Keith K. Lau

Serum levels of galactose-deficient IgA in children with IgA nephropathy and Henoch-Schönlein purpura

IgA nephropathy and Henoch-Schönlein purpura nephritis (HSPN) are related diseases characterized by deposits of IgA1-containing immune complexes in the renal mesangium. Adult patients with IgA nephropathy have aberrantly glycosylated IgA1 (galactose-deficient O-linked glycans) in the circulation and renal deposits. However, IgA1 glycosylation has not been studied in pediatric patients with IgA nephropathy. Using our quantitative lectin enzyme-linked immunosorbent assay (ELISA) test, we measured serum levels of galactose-deficient IgA1 of children with IgA nephropathy and HSPN and controls. Children with IgA nephropathy and HSPN had serum levels higher than those of healthy children or renal-disease controls with C1q nephropathy. Furthermore, lectin ELISA identified patients with HSPN whose clinical course mimicked that of IgA nephropathy. In summary, pediatric patients with IgA nephropathy and HSPN have an aberrancy in the glycosylation in IgA1 O-linked glycans that is similar to that in adults with IgA nephropathy.

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.

Pediatric en bloc kidney transplantation into pediatric recipients

Lau KK, Berg GM, Schjoneman YG, Perez RV, Butani L. Pediatric en bloc kidney transplantation into pediatric recipients. Pediatr Transplantation 2010: 14: 100–104.

Five years' experience with thymoglobulin induction in a pediatric renal transplant population

Abstract:  Antibody induction therapy is used in the majority of pediatric patients undergoing renal transplantation. Our center has previously reported short‐term outcomes with TMG as induction therapy. We now present our experience over the last five yr. Patients received TMG intra‐ and post‐operatively at a dose of 1.5 mg/kg/day. The dose was decreased to 0.75 mg/kg/day or held dependent on the patients WBC and platelet counts. Post‐transplant immunosuppression also included corticosteroids, MMF, and either TAC or CSA. Patient and graft survival, number of acute rejection episodes, creatinine clearance, incidence and type of infections, and trough levels of calcineurin inhibitor drugs were monitored during the follow‐up period. Thirty‐four renal transplants were performed in 33 pediatric patients ranging in age from 1.7 to 17.8 yr. Seventeen rejection episodes occurred during the time of follow‐up with three patients having more than one episode, but only three episodes occurred within the first year after transplantation. Three patients had graft loss in the first week after transplantation from primary non‐function (1) or technical failure/thrombosis (2). Graft losses occurred in seven additional patients during the time of follow‐up with the first loss occurring at 17.7 months. Among patients with functional grafts at one wk after transplant, graft survival at one and three yr was 100% and 73% respectively. There were no patient deaths. There were no cases of post‐transplant lymphoproliferative disease or other malignancy. One patient had symptomatic CMV disease. TMG is safe and effective as induction therapy in pediatric renal transplant patients. Late graft loss remains a challenge in the pediatric patient population, particularly in adolescents.

Rapid steroid discontinuation for pediatric renal transplantation: A single center experience

Abstract:  To determine the outcomes of pediatric renal transplant recipients who received immunosuppression consisting of early withdrawal of corticosteroids at a single Northern California center. Protocols using minimal steroid exposure have been recently reported in adult transplant recipients with successful results. We examined the outcomes of pediatric renal transplant recipients who were managed at our center using a protocol with very early discontinuation of steroids after renal transplantation. We retrospectively studied the medical records of all renal transplant recipients followed at the Children’s Hospital at the University of California, Davis Medical Center from 01/2004 to 12/2005. All patients were less than 18 yr of age at the time of transplantation. The immunosuppressive protocol included three tapering daily doses of methylprednisolone, together with five doses of thymoglobulin followed by maintenance therapy with tacrolimus and MMF. Eight patients with equal numbers of males and females were transplanted during this time period. There were equal numbers of Caucasians, African‐Americans, Hispanics, and Asians. A total of 37.5% (3/8) of the subjects received preemptive transplantation, 25% (2/8) received peritoneal, and 37.5% (3/8) received hemodialysis before transplantation. The median (range) age at transplantation was 12.3 (3.1–16.0) year with a follow‐up of 1.7 (0.9–2.8) year. At one yr post‐transplantation, 57% (4/7) of patients still required anti‐hypertensives. Three children required erythropoietin supplementation after transplantation. The mean delta height standard deviation score at 12 months was 0.20 ± 0.56. There were no episodes of clinical acute rejection. One patient switched from tacrolimus to sirolimus due to biopsy‐proven CAN. No patient became diabetic or required hypoglycemic agents. Surveillance biopsies showed no subclinical acute rejection in any patient. Steroid‐free immunosuppression is safe in children after renal transplantation. Larger number of patients and longer follow‐up are required to further confirm the effectiveness and safety of immunosuppression with rapid steroid discontinuation.

Mitochondrial encephalopathy with lactic acidosis and stroke-like episodes syndrome with hypothyroidism and focal segmental glomerulosclerosis in a paediatric patient

Herein, we report on a paediatric patient with mitochondrial encephalopathy, lactic acidosis and stroke-like episodes (MELAS) who was hospitalized for acute on chronic renal insufficiency, seizures and deterioration of the level of consciousness. She also had hypertension, hypothyroidism and nephrotic range proteinuria. Kidney biopsy revealed many sclerotic glomeruli and focal segmental glomerulosclerosis (FSGS). Glomerulopathy is rare in patients with MELAS, and FSGS has been reported only in a few patients. The histopathological features of the renal biopsy suggested that the aetiology of the FSGS may have been secondary to chronic renal injury rather than from a primary immunologic cause. Moreover, our case is unique in that, the coexistence of MELAS, hypothalamic hypothyroidism and FSGS has not been reported in the past. The purpose of this report is to increase the awareness of health-care professionals, especially in the fields of paediatrics, neurology, endocrinology and nephrology, regarding the manifestations and complications of MELAS.

Control of aquaporin 2 expression in collecting ducts of quail kidneys

Birds and mammals are the only vertebrates that can concentrate urine. Avian kidneys contain structurally primitive loopless nephrons and also more advanced looped nephrons, in the cortical and medullary regions, respectively. We have identified the gene sequence of an aquaporin 2 (AQP2)-homologue water channel in collecting ducts of kidneys from adult quail, Coturnix japonica. Although immunoreactive quail AQP2 (qAQP2) was found in both types of nephrons, the expression is enhanced more clearly in the medullary regions after water deprivation. We therefore hypothesized that regulation of qAQP2 expression in quail kidneys via antidiuretic hormone (ADH) may require more advanced nephron structure. In this study, we determined the expression of qAQP2 mRNA in tissues isolated from the cortical and medullary regions before and after water deprivation, by conventional reverse transcriptase-polymerase chain reaction (RT-PCR) and quantitative real-time PCR. In both normally hydrated and water-deprived groups, qAQP2 mRNA levels in the medullary regions were significantly higher (P<0.01) than in the cortical regions. In medullary areas, qAQP2 mRNA levels (real-time PCR normalized with 18S) were significantly higher (P<0.01, ANOVA) after water deprivation (1.09+/-0.10) than in normally hydrated controls (0.46+/-0.08). In cortical areas, qAQP2 mRNA levels were also higher after water deprivation (0.37+/-0.05) than in controls (0.11+/-0.02). qAQP2 mRNA signals determined by in situ hybridization of digoxigenin-labeled riboprobe were also enhanced after water deprivation in both cortical and medullary collecting ducts. The results suggest that, contrary to our hypothesis, the endogenous production of ADH by water deprivation stimulates qAQP2 mRNA in both loopless and looped nephrons.

Use of a "composite" vascular access graft in a young child on hemodialysis.

Although arterio‐venous fistulae (AVF) are currently considered to be the first choice of permanent vascular access for hemodialysis, there are some patients who are not candidates for fistulae and synthetic grafts provide other options. The Thoratec (Vectra™) polyurethane vascular access graft is a new prosthetic graft that may be cannulated within days of insertion due to “self‐sealing” properties. However, a tendency for kinking at the suture site due to the strong elasticity of this graft, leading to undesirable complications such as thrombosis, have been reported. We describe a surgical modification of the anastomosis by interposing a segment of expanded polytetrafluoroethylene graft (ePTFE, Venaflo™) between the native vessels and the polyurethane graft sections in a pediatric patient. This modification may overcome the kinking complication associated with use of the polyurethane graft and the resulting thrombosis.

Pediatric IgA nephropathy: Clinical features at presentation and outcome for African-Americans and Caucasians

AIM To determine the disease severity at onset and outcome for African-American and Caucasian pediatric patients with IgA nephropathy diagnosed at the Le Bonheur Childrens Medical Center since 1990. DESIGN/METHODS The study population included all patients diagnosed with IgA nephropathy at the Le Bonheur Childrens Medical Center from January 1990 through February 2004. All were below age 18 at biopsy. Clinical features assessed at diagnosis were age, gender, presence of hypertension, history of macroscopic hematuria, degree of proteinuria, severity of renal histology and pattern for immunofluorescent reactants. STATISTICS Students t-test was used to compare age at biopsy and length of follow-up between the 2 groups. Fishers exact test was used to compare features at presentation and patterns of immunofluorescence. Kidney survival was predicted by the Kaplan-Meier method. RESULTS Forty-seven patients (17 African-American, 29 Caucasian) were studied. Clinical features at diagnosis and pattern for all immunofluorescent reactants did not differ significantly between the 2 groups. Mesangial deposition of C1q occurred in 4/17 African-Americans as compared to 1/27 Caucasians (p = 0.06). Four patients (2 African-Americans, 2 Caucasians) progressed to end-stage renal disease. Predicted kidney survival was 96% (94% in African-Americans and 97% in Caucasians) at 1 year and 91% (94% in African-Americans and 89% in Caucasians) at 5 years from diagnosis. Mean time from diagnosis to end-stage renal disease or last follow-up was 3.3 years (3.8 for African-Americans, 3.0 for Caucasians). Macroscopic hematuria occurred prior to diagnosis for 90% of the Caucasian as compared to 61% of the African-American patients (p = 0.03). Urinalysis was normal at last follow-up visit for 24% of African-American patients and 32% of Caucasian patients. CONCLUSION In a relatively small sample from a single center, except for the difference in macroscopic hematuria, clinical features at diagnosis and outcome of IgA nephropathy appear similar for African-American and Caucasian pediatric patients.

Remission of membranoproliferative glomerulonephritis type I with the use of tacrolimus

Membranoproliferative glomerulonephritis, albeit uncommon, is associated with considerable morbidity and mortality in children. Corticosteroids are the mainstay of therapy for severe disease, although data supporting their use are limited. We report our experience in treating two children with nephrotic–nephritic syndrome from idiopathic membranoproliferative glomerulonephritis. Both children experienced a suboptimal response to prolonged courses of steroids and were started on tacrolimus as a steroid-sparing agent. Rapid and complete remission was achieved in both children after initiation of tacrolimus. The purpose of our report is to increase awareness of health care professionals to the potential benefits of this agent in inducing remission in children with severe membranoproliferative glomerulonephritis.