kidney-specific, HRQOL significantly improved post-transplant. No culturally related factors outside of medical mistrust significantly predicted change in any HRQOL outcome. Instead, demographic, knowledge, and clinical factors significantly predicted decline in each HRQOL domain: physical HRQOL-older age, more post-KT complications, higher pre-KT physical HRQOL; mental HRQOL-having less information pre-KT, greater pre-KT mental HRQOL; and, kidney-specific HRQOL-poorer kidney functioning post-KT, lower expectations for physical condition to improve, and higher pre-KT kidney-specific HRQOL. CONCLUSIONS: Instead of cultural factors, predictors of HRQOL decline included demographic, knowledge, and clinical factors. These findings are useful for identifying patient groups that may be at greater risk of poorer post-transplant outcomes, in order to target individualized support to patients.

Predicting Kidney Transplant Evaluation Non-attendance.

Non-attendance to kidney transplant evaluation (KTE) appointments is a barrier to optimal care for those with kidney failure. We examined the medical and socio-cultural factors that predict KTE non-attendance to identify opportunities for integrated medical teams to intervene. Patients scheduled for KTE between May, 2015 and June, 2018 completed an interview before their initial KTE appointment. The interview assessed various social determinants of health, including demographic (e.g., income), medical (e.g. co-morbidities), transplant knowledge, cultural (e.g., medical mistrust), and psychosocial (e.g., social support) factors. We used multiple logistic regression analysis to determine the strongest predictor of KTE non-attendance. Our sample (N = 1119) was 37% female, 76% non-Hispanic White, median age 59.4 years (IQR 49.2-67.5). Of note, 142 (13%) never attended an initial KTE clinic appointment. Being on dialysis predicted higher odds of KTE non-attendance (OR 1.76; p = .02; 64% of KTE attendees on dialysis vs. 77% of non-attendees on dialysis). Transplant and nephrology teams should consider working collaboratively with dialysis units to better coordinate care, (e.g., resources to attend appointment or outreach to emphasize the importance of transplant) adjusting the KTE referral and evaluation process to address access issues (e.g., using tele-health) and encouraging partnership with clinical psychologists to promote quality of life for those on dialysis.

Tocilizumab for treatment of chronic active antibody-mediated rejection in kidney transplant recipients.

BACKGROUND: The optimal treatment for chronic active antibody-mediated rejection (ca-AMR) remains unclear. Tocilizumab (TCZ), a monoclonal antibody against IL-6, has been proposed as a therapeutic option. We reported our experience treating ca-AMR with TCZ either as the first line option or as a rescue therapy. METHODS: We studied 11 adult kidney transplant recipients with biopsy-proven ca-AMR and preserved kidney function (eGFR 57 ± 18) who were treated with TCZ (8 mg/kg IV monthly). All biopsies were prompted by abnormal surveillance biomarker testing with DSA and/or dd-cfDNA. Clinical monitoring included dd-cfDNA and DSA testing every 3 months during the treatment with TCZ. RESULTS: In this cohort, ca-AMR was diagnosed at a median of 90 months (range 14-224) post-transplant, and 4 of 11 patients had DSA negative ca-AMR. Patients received a minimum of 3 months of TCZ, with 6 patients receiving at least 12 months of TCZ. Dd-cfDNA was elevated in all patients, with a median 2.24% at the start of TCZ treatment. After 6 months of TCZ treatment, 8/11 patients had dd- cfDNA <1%, and 3/11 had values <0.5%. Among those who completed at least 12 months of TCZ, dd-cfDNA decreased by 29% at 6 months (p = .05) and 47% by 12 months (p = .04). DSA also stabilized and, by 12 months, was reduced by 29% (p = .047). Graft function remained stable with no graft loss during treatment. There was a nonsignificant trend towards proteinuria reduction. During the course of treatment with tocilizumab, two patients experienced moderate to severe infections. CONCLUSIONS: In our early short-term experience, TCZ appears to reduce graft injury as measured by dd-cfDNA and modulate the immune response as evident by a modest reduction in immunodominant DSA MFI. Allograft function and proteinuria also stabilized.

Cognitive assessment in a predominantly Hispanic and Native American population in New Mexico and its association with kidney transplant wait-listing.

The association between cognitive function and the likelihood of kidney transplant (KT) wait-listing, especially in minority populations, has not been clearly delineated. We performed a retrospective review of our pre-KT patients, who consist mainly of Hispanics and Native Americans, over a 16-month period. We collected data on baseline demographics and the Montreal Cognitive Assessment (MoCA) score, at the initial KT evaluation. We defined cognitive impairment as MoCA scores of <24. We constructed linear regression models to identify associations between baseline characteristics with MoCA scores and used Cox proportional hazards models to assess associations between MoCA score and KT wait-listing. During the study period, 154 patients completed the MoCA during their initial evaluation. Mean (standard deviation) MoCA scores were 23.9 (4.6), with 58 (38%) participants scoring <24. Advanced age, lower education and being on dialysis were associated with lower MoCA scores. For every one-point increase in MoCA, the likelihood of being wait-listed increased 1.10-fold (95% CI 1.01-1.19, P = .022). Being Native American and having kidney disease due to diabetes or hypertension were associated with longer time to wait-listing. Cognitive impairment was common in our pre-KT patients and was associated with a lower likelihood of KT wait-listing.

Beta-2 microglobulin clearance in high-flux dialysis and convective dialysis modalities: a meta-analysis of published studies.

Background: Recent meta-analyses suggest that higher removal of beta-2 microglobulin (ß2M) with either high-flux (HFD) dialysis or hemodiafiltration (HDF) may be associated with decreased total and cardiovascular mortality in dialysis patients. However, there are limited data about the performance of high flux dialyzers and/or convective therapies in removing ß2M. Methods: This is a random effects meta-analysis and meta-regression of data extracted from randomized controlled trials and observational studies in hemodialysis, hemofiltration and HDF regarding the efficiency of high flux dialyzers to remove ß2M. Studies were searched using ProQuest in SCOPUS, EMBASE and MEDLINE. Results: We included 69 studies from 1 January 2001 to 12 June 2017 on 1879 patients with 6771 available measurements. Average ß2M clearance was 48.75 mL/min [95% confidence interval (CI) 42.50-55.21] for conventional HF dialysis, and 87.06 mL/min (95% CI 75.08-99.03) for convective therapies (hemofiltration and HDF) with substantial heterogeneity among studies [P (Q) ≤ 0.001]. In multivariable meta-regression analyses, we found significantly higher ß2M clearance for polyarylethersulfone dialyzers when used for HFD and polysulfone membranes in convective therapies. However, the mass of ß2M removed into the dialysate did not depend on membrane material. Adjusted dialysate-side (-22.279, 95% CI -9.8 to -34.757, P < 0.001) ß2M clearances were significantly lower than whole blood clearances, suggesting that adsorption contributes substantially to ß2M removal. Higher Kuf, blood flow and substitution fluid rates but not dialysate flow rates were associated with statistically significant and clinically meaningful elevation in ß2M clearance from the body independent of the dialysis modality. Conclusions: Membrane composition and characteristics, modality (convective versus diffusive), blood flow rates and substitution fluid rates in HDF play a significant role in the efficient removal of ß2M from the body in both diffusive and convective dialysis.

Neighborhood Socioeconomic Deprivation is Associated with Worse Outcomes in Pediatric Kidney Transplant Recipients.

BACKGROUND: Social determinants of health shape a child's transplant course. We describe the association between neighborhood socioeconomic deprivation, transplant characteristics, and graft survival in US pediatric kidney transplant recipients. METHODS: US recipients <18 years of age at listing transplanted January 1st, 2010, to May 31st, 2022 (N=9,178) were included from the Scientific Registry of Transplant Recipients. Recipients were stratified into three groups according to Material Community Deprivation Index score, with greater score representing higher neighborhood socioeconomic deprivation. Outcomes were modeled using multivariable logistic regression and Cox proportional hazards models. RESULTS: Twenty-four percent (N=110) of recipients from neighborhoods of high socioeconomic deprivation identified as being of Black race, versus 12% (N=383) of recipients from neighborhoods of low socioeconomic deprivation. Neighborhoods of high socioeconomic deprivation had a much greater proportion of recipients identifying as being of Hispanic ethnicity (67%, N=311), versus neighborhoods of low socioeconomic deprivation (17%, N=562). The hazard of graft loss was 55% higher (aHR 1.55, 95% CI: 1.24, 1.94) for recipients from neighborhoods of high versus recipients from low socioeconomic deprivation neighborhoods when adjusted for base covariates, race and ethnicity, and insurance status, with 59% lower odds (aOR 0.41, 95% CI: 0.30, 0.56) of living donor transplantation and, although not statistically significant, 8% lower odds (aOR 0.92, 95% CI: 0.72, 1.19) of preemptive transplantation. The hazard of graft loss was 41% higher (aHR 1.41, 95% CI: 1.25, 1.60) for recipients from neighborhoods of intermediate versus recipients from low socioeconomic deprivation neighborhoods when adjusted for base covariates, race and ethnicity, and insurance status, with 27% lower odds (aOR 0.73, 95% CI: 0.66, 0.81) of living donor transplantation and 11% lower odds (aOR 0.89, 95% CI: 0.80, 0.99) of preemptive transplantation. CONCLUSIONS: Children from neighborhoods of high socioeconomic deprivation have worse graft survival and lower utilization of preemptive and living donor transplantation. These findings demonstrate inequities in pediatric kidney transplantation that warrant further intervention.

Reexamining the Impact of Insurance Type on Kidney Transplant Waitlist Status and Posttransplantation Outcomes in the United States After Implementation of the Affordable Care Act.

Insurance type, a marker of socioeconomic status, has been associated with poor access to kidney transplant (KT) and worse KT outcomes before the implementation of the Affordable Care Act (ACA) and the revised Kidney Allocation System (KAS). In this study, we assessed if insurance type remained a risk marker for worse waitlist and transplant outcomes after ACA and KAS. Methods: Using Scientific Registry of Transplant Recipients data, we assessed insurance type of waitlisted candidates pre- (2008-2014) versus post- (2014-2021) KAS/ACA using chi-square tests. Next, we performed a competing risk analysis to study the effect of private versus public (Medicare, Medicaid, or government-sponsored) insurance on waitlist outcomes and a Cox survival analysis to study posttransplant outcomes while controlling for candidate, and recipient and donor variables, respectively. Results: The proportion of overall KT candidates insured by Medicaid increased from pre-KAS/ACA to post-KAS/ACA (from 12 667 [7.3%] to 21 768 [8.8%], P < 0.0001). However, KT candidates with public insurance were more likely to have died or become too sick for KT (subdistribution hazard ratio [SHR] = 1.33, confidence interval [CI], 1.30-1.36) or to receive a deceased donor KT (SHR = 1.57, CI, 1.54-1.60) but less likely to receive a living donor KT (SHR = 0.87, CI, 0.85-0.89). Post-KT, KT recipients with public insurance had greater risk of mortality (relative risks = 1.22, CI, 1.15-1.31) and allograft failure (relative risks = 1.10, CI, 1.03-1.29). Conclusions: Although the implementation of ACA marginally increased the proportion of waitlisted candidates with Medicaid, publicly insured KT candidates remained at greater risk of being removed from the waitlist, had lower probability of living donor kidney transplantation, and had greater probability of dying post-KT and allograft failure. Concerted efforts to address factors contributing to these inequities in future studies are needed, with the goal of achieving equity in KT for all.

Medication, Healthcare Follow-up, and Lifestyle Nonadherence: Do They Share the Same Risk Factors?

Barriers to medication adherence may differ from barriers in other domains of adherence. In this study, we assessed the association between pre-kidney transplantation (KT) factors with nonadherent behaviors in 3 different domains post-KT. METHODS: We conducted a prospective cohort study with patient interviews at initial KT evaluation (baseline-nonadherence predictors in sociodemographic, condition-related, health system, and patient-related psychosocial factors) and at ≈6 mo post-KT (adherence outcomes: medications, healthcare follow-up, and lifestyle behavior). All patients who underwent KT at our institution and had ≈6-mo follow-up interview were included in the study. We assessed nonadherence in 3 different domains using continuous composite measures derived from the Health Habit Survey. We built multiple linear and logistic regression models, adjusting for baseline characteristics, to predict adherence outcomes. RESULTS: We included 173 participants. Black race (mean difference in adherence score: -0.72; 95% confidence interval [CI], -1.12 to -0.32) and higher income (mean difference: -0.34; 95% CI, -0.67 to -0.02) predicted lower medication adherence. Experience of racial discrimination predicted lower adherence (odds ratio, 0.31; 95% CI, 0.12-0.76) and having internal locus of control predicted better adherence (odds ratio, 1.46; 95% CI, 1.06-2.03) to healthcare follow-up. In the lifestyle domain, higher education (mean difference: 0.75; 95% CI, 0.21-1.29) and lower body mass index (mean difference: -0.08; 95% CI, -0.13 to -0.03) predicted better adherence to dietary recommendations, but no risk factors predicted exercise adherence. CONCLUSIONS: Different nonadherence behaviors may stem from different motivation and risk factors (eg, clinic nonattendance due to experiencing racial discrimination). Thus adherence intervention should be individualized to target at-risk population (eg, bias reduction training for medical staff to improve patient adherence to clinic visit).

Reconsidering Donor Race in Predicting Allograft and Patient Survival Among Kidney Transplant Recipients.

Donor race should not be used in models to predict allograft and patient survival.Removing donor race from the Kidney Donor Risk Index may reduce kidney discard by reclassifying approximately 50% of high kidney donor profile index kidneys.Future prediction models should focus on using relevant biologic factors rather than social constructs when trying to predict outcomes.

Social Determinants of Health and Race Disparities in Kidney Transplant.

BACKGROUND AND OBJECTIVES: Black patients have a higher incidence of kidney failure but lower rate of deceased- and living-donor kidney transplantation compared with White patients, even after taking differences in comorbidities into account. We assessed whether social determinants of health (e.g., demographics, cultural, psychosocial, knowledge factors) could account for race differences in receiving deceased- and living-donor kidney transplantation. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Via medical record review, we prospectively followed 1056 patients referred for kidney transplant (2010-2012), who completed an interview soon after kidney transplant evaluation, until their kidney transplant. We used multivariable competing risk models to estimate the cumulative incidence of receipt of any kidney transplant, deceased-donor transplant, or living-donor transplant, and the factors associated with each outcome. RESULTS: Even after accounting for social determinants of health, Black patients had a lower likelihood of kidney transplant (subdistribution hazard ratio, 0.74; 95% confidence interval, 0.55 to 0.99) and living-donor transplant (subdistribution hazard ratio, 0.49; 95% confidence interval, 0.26 to 0.95), but not deceased-donor transplant (subdistribution hazard ratio, 0.92; 95% confidence interval, 0.67 to 1.26). Black race, older age, lower income, public insurance, more comorbidities, being transplanted before changes to the Kidney Allocation System, greater religiosity, less social support, less transplant knowledge, and fewer learning activities were each associated with a lower probability of any kidney transplant. Older age, more comorbidities, being transplanted before changes to the Kidney Allocation System, greater religiosity, less social support, and fewer learning activities were each associated with a lower probability of deceased-donor transplant. Black race, older age, lower income, public insurance, higher body mass index, dialysis before kidney transplant, not presenting with a potential living donor, religious objection to living-donor transplant, and less transplant knowledge were each associated with a lower probability of living-donor transplant. CONCLUSIONS: Race and social determinants of health are associated with the likelihood of undergoing kidney transplant.

Renal Considerations in COVID-19: Biology, Pathology, and Pathophysiology.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has emerged into a worldwide pandemic of epic proportion. Beyond pulmonary involvement in coronavirus disease 2019 (COVID-19), a significant subset of patients experiences acute kidney injury. Patients who die from severe disease most notably show diffuse acute tubular injury on postmortem examination with a possible contribution of focal macro- and microvascular thrombi. Renal biopsies in patients with proteinuria and hematuria have demonstrated a glomerular dominant pattern of injury, most notably a collapsing glomerulopathy reminiscent of findings seen in human immunodeficiency virus (HIV) in individuals with apolipoprotein L-1 (APOL1) risk allele variants. Although various mechanisms have been proposed for the pathogenesis of acute kidney injury in SARS-CoV-2 infection, direct renal cell infection has not been definitively demonstrated and our understanding of the spectrum of renal involvement remains incomplete. Herein we discuss the biology, pathology, and pathogenesis of SARS-CoV-2 infection and associated renal involvement. We discuss the molecular biology, risk factors, and pathophysiology of renal injury associated with SARS-CoV-2 infection. We highlight the characteristics of specific renal pathologies based on native kidney biopsy and autopsy. Additionally, a brief discussion on ancillary studies and challenges in the diagnosis of SARS-CoV-2 is presented.

Myocardial ischemia by radionuclide imaging and long-term outcomes after kidney transplantation.

PURPOSE: We examined the incidence of myocardial ischemia (MI) in kidney transplant recipients (KTR) using myocardial perfusion imaging (MPI), and its association with long-term outcomes after transplantation. METHODS: A retrospective observational study was conducted of asymptomatic KTRs who underwent post-transplant MPI screening for MI, as defined by moderate to severe myocardial perfusion defects, post-stress myocardial stunning or balanced ischemia. A composite outcome of all-cause mortality, graft loss, and major adverse cardiovascular events (MACE) was examined over minimum 5 years. RESULTS: We studied 135 KTRs who underwent 226 MPIs, with follow-up duration of 10 (7-13) years. 110 (81%) patients had normal MPIs, 11 (8%) had mild perfusion defects, and 14 (10%) had MI. Correspondingly, composite outcome developed in 6%, 27%, and 43% (p = 0.04), and MACE occurred in 7%, 0%, and 21% (p = 0.11), of the respective subgroups. Twenty-six patients developed the composite outcome after 5 (3-7) years post-transplantation, including 11 patients with MACE. On multivariate analysis, MI, higher low-density lipoprotein levels, and proteinuria > 0.3 g/day independently predicted the composite outcome; only MI predicted MACE (all p < 0.05). Ninety-one patients had two serial MPIs, which increased the positive predictive value for MACE from 17 to 25%. Absence of MI had negative predictive value of 83% for MACE and 93% for the composite outcome. CONCLUSION: MI that is detected early post-kidney transplantation predicts long-term mortality, graft loss, and MACE in KTRs, with excellent negative but poor positive predictive values.

Expanded Criteria Donor Kidneys With Kidney Donor Profile Index ≤ 85%: Are We Doing Enough to Counsel Our Patients?

BACKGROUND: Kidneys at higher risk for allograft failure are defined by the Kidney Donor Profile Index (KDPI) > 85% in the current kidney allocation system (KAS), replacing the historical concept of expanded criteria donor (ECD) kidneys in the previous KAS. Discrepancies exist in the classification of "high-risk kidneys" between the 2 KAS. In the current KAS, only recipients of KDPI > 85% kidneys are counseled about the high risk of allograft failure and are required to sign a consent. In this study, we evaluated the outcomes and allocation of kidneys with discordant classification. METHODS: Using the Scientific Registry of Transplant Recipients, kidneys transplanted between 01/2002 and 09/2016 were classified according to the old (standard criteria donor [SCD]/ECD) and current (KDPI) KAS. We then grouped them as concordant (KDPI ≤ 85% + SCD or KDPI > 85% + ECD) and discordant (KDPI ≤ 85% + ECD or KDPI > 85% + SCD) kidneys. RESULTS: Approximately 11% of transplanted kidneys were discordant in classification. Among kidneys with KDPI ≤ 85%, ECD status conferred a 64% (95% CI: 56%-73%) higher risk of allograft failure compared to SCD status. However, SCD/ECD status was not associated with differential outcomes in KDPI > 85% kidneys. These ECD kidneys have KDPIs > 50% and have been transplanted across all estimated post-transplant survival (EPTS) deciles. CONCLUSION: Adequate counseling about the risk and benefit of accepting ECD kidneys with KDPI ≤ 85% versus waiting on dialysis should be explored with the patients, especially those with lower EPTS.

Does Racial Disparity in Kidney Transplant Waitlisting Persist After Accounting for Social Determinants of Health?

BACKGROUND: African Americans (AA) have lower rates of kidney transplantation (KT) compared with Whites (WH), even after adjusting for demographic and medical factors. In this study, we examined whether the racial disparity in KT waitlisting persists after adjusting for social determinants of health (eg, cultural, psychosocial, and knowledge). METHODS: We prospectively followed a cohort of 1055 patients who were evaluated for KT between 3 of 10 to 10 of 12 and followed through 8 of 18. Participants completed a semistructured telephone interview shortly after their first KT evaluation appointment. We used the Wilcoxon rank-sum and Pearson chi-square tests to examine race differences in the baseline characteristics. We then assessed racial differences in the probability of waitlisting while accounting for all predictors using cumulative incidence curves and Fine and Gray proportional subdistribution hazards models. RESULTS: There were significant differences in the baseline characteristics between non-Hispanic AA and non-Hispanic WH. AA were 25% less likely (95% confidence interval, 0.60-0.96) to be waitlisted than WH even after adjusting for medical factors and social determinants of health. In addition, being older, having lower income, public insurance, more comorbidities, and being on dialysis decreased the probability of waitlisting while having more social support and transplant knowledge increased the probability of waitlisting. CONCLUSIONS: Racial disparity in kidney transplant waitlisting persisted even after adjusting for medical factors and social determinants of health, suggesting the need to identify novel factors that impact racial disparity in transplant waitlisting. Developing interventions targeting cultural and psychosocial factors may enhance equity in access to transplantation.

Vascular Access Site for Renal Replacement Therapy in Acute Kidney Injury: A Post hoc Analysis of the ATN Study.

BACKGROUND: Acute kidney injury requiring renal replacement therapy (RRT) in the intensive care unit portends a poor prognosis. The decisions regarding dialysis catheter placement is based mainly on physician discretion with little evidence to support the choice of dialysis catheter location. METHODS: The Veterans Affairs/National Institutes of Health Acute Renal Failure Trial Network Study was a multicenter, prospective, randomized trial of intensive vs. less intensive RRT in critically ill patients with AKI. We assessed the association of dialysis catheter location with dialysis catheter-related outcomes including catheter-related complications, mortality, dialysis dependence, and dialysis dose delivered. RESULTS: Of the 1,124 patients enrolled in the ATN study, catheter data were available in 1,016 (90.39%) patients. A total of 91 (8.96%) subclavian, 387 (38.09%) internal jugular, and 538 (52.95%) femoral dialysis catheters were inserted. The femoral group was younger (58.39 ± 16.27), had greater bleeding tendency [lower platelet count (96.00 ± 109.35) with higher INR (2.01 ± 2.19)], and had a higher baseline sequential organ failure assessment score on admission (14.59 ± 3.61) compared to the other two groups. Dialysis catheter-related complications were low in this study with no significant difference in the rates of complications among all catheter locations. Mortality and dialysis dependence was lowest in the subclavian group, while the dose of dialysis delivered (Kt/V) remained lowest in the femoral group, after propensity score and center adjustments. CONCLUSION: Patient characteristics influence the choice of dialysis catheter location with a tendency to place femoral catheters in younger, sicker, and more coagulopathic patients. There were no statistically significant differences in complication rates among the three catheter locations, although femoral catheters may be associated with a lower delivered dose of dialysis during intermittent hemodialysis. CLINICAL TRIAL REGISTRATION: www.ClinicalTrials.gov, identifier NCT00076219.

Rediscovering Beta-2 Microglobulin As a Biomarker across the Spectrum of Kidney Diseases.

There is currently an unmet need for better biomarkers across the spectrum of renal diseases. In this paper, we revisit the role of beta-2 microglobulin (ß2M) as a biomarker in patients with chronic kidney disease and end-stage renal disease. Prior to reviewing the numerous clinical studies in the area, we describe the basic biology of ß2M, focusing in particular on its role in maintaining the serum albumin levels and reclaiming the albumin in tubular fluid through the actions of the neonatal Fc receptor. Disorders of abnormal ß2M function arise as a result of altered binding of ß2M to its protein cofactors and the clinical manifestations are exemplified by rare human genetic conditions and mice knockouts. We highlight the utility of ß2M as a predictor of renal function and clinical outcomes in recent large database studies against predictions made by recently developed whole body population kinetic models. Furthermore, we discuss recent animal data suggesting that contrary to textbook dogma urinary ß2M may be a marker for glomerular rather than tubular pathology. We review the existing literature about ß2M as a biomarker in patients receiving renal replacement therapy, with particular emphasis on large outcome trials. We note emerging proteomic data suggesting that ß2M is a promising marker of chronic allograft nephropathy. Finally, we present data about the role of ß2M as a biomarker in a number of non-renal diseases. The goal of this comprehensive review is to direct attention to the multifaceted role of ß2M as a biomarker, and its exciting biology in order to propose the next steps required to bring this recently rediscovered biomarker into the twenty-first century.