Edward Nehus

Cystatin C-estimated Glomerular Filtration Rate in Pediatric Autologous Hematopoietic Stem Cell Transplantation

Formal evaluation of kidney function is essential to determine chemotherapy dosing based on established treatment protocols in children undergoing autologous stem cell transplantation. Cystatin C has been widely studied as a marker of the glomerular filtration rate (GFR), although data regarding its use in stem cell transplantation are limited. We evaluated the performance of cystatin C-based equations and determined their sensitivity to detect a nuclear GFR of <100 mL/min/1.73 m(2) in children undergoing autologous transplantation. We performed a retrospective cohort analysis in 16 children undergoing 26 transplantations using a modified Bland-Altman analysis to account for repeated measures. Cystatin C-based equations published by Hoek, Le Bricon, Rule, Filler, Zappitelli, Larsson, and Schwartz (the New Chronic Kidney Disease in Children formula, New CKiD formula) were evaluated and compared to the creatinine-based modified Schwartz equation. We found that cystatin C-based equations demonstrated improved sensitivity to detect a nuclear GFR of <100 mL/min/1.73 m(2) compared to the creatinine-based modified Schwartz equation, which significantly overestimated GFR. Most cystatin C-based equations, however, tended to underestimate the nuclear GFR. The New CKiD formula, combining cystatin C and creatinine, offered a sensitivity of 100% and a specificity of 95% for detecting a nuclear GFR <100 mL/min/1.73 m(2). Institutions using cystatin C-based GFR estimation should be aware of the specific prediction formula and GFR measurement techniques available at their center, as each methods performance can vary considerably. As more research becomes available, this easily measured marker should become a valuable component of GFR estimation, providing cost savings (a nuclear GFR is 5.5 times more costly than a cystatin C) and reducing radiation exposure.

Kidney function in severely obese adolescents undergoing bariatric surgery

Determine objective measures of kidney function and analyze factors associated with kidney dysfunction in severely obese adolescents undergoing weight loss surgery were described.

Focal segmental glomerulosclerosis in children: multivariate analysis indicates that donor type does not alter recurrence risk.

Background Focal 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. Methods Data 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. Results Trend 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. Conclusions FSGS 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.

Correlates of Resistin in Children with Chronic Kidney Disease: The Chronic Kidney Disease in Children Cohort

OBJECTIVE To test the hypothesis that resistin is associated with insulin resistance and inflammation in pediatric patients with chronic kidney disease (CKD). STUDY DESIGN This study is a cross-sectional analysis of 319 children in the Chronic Kidney Disease in Children cohort, a large cohort of children with stage II-IV CKD. Univariate and multivariate regression modeling was used to evaluate the association of serum resistin level with glomerular filtration rate (GFR), demographic data, and cardiovascular risk factors, including inflammatory cytokines, insulin resistance, and serum lipids. RESULTS In univariate analyses, serum resistin level was negatively correlated with GFR (P < .01). Increased serum resistin was associated with elevated inflammatory cytokines, including interleukin (IL)-6 (P < .01), IL-10 (P < .01), and tumor necrosis factor-α (P < .01). Resistin level was not associated with insulin resistance, although it was positively correlated with serum triglycerides (P < .01) and negatively correlated with high-density lipoprotein cholesterol (P < .01). In multivariate analysis, GFR (β = -0.01; P < .001), IL-6 (β = 0.18; P < .001), IL-10 (β = 0.09; P = .01), and pubertal status (β = 0.18; P < .01) were significantly associated with serum resistin level. CONCLUSION These results indicate that serum resistin level increases with GFR decline and is involved in the inflammatory milieu present in CKD.

Outcomes of Steroid‐Avoidance Protocols in Pediatric Kidney Transplant Recipients

Advances in immunosuppression have facilitated increased use of steroid‐avoidance protocols in pediatric kidney transplantation. To evaluate such steroid avoidance, a retrospective cohort analysis of pediatric kidney transplant recipients between 2002 and 2009 in the United Network for Organ Sharing database was performed. Outcomes (acute rejection and graft loss) in steroid‐based and steroid‐avoidance protocols were assessed in 4627 children who received tacrolimus and mycophenolate immunosuppression and did not have multiorgan transplants. Compared to steroid‐based protocols, steroid avoidance was associated with decreased risk of acute rejection at 6 months posttransplant (8.3% vs. 10.9%, p = 0.02) and improved 5‐year graft survival (84% vs. 78%, p < 0.001). However, patients not receiving steroids experienced less delayed graft function (p = 0.01) and pretransplant dialysis, were less likely to be African‐American and more frequently received a first transplant from a living donor (all p < 0.001). In multivariate analysis, steroid avoidance trended toward decreased acute rejection at 6 months, but this no longer reached statistical significance, and there was no association of steroid avoidance with graft loss. We conclude that, in clinical practice, steroid avoidance appears safe with regard to graft rejection and loss in pediatric kidney transplant recipients at lower immunologic risk.

Masked hypertension and allograft function in pediatric and young adults kidney transplant recipients

Masked hypertension is a common complication of pediatric kidney transplantation. While office hypertension is known to be associated with worse short‐ and long‐term graft function, the role of masked hypertension in allograft dysfunction is not clear. We conducted a retrospective cross‐sectional analysis of 77 consecutive pediatric kidney transplant recipients who had routine 24‐h ambulatory blood pressure monitoring with the aims to estimate the prevalence of masked hypertension and examine its association with allograft function. Masked hypertension was defined as a 24‐h systolic or diastolic blood pressure load ≥25%. Twenty‐nine percent of patients had masked hypertension. Patients with masked hypertension had significantly lower allograft function estimated using the creatinine‐based Schwartz‐Lyon formula, a cystatin C‐based formula, and combined cystatin C and creatinine‐based formulas than patients with normal blood pressure (all p values <0.05). In a multivariable analysis, masked hypertension remained independently associated with worse allograft function after adjustment for age, sex, race, time post‐transplant, rejection history, antihypertensive treatment, and hemoglobin level. We conclude that in young kidney transplant recipients, masked hypertension is common and is associated with worse allograft function. These results support the case for routine ambulatory blood pressure monitoring as the standard of care in these patients to detect and treat masked hypertension.

Clinical Practice of Steroid Avoidance in Pediatric Kidney Transplantation.

Steroid‐avoidance protocols have recently gained popularity in pediatric kidney transplantation. We investigated the clinical practice of steroid avoidance among 9494 kidney transplant recipients at 124 transplant centers between 2000 and 2012 in the Organ Procurement and Transplantation Network database. The practice of steroid avoidance increased during the study period and demonstrated significant variability among transplant centers. From 2008 to 2012, 39% of transplant centers used steroid avoidance in <10% of all discharged transplant recipients. Twenty‐one percent of transplant centers practiced steroid avoidance in 10–40% of transplant recipients, and 40% of transplant centers used steroid avoidance in >40% of discharged patients. Children receiving steroid avoidance more frequently received induction with lymphocyte‐depleting agents. Repeat kidney transplants were the least likely to receive steroid avoidance. Children who received a deceased donor kidney, underwent pretransplant dialysis, were highly sensitized, or had glomerular kidney disease or delayed graft function were also less likely to receive steroid avoidance. The variation in practice between centers remained highly significant (p < 0.0001) after adjustment for all patient‐ and center‐level factors in multivariate analysis. We conclude that significant differences in the practice of steroid avoidance among transplant centers remain unexplained and may reflect uncertainty about the safety and efficacy of steroid‐avoidance protocols.

Hyponatremia, hypo-osmolality, and seizures in children early post-kidney transplant.

Post‐transplant seizures are uncommon in young kidney transplant recipients but can be harbingers of devastating outcomes such as cerebral edema and death. We reviewed all transplants performed at our institution from January 2013 to January 2014 and compared three patients who seized within 24 h post‐transplant (cases) with the remaining 33 transplant recipients (controls). Records were reviewed for hyponatremia, hypocalcemia, hypomagnesemia, BUN clearance, osmolality shifts, and blood pressure control in the first 24 h post‐transplant. All cases had more pronounced (p < 0.001) shifts in serum sodium and calculated serum osmolality, with their sodium decreasing by >15 mmol/L to nadir values of 124, 131, and 131 mmol/L, respectively. There were no differences in serum calcium corrected for hypoalbuminemia, serum magnesium, urine output, or blood pressure control between the groups. Our study suggests that mild hyponatremia and an acute decrease in serum osmolality are risk factors for potentially severe postoperative neurologic complications following kidney transplantation. Thus, peri‐transplant management should be optimized to anticipate and prevent these abnormalities.

Intensive hemodialysis for cardiomyopathy associated with end-stage renal disease

Heart and kidney dysfunction often coexist, and increasing evidence supports the interaction of these two organs, as demonstrated by the clinical condition known as cardiorenal syndrome (CRS). We report a pediatric patient with end-stage renal disease (ESRD) who developed a dilated cardiomyopathy and decompensated heart failure after undergoing unilateral nephrectomy and while on maintenance peritoneal dialysis. He showed marked improvement in his cardiac function with the addition of intensive hemodialysis. We discuss the pathophysiology of cardiorenal syndrome in patients with ESRD and suggest that intensive dialysis may be an effective therapy for this condition.

Graft survival of pediatric kidney transplant recipients selected for de novo steroid avoidance—a propensity score-matched study

Background Steroid-avoidance protocols have gained popularity in pediatric kidney transplant recipients at low immunologic risk. The long-term safety of steroid avoidance in children with immunologic risk factors remains unknown. Methods Pediatric kidney transplant recipients from 2004 to 2014 in the Organ Procurement and Transplantation Network database who received tacrolimus and mycophenolate immunosuppression were investigated. Propensity score matching was used to compare graft survival in 1624 children who received steroid avoidance with 1624 children who received steroid-based immunosuppression. The effect of steroid avoidance on graft failure among immunologic risk strata was estimated using Cox proportional hazards regression in this propensity score-matched cohort. Results It was observed that 5-year graft survival was mildly improved in children receiving steroid avoidance (84.8% versus 81.2%, P = 0.03). This improvement in graft survival occurred in the first 2 years following transplant, when the hazard ratio (HR) for allograft failure in children receiving steroid avoidance was 0.62 [95% confidence interval (CI) 0.45-0.86]. In contrast, steroid avoidance was not associated with improved allograft survival during Years 2-10 following transplant (HR = 0.93; 95% CI 0.75-1.15). During this time period, HRs (95% CIs) for allograft failure within immunologic risk strata were not significantly different from the null value of 1: repeat kidney transplants, 1.84 (0.84-4.05); African-Americans, 1.02 (0.67-1.56); sensitized recipients, 1.24 (0.63-2.43); recipients of deceased donor kidneys, 1.02 (0.79-1.32); recipients of completely human leukocyte antigen-mismatched kidneys, 0.80 (0.47-1.37); and recipients with pretransplant glomerular disease, 0.94 (0.71-1.23). Conclusions In pediatric kidney transplant recipients receiving tacrolimus- and mycophenolate-based immunosuppression, steroid avoidance can be safely practiced in children with immunologic risk factors.