Lavjay Butani

Investigation of pediatric renal transplant recipients with heavy proteinuria after sirolimus rescue.

Background. Little is known about the incidence and evolution of proteinuria as a complication of sirolimus rescue in children. This study describes pediatric renal transplant (Tx) recipients who were treated with sirolimus and who developed heavy proteinuria. Risk factors for the development of proteinuria and its time course are explored. Methods. Data at various time points after sirolimus introduction were abstracted from the records of children treated at the author’s center. The repeated measures general linear model and the Student’s paired t test were used to analyze changes in laboratory values over time. Results. Of the 13 children on sirolimus, 12 developed heavy proteinuria after a mean interval of 1 month. The mean urine protein (Up)-to-creatinine (c) ratio increased from 1.1 to a peak value of 3.9 (P=0.003) at 4.6 months after the start of sirolimus. Although not statistically significant, children on no calcineurin inhibitor (CNI) had a greater increase in the Up/c than those on low-dose CNI. At last follow-up, with the use of angiotensin receptor blockers (ARB), the Up/c declined to 2.2. No predictors could be identified for the development of proteinuria. Conclusions. Heavy proteinuria is common after the use of sirolimus as rescue therapy in children with renal Tx. Whether this is attributable to a toxic effect of the sirolimus itself or to lower CNI exposure is uncertain. Early detection of proteinuria is important to enable prompt intervention. Most children have a reduction in their Up/c with the use of ARB and can therefore be continued on sirolimus.

Idiopathic hypercalciuria in children - How valid are the existing diagnostic criteria?

Idiopathic hypercalciuria is a common metabolic abnormality in children of all ages. There is evidence of an association of idiopathic hypercalciuria with nephrolithiasis, hematuria, and osteoporosis. However, much of this evidence is anecdotal and the precise role of hypercalciuria in the pathogenesis of these conditions is far from clear. Furthermore, the precise definition of idiopathic hypercalciuria has not yet been established. The methodologies for quantitating urinary calcium excretion have also not been standardized, adding another potential confounding factor to the accurate interpretation of urinary calcium excretion. Long-term studies on the natural history of unselected children with idiopathic hypercalciuria are needed to establish the true clinical significance of this condition. The focus of this review is to critically evaluate the methods currently being used to measure urinary calcium excretion in children and to assess the validity of existing criteria for diagnosing idiopathic hypercalciuria.

Are pitfalls of oscillometric blood pressure measurements preventable in children

Abstract.While the routine measurement of blood pressure (BP) in children is common practice, there is lack of uniformity in the types of devices used to measure BP in children. Oscillometric devices are replacing conventional sphygmomanometry in many medical centers. However, the BP determined by these two methods is not identical, nor is it systematically different. Moreover, there is paucity of normative data on oscillometric BP measurements in children. Since oscillometric devices may well ultimately replace conventional standard mercury and aneroid manometers, users of these devices need not only to ensure strict adherence to the technique of obtaining BPs as put forth by the National Heart, Lung and Blood Institute, but also to be certain that the specific device being used has been tested for accuracy in children of the target age in accordance with standard guidelines, and that they are regularly maintained and calibrated. Due to limited normative data on BPs using oscillometric devices in children, we feel that further studies are needed before the auscultatory methods can be altogether eliminated.

The Ped-APS Registry: the antiphospholipid syndrome in childhood

In recent years, antiphospholipid syndrome (APS) has been increasingly recognised in various paediatric autoimmune and nonautoimmune diseases, but the relatively low prevalence and heterogeneity of APS in childhood made it very difficult to study in a systematic way. The project of an international registry of paediatric patients with APS (the Ped-APS Registry) was initiated in 2004 to foster and conduct multicentre, controlled studies with large number of paediatric APS patients. The Ped-APS Registry is organised as a collaborative project of the European Forum on Antiphospholipid Antibodies and Juvenile Systemic Lupus Erythematosus Working Group of the Paediatric Rheumatology European Society. Currently, it documents a standardised clinical, laboratory and therapeutic data of 133 children with antiphospholipid antibodies (aPL)-related thrombosis from 14 countries. The priority projects for future research of the Ped-APS Registry include prospective enrolment of new patients with aPL-related thrombosis, assessment of differences between the paediatric and adult APS, evaluation of proinflammatory genotype as a risk factor for APS manifestations in childhood and evaluation of patients with isolated nonthrombotic aPL-related manifestations.

Corticosteroid-induced hypersensitivity reactions

OBJECTIVE To review and present data on the prevalence, clinical manifestations, diagnostic techniques, and management options in patients with hypersensitivity reactions to corticosteroid preparations. DATA SOURCES All English language articles pertaining to human subjects were reviewed using the Pubmed database from 1964 to June 2002. Indexing terms used were anaphylaxis OR allergic OR anaphylactoid OR hypersensitivity AND steroid OR corticosteroid. Further cross-references were obtained after reviewing articles from the aforementioned search. STUDY SELECTION A total of 11,493 articles were identified with the above search terms. Only those articles, including letters and editorials, describing systemic reactions to steroids were included in the review. Excluded from our review were articles dealing with contact dermatitis to topical steroid preparations. This resulted in a total of 80 articles which were reviewed. RESULTS Although rare, steroid-induced hypersensitivity reactions do occur. They range from minor rashes to the more serious cardiovascular collapse. The mechanisms of steroid-induced adverse events vary from patient to patient, some being classic immunoglobulin E-mediated whereas others are pseudoallergic in nature. Skin testing and provocative challenges offer two ways to diagnose such reactions. Treatment consists of substituting the steroid with an alternative preparation which can be tolerated by the patient. CONCLUSIONS Although little is known about the epidemiology of steroid-induced hypersensitivity, because most data are derived from case reports, it is clear that steroid-induced hypersensitivity is a heterogeneous entity, with no single uniform mechanism. A great deal of work still needs to be done so that the pathogenesis of such adverse events can be clearly determined and effective therapeutic interventions devised.

Adverse Effects Of Mycophenolate Mofetil In Pediatric Renal Transplant Recipients With Presumed Chronic Rejection

BACKGROUND Mycophenolate mofetil (MMF) has been shown to be superior to azathioprine in reducing the incidence of acute rejection in adult renal transplant recipients. Although MMF is also being widely used in pediatric transplant patients, data documenting its safety are limited. METHODS A retrospective review of the transplant records at St. Christophers Hospital for Children was conducted to identify patients who had received MMF. RESULTS Twenty-four children were switched from azathioprine to MMF, 4.8+/-2.9 years after transplantation. After an additional 0.8+/-0.4 years, MMF had been discontinued in 13 patients (54%) because of adverse effects (AE). The only variable that predicted the development of AE was a lower calculated creatinine clearance at the time of initiation of MMF. CONCLUSIONS In pediatric renal transplant recipients with impaired renal function, the use of MMF at the recommended dose is associated with an unacceptably high incidence of AE; in such patients, the MMF dose may require modification for the level of renal function.

Validity of protein-osmolality versus protein-creatinine ratios in the estimation of quantitative proteinuria from random samples of urine in children

BACKGROUND Proteinuria is an important marker of kidney disease. Simple methods to determine the presence of proteinuria in a semiquantitative fashion require measurement of either a protein-creatinine or protein-osmolality ratio. METHODS Urine samples from 134 healthy infants and children and 150 children from the pediatric nephrology practice were analyzed to develop normative data for protein-osmolality ratios on random urine samples and compare protein-osmolality with protein-creatinine ratio as a predictor of 24-hour urine protein excretion. Children were grouped according to age. Three groups were established: infants (<2 years), younger children (2 to 8 years), and older children (9 to 18 years). An adult cohort was similarly analyzed. RESULTS For healthy children older than 2 years, the optimal value discriminating normal from abnormal protein excretion was determined to be a protein-osmolality ratio of 0.15 mg x kg H2O/mOsm. L; for children between 2 and 8 years old, 0.14; and for children older than 8 years, 0.17 (P = not significant between age groups). The corresponding optimal cutoff value for protein-creatinine ratio for the entire group of children older than 2 years is 0.20. Area under the curve analysis of receiver operator characteristic curves showed protein-creatinine ratio was superior to protein-osmolality ratio for predicting abnormal amounts of proteinuria in children and adolescents (P < 0.0001). In adults, both ratios are equally accurate. CONCLUSION Given the superiority of protein-creatinine ratio in children, it would be appropriate to screen urine samples for proteinuria using protein-creatinine ratio rather than protein-osmolality ratio.

Long-term Outcome in Children After Henoch-Schönlein Purpura Nephritis

This study investigated predictors of renal survival in children with Henoch-Schönlein purpura glomerulonephritis. Records of patients with Henoch-Schönlein purpura glomerulonephritis evaluated at our center, from 1953-1990, were reviewed. Data were abstracted from records of patients seen within 5 years. Others were mailed a questionnaire or contacted by telephone. Primary outcome measures were renal survival and presence of urinary abnormalities or hypertension. Of the 65 eligible patients with Henoch Schönlein purpura glomerulonephritis, follow-up data was obtainable for 81.5%. The median follow-up was 20 years. At last follow-up, 66% of patients had normal renal function and urinalyses, and 21% had progressed to end-stage renal disease. The only factor associated with the development of end-stage renal disease was the use of cytotoxic agents. There are no features at initial presentation that identify children at risk of disease progression. Close follow-up of all children with Henoch Schönlein purpura glomerulonephritis is warranted.

Induction Therapy for Pediatric Focal Proliferative Lupus Nephritis: Cyclophosphamide Versus Mycophenolate Mofetil

PURPOSE OF THE STUDY Although cyclophosphamide has been used with success in children, mycophenolate may be a better alternative with less toxicity. The objective of this study is to determine the efficacy of mycophenolate compared with cyclophosphamide as induction therapy in children with class III lupus nephritis. METHODS We retrospectively studied pediatric patients with class III lupus nephritis from two pediatric centers from January 1991 to December 2005 who were treated either with monthly cyclophosphamide or mycophenolate mofetil for the first 6 months. Thirteen patients were studied, with seven patients in the cyclophosphamide group and six patients in the mycophenolate group. RESULTS At 6 months, in the cyclophosphamide group, no patient had achieved complete remission, while 57% were in partial remission. In the mycophenolate group, 66% had achieved complete remission, 17% were in partial remission, and 17% were not in remission. DISCUSSION In a small group of children with class III lupus nephritis, we observed a trend of more patients in the mycophenolate group achieving remission at 6 months. However, the long-term benefit of using mycophenolate as an induction agent is still unclear.

Effect of pretransplant dialysis modality and duration on long-term outcomes of children receiving renal transplants.

Background. Adults receiving preemptive renal transplants have better allograft survival. Our study investigated differences in graft and patient survival based on need for, and duration of, pretransplant dialysis in pediatric renal transplant recipients. Methods. Data on pediatric kidney transplants from January 1995 to December 2000 from the Organ Procurement and Transplantation Network were included. Multivariable Cox proportional hazards analysis was performed to determine the effect of pretransplant dialysis on graft and patient survival. Results. Of 3606 transplants, 28% were preemptive, 38% followed pretransplant hemodialysis (HD), and 34% peritoneal dialysis (PD). The 1-year acute rejection rate was lowest for the preemptive group (36%) compared with the HD (45.5%; P=0.0002) and PD (44.2%; P=0.0008) groups. On multivariable analysis, an increased relative risk of graft failure was seen with, among other variables, deceased donor transplantation and acute rejection within the first year, but not with pretransplant dialysis. When analyzed separately by donor source, pretransplant dialysis had no effect on graft survival for deceased donor graft recipients, whereas for living donor recipients, the use and duration of pretransplant HD adversely affected pediatric renal graft survival in a linear manner. No such effect was seen with pretransplant PD. Conclusions. There is a linear increase in the risk of graft failure with the use of and increasing duration of pretransplant HD for living donor grafts. This indicates another reason to minimize the need for and duration of pretransplant HD in children with chronic kidney disease.