Effect of overweight/obesity on recovery after post-infectious glomerulonephritis.

BACKGROUND: Children with post-infectious glomerulonephritis (PIGN) rapidly recover and have excellent long-term outcomes. After encountering several overweight/obese children with persistent urinary abnormalities during recovery from PIGN, we conducted this retrospective study to determine if overweight/obese status prolonged time to resolution of renal abnormalities after PIGN. METHODS: Records of 20 children with PSGN evaluated between 1/98 and 12/05 were abstracted for demographics, clinical and laboratory data. Primary outcome measures were time to resolution of hypertension, proteinuria, microhematuria, and low complement C3. The effect of overweight/obese status on outcomes was determined using Kaplan Meier Survival and the log-rank test. RESULTS: The median age was 8 years; 30% were overweight/obese. At presentation, 17 (85%) were hypertensive, 10 (50%) had impaired glomerular filtration (GFR), and 18 (90%) had proteinuria. At last follow-up (median 2.8 months) 12% had hypertension, 55% had microhematuria, 5% had proteinuria but none had low GFR. Median time to normalize was: 30 days (GFR), 45 days (blood pressure), 6 weeks (C3) and 6 months (microhematuria). Log rank test showed that proteinuria-, hypertension-, and hematuria-free survival were all lower in children who were overweight/obese although none of the differences were statistically significant. Time to normalization of C3 was shorter in obese/ overweight children. CONCLUSION: In conclusion, overweight/obese children appear to have greater residual renal injury after PIGN. The earlier C3 normalization in overweight/ obese children may indicate that the adverse effect of weight on recovery is from hemodynamic rather than inflammatory factors. Close follow-up of overweight/obese children who develop PIGN is warranted to ensure optimal long-term outcomes.

Determinants of urinary calcium and uric acid excretion in children after renal transplantation.

HC and HU predispose healthy children to develop hematuria and nephrolithiasis. The natural history of HC and HU has not been studied in renal transplant recipients who may be at greater risk of complications. Our study investigated the prevalence of HC and HU after Tx and determined independent predictors of urinary calcium and uric acid excretion. Twenty-five pediatric transplant patients were studied between one and 12 months after Tx. Demographic data and measurements of the random Uca/cr and uric acid excretion were collected. Multivariable regression analyses were used. The median age of the patients was 10.6 yr. The prevalence of HC and HU was 20% each at one month. At 12 months, 20% had HC and 13% had HU. There were no predictors for HC; for HU, the only predictor was systolic hypertension (p = 0.03). Our data demonstrate a high prevalence of HU and HC in pediatric renal Tx recipients. The long-term clinical implication of these metabolic abnormalities remains to be elucidated in prospective trials.

Predictive value of pretransplant inflammatory markers in renal allograft survival and rejection in children.

Pretransplant (pre-Tx) inflammation has been associated with acute rejection (AR) in adult Tx recipients. Our study was performed to determine whether a single pre-Tx serum C-reactive protein (CRP), Neopterin (Neo), and IL-12 determination could predict outcome in pediatric renal Tx recipients. Pre-Tx sera from 51 children transplanted between 1985 and 2000 were analyzed for serum CRP, Neo, and IL-12 for correlation with Tx-related variables. Endpoints were graft loss and AR. Kaplan-Meier and log-rank statistics were used to compare rejection-free and overall graft survival at different quartiles for each marker. Cox regression analysis was performed to determine the independent effects of various pre-Tx variables on the endpoints. The mean age of the children at Tx was 11 years. The mean CRP, Neo, and IL-12 were 1.3 mg/L, 1.78 ng/mL and 123 pg/mL, respectively. At last-follow-up (mean 4.9 years after Tx), 50% of the children had experienced AR and 29% had lost their grafts. The mean CRP, Neo, and IL-12 were not different between the patients with versus without AR or graft loss (P > .4 for all). Neither rejection-free survival nor graft survival was affected by CRP, Neo, or IL-12 quartiles (log-rank test). Cox regression analysis demonstrated no predictive value of any marker on the outcomes. Unlike adults, a single pre-Tx determination of inflammatory markers was not predictive of AR or graft loss in children. The pathogenesis of AR may be different in children with a lesser contribution of alloantigen-independent factors such as chronic infections.

Rapidly progressive lupus glomerulonephritis and concomitant microangiopathy in an adolescent.

We describe our experience managing a 16-year-old girl with systemic lupus erythematosus (SLE) who presented concomitantly with rapidly progressive glomerulonephritis (RPGN) and a thrombotic microangiopathic hemolytic anemia (TMAHA). Her renal biopsy showed evidence of diffuse proliferative glomerulonephritis without glomerular microthrombi. The patient was treated with a combination of intravenous corticosteroids and cyclophosphamide, as well as plasmapheresis, with an excellent response resulting in complete disease remission. The purpose of our report is to make health professionals more aware of TMAHA as a complication of SLE, since the occurrence of TMAHA may confuse the clinical picture, and since its treatment with plasmapheresis is life saving, if performed early.

Gastrostomy tube leak in a patient receiving peritoneal dialysis.

Aggressive nutritional support is imperative to ensure an optimal quality of life in the management of children with end stage renal disease (ESRD). Supplemental enteral feeds using a gastrostomy tube (G-tube) are commonly used for nutritional support to overcome the barrier posed by anorexia. Some of the reported complications of G-tube feeds in children simultaneously receiving peritoneal dialysis include G-tube exit site infection with concomitant peritonitis and G-tube obstruction. We are reporting our experience in managing an 8-year-old Caucasian male with ESRD who, while receiving peritoneal dialysis and G-tube feeds, developed medically intractable peritonitis due to separation of the stomach wall from the anterior abdominal wall, resulting in peritoneal contamination with gastric contents. This complication, which has not previously been reported in patients receiving peritoneal dialysis, had devastating consequences, culminating in the death of our patient.

Late onset of severe graft-versus-host disease in a pediatric liver transplant recipient.

We report the management of a patient with the late onset of chronic graft-versus-host disease (GVHD) after orthotopic liver transplantation. GVHD is a rare complication of solid organ transplants that usually presents early after transplantation and is fatal in the majority of cases. Our patient differs from the typical patient with GVHD in that the onset of her disease was very late. Although most treatment to date consisted of an increase in immunosuppressive therapy, our patient showed an excellent response to a reduction. This resulted in the abatement of the symptoms of GVHD and the preservation of her allograft function.

Conversion from tacrolimus to neoral for postrenal transplant diabetes.

Diabetes mellitus (DM) is a well-recognized complication of immunosuppressive therapy in the post-transplant (Tx) period. The DM encountered in the setting of tacrolimus therapy has been managed in the past by tacrolimus dose reduction and a rapid corticosteroid taper; frequently insulin therapy is also required to maintain normoglycemia. However, the dose reduction of immunosuppressive agents has often resulted in acute allograft rejection. We are reporting our experience in managing three pediatric renal Tx recipients who developed DM in the post-Tx period while on triple immunosuppressive therapy including tacrolimus and corticosteroids. All of our patients were managed by substitution of tacrolimus with conventional doses of neoral while maintaining their usual corticosteroid dose. All three patients had resolution of hyperglycemia and none experienced acute rejection. Tacrolimus was then successfully reinitiated 4.6 months later; at last follow-up, all of our patients have good allograft function and have maintained a normal blood sugar. In conclusion, we feel that conversion of patients from tacrolimus to neoral should be attempted as a safer alternative to tacrolimus dose reduction, for managing post-Tx DM in tacrolimus treated patients.

Transforming growth factor-beta levels in human allograft chronic fibrosis correlate with rate of decline in renal function.

BACKGROUND: Long-term renal transplant function is limited primarily by a progressive scarring process loosely termed "chronic rejection, chronic allograft nephropathy, or allograft fibrosis." Although the etiology of transplant fibrosis is uncertain, several possible factors including chronic cyclosporin A (CsA) exposure may contribute to its pathogenesis. CsA stimulates renal fibrosis perhaps through the induction of the potent pro-sclerotic growth factor, transforming growth factor beta (TGFbeta). Previously, we demonstrated that, in human transplant biopsies, acute CsA toxicity but not acute tubular necrosis is associated with elevated levels of renal TGFbeta protein. We now examine whether long-term CsA treatment (>1 year) is associated with elevated levels of intra-allograft TGFbeta and whether heightened expression of TGFbeta is clinically significant. METHODS: Using immunohistochemical techniques, we determined the relative level of expression of intrarenal TGFbeta protein in transplant biopsies. We studied biopsies obtained from 40 CsA-treated patients that were diagnosed as having chronic allograft fibrosis. Biopsies were scored as having minimal or high levels of TGFbeta. RESULTS: Seventy-two percent of patients expressed high levels of intra-allograft TGFbeta. This group of patients lost renal function at an average rate of -19.5+/-17.3 ml/min/year. In contrast, patients with minimal or no TGFbeta expression experienced a decline of only -6.2+/-4.1 ml/min/year (P=0.01). CONCLUSIONS: These results suggest that the majority of CsA-treated patients with biopsy proven chronic fibrosis have elevated levels of intra-graft TGFbeta that correlates with an increased rate of decline in renal function.

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. Christopher's 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.

Anti-lymphocyte antibodies late in the course of pediatric renal transplantation.

Beyond the immediate post-transplant period, physicians are often reluctant to use anti-lymphocyte preparations to treat episodes of acute renal functional deterioration attributable to acute rejection. This is due to the perception that such episodes are less likely to be reversible, and to concern regarding the potential adverse effects of anti-lymphocyte antibodies, including opportunistic infections, lymphoproliferative disorders, and the development of human anti-mouse antibodies. Records were reviewed for all 365 renal transplants performed in 267 patients at our center from 1971 to 1996. Anti-lymphocyte antibodies were used in an attempt to reverse 6 episodes of corticosteroid-resistant acute rejection in 5 children at a mean interval of 24.5 months following transplantation. The mean serum creatinine at initiation of therapy with the anti-lymphocyte agents was 2.9 mg/dl. Following treatment, the mean serum creatinine decreased to 1.3 mg/dl (P=0.03, Student's t-test). Two patients developed uncomplicated opportunistic infections after completion of anti-lymphocyte therapy; none have developed lymphoproliferative disorders or antibodies to OKT3. We conclude that in the correct clinical setting with corticosteroid-resistant acute rejection, the use of anti-lymphocyte antibodies should not be withheld solely on the basis of length of time since transplantation.

Predictive value of race in post-transplantation recurrence of focal segmental glomerulosclerosis in children.

BACKGROUND: Focal segmental glomerulosclerosis (FSGS) is a leading cause of end-stage renal disease (ESRD) in children, and one of the most difficult to manage because of its high recurrence rate post-transplantation (Tx). Several predictive factors have been associated with disease recurrence (DR) although one in particular, the role of recipient race, has not been adequately evaluated. Herein we report our experience with DR in the post-Tx period in eight patients. METHODS: Records were reviewed for all renal transplants performed at St Christopher's Hospital for Children from 1971 to 1997. RESULTS: Twenty patients received 27 allografts for ESRD due to FSGS. Ten (37%) grafts went to African-American (AA) children, and 16 (59%) to those of Caucasian (C) origin. DR was observed in eight (30%) grafts after Tx. No differences were noted between the patients who developed DR and those who did not, with respect to age at diagnosis or time to ESRD. DR was observed in one (10%) of 10 grafts in AA, compared to seven (41%) of 17 grafts in the other (O) racial groups (P=0.19). At last follow-up, the only AA recipient with DR has maintained stable renal function, while three (43%) of seven in O have lost their grafts. CONCLUSION: In conclusion, in our population post-Tx recurrence of FSGS occurred more frequently and represented a greater threat to graft survival in O recipients than in those of AA descent. Recipient race should therefore be taken into consideration during pre-Tx counselling of families of children with FSGS.

Pleural effusion complicating acute peritoneal dialysis in hemolytic uremic syndrome.

Hemolytic uremic syndrome (HUS) is a leading cause of acute renal failure (ARF) in children, and one for which treatment with peritoneal dialysis (PD) is often necessary. Between January 1982 and December 1996, 176 children received PD for ARF at St. Christopher's Hospital for Children; 34 (19%) of whom had HUS. Of these 34, 7 (20%) developed pleural effusions (PE) while receiving PD, whereas none of the remaining 142 children with other causes of ARF did so. The mean age of the 7 affected children was 5.2 (range 0.4-17) years; none had heart failure or nephrotic syndrome, nor had any of them undergone thoracic surgery. PE were diagnosed by chest radiograph at an interval of 2 (range 1-3) days after starting PD. Thereafter, 4 (57%) patients were successfully maintained on a modified PD prescription; 2 others were converted to hemodialysis and 1 to continuous venovenous hemodiafiltration. Although PE are a known complication of PD, none of the patients so treated for non-HUS related ARF developed them. Whether they represent a purely mechanical complication of PD, or are in some way attributable to HUS itself, is not entirely clear. Regardless, when children with HUS require PD, physicians should monitor for the development of this potential complication to minimize the risk of serious respiratory compromise.

Functional respiratory disorders.

LEARNING OBJECTIVES: Reading this article will enable health care providers to recognize and to diagnose paroxysmal sneezing, sighing dyspnea, habit cough, and vocal cord dysfunction and to reinforce their knowledge of the epidemiology, etiopathology, clinical features, and treatment of these disorders. DATA SOURCES: The literature was reviewed using a MEDLINE search for information relating to the above-mentioned disorders. Indexing terms used included psychogenic wheezing, vocal cord dysfunction, functional respiratory disorders, sighing dyspnea, paroxysmal sneezing, habit cough, and psychogenic stridor. Review was restricted to English language articles from 1966 onward, with cross-referencing to obtain older references. STUDY SELECTION: All human studies that clearly identified the above-mentioned disorders as being nonorganic on the basis of historic and appropriate laboratory evaluation were reviewed. No studies were rejected on the basis of subject age, although special emphasis was given to articles concerning children and adolescents (<18 years old). Of all initially identified studies, 95% fulfilled the inclusion criteria. RESULTS: Functional respiratory disorders are common and affect mostly children, adolescents, and young adults, resulting in considerable morbidity and contributing significantly to patient and physician cost and frustration. A history of a psychiatric disorder with temporally related psychogenic stressors is frequently found. Professionals disagree on the technical classification of some of these conditions (ie, psychosomatic versus somatoform), but there is agreement that treatment directed toward underlying stressors should be the cornerstone of therapy. CONCLUSIONS: Functional respiratory disorders must be considered in patients with atypical symptoms, especially those resistant to conventional therapy. Possible psychogenic stressors must be inquired into and, when identified, treated in a multidisciplinary manner. This may involve reassurance regarding the absence of significant organic abnormality, counseling, and occasional recourse to formal psychiatric intervention.

An unusual renal complication in a patient with osteogenesis imperfecta.

Osteogenesis imperfecta (OI) is a common 'rare' disorder with a reported incidence of 1/15,000 to 1/20,000 in newborns. Skeletal abnormalities in this condition are so striking that its equally important and diverse extraskeletal manifestations frequently remain unnoticed. Sensorineural deafness, blue sclerae, myopia, easy bruisability, dental anomalies, and floppy mitral valves are some of its more frequently reported extraskeletal features. Other less common features include pulmonary hypoplasia, joint contractures, hydrocephalus, and osteogenic sarcoma. Our patient, a 16-year-old boy, developed a previously unreported complication: chronic renal failure, which on subsequent evaluation was attributed to obstructive uropathy secondary to bony pelvic outlet deformities.