Transplantation-associated thrombotic microangiopathy (TA-TMA) is a challenging diagnosis after hematopoietic stem cell transplantation. Although endothelial injury represents the final common ...pathway of disease, the exact pathophysiology of TA-TMA remains unclear. Potential causes include infections, chemotherapy, radiation, and calcineurin inhibitors. Recent literature addresses the roles of cytokines, graft-versus-host disease, the coagulation cascade, and complement in the pathogenesis of TA-TMA. Current diagnostic criteria are unsatisfactory, because patients who have received a transplant can have multiple other reasons for the laboratory abnormalities currently used to diagnose TA-TMA. Moreover, our lack of understanding of the exact mechanism of disease limits the development and evaluation of potential treatments. Short- and long-term renal complications contribute to TA-TMA's overall poor prognosis. In light of these challenges, future research must validate novel markers of disease to aid in early diagnosis, guide current and future treatments, prevent long-term morbidity, and improve outcomes. We focus on TA-TMA as a distinct complication of hematopoietic stem cell transplantation, emphasizing the central role of the kidney in this disease.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Transplant-associated thrombotic microangiopathy (TMA) leads to generalized endothelial dysfunction that can progress to multiorgan injury, and severe cases are associated with poor outcomes after ...hematopoietic stem cell transplantation (HSCT). Identifying patients at highest risk for severe disease is challenging. We prospectively evaluated 100 consecutive HSCT recipients to determine the incidence of moderate and severe TMA and factors associated with poor overall outcomes. Thirty-nine subjects (39%) met previously published criteria for TMA. Subjects with TMA had a significantly higher nonrelapse mortality (43.6% vs 7.8%, P < .0001) at 1 year post-HSCT compared with those without TMA. Elevated lactate dehydrogenase, proteinuria on routine urinalysis, and hypertension were the earliest markers of TMA. Proteinuria (>30 mg/dL) and evidence of terminal complement activation (elevated sC5b-9) in the blood at the time of TMA diagnosis were associated with very poor survival (<20% at 1 year), whereas all TMA subjects without proteinuria and a normal sC5b-9 serum concentration survived (P < .01). Based on these prospective observations, we conclude that severe TMA occurred in 18% of HSCT recipients in our cohort and propose an algorithm to identify the highest-risk patients who might benefit from prompt clinical interventions.
•Proteinuria and elevated markers of complement activation at TMA diagnosis are associated with poor outcome.•Clinical interventions should be considered in HSCT patients with these high-risk features at the time TMA is diagnosed.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Abstract Hematopoietic stem cell transplantation (HSCT)-associated thrombotic microangiopathy (TA-TMA) is now a well-recognized and potentially severe complication of HSCT that carries a high risk of ...death. In those who survive, TA-TMA may be associated with long-term morbidity and chronic organ injury. Recently, there have been new insights into the incidence, pathophysiology, and management of TA-TMA. Specifically, TA-TMA can manifest as a multi-system disease occurring after various triggers of small vessel endothelial injury, leading to subsequent tissue damage in different organs. While the kidney is most commonly affected, TA-TMA involving organs such as the lung, bowel, heart, and brain is now known to have specific clinical presentations. We now review the most up-to-date research on TA-TMA, focusing on the pathogenesis of endothelial injury, the diagnosis of TA-TMA affecting the kidney and other organs, and new clinical approaches to the management of this complication after HSCT.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Dyslipidemia after kidney transplantation is a common complication that has historically been underappreciated, especially in pediatric recipients. It is also a major modifiable risk factor for ...cardiovascular disease, a top cause of morbidity and mortality of transplant patients. While most knowledge about post-transplant dyslipidemia has been generated in adults, recommendations and treatment strategies also exist for children and are presented in this review. Awareness of these applicable guidelines and approaches is required, but not sufficient, for the reliable management of dyslipidemia in our patients, and additional needs and opportunities for comprehensive care in this area (e.g., quality improvement) are outlined.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
BACKGROUNDFocal segmental glomerulosclerosis (FSGS), the second leading cause of end stage renal disease in children, appears to be increasing. Moreover, posttransplantation FSGS recurrence is a ...major problem, and there is concern that children receiving kidneys from living donors (LD) have increased recurrence risk.
METHODSData from the United Network for Organ Sharing from 1988 to 2008 were analyzed for number of de novo transplant recipients with a primary diagnosis of FSGS in children 1 to 20 years of age. Poisson regression was used for trend analysis. Univariate and multivariable logistic regression analyses were performed to examine the association of gender, race, human leukocyte antigen matching, age, and donor type with recurrence.
RESULTSTrend analysis of kidney transplantations for FSGS in children (n=2157) showed an increase in cases of 5.8% per year or 209% over 20 years (P<0.0001). Recurrence was reported in 327 (15%) cases overall, with a preponderance for white recipients (P<0.001) in younger age subgroups (P<0.01). Donor type was significant (P=0.02), with recurrence reported in 17% versus 14% of recipients of kidneys from LDs versus deceased donors. Using multivariate analysis, recipients’ young age (P=0.02) and white race (P<0.001) were identified as significant risk factors for recurrence, whereas receiving a LD kidney became insignificant.
CONCLUSIONSFSGS as a cause of pediatric end-stage renal disease leading to transplantation is on the rise. FSGS recurrence is highest in young, white children, whereas receiving a LD kidney is not independently associated with increased risk of recurrence.
BACKGROUND AND OBJECTIVES:
Hypertension is highly prevalent in pediatric kidney transplant recipients and contributes to cardiovascular death and graft loss. Improper blood pressure (BP) measurement ...limits the ability to control hypertension in this population. Here, we report multicenter efforts from the Improving Renal Outcomes Collaborative (IROC) to standardize and improve appropriate BP measurement in transplant patients.
METHODS:
Seventeen centers participated in structured quality improvement activities facilitated by IROC, including formal training in quality improvement methods. The primary outcome measure was the proportion of transplant clinic visits with appropriate BP measurement according to published guidelines. Prospective data were analyzed over a 12-week pre-intervention period and a 20-week active intervention period for each center and then aggregated as of the program-specific start date. We used control charts to quantify improvements across IROC centers. We applied thematic analysis to identify patterns and common themes of successful interventions.
RESULTS:
We analyzed data from 5392 clinic visits. At baseline, BP was measured and documented appropriately at 11% of visits. Center-specific interventions for improving BP measurement included educating clinic staff, assigning specific team member roles, and creating BP tracking tools and alerts. Appropriate BP measurement improved throughout the 20-week active intervention period to 78% of visits.
CONCLUSIONS:
We standardized appropriate BP measurement across 17 pediatric transplant centers using the infrastructure of the IROC learning health system and substantially improved the rate of appropriate measurement over 20 weeks. Accurate BP assessment will allow further interventions to reduce complications of hypertension in pediatric kidney transplant recipients.
Anti‐HLA DSAs are associated with ABMR and graft loss in KT recipients, yet the influence of DSA IgG subclass on outcomes in pediatric KT recipients is not completely understood. We performed a ...single‐center retrospective chart review of pediatric KT recipients with anti‐HLA DSAs, aiming to study the association between specific DSA IgG subclasses and graft outcomes, including ABMR and significant graft dysfunction (graft loss or 50% decrease in eGFR). Thirty‐six patients (mean age 15.4y) with DSAs initially detected 1 month‐14.3 years post‐transplantation were followed for a median of 2.8 years. Rates of IgG1, 2, 3, and 4 subclass detection were 92%, 33%, 58%, and 25%, respectively. Twenty‐two patients (61%) had clinical ABMR, whereas 19% had subclinical ABMR, and 13 (36%) experienced significant graft dysfunction. Patients with IgG3+ DSAs had a higher risk of graft dysfunction compared with IgG3‐ patients (52% vs 13%, P = .03). In a multiple Cox proportional regression analysis, the presence of IgG3+ DSA was independently associated with significant graft dysfunction (HR 10.45, 95% CI 1.97‐55.55, P = .006). In conclusion, IgG3 subclass DSAs are associated with graft dysfunction and may be useful for risk stratification and treatment decisions in DSA‐positive pediatric KT recipients.
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DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
Patient‐identified barriers to immunosuppressive medications are associated with poor adherence and negative clinical outcomes in transplant patients. Assessment of adherence barriers is not part of ...routine post‐transplant care, and studies regarding implementing such a process in a reliable way are lacking. Using the Model for Improvement and PDSA cycles, we implemented a system to identify adherence barriers, including patient‐centered design of a barriers assessment tool, identification of eligible patients, clear roles for clinic staff, and creating a culture of non‐judgmental discussion around adherence. We performed time‐series analysis of our process measure. Secondary analyses examined the endorsement and concordance of adherence barriers between patient‐caregiver dyads. After three methods of testing, the most reliable delivery system was an EHR‐integrated tablet that alerted staff of patient eligibility for assessment. Barriers were endorsed by 35% of caregivers (n=85) and 43% of patients (n=60). The most frequently patient‐endorsed barriers were forgetting, poor taste, and side effects. Caregivers endorsed forgetting and side effects. Concordance between patient‐caregiver dyads was fair (k=0.299). Standardized adherence barriers assessment is feasible in the clinical care of pediatric kidney transplant patients. Features necessary for success included automation, redundant systems with designated staff to identify and mitigate failures, aligned reporting structures, and reliable measurement approaches. Future studies will examine whether barriers predict clinical outcomes (eg, organ rejection, graft loss).
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DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
BACKGROUND: The use of therapeutic plasma exchange (TPE) in hematopoietic stem cell transplant–associated thrombotic microangiopathy (TA‐TMA) is controversial because the exact mechanism of injury in ...TA‐TMA is not yet understood.
STUDY DESIGN AND METHODS: The study objective was to retrospectively review the outcome of children receiving TPE for TA‐TMA at our institution. We hypothesized that patients initiating TPE earlier in their disease course would receive a greater benefit than those starting later, regardless of the therapeutic mechanism.
RESULTS: We identified 10 consecutive pediatric patients with TA‐TMA treated with TPE. Nine of these patients showed normalization of the laboratory variables associated with microangiopathy during their TPE course, but only five patients recovered renal function and survived TA‐TMA. The five survivors started TPE a median of 17 days (range, 4‐25 days) after TA‐TMA diagnosis while the five patients who died started TPE a median of 32 days (range, 17‐73 days) after TA‐TMA was diagnosed. Three of the five survivors had multiorgan failure at TA‐TMA diagnosis and completely recovered with early institution of TPE. These three survivors were able to discontinue renal replacement therapy, and all achieved a normal posttreatment creatinine. The five patients with later institution of TPE progressed to end‐stage renal disease and all died. There were no serious TPE‐related complications in either group.
CONCLUSION: This is the first report evaluating TPE response in regard to procedure initiation time after TA‐TMA diagnosis. Our data suggests that early initiation of TPE might be beneficial even in patients with multiorgan failure due to TA‐TMA.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
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