Allograft outcomes of treated children with kidney transplant who developed plasma cell-rich acute rejection (PCAR): A single center's experience.

INTRODUCTION: PCAR is a rare form of ACR that may compromise renal allografts. This review evaluates the outcomes of a protocol used to treat PCAR (Study group), and compares these outcomes with a matched cohort with ACR (Control group). METHODS: A retrospective analysis of 138 of pRTRs who underwent renal allograft biopsies between January 2008 and November 2016. RESULTS: Seven biopsies revealed in situ hybridization of EBER-negative PCAR (5%). Three Study group pRTRs lost their grafts within 3 months after rejection (43%). None of the Control group pRTRs lost their graft during this period. At the time of rejection, eGFR was different between the Control and Study groups (27.0 ± 19.9 mL/min per m2 vs 40.0 ± 10.6 mL/min/1.73 m2 , respectively; P < 0.05). Among Study group pRTRs with functioning allografts (n = 4), treatment resulted in an increase in eGFR from nadir levels (27.0 ± 19.9 vs 55.6 ± 18.3 mL/min/1.73 m2 , P < 0.05). In the Study group, complications included neutropenia, BK and EBV viremia, and infusion-related hypotension and hypertension. SUMMARY: (a) Graft loss in Study group while remaining high (43%) was lower than that reported in the published pediatric literature. (b) Our protocol was associated with improvement in eGFR in all surviving pRTRs within the Study group. (c) No life-threatening complications or malignancy were reported during the observation period.

Renal-Limited "Lupus-Like" Nephritis: How Much of a Lupus?

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by development of autoantibodies to nuclear and cytoplasmic antigens. A small subset of SLE patients who had the typical clinical features of SLE was reported to show persistently negative antinuclear antibody tests. Our report describes a 5-year-old male who presented with histopathological findings suggestive of lupus nephritis with no clinical signs or symptoms of SLE and negative autoantibodies. He was treated with corticosteroids, mycophenolate mofetil, and monthly intravenous cyclophosphamide. During the 2-year follow-up period, the proteinuria resolved and kidney function improved with continued negative autoantibody workup. This case presents a category of renal-limited "lupus-like" glomerulonephritis which can be challenging to treat and carries a poor prognosis.

Management of sensitized pediatric patients prior to renal transplantation.

BACKGROUND: Data on renal allograft outcome in sensitized children are scarce. We report the clinical courses of four children who received desensitization therapy prior to renal transplantation in our institution. METHODS: Between 2009 and 2011, four pediatric patients with stage 5 chronic kidney disease received desensitization therapy due to: (1) positive donor-specific antibodies (DSA) and/or crossmatches with potential living donors, (2) more than three positive crossmatches with deceased donors or (3) high calculated panel-reactive antibody of >80 %. Desensitization with rituximab, intravenous immunoglobulin and bortezomib was performed in all patients. Induction therapy included combinations of plasmapheresis and/or alemtuzumab or anti-thymocyte globulin. Standard post-transplant medications included tacrolimus, mycophenolate mofetil and prednisolone. RESULTS: Post-transplant screening revealed DSA in three patients. Biopsy showed no evidence of rejection at 1 month in two patients, one of whom developed chronic active antibody-mediated rejection 4.5 years later. One patient developed borderline acute cellular rejection at 1 month, but the serum creatinine level was stable and DSA disappeared without treatment 1 month later, with stable long-term allograft function at 3 years. Estimated or measured glomerular filtration rate of the patients ranged between 30 and 75 ml/min/1.73 m(2) after 1 to 4.5 years. CONCLUSIONS: The four sensitized patients reported here who received desensitization therapy had successful renal transplants with a low risk of immediate post-transplant rejection. Overall, long-term allograft functions and complications from immunosuppression were encouraging.

Growth in children with chronic kidney disease: a report from the Chronic Kidney Disease in Children Study.

BACKGROUND: Growth failure is common among children with chronic kidney disease (CKD). We examined the relationship of growth parameters with glomerular filtration rate (GFR), CKD diagnosis, sex and laboratory results in children with CKD. METHODS: Baseline data from 799 children (median age 11.0 years, median GFR 49.9 mL/min/1.73 m(2)) participating in the Chronic Kidney Disease in Children Study were examined. Growth was quantified by age-sex-specific height, weight, body mass index (BMI-age), and height-age-sex-specific BMI (BMI-height-age) standard deviation scores (SDS). RESULTS: Median height and weight SDS were -0.55 [interquartile range (IQR) -1.35 to 0.19] and 0.03 (IQR -0.82 to 0.97), respectively. Girls with non-glomerular CKD were the shortest (median height SDS -0.83; IQR -1.62 to -0.02). Compared to those with a serum bicarbonate (CO2) level of ≥ 22 mEq/L, children with CO2 of <18 mEq/L had a height SDS that was on average 0.67 lower [95 % confidence interval (CI) -0.31 to -1.03]. Only 23 % of children with a height SDS of ≤-1.88 were prescribed growth hormone therapy. Forty-six percent of children with glomerular CKD were overweight or obese (BMI-height-age ≥ 85th percentile). CONCLUSIONS: Growth outcomes in a contemporary cohort of children with CKD remain suboptimal. Interventions targeting metabolic acidosis and overcoming barriers to recombinant human growth hormone usage may improve growth in this population.

Validation of the CKiD formulae to estimate GFR in children post renal transplant.

BACKGROUND: The Chronic Kidney Disease in Children (CKiD) study reported new formulae to estimate glomerular filtration rate (eGFR). The study reported here aimed to assess the accuracy of these formulae in estimating levels and changes in GFR in pediatric renal transplant recipients and generate a new formula in our cohort. METHODS: Two hundred and fifty-two studies of plasma disappearance of (125)I-iothalamate (CIO) were used to measure GFR in 155 renal transplant recipients. The CKiD bedside formula (CKiD-BS) was compared with CIO. A mixed logistic regression model was fit to evaluate the performance of estimating change in posttransplant CIO using CKiD-BS. We used mixed-effects linear regression to fit a multiplicative model of CIO. The CKiD cystatin-C-based formula (CKiD-Cys) was also used for comparison in 32 additional transplant recipients. Comparisons were made using Bland-Altman plots. RESULTS: CKiD-BS underestimates CIO by 20 % for GFR >25 ml/min per 1.73 m(2). Percentage change in CKiD-BS performed reasonably well in estimating 15 % change of CIO beginning 6 months posttransplant [area under the curve (AUC) = 0.791)] The multiplicative constant in the CKiD-BS was recalibrated [R-Bedside = 0.461 × ht(cm)/SCr).]A GFR model [GFR-M) = 10.73 × [(ht(cm)]0.51/(SCr)0.90 × (BUN)0.23] has higher specificity but similar sensitivity for CIO compared with R-Bedside. CKiD-Cys overestimates CIO by 10 ml/min per 1.73 m(2) across a broad range of GFR. CONCLUSIONS: In our cohort, the CKiD-BS underestimates CIO; however, changes in CKiD-BS can be used to estimate changes in CIO. CKiD-Cys overestimates CIO and is not accurate in estimating CIO.

Highlights for the management of a child with hypertension.

Over the past several decades, childhood hypertension has undergone a considerable conceptual change, as hypertension is a predictor of future development of cardiovascular disease in adults. Childhood hypertension has distinctive features that distinguish it from hypertension in adults. Pediatric hypertension is often secondary. It is widely believed that therapeutic intervention at an early age favorably modifies the long-term outcome of hypertension. Despite its significance as a cause for morbidity, childhood hypertension is underdiagnosed and less studied with many basic issues remaining contentious.

Recurrence of focal segmental glomerulosclerosis in renal allograft: an in-depth review.

Focal segmental glomerulosclerosis is a major cause of chronic kidney disease requiring transplantation in children. Recurrence rate in the renal allograft transplantation is as high as 50%. Recurrence of FSGS is associated with renal dysfunction and early graft loss. To date, there is no established therapy for recurrent FSGS after renal transplant. We have reviewed the current English literature in order to summarize current practices with emphasis on graft outcome. We conclude that despite multiple approaches to the post transplant management of recurrent FSGS, none have been shown to be consistently beneficial. Currently, pheresis combined with high dose anti-calcineurin with or without rituximab seems to be the most promising. Further controlled studies are needed to define the optimal therapeutic regimens to treat recurrent of FSGS.

Strategies of treatment of pediatric hypertension.

Over the past two decades the attitudes of pediatric health care providers towards childhood hypertension, as a predictor of future development of hypertension in adults have undergone considerable conceptual change. Childhood hypertension has unique features that differentiate it from hypertension in adults. It is widely accepted that pediatric hypertension carries an increased risk for future cardiovascular morbidity and mortality. There is also a prevalent belief that therapeutic intervention at an early age may favorably modify the long-term outcome of hypertension. Despite its importance, childhood hypertension is understudied and several basic questions remain controversial. This article addresses several issues pertinent to the treatment of hypertension during childhood and discusses some of the newer pharmacological agents used in children.

The effect of rhGH on height velocity and BMI in children with CKD: a report of the NAPRTCS registry.

The aim of this investigation was to evaluate the impact of recombinant human growth hormone (rhGH) therapy on height velocity (HV), estimated glomerular filtration rate (eGFR) and body mass index (BMI) in a large cohort of children with chronic kidney disease (CKD). We reviewed longitudinal data from patients enrolled in the chronic renal insufficiency registry of the North American Pediatric Renal Trials and Collaborative Studies (NAPRTCS). Of the 7189 patients enrolled in the registry, 827 (11.5%) received rhGH. A total of 787 children with CKD previously rhGH naïve who received rhGH for 1-4 years (median 1.5 years) were paired with 787 control patients, and over 100 of the case-controls were followed for 4 years. The control group was matched for age, gender, height and length of time in the NAPRTCS registry. Height velocity was also compared to the general U.S. population. The eGFR of the treated group (37.5 ml/min per 1.73 m(2)) was significantly less than that of the control group (42.3 ml/min per 1.73 m(2); p < 0.001). The rhGH-treated group had a significantly greater HV standard deviation score (SDS) than the control group (p < 0.01) at each 6-months post-rhGH treatment initiation point for 2.5 years (p < 0.007). Among 220 pairs at 2 years, the height SDS of the rhGH group was 0.56 SDS higher than that of the control group (p < 0.05). Treatment with rhGH had no significant impact on the BMI or eGFR. As demonstrated in smaller cohorts, rhGH usage is associated with improved HV in children with CKD. In contrast, rhGH does not appear to have any impact on BMI or kidney function in this population of patients.

Successful split liver-kidney transplant for factor H associated hemolytic uremic syndrome.

BACKGROUND AND OBJECTIVES: A male infant with a family history of thrombotic microangiopathy developed atypical hemolytic uremic syndrome (aHUS). DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Case report. RESULTS: Genetic analysis demonstrated a heterozygous mutation (S1191L) of CFH, the gene coding complement factor H (CFH). The child suffered many episodes of HUS, each treated with plasma exchange. In time, despite initiation of a prophylactic regimen of plasma exchange, his renal function declined significantly. At the age of 4 yr he received a (split liver) combined liver-kidney transplant (LKT) with preoperative plasma exchange and enoxaparin anticoagulation. Initial function of both grafts was excellent and is maintained for nearly 2 yr. CONCLUSIONS: This report adds to the small but growing number of individuals in whom LKT has provided a favorable outcome for aHUS associated with CFH mutation, expands the technique of using a split liver graft, and describes the unique histologic features of subclinical liver disease in HUS.

Low bone mineral density in spinal muscular atrophy.

BACKGROUND AND PURPOSE: Pathological fractures are common in pediatric neuromuscular disorders. Dual-energy x-ray absorptiometry has become the most accepted technique for the measurement of bone mineral density (BMD) in adults and children. Limited data are available on BMD in pediatric neuromuscular diseases except Duchenne muscular dystrophy. METHODS: We retrospectively analyzed the results of all dual-energy x-ray absorptiometry scans done in a period of 23 months at a tertiary care pediatric neuromuscular center. BMD was performed on spine region L1-4. Osteopenia was classified as mild if the Z scores were between 0 and -1.5, moderate if Z scores were between -1.5 and -2.5, and severe if Z scores were > -2.5 standard deviation scores. RESULTS: Eighty-four dual-energy x-ray absorptiometry scans were performed on 79 patients between the ages of 4 months and 18 years with the mean age of 8 years. Z scores were used to compare their BMDs. BMD was lowest in patients with spinal muscular atrophy (SMA) with Z score of -2.25 +/- 0.31 standard deviation scores. The Z score for patients with Duchenne muscular dystrophy was -1.72 +/- 0.1. The BMD in nonambulatory patients with SMA was significantly decreased compared with ambulatory patients with SMA (P < 0.05). CONCLUSIONS: We conclude that osteopenia is common in children with neuromuscular disorders. Patients with SMA have the lowest BMD.

Urinary prostaglandins and the effect of indomethacin on phosphate excretion in children with hypophosphatemic rickets.

We recently reported the urinary prostaglandin E(2)/creatinine ratio (PGE(2)/Cr) was markedly elevated in Hyp mice, the animal model for X-linked hypophosphatemia, compared with control mice. We provided evidence for altered prostaglandin production mediating the phosphaturia and that indomethacin decreases urinary phosphate excretion in Hyp mice but not control mice. To determine the levels of urinary PGE(2)/Cr, the safety and efficacy of indomethacin on phosphate excretion in children with hypophosphatemic rickets (HPR), a prospective clinical trial was performed in 16 children with HPR and 16 age- and gender-matched healthy controls. Urinary PGE(2)/Cr excretion was determined on a 24 h timed urine collection. A randomized cross over, placebo versus indomethacin, clinical trial was performed in the 16 children with HPR. There was no difference in urinary PGE(2)/Cr excretion between controls and patients with HPR. In children with HPR, indomethacin treatment for 3 mo had no significant effect on serum phosphorus or urinary phosphate excretion. In conclusion, urinary prostaglandin excretion is similar in children with HPR compared with controls. Indomethacin had no significant effect on serum phosphorus or urinary phosphate excretion in children with HPR.

A major milestone in the history of Albanian kidney transplant.

Albania is a young Democracy emerging from under 40 yr of dictatorship. During this era Albanians were subjected to isolation, purges, shortages, repression of civil, political and religious rights. This resulted in the least developed healthcare system in Europe. After the mid 90 s, there have been relentless attempts to modernize Albania. Recently an international medical team collaborated with an Albanian team of physicians to perform the first successful renal transplant. With continued cooperation and perseverance developing a transplant program in Albania is within reach.

Hypertension in children: an update on treatment strategies.

PURPOSE OF REVIEW: Hypertension is among the more prevalent treatable diseases that afflict children. Pediatric hypertension carries significant short-term morbidity and long-term risk for the development of cardiovascular disease. This review addresses issues significant to the chronic management of hypertension and discusses common pharmacological agents currently used to treat elevated blood pressure in children. RECENT FINDINGS: The recent change in the Federal 2002 Best Pharmaceuticals for Children Act has led to the study and approval of new antihypertensive medications for use in pediatrics. Several antihypertensive medications are commercially available in liquid form or can be extemporaneously compounded for flexible dosing and ease of administration. SUMMARY: The availability of normative blood pressure data and several pharmacologic antihypertensive agents makes early detection and treatment of hypertension in children a realizable goal. The long-term effect of chronic antihypertensive therapy on growth, as well as the prevention of future development of cardiovascular disease, is not fully understood.

Use of rhGH in children with chronic kidney disease: lessons from NAPRTCS.

We evaluated the utilization and potential benefits of recombinant human growth hormone (rhGH) in children with chronic kidney disease (CKD) and following renal transplantation in a large patient cohort. We queried the chronic renal insufficiency (CRI), dialysis, and transplant registries of the North American Pediatric Renal Trials and Collaborative Studies (NAPRTCS) to characterize the frequency of rhGH utilization, factors related to its usage, and the relationship between rhGH usage and catch-up growth. Data from 6,505, 5,122, and 4,478 CRI, dialysis, and transplant patients, respectively, was evaluated. Percentage utilization of rhGH 2 years after registry entry was 22%, 33%, and 3% in children with a height standard deviation score (SDS)<-1 and age<17 years (termed candidate group) in CRI, dialysis, and transplant patients, respectively. Multivariate logistic regression analysis showed that the likelihood of using rhGH was significantly correlated with age, gender, geographical region of residence and height category within the candidate group (p<0.01). The use of rhGH was associated with catch-up growth in 27%, 11%, and 25% of candidate CRI, dialysis, and transplant patients, respectively. In the candidate group, percentage catch-up growth was highest in children who were Tanner stage 1-2, who comprised 19.4%, 7.1%, and 25.5% of the CRI, dialysis, and transplant patients, respectively. Using multiple regression analysis, the estimated impact of rhGH on final adult height (age>19 years) was 0.80, 0.50, and 0.19 SDS, in CRI, dialysis, and transplant patients, respectively. Thus, rhGH can improve height gain in some children with CKD. The use of rhGH appears to be most effective in prepubertal children with CRI.

Stature in children with chronic kidney disease: analysis of NAPRTCS database.

Despite recent advances in the management of children with chronic kidney disease (CKD), growth remains suboptimal. The purpose of this study was to evaluate factors associated with short stature in children with CKD. We evaluated the chronic renal failure registry of the North American Pediatric Renal Transplant Cooperative Studies (NAPRTCS) to determine the relations among primary diagnosis, age, race, residual renal function, acidosis, anemia, serum phosphorous, calcium, parathyroid hormone (PTH), albumin, and height at entry into the registry in children with CKD. A total of 5,615 patients were entered into the registry between January 1994 and January 2004. We found that older patients, those with glomerular filtration rate (GFR) >50 ml min(-1) 1.73 m(-2), black patients and patients with focal segmental glomerulosclerosis (FSGS) were at lower risk of being short at entry. Anemia (hematocrit below 33%) was an independent risk factor for short stature. Acidosis, serum phosphorous, calcium, albumin and PTH at registration were poor predictors of short stature. Age, race, primary diagnosis, and residual renal function were associated with short stature in children with CKD.

Impact of alendronate on quality of life in children with osteogenesis imperfecta.

Osteogenesis imperfecta (OI) is a debilitating clinical condition characterized by fragile bone and skeletal deformity. Over the past decade frequent reports have suggested that the cyclical administration of intravenous pamidronate has a positive impact on bone density and skeletal fractures; however, the impact of such therapy on the quality of life (QOL) has rarely been reported. Alendronate, an oral bisphosphonate, is widely used to treat osteoporosis. The purpose of this study was to evaluate the impact of daily alendronate on QOL and bone parameters in children with OI. A prospective double-blind crossover study was designed in which placebo was alternated with daily alendronate. Twenty children with types I, III, and IV OI were recruited. Seventeen patients completed the study. Markers of QOL were measured in children with type III and IV OI (n = 15) using total mobility (PEDI), self-care (WeeFIM), well-being, pain, and use of analgesic scores. After 1 year of alendronate therapy, vertebral bone mineral density (BMD) improved from a change in standard deviation score (z-score) of 0.89 +/- 0.19 to -0.12 +/- 0.14 after 1 year of placebo (P < 0.001). All QOL markers, except for mobility score, improved in response to alendronate therapy. Change in height z-score also improved in response to 1 year of alendronate therapy (0.41 +/- 0.21 vs. -0.09 +/- 0.11, P < 0.05). Alendronate therapy did not alter serum levels of calcium, osteocalcin, parathyroid hormone (PTH), 1, 5 (OH)2 vitamin D, cholesterol, or urinary hydroxyproline or any other biochemical marker evaluated. Alendronate decreased by 56% urinary cross-linked N-telopeptide of type 1 collagen divided by urinary creatinine (uNTX/uCr). Daily alendronate therapy was well tolerated. Only two patients had mild gastrointestinal discomfort, responding to minor adjustments in alendronate intake. Daily alendronate therapy is safe and effective in improving QOL in children with OI.

Patterns and time of initiation of dialysis in US children.

The purpose of this communication is to study the clinical patterns and level of residual renal function at the initiation of dialysis in children in the United States of America (US). Data were reviewed for 7,039 children under the age of 20 years and 647,600 adults extracted from the patient incidence report, obtained from the United States Renal Data Systems (USRDS), who were initiated on dialysis between January 1995 and September 2002. Based on pre-defined exclusion criteria, only 4,808 of the 7,093 (67.8%) pediatric entries were included in the analysis. About 6.9% of the entries were not used because of missing data only, 23.3% because of out of range data only, and 2.0% because of both missing and out of range data, a total of 32.2% exclusions. For adults, 570,808 (88.1%) had acceptable data. The percentage of the 4,808 children who were initiated on dialysis with an estimated GFR greater than 10 mL min(-1) per 1.73 m(2) (early start) was 49.6%. Using logistic regression, the factors affecting the probability of an early start were sex, race, type of insurance, region of the country, age at initiation of dialysis, and the year dialysis was initiated. The highest chance of starting dialysis early (0.77) was for a white male, aged 15-19 years, with insurance and residing in the Northwest part of the US The percentage of 4,808 children who initiated dialysis with an estimated GFR less than 5 mL min(-1) per 1.73 m(2) (late start) was 7.3%. The factors affecting the probability of a late start were sex, race, type of insurance, and the year dialysis was initiated. The greatest chance for a late start of dialysis was for black female patients without insurance (0.21). Mean estimated GFR at the start of dialysis was higher for children than for adults (10.7+/-4.6 vs 8.2+/-4.1 mL min(-1) per 1.73 m(2), respectively, P<0.0001). It was concluded that patterns of management of children with ESRD are not uniform among US children.