Background and objectives Formal evaluation of kidney function before and after hematopoietic cell transplant is important to determine conditioning regimens, type of transplant, and medication dosing. Serum creatinine and estimating equations may not accurately assess kidney function.Design, study, participants, & measurements Existing estimating equations for GFR were compared with an iohexol measure of GFR in a prospective cohort study of 50 patients undergoing hematopoietic cell transplant and subsequent care at the Fred Hutchinson Cancer Research Institute from 2009 to 2013. Patients underwent iohexol GFR, serum creatinine, and cystatin C determination at baseline and day 100 posthematopoietic cell transplant. Iohexol GFR measurements were compared with the CKD Epidemiology Collaboration, Inker CKD Epidemiology Collaboration cystatin C with and without serum creatinine, Modification of Diet in Renal Disease, and Cockcroft-Gault estimating equations using Bland-Altman analysis and McNemar's test. The iohexol measurements were also compared with blood samples collected simultaneously on filter paper.Results Mean differences between iohexol GFR and eGFR on the basis of Bland-Altman analyses ranged from 220.6 to +15.4 ml/min per 1.73 m 2 at baseline and 212.7 to +12.9 ml/min per 1.73 m 2 at day 100. The CKD Epidemiology Collaboration and Modification of Diet in Renal Disease estimating equations classified 64% of patients with a GFR,90 at baseline compared with 38% by iohexol GFR (P=0.003 and P,0.01, respectively). No statistically significant differences were seen at day 100. The filter paper GFR had a mean difference of 0 at baseline and 5.9 at day 100. Additionally, 21%-37% and 57%-89% of eGFRs were within 10% and 30%, respectively, of the iohexol GFR at baseline, and 16%-34% and 72%-84% were within 10% and 30%, respectively, of the iohexol GFR at day 100; 98% of the filter paper estimates at baseline were within 30%, and 46% were within 10% of iohexol GFR.Conclusions The estimating equations are neither accurate nor precise in the hematopoietic cell transplant population, and clinical decision may require measurement of GFR.

We compared urinary levels of cytokines in patients with and without albuminuria, proteinuria, and kidney disease (GFR < 60 ml/min/1.73m2) after hematopoietic cell transplant (HCT). Plasma and urine were collected at baseline and weekly through day-100 and monthly through year-1, for measurement of IL-6, gp130, sIL6r, IL10, IL15, MCP1 and urine albumin to creatinine ratios (ACR). Cox-proportional hazards modeling examined associations between urinary cytokine levels and development of these renal endpoints. The association of ACR with the hazard of overall mortality was assessed using Cox regression. Increasing urinary IL-6 and IL-15 were associated with an increased risk of developing proteinuria. Urinary MCP-1 during the first 100 days post-HCT was associated with kidney disease at 1 year. The degree of albuminuria at any time point in the first 100 days post-transplant was related to the subsequent risk of death (for ACR 30-299, HR=1.91; 95%CI:1.27-2.87; for ACR >300, HR=2.82; 95%CI:1.60-4.98). After HCT, elevated urinary levels of proinflammatory cytokines are associated with development of albuminuria and proteinuria, suggesting early intrarenal inflammation as an important pathogenetic mechanism. Albuminuria and proteinuria within the first 100 days post-HCT are associated with decreased overall survival.

Background and objectives Graft-versus-host disease (GVHD) is associated with kidney injury after hematopoietic cell transplantation (HCT). Because plasma elafin levels correlate with skin GVHD, this study examined urinary elafin as a potential marker of renal inflammation and injury.Design, setting, participants, & measurements Urine was collected prospectively on 205 patients undergoing their first HCT from 2003 to 2010. Collections were done at baseline, weekly through day 100, and monthly through year 1 to measure elafin and urine albumin-to-creatinine ratio (ACR). Associations between urinary elafin levels and microalbuminuria, macroalbuminuria, AKI and CKD, and mortality were examined using Cox proportional hazards or linear regression models. Available kidney biopsy specimens were processed for immunohistochemistry.Results Mean urinary elafin levels to day 100 were higher in patients with micro-or macroalbuminuria (adjusted mean difference, 529 pg/ml; P=0.03) at day 100 than in those with a normal ACR (adjusted mean difference, 1295 pg/ml; P,0.001). Mean urinary elafin levels were higher in patients with AKI compared with patients without AKI (adjusted mean difference, 558 pg/ml; P,0.01). The average urinary elafin levels within the first 100 days after HCT were higher in patients who developed CKD at 1 year than in patients without CKD (adjusted mean difference, 894 pg/ml; P=0.002). Among allogeneic recipients, a higher proportion of patients with micro-or macroalbuminuria at day 100 also had grade II-IV acute GVHD (80% and 86%, respectively) compared with patients with a normal ACR (58%; global P,0.01). Each increase in elafin of 500 pg/ml resulted in a 10% increase in risk of persistent macroalbuminuria (hazard ratio, 1.10; 95% confidence interval [95% CI], 1.06 to 1.13; P,0.001) and a 7% increase in the risk of overall mortality (95% CI, 1.02 to 1.13, P,0.01). Renal biopsy specimens from a separate cohort of HCT survivors demonstrated elafin staining in distal and collecting duct tubules. ConclusionHigher urinary elafin levels are associated with an increased risk of micro-and macroalbuminuria, AKI and CKD, and death after HCT.

Adult HCT recipients have a high risk of decreased eGFR by 1 year after HCT. Although eGFR remains fairly stable thereafter, a decreased eGFR is significantly associated with higher risk of mortality, with a progressively increased risk as eGFR declines.

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Hematopoietic cell transplantation (HCT) is a common treatment for many disorders. Albuminuria post-HCT, which may represent endothelial injury or inflammation from graft- versus-host disease, increases the risk of chronic kidney disease and nonrelapse mortality at 1 year. HCT recipients also have abnormal blood pressure (BP) and increased rates of cardiovascular complications. We sought to determine the relationships among albuminuria, endothelial dysfunction, and BP in HCT recipients. Patients age  ≥12 years who underwent their first allogeneic HCT between 2012 and 2015 and survived through day 80 post-HCT were eligible. Peripheral endothelial function was assessed using the EndoPAT2000 device at day 80 along with 24-hour ambulatory BP monitoring (ABPM). Clinical and laboratory data were collected along with a urine sample for calculation of the albumin-to-creatinine ratio. Both logistic and linear regression analyses were used to identify associations between EndoPAT score and clinical variables. Sixty patients (median age, 48 years; range, 14 to 69 years) completed the study. The median EndoPAT score was 2.05 (range, 1.02 to 4.45), and 17 patients (28%) had abnormal endothelial function. Forty-two patients (72%) had ambulatory hypertension (HTN), and 38 (63%) had blunted nocturnal dipping. HTN on ABPM (P = .045) and blunted nocturnal dipping (P = .04) were associated with a lower EndoPAT score. Albuminuria was not associated with EndoPAT score. There was a lack of agreement between our clinical definition of HTN (office BP and/or use of medications) and ABPM results (P = .04). We did not find an association between lower EndoPAT scores and albuminuria, but did find an association between an abnormal nocturnal dip and HTN diagnosed by ABPM. This suggests that albuminuria may reflect local endothelial injury and inflammation rather than a systemic process. Office BP readings do not accurately reflect true BP, suggesting that 24-hour ABPM studies are needed to diagnose and treat HTN appropriately.

Acute kidney injury (AKI) is common after hematopoietic cell transplant (HCT). The etiology of AKI is unknown because biopsies are rarely performed. The pathophysiology of injury is inferred from clinical data. Thrombotic microangiopathy (TMA) is often invoked as the cause of renal injury. Patients > 2 years undergoing their first HCT at Fred Hutchinson Cancer Research Center (FHCRC) participated in this study. We prospectively measured plasma markers of coagulation activation, (PAI-1 and tPA) and fibrinolyis (D-dimer) weekly in 149 patients during the first 100 days post-transplant. Cox proportional hazards modeling was used to determine associations between these markers and AKI (doubling of baseline serum creatinine). Kruskal-Wallis test was used to determine associations between day 100 urinary albumin to creatinine ratios (ACR) and these markers. Thirty one percent of patients developed AKI. Though elevations in these markers occurred frequently, neither PAI-1 nor tPA were associated with development of AKI. D-dimer was associated with a slightly increased risk of AKI (RR=1.76; p-value 0.04). None of these markers were associated with micro- or macroalbuminuria at day 100. The lack of an association with AKI suggests that endothelial injury in the form of TMA is not a common cause of AKI early after transplant.