Pulse cyclophosphamide induction treatment in Thai children with diffuse proliferative lupus nephritis.

AIM: To report the effectiveness of pulse cyclophosphamide induction therapy and to identify predictors for unresponsiveness to treatment in Thai children. METHODS: Children with biopsy-proven diffuse proliferative lupus nephritis admitted to Chiang Mai University hospital between 2001 and 2006 were retrospectively studied. Patients received a test dose of 750 mg/m(2) at the first month followed by six cycles of monthly cyclophosphamide (IVCY) at a dose of 1 g/m(2) (maximum 1 g) as induction therapy. Responsiveness to treatment, defined as urinary protein to creatinine ratio of less than 0.3 with normalization of C3 level and clinical remission, was assessed at the end of the induction period. Gender, age at onset, duration of disease before treatment, hypertension, clinical nephrotic syndrome, amount of proteinuria, serum creatinine, creatinine clearance, serum C3 level and crescentic formation were compared between responsive and nonresponsive groups. Maintenance therapy with quarterly pulse IVCY or Azathioprine or Mycophenolate mofetil was given for 18-24 months after remission. RESULTS: Twenty nine patients with a mean age of 10.3 ± 2.6 years were studied. Hypertension, microscopic haematuria and nephrotic-range proteinuria were seen in 66%, 86% and 60% of the patients, respectively. Forty-one per cent of biopsies showed cellular or fibrocellular crescents. Twenty patients (69%) achieved remission at the end of induction therapy. There were no significant differences in all parameters studied between responsive and nonresponsive groups. The relapse rate after maintenance therapy was 58.8%. CONCLUSION: Our results show that pulse cyclophosphamide is an effective regimen for induction therapy in children with diffuse proliferative glomerulonephritis. No definite predictor for unresponsiveness was detected in this study.

Psychosocial functioning of children with systemic lupus erythematosus.

AIMS: Systemic lupus erythematosus (SLE) is a chronic illness in children. Involvement of multiple systems; the chronicity, as well as the treatment, has had great impact on children and their families. The objective of this study was to assess emotional and behavioural problems in childhood lupus during disease remission. METHODS: Children with SLE and healthy controls, aged 8-15 years, were studied. Disease remission was confirmed by using the SLE Disease Activity Index (SLEDAI). The Children's Depression Inventory (CDI) and Multidimensional Anxiety Scale for Children (MASC) were rated by the children themselves. The Child Behaviour Checklist was completed by their parents. RESULTS: The sample included 40 children with SLE and 40 controls. Their mean age was 12.9 ± 2.1 and 12.1 ± 1.8 years in the SLE and control groups, respectively. The average duration of the disease was 2.6 years. The SLEDAI in the SLE group ranged from 0-1, indicating inactive disease. The mean CDI scores were 8.9 and 10.9 in lupus children and controls, respectively. The mean MASC score was 44.7 in children with SLE and 48.4 in controls. The internalizing, externalizing and total behavioural scores were not significantly different in both groups (9.0 vs. 10.6; 6.6 vs. 8.1; 27.3 vs. 32.5). Only the social competence score was lower in children with SLE (P= 0.03). CONCLUSIONS: SLE is a multi-system involvement disease with wide ranging effects on children's physical and psychosocial functioning. However, children with SLE, during inactive disease, were not found to be at increased risk of psychosocial dysfunctions.

Interventions for preventing and treating kidney disease in Henoch-Schönlein Purpura (HSP).

BACKGROUND: To determine the benefits and harms of therapies used to prevent or treat kidney disease in Henoch-Schönlein Purpura (HSP). OBJECTIVES: To evaluate the benefits and harms of different agents (used singularly or in combination) compared with placebo or no treatment or another agent for the prevention or treatment of kidney disease in patients with HSP. SEARCH STRATEGY: Randomised controlled trials (RCTs) and quasi-RCTs were identified from the Cochrane Renal Group's specialised register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE using optimally sensitive search strategies combined with search terms for HSP. SELECTION CRITERIA: RCTs comparing any intervention used to prevent or treat kidney disease in HSP compared with placebo, no treatment or other agents were included. DATA COLLECTION AND ANALYSIS: Three authors independently assessed trial quality and extracted data from each study. Statistical analyses were performed using the random effects model and the results were expressed as risk ratio (RR) for dichotomous outcomes and mean difference (MD) for continuous outcomes with 95% confidence intervals (CI). MAIN RESULTS: Ten studies (1230 children) were identified. There was no significant difference in the risk of persistent kidney disease at six months (3 studies, 379 children: RR 0.51, 95% CI 0.24 to 1.11) and 12 months (3 studies, 498 children: RR 1.02, 95% CI 0.40 to 2.62) in children given prednisone for 14 to 28 days at presentation of HSP compared with placebo or supportive treatment. In children with severe kidney disease, there was no significant difference in the risk of persistent kidney disease with cyclophosphamide compared with supportive treatment (1 study, 56 children: RR 1.07, 95% CI 0.65 to 1.78) and with cyclosporin compared with methylprednisolone (1 study, 19 children: RR 0.39, 95% CI 0.14 to 1.06). AUTHORS' CONCLUSIONS: Data from RCTs for any intervention used in improve kidney outcomes in children with HSP are very sparse except for short-term prednisone. There was no evidence of benefit of prednisone in preventing serious long-term kidney disease in HSP.

Hematological abnormalities in patients with distal renal tubular acidosis and hemoglobinopathies.

Mutations of the human SLC4A1 gene encoding erythroid and kidney isoforms of anion exchanger 1 (AE1, band 3) result in erythrocyte abnormalities or distal renal tubular acidosis (dRTA) and such mutations are observed in Southeast Asia, where hemoglobinopathies are prevalent. Genetic and hematological studies in 18 Thai patients with dRTA have shown that 12 of them (67%) carried SLC4A1 mutations (7 G701D/G701D, 3 SAO/G701D, and 2 G701D/A858D). Of these 12 patients, three had homozygous G701D/G701D and heterozygous Hb E; one compound heterozygous SAO/G701D and heterozygous alpha(+)-thalassemia; and one compound heterozygous G701D/A858D and heterozygous Hb E. Of 6 patients without SLC4A1 mutation, two each carried heterozygous or homozygous Hb E and one of the latter also had Hb H disease (--(SEA)/-alpha(4.2)). The blood smears of patients with homozygous G701D/G701D showed approximately 25% ovalocytes. Strikingly, the patients with coexistence of homozygous G701D/G701D and heterozygous Hb E had 58% ovalocytes. Similarly, the patients who had compound heterozygous SAO/G701D showed 49% ovalocytes, but the patient with coexistence of compound heterozygous SAO/G701D and heterozygous alpha(+)-thalassemia had 70% ovalocytes. Our previous study has shown that under metabolic acidosis, the patients with homozygous G701D/G701D or compound heterozygous SAO/G701D had reticulocytosis, indicating compensated hemolysis. A patient with compound heterozygous SAO/G701D and heterozygous alpha(+)-thalassemia presented with hemolytic anemia and hepatosplenomegaly which was alleviated by alkaline therapy. Taken together, the coexistence of both homozygous or compound heterozygous SLC4A1 mutations and hemoglobinopathy has a combined effect on red cell morphology and degree of hemolytic anemia, which is aggravated by acidosis.

Distal renal tubular acidosis associated with anion exchanger 1 mutations in children in Thailand.

BACKGROUND: Mutations in the anion exchanger 1 (AE1) gene encoding the erythroid and kidney anion (chloride-bicarbonate) exchanger 1 may result in hereditary distal renal tubular acidosis (dRTA). Hemoglobinopathies are common in Thailand. We analyzed AE1 and hemoglobin mutations in children in Thailand with dRTA to evaluate their association with clinical manifestations. STUDY DESIGN: Case series. SETTING & PARTICIPANTS: 17 patients were recruited from 6 referral hospitals in 4 regions of Thailand. PREDICTORS: AE1 mutations were detected by means of nucleotide sequence alterations. Hemoglobin E (HbE) was detected by means of hemoglobin typing, and thalassemia, by means of analysis of globin genes. Hemolytic anemia was indicated by decreased hemoglobin and hematocrit values in the presence of reticulocytosis. OUTCOMES & MEASUREMENTS: Leading clinical manifestations in patients were failure to thrive and muscle weakness. Compensated or overt anemia was identified in some cases. Coexistence of AE1 mutations with HbE or alpha(+)-thalassemia was present in a number of patients. RESULTS: 12 of 17 patients (70%) carried AE1 mutations, 7 patients (41%) had HbE, and 1 patient (6%) had alpha(+)-thalassemia. Patients with AE1 mutations presented with compensated hemolysis when they had metabolic acidosis. A patient with compound heterozygous Southeast Asian ovalocytosis/G701D and heterozygous alpha(+)-thalassemia showed severe hemolytic anemia. LIMITATIONS: 5 patients (30%) without detectable AE1 mutation also were unknown for other genetic abnormalities. CONCLUSIONS: Most of the patients with dRTA studied carried autosomal recessive AE1 mutations. Metabolic acidosis, which could be alleviated by adequate alkaline therapy, induced variable degrees of hemolysis in patients with dRTA associated with autosomal recessive AE1 mutations, especially in the presence of thalassemia.

Methylprednisolone treatment in children with nephrotic primary focal segmental glomerulosclerosis.

OBJECTIVE: To examine the effectiveness of pulse methylprednisolone in children with nephrotic primary focal segmental glomerulosclerosis. MATERIAL AND METHOD: Medical records of children, who were treated with a pulse methylprednisolone regimen for nephrotic syndrome resulting from primary focal segmental glomerulosclerosis between 1987 and 2005, were retrospectively reviewed. The age, gender, urine protein, serum creatinine, and glomerular filtration rate at the onset of nephrotic syndrome were recorded. Urine protein, serum creatinine, glomerular filtration rate, and percentile of height before and after methylprednisolone treatment were compared. RESULTS: There were six patients (4 male, 2 female) in the present report. The mean age at onset was 9.5 +/- 2.2 years. Hypertension was noted in four patients and mild renal insufficiency in three. All patients had nephrotic-ranged proteinuria at onset and they were initially treated with prednisolone. Two were steroid-dependent and four were steroid-resistant. All of the steroid resistant cases were also resistant to oral cyclophosphamide. After methylprednisolone treatment, remission of proteinuria was noted in five patients (83%) (2 complete, 3 partial). Mean duration to remission was 20.8 weeks. There were no significant changes in serum creatinine (p = 0.43), GFR (p = 0.78) and percentile of height before and after treatment. No hypertension or cardiac arrhythmia was detected during methylprednisolone administration. The follow-up period after completion of the methylprednisolone regimen was 19.5 +/- 15.2 months (range 4-36 months). The clinical course of five patients with remission was characterized by sustained remission in three patients. Two patients relapsed at 2 and 8 months after treatment. CONCLUSION: Methylprednisolone was effective and safe in treating nephrotic children with primary focal segmental glomerulosclerosis. There was a high incidence of relapse shortly after the cessation of treatment. However, a larger number of patients and longer period of follow-up are needed to confirm this conclusion.

Infantile osteopetrosis in four Thai infants.

Four Thai infants, aged between 4 and 23 months, had progressive abdominal distension, pallor and delayed or regressed developmental milestones, with age at onset of 1 month, 3 months, 4 months and 1 month, respectively. Clinical findings consisted of growth and developmental retardation, anemia, frontal bossing, marked hepatosplenomegaly, and hearing and visual impairment. Laboratory findings revealed moderate anemia, leukocytosis and thrombocytopenia. The radiographic findings comprised generalized sclerosis of all bones, including the cranial base, and obliteration of the medullary canals and trabecular patterns. The first and second patients, who had swelling of the wrist joints and prominent costochondral junctions, had hypophosphatemia, elevated levels of serum alkaline phosphatase, and metaphyseal flaring on their radiographs, which was consistent with infantile osteopetrosis complicated by rickets. After Stoss therapy, there were biochemical and radiological responses suggesting vitamin D deficiency in the first patient, but not in the second. The third patient, who had hypocalcemia, hypophosphatemia and normal levels of serum alkaline phosphatase, received vitamin D at 3000 units per day, without improvement. Despite frequent blood transfusions, all patients continued to deteriorate and were finally lost to follow-up. Rickets should be identified and treated at the onset, because treatment of rickets leads to improvement in well-being and an adequate clinical response to bone marrow transplantation.

Transient hyperkalemia and hypoaldosteronism in a patient with acute glomerulonephritis.

The authors describe a 7-year-old boy with acute glomerulonephritis, who developed acute renal failure in the early course of his disease. While the renal function and other clinical manifestations gradually improved, hyperkalemia occurred unexpectedly, and returned to normal level spontaneously after a short period of symptomatic treatment. With the result of a low transtubular potassium gradient (TTKG) level, it was concluded that hypoaldosteronism was the major cause of hyperkalemia in this patient.

Infection in children with lupus nephritis receiving pulse and oral cyclophosphamide therapy.

Infection is the major complication of cyclophosphamide therapy in patients with lupus nephritis. The objectives of this study were to report and compare the rate of infection between children with lupus nephritis who had received intravenous pulse cyclophosphamide (IVCY) and those who had received oral cyclophosphamide (OCY) and to determine the risk factors for infection during treatment with cyclophosphamide in these groups. Records of nine patients who had received IVCY from the beginning [pure intravenous cyclophosphamide (PIVCY) group], 11 patients who had received prior oral cyclophosphamide and later switched to IVCY [combined intravenous cyclophosphamide (CIVCY) group] and 41 patients who had received OCY were reviewed. Infection occurred in 21 of 61 patients (34%). In the PIVCY group, four episodes of infection occurred in three of nine patients (33%). In the CIVCY group, six episodes of infection occurred in four of 11 patients (36%). In the OCY group, 18 episodes of infection occurred in 14 of 41 patients (34%). The rate of infection between these groups was not different (P=0.99). None of the following parameters were risk factors for infection: cumulative dose of cyclophosphamide, leukopenia and neutropenia. On the contrary, white blood cell (WBC) count and polymorphonuclear cell (PMN) count were significantly less in the no-infection group (P=<0.001, P<0.001, respectively), with odds ratios for leukopenia (WBCs <4,000 mm(3)) and neutropenia (PMNs <1,500 mm(3)) between the infection and the no-infection group equal to 0.18 (95%CI 0.05-0.63) and 0 (95%CI 0-0.19), respectively. Most of the patients who had infection received prednisolone at a dosage of more than 0.5 mg/kg per day (67% of the PIVCY group, 50% of the CIVCY group and 83% of the OCY group). Fatal infections occurred in two patients who had concomitant active systemic lupus erythematosus (SLE). Although lymphopenia (lymphocyte count <1,500/mm(3)) was not the risk factor for infection, it was observed that six of seven patients with herpes zoster had lymphopenia. Herpes zoster seemed to occur more frequently in the OCY group (15%) than in the whole IVCY group (5%), but there was no statistical difference (P=0.41). We conclude that the rate of infection in the IVCY and OCY group was not different. Infection is likely to occur in patients receiving a concomitant high dose of prednisolone. The occurrence of fatal infection in patients with active disease should be noted. No single risk factor was detected in this study.

Steroid-resistant nephrotic syndrome associated with Kimura's disease.

Kimura's disease is a chronic inflammatory disease characterized by tumor-like lesions in the soft tissue and lymph nodes of head and neck area or parotid gland. It has a high frequency of an association with nephrotic syndrome. Reported cases of nephrotic syndrome and Kimura's disease were mostly from adult patients with only 5 children mentioned. This study reports the case of a 15-year-old-boy who manifested with steroid-resistant nephrotic syndrome for 4 years. Pathological examination of the kidney revealed mild mesangial proliferation. Subsequently, he developed a soft-tissue mass in the parotid gland area. Histopathological investigation of the mass revealed eosinophilic infiltration together with plasma cells and mast cells which is a main characteristic of Kimura's disease. The patient, however, continued to have nephrotic-range proteinuria after removing the subcutaneous mass.

A girl with Takayasu arteritis associated with possible systemic lupus erythematosus.

Takayasu arteritis is an inflammatory disease that affects the aorta and its main branches. Its etiology is obscure. Its association with systemic lupus erythematosus has been reported in the English literature in about 20 cases worldwide, and a relationship with a positive tuberculin test, either with or without tuberculosis, has also been mentioned. We report a pediatric patient who presented with renovascular hypertension secondary to Takayasu arteritis associated with a strongly positive tuberculin test and who subsequently developed possible systemic lupus erythematosus 8 months later.